Pharmacokinetics of daily daptomycin in critically ill patients undergoing continuous renal replacement therapy.

BACKGROUND: The optimal daptomycin dosing regimen for critically ill patients undergoing continuous renal replacement therapy (CRRT) has still to be established. METHODS: Daptomycin pharmacokinetics was determined in 9 patients after administration of 6 mg/kg/day over 5 days. RESULTS: At steady state, which was reached by day 3, the area under the curve over 24 h (AUC24h) was 667.4 ± 356.6 mg·h/l, and the maximum concentration (Cmax) was 66.9 ±25.3 mg/l. Mean CRRT clearance accounted for 48% (range 32-67%) of total clearance (mean 10.2 ml/min, range 6.1-18 ml/min). Significant correlations were observed between Cmax, minimum concentration (Cmin) and AUC24h (R(2) = 0.91, p < 0.001, and R(2) = 0.94, p < 0.001) and between albumin plasma concentration and free daptomycin (R(2) = 0.7, p = 0.009). CONCLUSION: No significant accumulation occurred with a daily daptomycin dose of 6 mg/kg in patients undergoing CRRT with an effluent flow rate of >30 ml/kg/h. The quantification of trough concentrations (Cmin) appears to be a good surrogate to estimate AUC24h and to monitor daptomycin treatment in patients undergoing CRRT.

Comparative evaluation of the drug interaction screening programs MediQ and ID PHARMA CHECK in neurological inpatients.

PURPOSE: The comparative evaluation of clinical decision support software (CDSS) programs regarding their sensitivity and positive predictive value for the identification of clinically relevant drug interactions. METHODS: In this research, we used a cross-sectional study that identified potential drug interactions using the CDSS MediQ and the ID PHARMA CHECK in 484 neurological inpatients. Interactions were reclassified according to the Zurich Interaction System, a multidimensional classification that incorporates the Operational Classification of Drug Interactions. RESULTS: In 484 patients with 2812 prescriptions, MediQ and ID PHARMA CHECK generated a total of 1759 and 1082 alerts, respectively. MediQ identified 658 unique potentially interacting combinations, 8 classified as "high danger," 164 as "average danger," and 486 as "low danger." ID PHARMA CHECK detected 336 combinations assigned to one or several of 12 risk and management categories. Altogether, both CDSS issued alerts relating to 808 unique potentially interacting combinations. According to the Zurich Interaction System, 6 of these were contraindicated, 25 were provisionally contraindicated, 190 carried a conditional risk, and 587 had a minimal risk of adverse events. The positive predictive value for alerts having at least a conditional risk was 0.24 for MediQ and 0.48 for ID PHARMA CHECK. CONCLUSIONS: CDSS showed major differences in the identification and grading of interactions, and many interactions were only identified by one of the two CDSS. For both programs, only a small proportion of all identified interactions appeared clinically relevant, and the selected display of alerts that imply management changes is a key issue in the further development and local setup of such programs.

Can observers link dream content to behaviours in rapid eye movement sleep behaviour disorder? A cross-sectional experimental pilot study.

Motor activity in rapid eye movement (REM) sleep behaviour disorder (RBD) has been linked to dream content. Systematic and controlled sleep laboratory studies directly assessing the relation between RBD behaviours and experienced dream content are, however, largely lacking. We aimed to investigate whether a link can be established between RBD behaviours and dream content when both are systematically sampled in a controlled setting. We investigated six patients with Parkinson syndrome and RBD who underwent 2-3 nights of video-polysomnographic recording during which they were awakened from REM sleep (10 min after the onset of the second and successive REM periods). Spontaneous free-worded dream reports and a structured dream questionnaire were obtained. Video recordings of motor manifestations were each combined with four dream reports, and seven judges had to match the video clip with the correctly reported dream content from a choice of four possibilities. Of the 35 REM sleep awakenings performed, a total of 17 (48.6%) motor-behavioural episodes with recalled dream content were obtained. The mean of correctly identified video-dream pairs was 39.5% (range 0-100%). Our data showed that reported dream content can be linked to motor behaviours above chance level. Matching accuracy was affected mainly by the clarity of dream reports and the specific nature of movements manifest in video recordings.

REM sleep behavior disorder in 703 sleep-disorder patients: the importance of eliciting a comprehensive sleep history.

OBJECTIVES: The aim of our study was to evaluate the frequency of REM sleep behavior disorder (RBD) in a mixed sleep laboratory population and to assess potential associations. Moreover, we investigated referral diagnoses of patients subsequently diagnosed with RBD and assessed the frequency of incidental RBD. METHODS: Charts and polysomnographic reports of 703 consecutive patients comprising the full spectrum of ICSD-2 sleep disorders [501 males, 202 females; mean age, 51.0+/-14.1 years (range: 10-82 years)] were carefully reviewed. The vast majority of patients were adults (98.7%). Patients were categorized into those with and without RBD. For associations, all concomitant sleep and neurological diagnoses and medications were evaluated. RESULTS: Thirty-four patients (4.8%) were diagnosed with RBD (27 men; 7 women, mean age, 57.7+/-12.3 years). RBD was idiopathic in 11 patients (1.6%; 9 men) and symptomatic in 23 patients (3.3%; 18 men) secondary to Parkinsonian syndromes (n=11), use of antidepressants (n=7), narcolepsy with cataplexy (n=4), and pontine infarction (n=1). Six out of 34 patients were referred for suspected RBD, 20 reported RBD symptoms only on specific questioning, and 8 patients had no history of RBD but showed typical RBD behavioral manifestations in the video-polysomnography. Logistic regression analysis revealed significant associations between RBD and the presence of Parkinsonian syndromes (odds ratio [OR] 16.8, 95%CI: 6.4-44.1; P<0.001), narcolepsy with cataplexy (OR 10.7, 95%CI: 2.9-40.2; P<0.001), SSRI use (OR 3.9, 95%CI: 1.6-9.8; P=0.003), and age (OR 1.5/10-year increase, 95%CI: 1.0-2.0; P=0.039). CONCLUSION: In this population of 703 consecutive sleep-disorder patients, RBD was uncommon. Its etiology was predominantly symptomatic. The majority of RBD patients reported RBD symptoms on specific questioning only, underlining the importance of eliciting a comprehensive sleep history for the diagnosis of RBD.

Multiple sleep latency measures in narcolepsy and behaviourally induced insufficient sleep syndrome.

BACKGROUND: Short mean latencies to the first epoch of non-rapid eye movement sleep stage 1 (NREM1) and the presence of >or= 2 sleep onset REM (SOREM) periods on multiple sleep latency test (MSLT) occur in both narcolepsy-cataplexy (NC) and behaviourally induced insufficient sleep syndrome (BIISS). It is not known whether specific MSLT findings help differentiate the two disorders. METHODS: We analyzed MSLT data including sleep latencies to and between different sleep stages of 60 age-, gender- and body mass index (BMI)-matched subjects (hypocretin-deficient NC, actigraphy-confirmed BIISS, healthy controls: each 20). RESULTS: Mean latency (in minutes) to NREM1 sleep was significantly shorter in NC (1.8+/-1.5) than in BIISS (4.7+/-2.1, p<0.001) and controls (11.4+/-3.3, p<0.001). Mean latency to NREM2 sleep was similar in NC (8.6+/-4.7) and BIISS (8.1+/-2.7, p=0.64); latency to either NREM2 or rapid eye movement (REM) sleep (i.e., the sum of the sleep latency to NREM1 and the duration of the first NREM1 sleep sequence), however, was shorter in NC (4.4+/-2.9) than in BIISS (7.9+/-3.5, p<0.001). Referring to all naps with SOREM periods, the sequence NREM1-REM-NREM2 was more common (71%) in NC than in BIISS (15%, p<0.001), reflecting the shorter latency from NREM1 to NREM2 in BIISS (3.7+/-2.5) than in NC (6.1+/-5.9, p<0.001). CONCLUSIONS: Our findings show that both sleepiness (as measured by NREM1 sleep latency) and REM sleep propensity are higher in NC than in BIISS. Furthermore, our finding of frequent REM sleep prior to NREM2 sleep in NC is in line with the recent assumption of an insufficient NREM sleep intensity in NC. Together with detailed clinical interviews, sleep logs, actigraphy, and nocturnal polysomnography, mean sleep latencies to NREM1