Pharmacokinetics of etoricoxib in patients with renal impairment

The effect of renal insufficiency on the pharmacokinetics of etoricoxib, a selective inhibitor of cyclooxygenase-2, was examined in 23 patients with varying degrees of renal impairment (12 moderate [creatinine clearance between 30 and 50 mL/min/1.73 m2], 5 severe [creatinine clearance below 30 mL/min/1.73 m2], and 6 with end-stage renal disease requiring hemodialysis) following administration of single 120-mg oral doses of etoricoxib. Even the most severe renal impairment was found to have little effect on etoricoxib pharmacokinetics. The low recovery of etoricoxib in dialysate (less than 6% of the dose) supports that hemodialysis also has little effect on etoricoxib pharmacokinetics, and binding of etoricoxib to plasma proteins was generally unaffected by renal disease. Single doses of etoricoxib were generally well tolerated by patients with renal impairment. Based on pharmacokinetic considerations, dosing adjustments are not necessary for patients with any degree of renal impairment. However, because patients with advanced renal disease (creatinine clearance below 30 mL/min/1.73 m2) are likely to be very sensitive to any further compromise of renal function, and there is no long-term clinical experience in these patients, the use of etoricoxib is not recommended in patients with advanced renal disease.     

Comparative effects of the antipsychotics sulpiride and risperidone in female rats on energy balance, body composition, fat morphology and macronutrient selection

Previous studies showed that the antipsychotic drugs (APDs) sulpiride (SUL) and risperidone (RIS) induced body weight gain (BWG), hyperphagia, and increased serum levels of leptin, prolactin and corticosterone in female rats. Neither SUL nor RIS increased BWG or food intake (FI) in male rats. To further develop the animal model of APD-induced obesity, SUL (20 mg/kg/sc), RIS (0.5 mg/kg/sc) or vehicle (1 cm³/kg/sc) were administered to female Wistar rats for 10 or 12 days. Body composition, fat tissue morphology, energy expenditure and food efficiency were assessed in animals fed a high-fat diet. In another experiment, macronutrient selection was evaluated in animals fed with pure diets. SUL and RIS significantly increased BWG and FI, with a stronger effect of SUL. Both drugs increased fat gain and food efficiency, and did not modify energy expenditure. Obesity was due to adipocyte hyperplasia. SUL-treated rats significantly decreased fat intake (p=0.039), showed a tendency to increase protein intake and did not modify carbohydrate consumption. No differences were observed between the RIS and the vehicle group. The macronutrient selection pattern differs from that observed in obese people undergoing APD treatment and in most animal models of obesity. Those findings suggest that SUL administration does not properly model APD treatment in humans. Results on macronutient selection in RIS-treated rats must be considered as preliminary, since in this experiment the animals did not gain weight significantly. Other diet protocols and lower APD doses must be tested to further characterize the RIS model.     

Minimal difference in pain associated with change in quality of life in children with rheumatic disease

OBJECTIVE: To establish the minimal change on a pain visual analog scale (VAS) associated with change in self-reported quality of life in pediatric rheumatology patients. METHODS: Subjects were a cohort of 533 pediatric rheumatology patients in Toronto. Pain and perceived quality of life were measured at 2 consecutive visits to a clinic. RESULTS: Among patients who rated quality of life at the second visit as "a little better" and "much better," the mean change in pain score on a 10-cm VAS was reduced by 0.82 and 1.45 cm, respectively. For those whose quality of life changed to "a little worse" and "much worse," the pain scores increased by 1.90 and 3.69 cm. CONCLUSION: Our results suggest that future studies of the assessment and treatment of pain in this population should aim for a minimum reduction in pain score of 0.82 cm on a 10-cm VAS to achieve clinical improvement in quality of life.     

Compensatory cortical activation observed by fMRI during a cognitive task at the earliest stage of MS

Recent functional magnetic resonance imaging (fMRI) studies have suggested that functional cortical changes seen in patients with early relapsing-remitting multiple sclerosis (MS) can have an adaptive role to limit the clinical impact of tissue injury. To determine whether cortical reorganization occurs during high cognitive processes at the earliest stage of multiple sclerosis (MS), we performed an fMRI experiment using the conventional Paced Auditory Serial Addition Test (PASAT) as paradigm in a population of ten patients with clinically isolated syndrome suggestive of multiple sclerosis (CISSMS). At the time of the fMRI exploration, mean disease duration was 6.8 +/- 3.3 months. We compared these results to those obtained in a group of ten education-, age-, and sex-matched healthy controls. Subjects were explored on a 1.5 T MRI system using single-shot gradient-echo EPI sequence. Performances of the two groups during PASAT recorded inside the MR scanner were not different. Statistical assessment of brain activation was based on the random effect analysis (between-group analysis two-sample t-test P < 0.005 confirmed by individual analyses performed in the surviving regions P < 0.05 Mann Whitney U-test). Compared to controls, patients showed significantly greater activation in the right frontopolar cortex, the bilateral lateral prefrontal cortices, and the right cerebellum. Healthy controls did not show greater activation compared to CISSMS patients. The present study argues in favor of the existence of compensatory cortical activations at the earliest stage of MS mainly located in regions involved in executive processing in patients performing PASAT. It also suggests that fMRI can evidence the active processes of neuroplasticity contributing to mask the clinical cognitive expression of brain pathology at the earliest stage of MS.     

Involvement of the hippocampus in implicit learning of supra-span sequences: The case of sj

Learning of supra-span sequences was assessed in a densely amnesic individual (SJ) who suffers from a substantial circumscribed bilateral lesion to the hippocampus. SJ's ability to lay down information originating from repetitive memory recall episodes was assessed using Hebb's supra-span procedure. After assessment of short-term memory span, 25 sequences of span +1 items were presented to SJ for immediate serial recall (ISR), one sequence being presented repeatedly eight times. Learning was deduced by the comparison of ISR scores on the repeated versus nonrepeated sequences of span +1 items. SJ's learning capacity was examined using four different types of stimuli: digits, spatial locations (Corsi block tapping test), words, and pseudowords. Implicit learning of sensorimotor sequences was also assessed in SJ using a serial reaction time (SRT) paradigm. Findings with the supra-span ISR task revealed evidence of learning in SJ with all four types of stimuli. The learning magnitude, as well as learning rate, observed in SJ were comparable to those observed in matched control participants. SJ showed evidence of implicit learning on the SRT paradigm. We conclude that the hippocampus is not required to learn certain types of recurrent information, and that the supra-span ISR task can be considered as an implicit-based learning paradigm. These findings have significant implications for our conceptualisation of implicit learning, and for understanding of the role of the hippocampus in learning.     

Étude du Transport INTrA-Hospitalier du MAlade de Réanimation (TINTAHMAR)

Introduction

Intra-hospital transport (IHT) of critically ill patients is a frequent care associated with an important risk of adverse events (AEs). To decrease the occurrence of AEs, recent guidelines have been edited. Their consequences on adverse event incidence and nurse workload have not been assessed.

Aim of study

The primary objective was to assess the time necessary for the achievement of IHT. Secondary objectives were to describe practices related to IHT, to compare workload according to the presence of nurses during the IHT, and to assess the occurrence of AEs.

Patients and methods

This French multicentric observational study conducted by the SRLF was conducted in 18 French-speaking intensive care units. All critically ill adults requiring IHT were included.

Results

Three hundred and ninety-six IHTs (mean age 61 ±19, mean IGS II 46±24) were assessed. The mean duration of IHT was 67±35 minutes. There was a training program of IHT in only 11% of centers, a check-list in 22%, and traceability procedures in 17%. There was a nurse during the IHT in 51% of cases. The presence of a nurse had no consequence on IHT durations. Adverse events occurred in 15% of IHT. In multivariable analysis, nurse presence was not associated with IHT associated AEs.

Conclusion

An IHT requires time. Despite the poor adherence to the guidelines, this care was associated with low incidence of AES. The presence of nurses during the IHT had no consequence on IHT duration and AEs occurrence.

     

Preoperative antihypertensive medication intake and acute kidney injury after major vascular surgery

Objective

Postoperative acute kidney injury (AKI) is frequent after major vascular surgery and is associated with significant morbidity and mortality. It remains unclear whether the administration of combined oral antihypertensive medications on the day of surgery can increase the risk of postoperative AKI.

Future of non conventional MR techniques in MS

Although conventional magnetic resonance imaging (MRI) is used for diagnosing multiple sclerosis (MS) and monitoring disease activity and course, the correlation between conventional MRI data and clinical findings remains weak. This "clinical-MRI paradox" could be partly due to the lack of MRI specificity related to the heterogeneous pathological substrates of MS and to its inability to quantify the extent of damage in the normal-appearing tissue. Recently, non-conventional MRI techniques, including magnetization transfer MRI, diffusion tensor MRI, and proton MR spectroscopy have been applied to improve our understanding of the pathophysiology of MS. These techniques may provide information about structural and biochemical changes occurring within and outside macroscopic MS lesions (inflammation, demyelination, axonal loss), in particular in the normal-appearing white and grey matter. These techniques could also significantly improve our ability to monitor inflammatory demyelination and axonal injury. In the same way, functional MRI gives us the potential substrate to assess the mechanisms of adaptive cortical reorganization, which may limit the irreversible consequences of MS tissue injury.