Canadian Consensus Recommendations for the Optimal Use of Enfuvirtide in HIV/AIDS Patients.

BACKGROUND AND OBJECTIVES: An eight-member group consisting of Canadian infectious disease and immunology specialists and a family physician with significant experience in HIV management was convened to update existing recommendations, specifically intended for use by Canadian HIV-treating physicians, on the appropriate use of enfuvirtide in HIV/AIDS patients with resistance to other antiretroviral drugs. METHODS: Evidence from the literature and expert opinions of the group members formed the basis of the guidelines. Comments on the draft guidelines were obtained from other physicians across Canada with HIV expertise. The final guidelines represent the group's consensus agreement. RESULTS AND CONCLUSIONS: The recommendations were developed to guide physicians in optimal practices in patient selection for enfuvirtide treatment and subsequent patient management. The issues considered include positive predictors of response to enfuvirtide, stage of disease, optimization of the background regimen, early indicators of enfuvirtide response, and patient education and support.     

Deliberate hypotension in orthopedic surgery reduces blood loss and transfusion requirements: A meta-analysis of randomized controlled trials

PURPOSE: To determine if deliberate hypotension decreases blood loss and transfusion requirements in patients undergoing orthopedic surgery, a systematic review of all randomized trials addressing this issue was undertaken. METHODS: Electronic databases, citations lists and review articles were searched for potential articles. Relevant articles met the following inclusion criteria: English language, humans undergoing orthopedic surgery, deliberate hypotension used by any method, intraoperative blood loss measured as an outcome, and the trial methodology being randomized and controlled. Four outcomes were analyzed, including estimated blood loss, blood transfused, surgery duration, and quality of the surgical field. For all analyses, the random-effects model was used. RESULTS: Seventeen articles met the inclusion criteria. The surgeries studied included total hip arthroplasty (seven), orthognathic surgery (eight), total knee arthroplasty (one) and spinal fusion (one). A total of 636 patients were randomized across all studies. For blood loss, the overall weighted mean difference favoured treatment, with a savings of about 287 mL of blood [95% confidence interval (CI): -447, -127]. The mean differences also showed a statistically significant benefit for deliberate hypotension in reducing transfusion requirements (-667 mL of blood transfused; 95% CI: -963, -370). Deliberate hypotension was not shown to reduce the duration of surgery (-1.9 min of surgery; 95% CI: -7.2, 3.5) or improve surgical conditions (surgical field quality rating -0.5; 95% CI: -1.1, 0.2). CONCLUSION: This review provides some support for the use of deliberate hypotension in reducing blood loss and transfusion requirements in orthopedic surgery, but these results are tempered by the small sample sizes and poor methodological quality of published studies.     

Effects of l-glutamic acid diethyl ester on discrimination learning in rats

The acquisition of a visuo-tactile simultaneous discrimination task for food reward was evaluated in male albino rats given 0, 120, 240 and 360 mg/kg of l-glutamic acid diethyl ester, an antagonist of quisqualate and kainate receptors. There was an increase in the number of trials to reach the criterion and in the number of errors at the two highest doses of l-glutamic acid diethyl ester in comparison to the two lowest doses. These results indicate a possible role for non-NMDA amino acid receptors in discrimination learning.     

Postpartum hemorrhage today: ICM/FIGO initiative 2004-2006.

Postpartum hemorrhage (PPH) is the main cause of maternal mortality. Yet, even though solutions have been identified, governments and donor countries have been slow to implement programs to contain the problem. While poverty and low educational level remain the underlying cause of PPH, the current literature suggests that active management of the third stage of labor can prevent it. The International Confederation of Midwives (ICM) and the International Federation of Gynecology and Obstetrics (FIGO) are attempting to address the chronic PPH crisis by educating their members on best practices and on troubleshooting where resources are inadequate. Some studies found oxytocin to be preferable to misoprostol in settings where active management is the norm. However, secondary clinical effects may prove more troublesome with oxytocin than with misoprostol, and misoprostol may prove to be more practical and equally effective in low-resource settings. Two new interventions are also proposed, the anti-shock garment and the balloon tamponade.     

A Process and Outcomes Evaluation of the International AIDS Conference: Who Attends? Who Benefits Most?

The objective of the study was to conduct a process and outcomes evaluation of the International AIDS Conference (IAC). Reaction evaluation data are presented from a delegate survey distributed at the 2004 IAC held in Thailand. Input and output data from the Thailand IAC are compared to data from previous IACs to ascertain attendance and reaction trends, which delegates benefit most, and host country effects. Outcomes effectiveness data were collected via a survey and intercept interviews. Data suggest that the host country may significantly affect the number and quality of basic science IAC presentations, who attends, and who benefits most. Intended and executed HIV work‐related behavior change was assessed under 9 classifications. Delegates who attended 1 previous IAC were more likely to report behavior changes than attendees who attended more than 1 previous IAC. The conference needs to be continually evaluated to elicit the required data to plan effective future IACs.     

A Single-Blind, Crossover Comparison of the Pharmacokinetics and Cognitive Effects of a New Diazepam Rectal Gel with Intravenous Diazepam

Summary: Purpose: The objective of this study was to compare the pharmacokinetics and cognitive effects of a new diazepam (DZP) rectal gel (Diastat®) with intravenously administered DZP.
Methods: Twenty healthy volunteers were enrolled in a single-blind, randomized, double-dummy, two-period, crossover study. Subjects received either 15 mg of DZP rectal gel or 7.5 mg of DZP by intravenous infusion. Blood samples for DZP and desmethyldiazepam analysis were obtained before the dose and from 3 min to 240 h after the dose. Heart rate and blood pressure were measured over the first 24-h period. Subjects also completed five repetitions of a neuropsychological test battery over the first 8-h period.
Results: Diazepam rapidly appeared in plasma after rectal administration, exceeding 200 ng/mL within 15 min and reaching an initial maximum of 373 ng/ml at 45 min and a second maximum of 447 ± 91.1 ng/ml at ∼70 min. The absolute bioavailability of DZP rectal gel was 90.4%. Subjects receiving intravenous DZP were less alert and performed less efficiently on the WAIS Digit Symbol test 6 min after the dose. Subjects receiving DZP rectal gel performed less well on the WAIS Digit Span test 1 h after the dose and required more time to complete the Letter Cancellation and Grooved Pegboard tests 1 and 2 h after drug administration.
Conclusions: Diastat® displayed rapid, consistent absorption and was well tolerated. Alterations in cognition were mild and dissipated within 4 h of drug administration. This new rectal drug-delivery system offers an easy, safe, and bioavailable method to administer DZP.     

Patient-centred evaluation and rehabilitative care

The evaluation of health care outcomes is becoming increasingly important in today's health service The wide range of measures used to evaluate these outcomes often makes clinical audit difficult and the comparison of research papers almost impossible In this paper we will discuss some of the issues surrounding outcome measurement in rehabilitative care, examine one of the most commonly used outcome measures from this area (the Barthel Index) and consider Goal Attainment Scaling, a technique which offers both clinicians and researchers the opportunity to evaluate health care outcomes on the basis of patient-centred practice We have identified certain methodological problems that need to be addressed if Goal Attainment Scaling is to become an acceptable measure in the area of physical rehabilitative care     

Motor coordination in mice with hotfoot, Lurcher, and double mutations of the Grid2 gene encoding the delta-2 excitatory amino acid receptor

Grid2(ho/ho) is a loss of function gene mutation resulting in abnormal dendritic arborizations of Purkinje cells. These mutants were compared in a series of motor coordination tests requiring balance and equilibrium to nonataxic controls (Grid2(ho/+)) and to a double mutant (Grid2(ho/Lc)) with an inserted Lc mutation. The performance of Grid2(ho/ho) mutant mice was poorer than that of controls on stationary beam, coat hanger, unsteady platform, and rotorod tests. Grid2(ho/Lc) did not differ from Grid2(Lc/+) mice. However, the insertion of the Lc mutation in Grid2(ho/Lc) potentiated the deficits found in Grid2(ho/ho) in stationary beam, unsteady platform, and rotorod tests. These results indicate a deleterious effect of the Lc mutation on Grid2-deficient mice.     

Regional brain variations of cytochrome oxidase activity and motor coordination in Lurcher mutant mice

Lurcher mutant mice are characterized by massive degeneration of cerebellar Purkinje cells and granule cells and by deficits in motor coordination. Regional brain variations of cytochrome oxidase (CO) activity were analyzed to identify those brain regions with abnormal metabolic activity as a secondary consequence of the cerebellar atrophy and to establish the relationship between CO activity and motor deficits. Lurcher mutants had higher CO activity in all three cerebellar deep nuclei than normal littermate controls of the same background strain. Higher CO activity was also found in Lurcher mutants in brain regions directly connected to the cerebellum, such as the lateral vestibular nucleus, the cochlear nucleus, the red nucleus, the ventrolateral thalamus, the dorsal raphe, the interpeduncular nucleus, and the inferior colliculus. By contrast, there was a sharp decrease in CO activity in the inferior olive. As for brain regions not directly connected to the cerebellum, higher CO activity was observed in the trigeminal motor nucleus and the CA1 molecular layer of the hippocampus, which highlights probable transsynaptic alterations as a secondary consequence of cerebellar atrophy. A positive correlation between CO activity in the red nucleus and latencies before falling in two motor-coordination tests indicates that a compensatory increase of metabolic activity in a cerebellar efferent region is associated with improved behavior. Received: 15 September 1997 / Accepted: 3 March 1998