Subject Review: A conceptual model for treatment of externalizing behaviour in acquired brain injury

This paper describes a conceptual model for treatment of the externalizing behavioural sequelae to an acquired brain injury and discusses relevant research. Use of the model by practitioners should lead to sophisticated and minimally intrusive intervention. In the model, there are two different categories of approaches. The first category is remedial approaches. These interventions are typically used in the post-acute environment for teaching adaptive skills to replace aberrant behaviour patterns. Skills provided with such training allow the individual to self-manage difficult everyday situations effectively, without external control by others. The second category is moderating approaches, which can be used in the acute phase of ABI recovery for management of severe behavioural episodes that may be associated with conditions present at this time, such as agitation and confusion. Moderating approaches can also be used as a prelude to remedial approaches in the post-acute environment when problem behaviours occur at a high frequency or intensity and render the use of remedial approaches difficult.     

Piperacillin and Tazobactam Exhibit Linear Pharmacokinetics after Multiple Standard Clinical Doses

A population pharmacokinetic (PK) analysis was conducted to determine if piperacillin and tazobactam exhibited linear or nonlinear PKs and if incremental changes in the daily dosage of piperacillin affected tazobactam PKs. Four dosage groups were evaluated after multiple dosing regimens. Concentrations of drug in plasma and amounts in urine were best fitted by using a linear two-compartment PK model. No significant difference between dosing groups was seen for any piperacillin or tazobactam PK parameters. Both drugs exhibited linear PKs when given at usual clinical doses. Tazobactam PKs did not appear to be affected by the different dosing regimens of piperacillin.     

Partnership in research: a tandem of opportunities and constraints

Partnership is a term that is occurring more and more frequently in the research lexicon, an approach that is gradually becoming a sine qua non in the field of health and healthcare research in Canada. The purpose of this article is to share thoughts and experiences regarding research carried out in partnership. The relevance and necessity of partnerships in strategic health research will be examined, and the contribution of partnerships to the development and "re-centring" of intra- and interdisciplinary knowledge and knowledge transfer will be discussed. Based on the nursing and related-fields literature, the key elements of partnership, and the advantages and disadvantages of this strategy to pursuing research projects will be presented. An important issue in a professional discipline such as nursing will be discussed, i.e. the intra-disciplinary partnership between researchers and clinicians. Strategies that could enhance this particular type of partnership and avenues for catalyzing the synergy that must perforce develop, over the coming years, will be proposed.     

Possible mechanisms of valproate in migraine prophylaxis

Valproate has been shown to be an effective prophylactic treatment in migraine. Investigation of the mechanism of its antimigraine action is difficult due to the broad range of its biochemical effects and the complex nature of migraine pathophysiology. Valproate increases brain GABA levels and, in doing so, may suppress migraine-related events in the cortex, perivascular parasympathetics or trigeminal nucleus caudalis. There is experimental evidence that it suppresses neurogenic inflammation and directly attenuates nociceptive neurotransmission. In addition, valproate reportedly alters levels of excitatory and inhibitory neurotransmitters and exerts direct effects on neuronal membranes in vitro. Valproate's observed effect may ultimately result from a combination of actions at different loci.     

Caregivers of elderly people with loss of autonomy in Lebanon: what is the context of their health care?

The primary objective of this pan Lebanese study was to describe the health care context of family caregivers cohabiting with an elderly relative with loss of autonomy while the secondary objective consisted in the qualitative documentation of their positive and negative perceptions as to the role of the caregivers. The study uses a theoretical framework of stress. The results indicate that the caregivers (N = 319) take care of relatives (40% with memory troubles) having a moderate level of loss of autonomy and who present more depressive behaviors than "disturbing" behaviors. The caregivers are particularly affected by the behaviors of their relatives. They accomplish several health care tasks and very few receive formal services to support them. Their neighborhood offers them more emotional support than instrumental support. More caregivers perceive positive aspects than negative aspects in their role. Recommendations are formulated to guide the elaboration of a national policy of support to caregivers and the development of innovative community care practices.     

Improved survival of children with sepsis and purpura: effects of age,gender, and era

Background  

To gain insight into factors that might affect results of future case-control studies, we performed an analysis of children with sepsis and purpura admitted to the paediatric intensive care unit (PICU) of Erasmus MC-Sophia Children's Hospital (Rotterdam, The Netherlands).     

6',7'-Dihydroxybergamottin in grapefruit juice and Seville orange juice: effects on cyclosporine disposition, enterocyte CYP3A4, and P-glycoprotein

BACKGROUND: 6',7'-Dihydroxybergamottin is a furanocoumarin that inhibits CYP3A4 and is found in grapefruit juice and Seville orange juice. Grapefruit juice increases the oral bioavailability of many CYP3A4 substrates, including cyclosporine (INN, ciclosporin), but intestinal P-glycoprotein may be a more important determinant of cyclosporine availability. OBJECTIVES: To evaluate the contribution of 6',7'-dihydroxybergamottin to the effects of grapefruit juice on cyclosporine disposition and to assess the role of CYP3A4 versus P-glycoprotein in this interaction. METHODS: The disposition of oral cyclosporine was compared in healthy subjects after ingestion of water, grapefruit juice, and Seville orange juice. Enterocyte concentrations of CYP3A4 were measured in 2 individuals before and after treatment with Seville orange juice. The effect of 6',7'-dihydroxybergamottin on P-glycoprotein was assessed in vitro. RESULTS: Area under the whole blood concentration-time curve and peak concentration of cyclosporine were increased by 55% and 35%, respectively, with grapefruit juice (P < .05). Seville orange juice had no influence on cyclosporine disposition but reduced enterocyte concentrations of CYP3A4 by an average of 40%. 6',7'-Dihydroxybergamottin did not inhibit P-glycoprotein at concentrations up to 50 micromol/L. CONCLUSIONS: 6',7'-Dihydroxybergamottin is not responsible for the effects of grapefruit juice on cyclosporine. Because the interaction did not occur with Seville orange juice despite reduced enterocyte concentrations of CYP3A4, inhibition of P-glycoprotein activity by other compounds in grapefruit juice may be responsible. Reduced enterocyte CYP3A4 by 6',7'-dihydroxybergamottin could be important for other drugs whose bioavailability is less dependent on P-glycoprotein.     

Counselor attitudes toward the use of motivational incentives in addiction treatment

Counselor attitudes toward evidence-based practices, such as motivational incentives/contingency management (MI/CM), are important in bridging the gap between research and practice. Mailed surveys from 1,959 substance abuse treatment counselors showed ambivalence toward MI/CM and strong disagreement with using monetary rewards for achievement of treatment goals. Attitudes were associated with counselors' educational attainment, a 12-step treatment ideology, affiliation with NIDA's Clinical Trials Network, and working in opioid treatment programs. Exposure to MI/CM via training was more strongly associated with attitudes when counselors worked in programs that had adopted MI/CM. While there is substantial resistance to MI/CM, dissemination and training about the essential elements of MI/CM may enhance counselors' receptivity toward this intervention.     

Harmonization of regulatory approaches for evaluating therapeutic equivalence and interchangeability of multisource drug products: workshop summary report

Regulatory approaches for evaluating therapeutic equivalence of multisource (or generic) drug products vary among different countries and/or regions. Harmonization of these approaches may decrease the number of in vivo bioequivalence studies and avoid unnecessary drug exposure to humans. Global harmonization for regulatory requirements may be promoted by a better understanding of factors underlying product performance and expectations from different regulatory authorities. This workshop provided an opportunity for pharmaceutical scientists from academia, industry and regulatory agencies to have open discussions on current regulatory issues and industry practices, facilitating harmonization of regulatory approaches for establishing therapeutic equivalence and interchangeability of multisource drug products.