Utilizing PBPK Modeling to Evaluate the Potential of a Significant Drug-Drug Interaction Between Clopidogrel and Dasabuvir: A Scientific Perspective.

Dasabuvir, a component of VIEKIRA PAK, is a substrate of CYP2C8 enzymes. Prescribing information for VIEKIRA PAK contraindicates gemfibrozil, a strong CYP2C8 inhibitor, because coadministration significantly increases dasabuvir exposures, which may increase the risk of QT prolongation. Clopidogrel may increase dasabuvir exposures primarily due to CYP2C8 inhibition by clopidogrel-acyl-ß-D-glucuronide. This commentary outlines the US Food and Drug Administration (FDA) interdisciplinary review team's scientific perspective to address the potential for a significant drug-drug interaction (DDI) between clopidogrel and VIEKIRA PAK.

Barriers to the implementation of self management support in long term lung conditions.

Background Self-management improves outcomes in asthma and COPD and is strongly recommended in national and international guidelines; however implementation of the guidelines such as use of written action plans in practice is often poor. Setting A questionnaire survey was undertaken to identify the healthcare professional barriers to implementation of self-management for asthma and COPD in West London. Question Why is self-management education not being undertaken in respiratory conditions? Methods A questionnaire was designed to elicit healthcare professionals' views about barriers to implementation of self-management in asthma and COPD. Results Response rates were 33% (58/175). Results showed strong support for guideline recommendations, however implementation was patchy. Seventy six percent of respondents discussed asthma self-management with patients; however only 47.8% of patients received a written action plan. For COPD patients, 55.1% discussed self-management, with 41% receiving a written action plan. In COPD, there was greater GP involvement and less delegation of self-management. Barriers to implementation included patient factors (compliance, literacy and patient understanding), time constraints and insufficient resources. Those who believed they had witnessed improved health outcomes with self-management (53%, 31/58) were more likely to give written action plans (78%, 24/31, 'nearly always/sometimes' gave written action plans), Nearly a third of healthcare professionals reported lacking confidence in constructing written action plans (33% 19/58; GPs 43%, nurses 43%). Conclusion Despite overwhelming evidence self-management support is still not being implemented into routine clinical practice, identified barriers included time constraints, lack of training, lack of belief in patients ability to self-manage and lack of confidence completing self-management plans. Practice implications These issues need to be addressed if self-management support is to be delivered in a meaningful and effective way.

Taking the 'ouch' out - effect of buffering commercial xylocaine on infiltration and procedure pain - a prospective, randomised, double-blind, controlled trial.

AIMS: To compare the effect of buffered commercial 1% xylocaine (with 1:200,000 adrenaline) and the unbuffered commercial 1% xylocaine (with 1:200,000 adrenaline) preparation on pain during infiltration and procedure. PATIENTS AND METHODS: A randomised, double blind controlled trial involving 85 patients who underwent bilateral vasectomy under local infiltration anaesthesia. RESULTS: Each patient served as his own control by receiving the buffered commercial preparation on one side and unbuffered commercial preparation on the other. Linear analogue pain scores during infiltration and procedure were recorded and analysed. The study demonstrated that pain perceived by the patient both during infiltration and the procedure was significantly lower when buffered commercial xylocaine was used as compared to the pain perceived with the use of unbuffered commercial xylocaine. CONCLUSIONS: Use of buffered xylocaine is a simple, inexpensive and significantly effective way of reducing pain during infiltration and in surgical procedures performed under local anaesthesia.

A study of depression among Alexandria preparatory school adolescents.

Using a constructed Arabic version of Children Depression Inventory (CDI), screening of a stratified random sample of 1% (1561) of Alexandria Preparatory school adolescents was carried out. The prevalence of depressive scorers was 10.25% of total sample. A sub-sample of depressed scorers (111 pupils) were compared with controls (non-depressed scorers) matched on age and sex to study a variety of personal, familial, medical and scholastic ecological variables. Pupils neuroticism scorers were most predictive of depressive scorers where they explained 59.79% of the variance. Other ecological factors including peer and sibling relationships, introversive and lie scale scorers and scholastic performance explained an additional 14.87% of the variance. Using Beck Depression Inventory (BDI) and Mother-Father relationship check list, a sub-sample of depressed pupils' mothers were compared with controls of non-depressed pupils' mothers (42 mothers for each). Results indicated a strong positive correlation between pupils, CDI scores and their mothers BDI scores. On the other hand poor mother-father relationship was significantly associated with depressive scores of pupils. Findings, pointed to the need for reconsideration of school mental health program, since the presented medical and social services to depressed pupils were very poor.