Identifying ligand-specific signalling within biased responses: focus on δ opioid receptor ligands.

UNLABELLED: Opioids activate GPCRs to produce powerful analgesic actions but at the same time induce side effects and generate tolerance, which restrict their clinical use. Reducing this undesired response profile has remained a major goal of opioid research and the notion of 'biased agonism' is raising increasing interest as a means of separating therapeutic responses from unwanted side effects. However, to fully exploit this opportunity, it is necessary to confidently identify biased signals and evaluate which type of bias may support analgesia and which may lead to undesired effects. The development of new computational tools has made it possible to quantify ligand-dependent signalling and discriminate this component from confounders that may also yield biased responses. Here, we analyse different approaches to identify and quantify ligand-dependent bias and review different types of confounders. Focus is on δ opioid receptor ligands, which are currently viewed as promising agents for chronic pain management. LINKED ARTICLES: This article is part of a themed section on Opioids: New Pathways to Functional Selectivity. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue-2.

[1998 Quebec Social and Health Survey: determinants of chronic respiratory diseases]. / Enquête sociale et de santé de 1998 au Québec: divers déterminants des maladies chroniques respiratoires.

In the course of the "1998 Health and Social Survey", questions were included to verify the prevalence of chronic respiratory diseases and also of wheezing. The objectives of this study were 1) to verify the prevalence of wheezing and its validity as an indicator of chronic respiratory diseases in Québec; and 2) to examine the relationship between chronic respiratory diseases and some of their potential determinants. A total of 30,386 individuals participated in the study. For all ages, the prevalence of wheezing was 5.4%. It was associated with asthma, allergies, chronic bronchitis and emphysema. A low familial income and tobacco smoking were associated with wheezing, asthma, chronic bronchitis and emphysema. Passive smoking was associated with wheezing whereas the presence of carpets was associated with wheezing and asthma. Between 32 and 48% of families with an asthmatic or an allergic member modified their dwelling to alleviate respiratory problems. The prevalence of wheezing documented here was lower than in anglosaxon countries. This result could be explained by a cultural factor (the French translation or the perception of wheezing). This study emphasizes the role of reducing tobacco smoking in the prevention of chronic respiratory diseases.

Cerebrospinal fluid otorrhoea: a rare presentation of Langerhans' cell histiocytosis of the temporal bone.

OBJECTIVE: To report a case of Langerhans cell histiocytosis of the temporal bone presenting with cerebrospinal fluid fistula. PATIENT: A Caucasian woman presented to a tertiary care centre in Quebec, Canada, with a new onset of cerebrospinal fluid fistula. She had a significant destructive lesion of the temporal bone, and was diagnosed with Langerhans cell histiocytosis on biopsy. INTERVENTIONS: The patient underwent surgical resection with reconstruction of the posterior fossa and tegmen. She suffered a relapse less than one year after surgery, and was finally treated with chemotherapy. MAIN OUTCOME AND RESULTS: The patient was free of disease at three-year follow up. No recurrence of the cerebrospinal fluid leak was observed after treatment. CONCLUSION: Langerhans cell histiocytosis of the temporal bone with intra-cranial involvement is rare in adults, with only two cases previously reported. Eleven paediatric cases have been reported. To our knowledge, this patient represents the first report of cerebrospinal fluid fistula as the initial presentation of the disease.

[Development of a computer clinical instruction program. Is the game worth the candle?]. / Concevoir un logiciel d'enseignement clinique. Le jeu en vaut-il la chandelle?

PROBLEM BEING ADDRESSED: Use of computers in medicine, as tools for information and education, is increasing. Many computer-assisted learning tools have been marketed. For clinician-teachers, computer-assisted learning offers interesting possibilities. Is this educational technology within the reach of family physicians? OBJECTIVE: To describe development of a computer-based learning tool and to suggest indications for its use. DESCRIPTION OF PROJECT: A team of clinician-teachers and information technologists developed a tool called Didacticiel sur l'Aviseur to train family physicians and family medicine residents on a clinical decision-making tool called l'Aviseur pharmacothérapeutique, which consists of a database and nine search functions. The Didacticiel in turn consists of an interactive guided tour, a series of exercises with formative evaluation and feedback, a real-time test with a final evaluation, and an integrated, multidimensional project evaluation program. CONCLUSION: Developing a computerized learning tool is a worthwhile investment if the content has longevity; the learning process is highly interactive; there is a market for the product; and the tool is developed by a team of experienced, committed information technologists.

[How effective is the teaching of critical analysis of scientific publications? Review of studies and their methodological quality]. / L'enseignement de l'analyse critique des publications scientifiques médicales est-il efficace? Révision des études et de leur qualité méthodologique.

OBJECTIVE: To evaluate studies assessing the effectiveness of teaching critical appraisal of the literature to medical students. DATA SOURCES: French and English articles published between 1980 and 1990 indexed on MEDLINE or FAMLI as well as articles identified from the bibliographies. STUDY SELECTION: Studies were evaluated if the subjects were undergraduate or postgraduate medical students and if the teaching intervention was aimed at improving one or more of the following areas: knowledge in clinical epidemiology and biostatistics, reading habits and ability to critically appraise a scientific article. DATA EXTRACTION: The methodologic quality of the articles was assessed by three evaluators, who used a modified version of Poynard's checklist to assign a score. Articles with a score of 60% or more were considered satisfactory. The reliability of the checklist was evaluated by means of the kappa (kappa) coefficient and a coefficient of intraclass correlation. DATA SYNTHESIS: For the three evaluators the mean kappa coefficient was 0.33 and the coefficient of intraclass correlation 0.70. Five of the 10 studies had an overall score of 60% or higher. The quality of the individual sections of the articles varied: purpose of the study 85%, description of the population 58%, methods 44%, analysis of results 50%, and conclusions 90%. CONCLUSIONS: The effectiveness of teaching critical appraisal of the literature remains uncertain. More rigorous methods are needed in research in this area.

Consensus on ambulatory care among Quebec otolaryngologists.

OBJECTIVES: The aims of this study were to obtain consensus on the suitability (or nonsuitability) of outpatient facilities for 15 ENT surgical procedures, to identify the factors involved in the decision making, and to use the Delphi method to evaluate it for this purpose. METHOD: A prospective study of 26 practising otolaryngologists in the Province of Quebec, using the Delphi method (3 rounds), was conducted. Fifteen adult and nine paediatric surgical procedures were included. RESULTS: Consensus (85% agreement) was obtained for eight procedures: septoplasty, rhinoplasty, endoscopic sinus surgery, otoplasty, mastotympanoplasty, lymph node biopsy, and branchial cyst excision (outpatient procedures) and tracheostomy (inpatient procedure). CONCLUSION: The Delphi method has been useful in initiating a process of rationalization about outpatient surgery.

Intraparotid facial nerve schwannoma.

Intraparotid facial nerve schwannomas have been documented sporadically throughout the medical literature. These benign tumours of neurogenic origin should be considered in the differential diagnosis of parotid region masses. A case report is presented, followed by a brief literature review and discussion of appropriate diagnostic and treatment modalities.