Rethinking Canadian Discourses of “Reasonable Accommodation”

This article maps the repercussions of the use of reasonable accommodation, a recent framework referenced inside and outside Canadian courtrooms to respond to religiously framed differences. Drawing on three cases from Ontario and Quebec, we trace how the notion of reasonable accommodation—now invoked by the media and in public discourse—has moved beyond its initial legal moorings. After outlining the cases, we critique the framework with attention to its tendency to create theological arbitrators who assess reasonableness, and for how it rigidifies ‘our values’ in hierarchical ways. We propose an alternative model that focuses on navigation and negotiation and that emphasizes belonging, inclusion and lived religion

Continuing versus stopping prestroke antihypertensive therapy in acute intracerebral hemorrhage: a subgroup analysis of the efficacy of nitric oxide in stroke trial

Background and purpose: More than 50% of patients with acute intracerebral haemorrhage (ICH) are taking antihypertensive drugs before ictus. Although antihypertensive therapy should be given long term for secondary prevention, whether to continue or stop such treatment during the acute phase of ICH remains unclear, a question that was addressed in the Efficacy of Nitric Oxide in Stroke (ENOS) trial. Methods: ENOS was an international multicenter, prospective, randomized, blinded endpoint trial. Among 629 patients with ICH and systolic blood pressure between 140 and 220 mmHg, 246 patients who were taking antihypertensive drugs were assigned to continue (n = 119) or to stop (n = 127) taking drugs temporarily for 7 days. The primary outcome was the modified Rankin Score at 90 days. Secondary outcomes included death, length of stay in hospital, discharge destination, activities of daily living, mood, cognition, and quality of life. Results: Blood pressure level (baseline 171/92 mmHg) fell in both groups but was significantly lower at 7 days in those patients assigned to continue antihypertensive drugs (difference 9.4/3.5 mmHg, P < .01). At 90 days, the primary outcome did not differ between the groups; the adjusted common odds ratio (OR) for worse outcome with continue versus stop drugs was .92 (95% confidence interval, .45- 1.89; P = .83). There was no difference between the treatment groups for any secondary outcome measure, or rates of death or serious adverse events. Conclusions: Among patients with acute ICH, immediate continuation of antihypertensive drugs during the first week did not reduce death or major disability in comparison to stopping treatment temporarily

Appetite Enhancement and Weight Gain by Peripheral Administration of TrkB Agonists in Non-Human Primates

Loss of function mutations in the receptor tyrosine kinase TrkB pathway resulted in hyperphagia and morbid obesity in human and rodents. Conversely, peripheral or central stimulation of TrkB by its natural ligands BDNF or NT4 reduced body weight and food intake in mice, supporting the idea that TrkB is a key anorexigenic signal downstream of the melanocortin-4 receptor (Mc4r) system. Here we show that in non-human primates TrkB agonists were anorexigenic when applied centrally, but surprisingly orexigenic, leading to gain in appetite, body weight, fat deposits and serum leptin levels, when given peripherally. The orexigenic and pro-obesity effects of peripherally administered TrkB agonists appear to be dose dependent, not associated with fluid retention nor with evidence of receptor down regulation. Our findings revealed that TrkB signaling exerts dual control on energy homeostasis in the primates that could be targeted for the treatment of either wasting disorders or obesity

Performance characteristics of methods for quantifying spontaneous intracerebral haemorrhage: data from the Efficacy of Nitric Oxide in Stroke (ENOS) trial

Background: Poor prognosis after intracerebral haemorrhage (ICH) is related to haemorrhage characteristics. Along with developing therapeutic interventions, we sought to understand the performance of haemorrhage descriptors in large clinical trials.Methods: Clinical and neuroimaging data were obtained for 548 participants with ICH from the Efficacy of Nitric Oxide in Stroke (ENOS) trial. Independent observers performed visual categorisation of the largest diameter, measured volume using ABC/2, modified ABC/2, semiautomated segmentation (SAS), fully automatic measurement methods; shape, density and intraventricular haemorrhage were also assessed. Intraobserver and interobserver reliability were determined for these measures.Results: ICH volume was significantly different among standard ABC/2, modified ABC/2 and SAS: (mean) 12.8 (SD 16.3), 8.9 (9.2), 12.8 (13.1) cm3, respectively (p less than 0.0001). There was excellent agreement for haemorrhage volume (n=193): ABC/2 intraobserver intraclass correlation coefficient (ICC) 0.96–0.97, interobserver ICC 0.88; modified ABC/2 intraobserver ICC 0.95–0.97, interobserver ICC 0.91; SAS intraobserver ICC 0.95–0.99, interobserver ICC 0.93; largest diameter: (visual) interadjudicator ICC 0.82, (visual vs measured) adjudicator vs observer ICC 0.71; shape intraobserver ICC 0.88 interobserver ICC 0.75; density intraobserver ICC 0.86, interobserver ICC 0.73. Graeb score (mean 3.53) and modified Graeb (5.22) scores were highly correlated. Using modified ABC/2, ICH volume was underestimated in regular (by 2.2-2.5 cm3, p less than 0.0001) and irregular-shaped haemorrhages (by 4.8-4.9 cm3, p less than 0.0001). Fully automated measurement of haemorrhage volume was possible in only 5% of cases.Conclusions: Formal measurement of haemorrhage characteristics and visual estimates are reproducible. The standard ABC/2 method is superior to the modified ABC/2 method for quantifying ICH volume

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Gentamicin use - more clinical outcome evidence needed

There is currently a looming world-wide problem in antimicrobial resistance. Methods to make antimicrobial prescribing more appropriate and incorporate quality use of medicines guidelines have clearly been ineffective. Further there is a dearth of ‘new’ antimicrobials in the pharmaceutical industry pipeline. The optimal use of older, effective drugs are therefore of clinical relevance. Gentamicin is an antibiotic that is inexpensive and has proven efficacy. However, its use is becoming restricted, due to toxicity concerns. Research to improve knowledge in this area is thus urgently needed

Le Terroriste, l’Homme éclairé et le Patriarche : Les figures qui hantent le quotidien des musulmanes

Les personnes de confession musulmane en général et les femmes musulmanes en particulier – plus encore celles d’entre elles installées en Occident –, se trouvent face à une situation délicate : elles sont quotidiennement confrontées à des figures hégémoniques. Dans cet article, nous examinons comment ces figures affectent la vie de nos participantes musulmanes canadiennes, et comment ces mêmes figures délimitent, dans une certaine mesure, les discours et actions de nos participantes. Notre réflexion s’ancre dans l’étude de trois archétypes masculins qui ont émergé inductivement lors de nos analyses, à savoir : le Terroriste, l’Homme éclairé et le Patriarche. Ceux-ci apparaissent régulièrement dans les interactions quotidiennes de nos participantes. Nous nous intéressons en particulier à leurs manières de réagir à ces figures : dans certains cas, elles les (re)produisent ou activent des figures féminines qui répondent à ces figures masculines ; dans d’autres, elles se les (ré)approprient et, dans d’autres cas encore, elles décident simplement de se distancer de toutes ces figures dans lesquelles elle ne se reconnaissent pas. Nous suggérons que les modes de (dé)subjectivation de ces femmes s’insèrent dans leurs pratiques qui consistent à faire ou à défaire, à co-construire ou à déconstruire ces figures. Dans tous les cas, elles ne peuvent pas les éviter. À partir de l’analyse d’entrevues qualitatives réalisées avec des femmes s’identifiant comme musulmanes à Montréal et à Saint-Jean de Terre Neuve, cet article s’articule autour de deux objectifs centraux. Premièrement, nous souhaitons mettre en exergue les relations qui existent entre les différentes figures qui se trouvent être, non pas mutuellement exclusives mais plutôt intimement reliées : elles s’activent l’une l’autre. Deuxièmement, nous souhaitons saisir la complexité de la position dans laquelle le sujet féminin musulman se trouve aujourd’hui. L’emphase mise sur les figures masculines agit comme un révélateur des processus mis en oeuvre par les musulmanes canadiennes pour enclencher et entretenir des modes de (re)subjectivation qui leur sont propres.This article examines the experiences of Muslim Canadian women who find themselves in a position in which they are confronted with and haunted by a series of discursive figures. More precisely, we consider how these hegemonic figures affect our female Muslim Canadian participants and how these figures delimit, to a certain extent, their discourses and actions. Feminine figures also exist and circulate in significant ways, but we focus here on three masculine archetypes, which were recurrent in our data that we have named : the Terrorist, the Enlightened Man, and the Patriarch. While masculine figures, they appeared most often in the narratives of the daily lives of our female participants. Specifically, we consider how our female participants engaged with these figures : in certain cases, they (re)produced or (re)activated them, in others they (re)appropriated them, and in others still, they ignored and silenced them. Their hegemony meant that our participants were inevitably impelled to construct, reconstruct and deconstruct these ever-present figures. Drawing on qualitative interviews conducted with self-defined Muslims in Montreal, Quebec and St. John’s, Newfoundland and Labrador, this article makes two arguments in relation to these figures. In the first place, with reference to, and in contrast with, previous theoretical interventions on figures, we trace the relationships between them and show how they are not mutually exclusive ; rather, they activate one another. In the second place, we point to the complexities laden in the positions in which our female participants find themselves. In sum, even if we focus on masculine figures, more generally we engage with them to think more broadly about the fields of power in which Muslim Canadians are forced to engage.Las personas de confesión musulmana en general y las mujeres musulmanas en particular, más aun aquellas instaladas en Occidente, se encuentran ante una situación delicada en la cual están cotidianamente confrontadas a figuras hegemónicas. En este artículo examinamos cómo esas figuras delimitan, en cierta medida, los discursos y acciones de nuestras participantes. Nuestra reflexión se apoya en el estudio de tres arquetipos masculinos que surgieron inductivamente de nuestros análisis, a saber : el Terrorista, El Hombre ilustrado y el Patriarca. Estos aparecen regularmente en las interacciones cotidianas de nuestros participantes. Nos interesamos en particular en las maneras en que nuestros participantes reaccionan ante dichas figuras : en algunos casos, ellas los (re)producen o activan las figuran femeninas que responden a dichas figuras masculinas ; en otros contextos, ellas se las (re)apropian y, aun en otros casos, ellas deciden simplemente de distanciarse de todas esas figuras en las que no se reconocen. Sugerimos que los modos de (des)subjetivación de esas mujeres se insertan en sus prácticas, que consisten en hacer o deshacer, (co)construir o desconstruir esas figuras. En todos los casos, no pueden evitarlas. A partir de un análisis de entrevistas cuantitativas realizadas con mujeres que se identificaron como musulmanas en Montreal y en San Juan de Terranova, este artículo se articula en torno a dos objetivos centrales. Por principio deseamos destacar las relaciones que existen entre las diferentes figuras que no son mutualmente excluyentes sin más bien íntimamente ligadas : la activación de una tiene resonancia en la presencia de la otra. En segundo lugar, deseamos captar la complejidad de la posición en la cual el sujeto femenino musulmán se encuentra actualmente. El énfasis que ponemos en las figuras masculinas funciona como una puerta de entrada a los procesos que realizan las musulmanas canadienses para iniciar y mantener los modos de (re)subjetivación que les son propios

Individualised medicine: why we need Bayesian dosing

Individualised drug dosing has been shown to improve patient outcomes and reduce adverse drug events. One method of individualised medicine is the Bayesian approach, which uses prior information about how the population responds to therapy, to inform clinicians about how a specific individual is responding to their current therapy. This information is then used to make changes to the dose. Studies using a Bayesian approach to adjust drug dosing have shown that clinicians are able to achieve a therapeutic range quicker than standard practice. If concentration is related to a pharmacodynamic end-point, this means that the drug will be more effective, and the side-effects will be minimised. Unfortunately, the software options to assist with Bayesian dosing in Australia are limited. The aims of this article are to demystify the concepts of Bayesian dosing, set the context of the Bayesian approach using reference to other dosing strategies and discuss its benefits over current dosing methods for a number of drugs. The article is targeted to medical and pharmacy clinicians, and there is a practical clinical case to demonstrate how this method could be used in everyday clinical practice

Defining and classifying terminology for medication harm: a call for consensus

Purpose: The multiplicity in terms and definitions of medication-related harm has been a long-standing challenge for health researchers, clinicians, and regulatory bodies. The purpose of this narrative review was to report the diversity of terms; compare definitions, classifications, and models describing medication harm; and suggest which may be useful in both clinical practice and the research setting. Methods: A narrative review of key studies defining and/or classifying medication harm terminology was undertaken. Results: This review found that numerous terms are used to describe medication harm, and that there is a lack of consistency in current definitions, classifications, and applications. This lack of consistency applied across clinical jurisdictions and regulatory terminologies. A number of limitations in current definitions and classifications were identified. These included the exclusion of key types of medication harm events, ambiguous wording, and a lack of clarity and consensus on subclassifications. In general, there was some overlap in key models from the literature and these were presented to describe similarities and differences. Conclusion: Without uniformity quantifying, comparing, combining, or extrapolating medication harm data, such as a rate of harm in a specific population, is a challenge for those involved in medication safety and pharmacovigilance. There is a pressing need for further discussion and international consensus on this topic. Adoption of standard descriptors by practitioner groups, regulatory and policy organisations would foster quality improvement and patient safety