X-linked Alport syndrome presenting in mother and son with the same unique histopathological features.

Alport syndrome has been linked to three different genes, that is, COL4A3, COL4A4 and COL4A5. It is characterized by progressive and non-specific glomerulosclerosis with irregular thickening of the glomerular basement membrane (GBM). At times, the histopathologic picture is dominated by lesions that are consistent with focal and segmental glomerulosclerosis or IgA nephropathy. Here, we report the cases of two related individuals (mother and son) who were diagnosed with COL4A5-related Alport syndrome due to a missense variant (p.Gly1170Ser) in a G-X-Y repeat and found to present the same highly unusual histopathological abnormalities on their kidney biopsies. One of the abnormalities shared, which does not appear to have been reported, was reduced COL4A5 immunolabeling that was limited to Bowman's capsule even though the ultrastructure of the GBM was distorted. The other abnormality was superimposed segmental IgA deposition in both individuals, accompanied by mesangial changes in the mother. We feel that these findings provide novel insight into the mechanisms of disease manifestation in Alport syndrome. They suggest, in particular, that collagen expression and/or assemblies in Bowman's capsule is more vulnerable to missense mutations in COL4A5 than elsewhere in the kidney. Our findings also suggest that certain coinherited gene polymorphisms act as unexpectedly important phenotypic determinants in COL4A-related disorders.

High levels of pesticides found in illicit cannabis inflorescence compared to licensed samples in Canadian study using expanded 327 pesticides multiresidue method.

BACKGROUND: As Cannabis was legalised in Canada for recreational use in 2018 with the implementation of the Cannabis Act, Regulations were put in place to ensure safety and consistency across the cannabis industry. This includes the requirement for licence holders to demonstrate that no unauthorized pesticides are used to treat cannabis or have contaminated it. In this study, we describe an expanded 327 multi-residue pesticide analysis in cannabis inflorescence to confirm if the implementation of the Cannabis Act is providing safer licensed products to Canadians in comparison to those of the illicit market. METHODS: An extensive multi-residue method was developed using a modified quick, easy, cheap, effective, rugged, and safe (QuEChERS) sample preparation method using a combination of gas chromatography-triple quadrupole mass spectrometry (GC-MS/MS) and liquid chromatography-triple quadrupole mass spectrometry (LC-MS/MS) for the simultaneous quantification of 327 pesticide active ingredients in cannabis inflorescence. RESULTS: Application of this method to Canadian licensed inflorescence samples revealed a 6% sample positivity rate with only two pesticide residues detected, myclobutanil, and dichlobenil, at the method's lowest calibrated level (LCL) of 0.01 µg/g. Canadian illicit cannabis inflorescence samples analysed showed a striking contrast with a 92% sample positivity rate covering 23 unique pesticide active ingredients with 3.7 different pesticides identified on average per sample. Chlorpyrifos, imidacloprid, and myclobutanil were measured in illicit samples at concentrations up to three orders of magnitude above the method LCL of 0.01 µg/g. CONCLUSION: These results demonstrate the need of an extensive multiresidue method capable of analysing hundreds of pesticides simultaneously, to generate data for future policy and regulatory decision-making, and to enable Canadians to make safe cannabis choices.

The effects of the COVID-19 pandemic on French-Canadian adolescents' academic motivation: A follow-up study.

We previously shared results suggesting that the academic motivation of a sample of French-Canadian adolescents remained stable from few weeks before the first wave to the second wave of the COVID-19 pandemic. We here examine if this pattern persisted using data collected at a third time point.

Contextual cues about reciprocity impact ratings of smile sincerity.

Research has shown that context influences how sincere a smile appears to observers. That said, most studies on this topic have focused exclusively on situational cues (e.g. smiling while at a party versus smiling during a job interview) and few have examined other elements of context. One important element concerns any knowledge an observer might have about the smiler as an individual (e.g. their habitual behaviours, traits or attitudes). In this manuscript, we present three experiments that explored the influence of such knowledge on ratings of smile sincerity. In Experiments 1 and 2, participants rated the sincerity of Duchenne and non-Duchenne smiles after having been exposed to cues about the smiler's tendency to reciprocate (this person always, never or occasionally returns favours). In Experiment 3 they performed the same task but with cues about the smiler's love of learning (this person always, never or occasionally enjoys learning new tasks). The results show that cues about the smiler's reciprocity tendency influenced participants' ratings of smile sincerity and did so in a stronger manner than cues about the smiler's love of learning. Overall, these results both strengthen and broaden the literature on the role of context on judgements of smile sincerity.

Synthetic ACTH for Treatment of Glomerular Diseases: A Case Series.

RATIONALE: Synthetic adrenocorticotropic hormone (Tetracosactide) has been used in the treatment of refractory glomerular diseases. Literature surrounding the use of this medication is limited to small case series and there is conflicting data on the rate of adverse events associated with this medication. PRESENTING CONCERNS OF THE PATIENT: Glomerulonephritis not in remission after at least 6 months of treatment with conservative care. Stable doses of concurrent immunosuppression were permitted. DIAGNOSES: Membranous nephropathy, IgA nephropathy, minimal change disease, and focal and segmental glomerulosclerosis. INTERVENTION: Intramuscular synthetic adrenocorticotropic hormone (Tetracosactide, Synacthen Depot) with doses of either 1 mg weekly or 1 mg twice weekly. OUTCOMES: Five of 12 patients had at least a partial remission with Tetracosactide. Median time to response was 6 months for responders. Five of the 12 patients had adverse events documented, 2 of which led to treatment discontinuation. No patients with focal and segmental glomerulosclerosis responded to treatment. LESSONS LEARNED: Higher rate of adverse events than previously reported with synthetic adrenocorticotropic hormone and uncertain treatment efficacy.

JUSTIFICATION: L'hormone adrénocorticotrope synthétique (tétracosactide) a été utilisée pour le traitement des maladies glomérulaires réfractaires. La littérature portant sur l'utilisation de ce médicament est limitée à de petites séries de cas et les données sur le taux d'événements indésirables associés à ce médicament sont contradictoires. PRÉSENTATION DES CAS: Glomérulonéphrites qui ne sont pas en rémission après un minimum de six mois de traitement conservateur. Des doses stables de traitement immunosuppresseur concomitant étaient autorisées. DIAGNOSTICS: Néphropathie membraneuse, néphropathie à IgA, néphropathie à lésion glomérulaire minime, hyalinose segmentaire et focale. INTERVENTIONS: Des doses soit de 1 mg par semaine soit de 1 mg deux fois par semaine d'hormone adrénocorticotrope synthétique (Tetracosactide, Synacthen Depot) administrées par voie intramusculaire. RÉSULTATS: Cinq patients sur douze ont connu au moins une rémission partielle avec le tétracosactide. Le délai de réponse médian était de six mois pour les patients qui répondaient au traitement. Cinq des douze patients ont eu des réactions indésirables documentées, dont deux ont entraîné l'arrêt du traitement. Aucun des patients présentant une hyalinose segmentaire et focale n'a répondu au traitement. ENSEIGNEMENTS TIRÉS: Un taux de réactions indésirables plus élevé que celui rapporté précédemment avec l'hormone adrénocorticotrope synthétique et une efficacité incertaine du traitement.

Existential Therapy for Children: Impact of a Philosophy for Children Intervention on Positive and Negative Indicators of Mental Health in Elementary School Children.

BACKGROUND: Philosophy for children (P4C) was initially developed in the 1970s and served as an educational program to promote critical thinking, caring, creative reasoning and inquiry in the educational environment. Quasi-experimental research on P4C, a school-based approach that aims to develop children's capacity to think by and for themselves, has suggested it could be an interesting intervention to foster greater basic psychological need satisfaction in children in school settings. OBJECTIVE: The goal of the present study was to evaluate the impact of P4C on basic psychological need satisfaction and mental health in elementary school students. METHOD: Students from grades one to three (N = 57) took part in this study and completed pre- and post-intervention questionnaires. A randomized cluster trial with a wait-list control group was implemented to compare the effects of P4C on students' mental health. RESULTS: Analyses of covariance (ANCOVAs) revealed a significant effect of group condition on levels of autonomy and anxiety, after controlling for baseline levels. Participants in the experimental group showed higher scores in autonomy, when compared to participants in the control group, and participants in the experimental group showed lower anxiety scores, when compared to participants in the control group. CONCLUSION: Overall, results from this study show that P4C may be a promising intervention to foster greater autonomy in elementary school children, while also improving mental health.

Three Weeks of Team-Based Leaning Do Not Overload Undergraduate Students.

CONTEXT: Team-based learning (TBL) is a flipped-classroom approach requiring students to study before class. Fully flipped curricula usually have fewer in-class hours. However, for practical reasons, several programs implement a few weeks of TBL without adjusting the semester timetable. Students fear that they will be overloaded by the individual and collaborative study hours needed to prepare for TBL. METHODS: We implemented three consecutive weeks of TBL in a 15-week lecture-based course on the renal system. In-class time and assessments were unchanged for all courses. Four hundred fifty-nine first-year undergraduate medical students (229 in 2018; 230 in 2019) were invited to complete weekly logs of their individual and collaborative study hours during lectures and TBL, along with questionnaires on cognitive load and perception of the course. Our program changed from A to E grading in 2018 to pass-fail grading in 2019. RESULTS: Participants (n = 324) spent a similar number of hours studying for TBL vs. lectures with a mean of 3.1 h/week. Collaborative study was minimal outside class (median 0.1 h/week). Results remained similar with pass-fail grading. If in-class time were reduced, 18% of participants said they would have used freed-up time to study for TBL. Studying for TBL generated similar extraneous cognitive load and lower intrinsic load compared to studying for lectures; students were less stressed, and maintained high levels of motivation and self-perceived learning. CONCLUSIONS: Three weeks of lectures were replaced by TBL without reducing in-class time. Students did not report overload in study hours or in cognitive load. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40670-021-01314-x.

Health literacy level in a various nephrology population from Québec: predialysis clinic, in-centre hemodialysis and home dialysis; a transversal monocentric observational study.

BACKGROUND: Health literacy refers to the ability of individuals to gain access to, use, and understand health information and services in order to maintain a good health. It is especially important in nephrology due to the complexity of chronic kidney disease (CKD). The present study sought to define health literacy levels in patients followed in predialysis clinic, in-center dialysis (ICHD), peritoneal dialysis (PD) and home hemodialysis (HHD). METHODS: This transversal monocentric observational study analysed 363 patients between October 2016 and April 2017. The Brief Health Literacy Screen (BHLS) and the Health Literacy Questionnaire (HLQ) were used to measure health literacy. Multivariate linear regressions were used to compare the mean scores on the BHLS and HLQ, across the four groups. RESULTS: Patients on PD had a significantly higher BHLS'score than patients on ICHD (p = 0.04). HLQ's scores differed across the groups: patients on HHD (p = 0.01) and PD (p = 0.002) were more likely to feel understood by their healthcare providers. Compared to ICHD, patients on HHD were more likely to have sufficient information to manage their health (p = 0.02), and patients in the predialysis clinic were more likely to report high abilities for health information appraisal (p < 0.001). CONCLUSION: In a monocentric study, there is a significant proportion of CKD patients, especially in predialysis clinic and in-centre hemodialysis, with limited health literacy. Patients on home dialysis (HHD and PD) had a higher level of health literacy compared to the other groups.

Philosophy for children and mindfulness during COVID-19: Results from a randomized cluster trial and impact on mental health in elementary school students.

BACKGROUND: Preliminary evidence suggests that the COVID-19 pandemic has had a negative impact on children's mental health. Given these problems can have significant impacts throughout the lifespan, preventing the negative repercussions of COVID-19 on children's mental health is essential. Philosophy for children (P4C) and mindfulness-based interventions (MBIs) show promise in this regard. OBJECTIVE: The goal of the present study was to compare the impact of online MBI and P4C interventions on mental health, within the context of the COVID-19 pandemic. We used a randomized cluster trial to assess and compare the impact of both interventions on elementary school students' (N = 37) anxiety and inattention symptoms as well as on their basic psychological need satisfaction (BPN). RESULTS: ANCOVAs revealed a significant effect of the P4C intervention on mental health difficulties, controlling for baseline levels. Participants in the P4C group showed lower scores on the measured symptoms at post-test than participants in the MBI group. Significant effects of the MBI on levels of BPN were also found. Participants in the MBI intervention reported greater BPN satisfaction at post-test than participants in the P4C intervention. CONCLUSION: Results from this study suggest that, in the current context of the COVID-19 pandemic, a P4C intervention centered around COVID-19 related themes may be helpful to reduce mental health difficulties, that a MBI may be useful to satisfy BPN, and that both interventions were easy to offer online to elementary school students. Future work including a larger sample size and follow-up measures is warranted. PUBLIC SIGNIFICANCE: Practice: Philosophy for children (P4C) and mindfulness-based interventions (MBIs) can be used to foster mental health in elementary school students, in the current COVID-19 context. Policy: As we do not anticipate that facilitators will be allowed in schools during the 2020-2021 school year and that children will, most likely, be attending school in the current COVID-19 context, policymakers who want to implement psychological support measures in elementary schools should consider an online modality, which has shown in this study to work well, be feasible, and yield positive results on youth mental health.

Impact of a Combined Philosophy and Mindfulness Intervention on Positive and Negative Indicators of Mental Health Among Pre-kindergarten Children: Results From a Pilot and Feasibility Study.

Background: Fostering greater resiliency to stress, optimal psychosocial development and promoting better mental health and well-being in youth is an important goal of the Canadian and American elementary school systems (1, 2). Recent research on mindfulness and philosophy for children (P4C) has yielded promising results regarding innovative interventions that may be implemented in elementary school settings to foster greater child resiliency and well-being (3-5). Goal: The goal of this feasibility study was to pilot a new intervention, which combines mindfulness meditation and P4C activities, with the goal of improving mental health in pre-kindergarten children, assessed with positive (i.e., social skills and adaptability) and negative (i.e., internalized symptoms, comprises depression, anxiety, inattention; and hyperactivity) indicators. Methods: A randomized cluster trial with a wait-list control group was employed to evaluate the impact of the combined MBI and P4C intervention on child mental health. Two classrooms of pre-kindergarten children (N = 38, mean age = 4.6 years old) took part in this study and were randomly allocated to the experimental or wait-list control conditions. Teachers completed pre- and post-intervention questionnaires. Results: ANCOVAs did not reveal a significant effect of condition on internalized symptoms, controlling for baseline levels. Sensitivity analyses indicated that for the whole sample, internalized symptom scores were statistically significantly lower at post-intervention, when compared to pre-intervention scores. No impact of group on levels of hyperactivity was found, however, sensitivity analyses indicated that for both the experimental and control groups, hyperactivity scores were statistically significantly lower at post-intervention, when compared to pre-intervention scores. Finally, no impact of group on levels of social skills and adaptability were found. Sensitivity analyses conducted using paired t-tests did not indicate statistically significant pre-to-post changes in scores for both variables. Conclusion: These preliminary results suggest that mindfulness and philosophy for children may not be the most effective intervention to foster short-term resiliency, well-being and better mental health in children. Yet, group differences were often small and past research suggested the effectiveness of this type of intervention. Further research considering the impact of moderators such as age or baseline levels of psychopathology, using longer time frames and comparing the effectiveness of this combined intervention with other types of school-based interventions with similar aims (such as, e.g., P4C or MBI alone) is warranted, to evaluate if mindfulness and P4C interventions have an added value compared to other types of interventions implemented in school settings.

Smart Home Technology: A New Approach for Performance Measurements of Activities of Daily Living and Prediction of Mild Cognitive Impairment in Older Adults.

BACKGROUND: Functional assessment is of paramount importance when mild cognitive impairment is suspected, but common assessment tools such as questionnaires lack sensitivity. An alternative and innovative approach consists in using sensor technology in smart apartments during scenario-based assessments of instrumental activities of daily living (IADL). However, studies that investigate this approach are scarce and the technology used is not always transposable in healthcare settings. OBJECTIVE: To explore whether simple and wireless technology used in two different smart environments could add value to performance and rater-based measures of IADL when it comes to predicting mild cognitive impairment (MCI) in older adults. METHODS: Twenty-six (26) cognitively healthy older adults (CH) and 22 older adults with MCI were recruited. Functional performance in a set of five scripted tasks was evaluated with sensor-based observations (motion, contact, and electric sensors) and performance-based measures (rated with videotapes). The five tasks could be performed in any order and were detailed on an instruction sheet given to participants. RESULTS: Sensor-based observations showed that participants with MCI spent more time in the kitchen and looking into the fridge and kitchen cabinets than CH participants. Moreover, these measures were negatively associated with memory and executive performances of participants and significantly contributed to the prediction of MCI. CONCLUSION: Simple, wireless, and sensor-based technology holds potential for the detection of MCI in older adults as they perform daily tasks. However, some limits are discussed and we offer recommendations to improve the usefulness of this innovative approach.

Using reflective practice in interprofessional education and practice: a realist review of its characteristics and effectiveness.

This article presents the results of a realist review of the use of reflective practice interventions aimed at improving interprofessional education and collaborative practice (IPECP). Reflective practice is recognized as one of the determining factors in health and social service professionals' skills development and maintenance, as well as in the establishment of good collaboration practices. In this respect, it is a key element of interprofessional education (IPE) and its relevance in this field is being asserted more and more strongly. However, few studies have been conducted to document its effectiveness. The purpose of this article is therefore to advance knowledge in this field. Searches in health and social services electronic databases identified six studies presenting reflective practice interventions in IPECP aimed at enhancing collaboration among students or practicing professionals. Analysis provided preliminary answers as to the effectiveness of reflective practice interventions in IPECP, as well as pertinent information on the best methods for achieving effectiveness. It concludes by proposing recommendations designed to change reflective practice interventions in IPECP and by stressing the importance of further research in order to document more fully the effectiveness of reflective practice in IPECP and to identify the most promising intervention methods in this regard.

Multiresidue Method of Analysis of Pesticides in Medical Cannabis.

Three related analytical methods were developed and validated for the determination of pesticides in cannabis leaves, dried cannabis flowers, and cannabis oil. The methods follow the generic sequence of an acetonitrile extraction, followed by solid-phase extraction cleanup and analysis by HPLC-tandem mass spectrometry (HPLC-MS/MS), GC-MS/MS, and GC-MS. These methods were developed to accommodate sample quantity and lipid content of the different matrices. Validation at a spiking level of 0.01 µg/g was successful for 39 pesticides in cannabis leaves and 40 pesticides in cannabis oil, and at 0.02 µg/g for 32 pesticides in cannabis flowers, with the majority of analytes showing recoveries within the acceptable range of 70-130%. With these methods established, unannounced inspections of Canadian licensed producers of cannabis revealed that out of 144 samples collected, 26 showed the presence of unauthorized pest control products.

The use of vascular access audit and infections in home hemodialysis.

Vascular access-related infection is an important adverse event in home hemodialysis (HHD). We hypothesize that errors in self-cannulation or manipulation of dialysis vascular access are associated with increased incidence of access-related infection. We conducted a retrospective cohort study of all prevalent HHD patients at the University Health Network. All vascular access-related infections were recorded from 2006 to 2013. Errors in dialysis access were ascertained by nurse-administered vascular access checklist. Ninety-two patients had completed at least one vascular access audit. Median HHD vintage was 2.3 (0.9-5.0) years in patients with appropriate vascular access technique and 5.8 (1.5-9.4) years in patients with erroneous vascular access technique. The overall rate of infection between patients with and without appropriate vascular access technique was similar (0.27 and 0.28 infections per year, P = 0.166). Among patients who were identified with errors in dialysis access manipulation, patients with five or more errors were associated with higher rate of access-related infection (mean of 0.47 vs. 0.16 infection per patient-year, P < 0.001). The use of vascular access audit is a feasible strategy, which can identify errors in vascular access technique. Patients with a longer median HHD vintage are associated with higher risk of inappropriate vascular access technique. Patients with multiple errors in vascular access technique are associated with a higher risk of dialysis access-related infection. Prospective evaluation of the impact of vascular access audit on adverse vascular access events is warranted.

All-fiber amplifier similariton laser based on a fiber Bragg grating filter.

This article presents, for the first time to our knowledge, an all-fiber amplifier similariton laser based on a fiber Bragg grating filter. The laser emits 2.9 nJ pulses at a wavelength of 1554 nm with a repetition rate of 31 MHz. The dechirped pulses have a duration of 89 fs. The characteristic features of the pulse profile and spectrum along with the dynamics of the laser are highlighted in representative simulations. These simulations also address the effect of the filter shape and detuning with respect to the gain spectral peak.

Effectiveness of Haemodiafiltration with Heat Sterilized High-Flux Polyphenylene HF Dialyzer in Reducing Free Light Chains in Patients with Myeloma Cast Nephropathy.

INTRODUCTION: In cases of myeloma cast nephropathy in need of haemodialysis (HD), reduction of free light chains using HD with High-Cut-Off filters (HCO-HD), in combination with chemotherapy, may be associated with better renal recovery. The aim of the present study is to evaluate the effectiveness of haemodiafiltration (HDF) in reducing free light chain levels using a less expensive heat sterilized high-flux polyphenylene HF dialyzer (HF-HDF). METHODS: In a single-centre prospective cohort study, 327 dialysis sessions were performed using a 2.2 m2 heat sterilized high-flux polyphenylene HF dialyzer (Phylther HF22SD), a small (1.1m2) or large (2.1 m2) high-cut-off (HCO) dialyzer (HCOS and HCOL) in a cohort of 16 patients presenting with dialysis-dependent acute cast nephropathy and elevated free light chains (10 kappa, 6 lambda). The outcomes of the study were the mean reduction ratio (RR) of kappa and lambda, the proportion of treatments with an RR of at least 0.65, albumin loss and the description of patient outcomes. Statistical analysis was performed using linear and logistic regression through generalized estimating equation analysis so as to take into account repeated observation within subjects and adjust for session duration. RESULTS: There were no significant differences in the estimated marginal mean of kappa RR, which were respectively 0.67, 0.69 and 0.70 with HCOL-HD, HCOS-HDF and HF-HDF (P = 0.950). The estimated marginal mean of the proportions of treatments with a kappa RR ≥0.65 were 68%, 63% and 71% with HCOL-HD, HCOS-HDF and HF-HDF, respectively (P = 0.913). The estimated marginal mean of lambda RR were higher with HCOL-HDF (0.78), compared to HCOL-HD and HF-HDF (0.62, and 0.61 respectively). The estimated marginal mean proportion of treatments with a lambda RR ≥0.65 were higher with HCOL-HDF (81%), compared to 57% in HF-HDF (P = 0.042). The median albumin loss were 7, 21 and 63 g/session with HF-HDF, HCOL-HD and HCOL-HDF respectively (P = 0.044). Among survivors, 9 out of 10 episodes of acute kidney injuries became dialysis-independent following a median time of renal replacement therapy of 40 days (range 7-181). CONCLUSION: Therefore, in patients with acute dialysis-dependent myeloma cast nephropathy, in addition to chemotherapy, HDF with a heat sterilized high-flux polyphenylene HF dialyzer could offer an alternative to HCO dialysis for extracorporeal kappa reduction with lower albumin loss.

Children's ability to recognize emotions from partial and complete facial expressions.

The authors investigated children's ability to recognize emotions from the information available in the lower, middle, or upper face. School-age children were shown partial or complete facial expressions and asked to say whether they corresponded to a given emotion (anger, fear, surprise, or disgust). The results indicate that 5-year-olds were able to recognize fear, anger, and surprise from partial facial expressions. Fear was better recognized from the information located in the upper face than those located in the lower face. A similar pattern of results was found for anger, but only in girls. Recognition improved between 5 and 10 years old for surprise and anger, but not for fear and disgust.

French-speaking children's freely produced labels for facial expressions.

In this study, we investigated the labeling of facial expressions in French-speaking children. The participants were 137 French-speaking children, between the ages of 5 and 11 years, recruited from three elementary schools in Ottawa, Ontario, Canada. The facial expressions included expressions of happiness, sadness, fear, surprise, anger, and disgust. Participants were shown one facial expression at a time, and asked to say what the stimulus person was feeling. Participants' responses were coded by two raters who made judgments concerning the specific emotion category in which the responses belonged. 5- and 6-year-olds were quite accurate in labeling facial expressions of happiness, anger, and sadness but far less accurate for facial expressions of fear, surprise, and disgust. An improvement in accuracy as a function of age was found for fear and surprise only. Labeling facial expressions of disgust proved to be very difficult for the children, even for the 11-year-olds. In order to examine the fit between the model proposed by Widen and Russell (2003) and our data, we looked at the number of participants who had the predicted response patterns. Overall, 88.52% of the participants did. Most of the participants used between 3 and 5 labels, with correspondence percentages varying between 80.00% and 100.00%. Our results suggest that the model proposed by Widen and Russell (2003) is not limited to English-speaking children, but also accounts for the sequence of emotion labeling in French-Canadian children.

Dabigatran versus warfarin under standard or pharmacogenetic-guided management for the prevention of stroke and systemic thromboembolism in patients with atrial fibrillation: a cost/utility analysis using an analytic decision model.

BACKGROUND: Atrial fibrillation (AF) is the most common form of heart arrhythmia and a leading cause of stroke and systemic embolism. Chronic anticoagulation is recommended for preventing those complications. Our study aimed to compare the cost/utility (CU) of three main anticoagulation options: 1) standard warfarin dosing (SD-W) 2) warfarin dosage under the guidance of CYP2C9 and VKORC1 genotyping (GT-W) and 3) dabigatran 150 mg twice a day. METHODS: A Markov state transition model was built to simulate the expected C/U of dabigatran, SD-W and GT-W anticoagulation therapy for the prevention of stroke and systemic thromboembolism in patients with atrial fibrillation over a period of 5 years under the perspective of the public health care system. Model inputs were derived from extensive literature search and government's data bases. Outcomes considered were the number of total major events (thromboembolic and hemorrhagic events), total costs in Canadian dollars (1CAD$ = 1$US), total quality-adjusted life years (QALYs), costs/QALYs and incremental costs/QALYs gained (ICUR). RESULTS: Raw base case results show that SD-W has the lowest C/U ratio. However, the dabigatran option might be considered as an alternative, as its cost per additional QALY gained compared to SD-W is CAD $ 4 765, i.e. less than 50 000, the ICUR threshold generally accepted to adopt an intervention. At the same threshold, GT-W doesn't appear to be an alternative to SD-W. Our results were robust to one-way and multi-way sensitivity analyses. CONCLUSION: SD-W has the lowest C/U ratio among the 3 options. However, dabigatran might be considered as an alternative. GT-W is not C/U and should not currently be recommended for the routine anticoagulotherapy management of AF patients.