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Background: In recent years, community pharmacists have seen their profession transition from a dispensing-focused role to a rapidly evolving clinically oriented practice. In Québec, Bill 31, adopted in 2020, increased the clinical opportunities for pharmacists with independent prescribing privileges in various defined clinical situations. As this expanded role can lead to different barriers, it is crucial to explore pharmacists' comfort levels with implementing such changes in their practice., Methods: A web-based survey was conducted from March 25 to May 28, 2021, among community pharmacists in Québec. We collected data with a questionnaire developed for this study. Questions were grouped into 4 domains: (1) characteristics of the respondents; (2) workload and work setting; (3) comfort level with, and barriers to, adjusting medications and following up pharmacologic treatments (86 clinical situations evaluated); and (4) general barriers and facilitators to implementation., Results: A total of 146 community pharmacists completed the questionnaire. Most were women (71.9%), younger than 50 years of age (86.2%), had a bachelor's degree (64.4%) as their highest academic level and had more than 10 years of experience as pharmacists (56.8%). Most of them worked exclusively in a community pharmacy (86.3%). Among the 86 clinical situations evaluated, there were 16 in which at least 80% of respondents felt comfortable. The main barriers identified were a lack of knowledge, experience and dedicated time and difficulties integrating these activities into the workflow; facilitators were having an adequate environment and resources., Conclusion: This study shows community pharmacists can confidently adjust pharmacotherapy for several conditions. However, they must have adequate time and resources. Also, the more complex the clinical situations were, the less comfortable community pharmacists felt adjusting pharmacotherapy. This study identified several areas where continuing education, training and mentoring could be offered and where the work environment and organization could be improved., Competing Interests: The authors declare no potential conflicts of interest concerning the research, authorship and/or publication of this article., (© The Author(s) 2024.)

Diabetes is a global public health issue. The Public Health Agency of Canada published a Diabetes Framework 2022 which recommends collaborative work across sectors to mitigate the impact of diabetes on health and quality of life. Since 2020, the INMED-COMMUNITY pathway has been implemented in Laval, Québec developing collaboration between healthcare and community sectors through a participatory action research approach. The aim of this article is to gain a better understanding of the INMED-COMMUNITY pathway implementation process, based on the mobilization of network actor theory. Qualitative analysis of semi-structured interviews conducted from January to March 2023 with 12 participants from 3 different sectors (community, health system, research), were carried out using actor-network theory. The results explored the conditions for effective intersectoral collaboration in a participatory action research approach to implement the INMED-COMMUNITY pathway. These were: (1) contextualization of the project, (2) a consultation approach involving various stakeholders, (3) creation of new partnerships, (4) presence of a project coordinator, and (5) mobilization of stakeholders around a common definition of diabetes. Mediation supported by a project coordinator contributed to the implementation of an intersectoral collaborative health intervention, largely due to early identification of controversies., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Type 2 diabetes is a complex chronic disease that requires ongoing monitoring by an interprofessional team to prevent complications. The INMED (INterprofessional Management and Education in Diabetes) care pathway was developed by our team to optimize primary care services for these patients and their families. The objective of this study is to describe the preliminary results of its adoption and implementation. The INMED care pathway is organized into four axes: (a) continuing professional education, (b) self-management support, (c) case management, and (d) ongoing evaluation of the quality of diabetes care and services. A multiple-case study is underway to document its effects on practice change using the Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) framework. Preliminary results on the adoption and implementation revealed some strengths: (a) regular patient follow-up by the case manager, (b) scheduling of physician appointments when required, and (c) regular screening for risk factors. Barriers were also identified: (a) lack of clear understanding of the case manager role, (b) lack of referrals to team members, and (c) lack of use of the motivational interview approach. The INMED care pathway is being adopted by primary care teams but challenges need to be overcome to improve its reach and effectiveness.

Purpose: Patients on hemodialysis have a high risk of medication-related problems. Studies using deprescribing algorithms to reduce the number of inappropriate medications in this population have been published, but none have used a patient-partnership approach. Our study evaluated the impact of a similar intervention with a patient-partnership approach., Methods: The objective was to describe the implementation of a pharmacist-led intervention with a patient-partnership approach using deprescribing algorithms and its impact on the reduction of inappropriate medications in patients on hemodialysis. Eight algorithms were developed by pharmacists and nephrologists to assess the appropriateness of medications. Pharmacists identified patients taking targeted medications. Following patient enrollment, pharmacists assessed medications with patients and applied the algorithms. With patient consent, deprescription was suggested to nephrologists if applicable. Specific data on each targeted medication were collected at 4 and 16 weeks. Descriptive statistics were used to examine the effects of the deprescribing intervention., Results: Of 270 patients, 256 were taking at least one targeted medication. Of the 122 patients taking at least one targeted medication who were approached to participate, 66 were included in the study. At enrollment, these patients were taking 252 targeted medications, of which 59 (23.4%) were determined to be inappropriate. Deprescription was initiated for 35 of these 59 medications (59.3%). At 4 weeks, 33 of the 59 medications (55.9%) were still deprescribed, while, at 16 weeks, 27 of the 59 medications (45.8%) were still deprescribed. Proton pump inhibitors and benzodiazepines or Z-drugs were the most common inappropriate medications, and allopurinol was the most deprescribed medication., Conclusion: A pharmacist-led intervention with a patient-partnership approach and using deprescribing algorithms reduced the number of inappropriate medications in patients on hemodialysis., (© American Society of Health-System Pharmacists 2022. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: In 2018, a virtual community of practice (CoP) for pharmacists working in family medicine groups (FMGs) in Quebec province was developed. The aim of this CoP-called Réseau Québécois des Pharmaciens GMF (RQP GMF)-was to foster best practices by supporting FMG pharmacists. This study assesses the processes and outcomes of this CoP 2 years after its creation., Methods: We performed a cross-sectional web-based study from March to May 2020. All FMG pharmacists who were registered as members of the RQP GMF ( n = 326) were sent an invitation via a newsletter. The link to the questionnaire was also publicized in the CoP Facebook group. The questionnaire comprised a 38-item validated instrument assessing 8 dimensions of the CoP. A descriptive analysis was performed., Results: A total of 112 FMG pharmacists (34.4%) completed the questionnaire. Respondents agreed that the RQP GMF was a joint enterprise (mean score, 4.18/5), that members shared their knowledge (mean score, 3.94/5) and engaged mutually (mean score, 3.50/5) and that the RQP GMF provided support (mean score, 3.92/5) and capacity building (mean score, 4.01/5). In general, they were satisfied with the implementation process (mean score, 3.68/5) and with activities proposed (mean score, 3.79/5). A lower proportion of respondents agreed that their participation in the RQP GMF generated external impacts, which led to a smaller mean score (3.37/5) for this dimension., Conclusion: The RQP GMF, one of the first communities of practice for pharmacists practising in family medicine groups, attained most of the objectives initially intended by the CoP. These results will facilitate the adaptation of processes and activities to better fulfil members' needs. Can Pharm J (Ott) 2021;154:xx-xx., Competing Interests: Conflict of interest: The authors have no conflicts to declare., (© The Author(s) 2021.)

To develop collaborative competencies of future health and social services professionals, the Université de Montréal (UdeM) offers interprofessional education (IPE) in partnership with patients. To meet the challenges of IPE, UdeM turned to digital tools to enable interprofessional teams of students to collaborate online and face-to-face. The collaborative flipped classroom for IPE with patient partnership is the conceptual framework for the pedagogical method used for this study. It is based on: 1) a competency framework and 2) collaborative learning concept and dimensions. The study aimed to: 1) demonstrate how interprofessional teams of students mobilize framework competencies and care approaches during online and face-to-face collaborative learning activities; and 2) analyze how students collaborate during a hybrid IPE course using a patient partnership approach. Using a qualitative methodology, the contents of the online collaborative journals (OCJs) of 12 interprofessional student teams were analyzed, along with the individual comments (n = 994) of IPE course learners collected through the Interprofessional Team Collaboration questionnaire (n = 321). The results suggest that the course under study enabled teams to collaborate online and face-to-face throughout the term, and indicate that students were better prepared to adopt a patient partnership approach.

Rationale, Aims and Objectives: Patients undergoing haemodialysis receive on average 10-17 medications, which increase the risk of falls, adverse drug reactions and hospitalizations. Supervised discontinuation of potentially inappropriate medications may lower these risks. Although many calls have been made for deprescribing in the haemodialysis setting, little is known about how patients and providers in this setting experience it. The aim of this study is to explore patient and provider experiences and perceptions of one of the rare deprescribing intervention in haemodialysis., Methods: Ten semi-structured interviews were held with patients, and a focus group was done with dialysis clinic team members at a Montreal area health network's haemodialysis clinic after the implementation of a standardized deprescribing intervention using the patient-as-partner approach. The interviews and focus group were recorded, and verbatims were coded to determine emerging themes. Grounded theory was used for interview guide design and data analysis., Results: The three emerging themes were (1) ambivalence towards medication creating a favourable context for deprescribing, (2) the empowering elements of the deprescribing process and (3) the uncertain future of deprescribing in the clinics even though the intervention was considered successful., Conclusion: Haemodialysis patients and providers viewed deprescribing favourably, believed the intervention was valuable, and offered suggestions for long term implementation while expressing concerns about feasibility. Notwithstanding the underlying uncertainties, a structured and integrated approach in routine practice involving all members of the care team may facilitate the continuity of deprescribing as an intervention in the setting of a haemodialysis clinic., (© 2020 Royal Pharmaceutical Society.)

Methods: Opioid misuse has reached epidemic status in many countries. This crisis-recognized since 2014-questions the practices of prescribing and dispensing. Did this public health issue change pharmaceutical practices? This literature review presents pharmaceutical practices regarding treatment of noncancer pain. We will assess whether these practices changed after the declaration of the crisis. We will also present barriers and facilitators to their implementation in real life to understand the distance between them and current practices. A scoping review of the literature was conducted on PubMed, Medline, and Embase for references dealing with pharmaceutical practices regarding noncancer pain management, in French and English, from 2000 to 2018., Results: The search yielded 250 results, with 25 studies surviving the exclusion process. Twenty studies took place in the United States, the country most affected by the crisis. Interventions took place as interprofessional collaboration (n = 14), patient counseling (6), or a combination of these (5). Although the nature of the interventions remained constant through the crisis, the number of publications greatly increased over time. The studies demonstrated pharmacists' upstream contributions regarding pain management and opioid use. Several large-scale implementation issues, including knowledge gaps and communication barriers, have been reported in these studies and in others that gathered opinions and perspectives of prescribers, pharmacists, and patients., Conclusion: Our review showed that the opioid crisis did not modify the nature of pharmaceutical practices regarding pain treatment and opioid management, but the number of studies reporting these practices greatly increased since its onset. Barriers to implementing the best practices to reduce opioid harm have been identified to explain slow integration in daily practice. Adjustments to teaching and practice methods such as a reviewed pain treatment curriculum, standardized tools, and decision-making algorithms could prove beneficial., (Copyright © 2020 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.)

What Is Known and Objective: Pharmacists' responsibilities and practices have expanded over the years to be more clinical. Working in other settings and collaborating with other healthcare professionals can lead to new needs that are unmet by actual training. This study was performed to describe the characteristics and practices of pharmacists working in family medicine groups (FMGs) and to assess their needs to develop a practice-based network fostering best practices., Methods: A Quebec province-wide cross-sectional study was performed from May to August 2018. Pharmacists practising in FMGs were identified through phone calls to all listed FMGs and via direct emails. All identified pharmacists were emailed an invitation to complete an online questionnaire comprising questions to assess their sociodemographic characteristics, to describe their FMG and to assess their needs to reach an optimal practice. The link to the questionnaire was also publicized in a Facebook group of FMG pharmacists and by several professional organizations. A descriptive analysis was performed and discussed with two committees: a working group of FMG pharmacists and an advisory committee comprising key stakeholders., Results and Discussion: A total of 299 FMG pharmacists were identified, and 178 (59.5%) completed the online questionnaire. Most were women (71.9%), were less than 40 years old (71.9%) and also practised as community pharmacists (76.4%). Reviewing medication to optimize pharmacotherapy and answering questions related to specific issues were the most frequent activities, with 86.0% and 90.4% of pharmacists, respectively, reporting that they performed these often or very often. The most frequently mentioned needs were training and mentorship adapted to the FMG practice and improvement in the understanding that other healthcare professionals have about the role of the FMG pharmacist. Performing comprehensive medication assessments and developing thorough pharmaceutical care plans were among the clinical competencies that pharmacists wanted to develop. Scientific and interprofessional communication was also among the abilities they wished to optimize., What Is New and Conclusion: This study provided unique information about pharmacists practising in FMGs and elicited several needs. The results will inform the development of a practice-based network aimed at fulfilling these needs., (© 2019 John Wiley & Sons Ltd.)

A needs assessment study of pharmacists working in family medicine groups (FMG) demonstrated the necessity to build a practice-based network. This network would foster a faster integration into FMG and a more efficient collaborative practice. It would also take advantage of an existing practice-based research network (PBRN)-the STAT ( Soutien Technologique pour l'Application et le Transfert des pratiques novatrices en pharmacie ) network. A working group of nine FMG pharmacists from the different regions of the province of Quebec, Canada, and a committee of partners, including the key pharmacy organizations, were created. Between January 2018 and May 2019, nine meetings took place to discuss the needs assessment results and deploy an action plan. The practice-based network first year activities allowed identifying pharmacists working in FMGs across the province. A directory of these pharmacists was published on the STAT network. The vision, mission, mandate, name (« Réseau Québécois des Pharmaciens GMF ») and logo were developed. The first few activities include: Bi-monthly newsletters; a mentorship program; short evidence-based therapeutic letters (pharmacotherapeutic capsules) and a start-up kit to facilitate integration of these pharmacists. The Quebec FMG pharmacist practice-based network has been launched. It is planned to evaluate the members' satisfaction in late Spring 2020 with regards to activities and resources provided.

A promising approach to improve the population's health and the quality of care and services provided by the health system consists of patient engagement at all levels of the health system together with training of health professionals. Since 2010, a new rational model based on the partnership between patients and healthcare professionals has been developed at the University of Montreal's Faculty of Medicine. This patient partnership model is based on the recognition of the patient's experiential knowledge gained from living with a disease, which is complementary to the healthcare professional's scientific knowledge. This partnership is part of a continuum of patient engagement and can be applied in healthcare, professional training, education and research settings. This article describes the theoretical basisfor patient partnerships and how this new model can be implemented in clinical, organizational and systemic levels, as well as the success factors in both patients and healthcare professionals. The Montreal Model provides relevant outlooks for chronic disease management by making patients essential partners in all decisions affecting them and by treating them as experts in the organisation of care. This model should have a significant impact on the population's health by improving physical, psychological health, as well as the patient's well-being. As part of this new framework, several research programs are currently underway to evaluate the impact of this model.

Université de Montréal implemented an interprofessional education (IPE) curriculum on collaborative practice in a large cohort of students (>1,100) from 10 health sciences and psychosocial sciences training programs. It is made up of three one-credit undergraduate courses (CSS1900, CSS2900, CSS3900) spanning the first 3 years of training. The course content and activities aim for development of the six competency domains identified by the Canadian Interprofessional Health Collaborative. This paper describes the IPE curriculum and highlights the features contributing to its success and originality. Among main success key factors were: administrative cooperation among participating faculties, educators eager to develop innovative approaches, extensive use of clinical situations conducive to knowledge and skill application, strong logistic support, close cooperation with health care delivery organizations, and partnership between clinicians and patients. A distinguishing feature of this IPE curriculum is the concept of partnership in care between the patient and caregivers. Patients' representatives were involved in course planning, and patients were trained to become patients-as-trainers and cofacilitate interprofessional discussion workshops. They give feedback to students regarding integration and application of the patient partnership concept from a patient's point of view.

Background: Few studies have reported the efficacy of collaborative care involving family physicians and community pharmacists for patients with dyslipidemia., Methods: We randomly assigned clusters consisting of at least two physicians and at least four pharmacists to provide collaborative care or usual care. Under the collaborative care model, pharmacists counselled patients about their medications, requested laboratory tests, monitored the effectiveness and safety of medications and patients' adherence to therapy, and adjusted medication dosages. After 12 months of follow-up, we assessed changes in low-density lipoprotein (LDL) cholesterol (the primary outcome), the proportion of patients reaching their target lipid levels and changes in other risk factors., Results: Fifteen clusters representing a total of 77 physicians and 108 pharmacists were initially recruited, and a total of 51 physicians and 49 pharmacists were included in the final analyses. The collaborative care teams followed a total of 108 patients, and the usual care teams followed a total of 117 patients. At baseline, mean LDL cholesterol level was higher in the collaborative care group (3.5 v. 3.2 mmol/L, p = 0.05). During the study, patients in the collaborative care group were less likely to receive high-potency statins (11% v. 40%), had more visits with health care professionals and more laboratory tests, were more likely to have their lipid-lowering treatment changed and were more likely to report lifestyle changes. At 12 months, the crude incremental mean reduction in LDL cholesterol in the collaborative care group was -0.2 mmol/L (95% confidence interval [CI] -0.3 to -0.1), and the adjusted reduction was -0.05 (95% CI -0.3 to 0.2). The crude relative risk of achieving lipid targets for patients in the collaborative care group was 1.10 (95% CI 0.95 to 1.26), and the adjusted relative risk was 1.16 (95% CI 1.01 to 1.34)., Interpretation: Collaborative care involving physicians and pharmacists had no significant clinical impact on lipid control in patients with dyslipidemia. International Standard Randomized Controlled Trial register no. ISRCTN66345533.

Background: In a collaborative care model (CCM) for managing oral anticoagulant therapy, patients are followed at a pharmacist-managed anticoagulation service and, once stabilized, are transferred to their primary care physician. The objective of this study was to describe physicians' clinical practices and the practice characteristics associated with better international normalized ratio (INR) control in a CCM., Methods: A telephone questionnaire about their practices was administered to 121 physicians exposed to a CCM. The physicians followed 121 patients for a mean of 14.5 weeks. The percentage of time within the exact INR target range was computed and dichotomized (> or = or < median time within target range). Determinants of better INR control were identified using logistic regression models., Results: The survey revealed that, after discharge from the pharmacist-managed anticoagulation service, patients are followed mainly by physicians and their secretaries. Physicians do not often consult other health professionals. Few report using technological resources to obtain INR results (39.7%), document medical follow-up (6.6%), or detect drug (32.2%) and food (9.9%) interactions. The median percentage of time within the exact INR target range was 84%. Determinants of better INR control include using computerized support to monitor patients (odds ratio [OR] 9.16, 95% CI 1.77-47.4) and detect drug interactions (OR 3.49, 95% CI 1.71-7.10) and consulting specialists (OR 5.92, 95% CI 1.49-32.48)., Conclusions: Primary care physicians are poorly supported by technological and human resources to monitor patients on oral anticoagulant. Even in a CCM, interprofessional collaboration and better technological support may be associated with optimal INR control., (Copyright (c) 2010 Mosby, Inc. All rights reserved.)

Introduction: In a physician-pharmacist collaborative-care (PPCC) intervention, community pharmacists were responsible for initiating lipid-lowering pharmacotherapy and adjusting the medication dosage. They attended a 1-day interactive workshop supported by a treatment protocol and clinical and communication tools. Afterwards, changes in pharmacists' knowledge, their skills, and their satisfaction with the workshop were evaluated., Methods: In a descriptive study nested in a clinical trial, pharmacists assigned to the PPCC intervention (n = 58) completed a knowledge questionnaire before and after the workshop. Their theoretical skills were evaluated with the use of a vignette approach (n = 58) after the workshop and their practical skills were assessed by direct observation with study patients (n = 28)., Results: The mean (SD) overall knowledge score was 45.8% (12.1%) before the workshop; it increased significantly to 89.3% (8.3%) afterwards (mean difference: 43.5%; 95% CI: 40.3%-46.7%). All the pharmacists had an overall theoretical-skill score of at least 80%, the minimum required to apply the PPCC in the trial. From 92.9% to 100% of the pharmacists' interventions with study patients complied with the treatment protocol., Discussion: In primary care, a short continuing-education program based on a specific treatment protocol and clinical tools is necessary and probably sufficient to prepare pharmacists to provide advanced pharmaceutical care.

Purpose: The effect of a medication discharge plan (MDP) on the rate of medication discrepancies between hospital and outpatient settings was evaluated., Methods: In a pragmatic, open, randomized, controlled trial, MDPs were completed for all patients before discharge from the hospital. Patients were then assigned to either an MDP group, for whom MDPs were sent to community pharmacies and treating physicians, or a usual care group, for whom an MDP was not sent. Discrepancies between MDPs and community pharmacy dispensing records and medication use reported by patients during a telephone interview were documented. The percentage of patients with discrepancies and the mean percentage of medications with discrepancies were compared between the two groups. The clinical severity of discrepancies was blindly evaluated., Results: A total of 83 patients agreed to participate in the study. The percentage of patients with at least one discrepancy was high and similar in both groups when MDPs were compared with pharmacy dispensing records and patient self-reports. Comparison of MDPs to pharmacy dispensing records revealed discrepancies for 13-15% of medications; more than a third were clinically significant. Comparison of MDPs to patient self-reports revealed discrepancies for 10-12% of medications; 48% were clinically significant. No significant differences were observed between the two groups., Conclusion: The rate of medication discrepancies was not decreased in patients whose MDP was provided to their community pharmacy and physician at the time of hospital discharge compared with the rate in patients who received usual care.

Background: Some pharmacist-managed anticoagulation services (PMAS) provide initial follow-up to patients on oral anticoagulant, who are transferred to their physician once they are stabilized. This may be as effective as and less expensive than long-term PMAS follow-up., Methods: Once PMAS patients were stabilized and ready for discharge, they were randomized to be transferred to their physician or stay with the PMAS. Quality of international normalized ratio (INR) control, incidence of complications, health-related quality of life, use of health care services, and direct incremental cost of PMAS follow-up were evaluated., Results: One hundred thirty-eight physicians and 250 patients participated. Patients were initially followed at the PMAS for a mean of 11.3 weeks and afterwards were followed by their physician (n = 122) or by the PMAS pharmacists (n = 128) for a mean of 14.9 and 14.5 weeks, respectively. Pharmacist-managed anticoagulation services' and physician's patients were within the exact target range 77.3% and 76.7% of the time (95% CI of the difference -4.9% to 6.0%) and within the extended range 93.0% and 91.6% of the time (95% CI -2.1% to 4.7%), respectively. Pharmacist-managed anticoagulation services patients have seen their family physician less often (95% CI -3.1 to -0.1 visit per year). Number of INR tests, incidence of complications, and health-related quality of life were similar in both groups. The incremental cost of PMAS follow-up was estimated at CAN$123.80 per patient year., Conclusion: Once PMAS patients are well stabilized, maintaining a PMAS follow-up or transferring them to their physician is associated with excellent INR control. However, long-term PMAS follow-up may be more expensive.

The relative contribution of phenotypic measures and CYP2C9-vitamin K epoxide reductase complex subunit 1 (VKORC1) polymorphisms to warfarin dose requirements at day 14 was determined in 132 hospitalized, heavily medicated patients. Phenotypic measures were (1) the urinary losartan metabolic ratio before the first dose of warfarin, (2) the S:R-warfarin ratio at day 1, and (3) a dose-adjusted international normalized ratio (INR) at day 4. CYP2C9 and VKORC1 genotypes were determined by gene chip analysis. In multivariate analyses, the dose-adjusted INR at day 4 explained 31% of variability observed in warfarin doses at day 14, whereas genotypic measures (CYP2C9-VKORC1) contributed 6.5%. When S:R-warfarin ratio was used, genotypes contributed more significantly (23.5%). Finally, urinary losartan metabolic ratio was of low predictive value. The best models obtained explained 51% of intersubject variability in warfarin dose requirements. Thus, combination of a phenotypic measure to CYP2C9-VKORC1 genotypes represents a useful strategy to predict warfarin doses in patients receiving multiple drugs (11+/-4 drugs/day).

Unlabelled: In a pharmacist-managed anticoagulation clinic, portable point-of-care coagulation devices may facilitate patient monitoring by providing rapid INR measurement. Few studies, however, have validated this type of device., Objective: To evaluate the reliability, validity and ease of use of the CoaguChek S, a new portable coagulation device., Methods: A total of 100 patients followed at a pharmacist-managed anticoagulation clinic attended two study visits. INRs were measured using the CoaguChek S and the standard laboratory technique., Results: Reliability: The test-retest reliability (precision) of the CoaguChek S, estimated by the intraclass correlation coefficient (ICC) and a 95% confidence interval (95% CI), was high (0.98 (0.98-0.99)) and comparable to the standard laboratory technique (0.99 (0.98-0.99)). Interrater reliability was also high (0.97 (0.95-0.98)). Reliability coefficients did not vary with the test-strip lot number nor the CoaguChek S operator., Validity: When compared with standard laboratory procedure, the ICC (95% CI) was equal to 0.93 (0.91-0.95). The mean difference (95% CI) between INR measured by the laboratory and the CoaguChek S was equal to -0.02 units (-0.06-0.03). The mean absolute and relative absolute differences (95% CI) were equal to 0.24 units (0.21-0.27) and 9% (8%-10%), respectively. Differences tended to increase for INRs greater than 3 units as seen by a mean difference (95% CI) of -0.17 units (-0.35-0.02). This represented a mean absolute difference (95% CI) of 0.44 units (0.33-0.55) and a mean relative absolute difference of 12% (9%-15%). Concordance between therapeutic decisions based on CoaguChek S and laboratory results was high (Kappa = 0.68). In 34 cases (18%), the therapeutic decision would have been different. However, in 15 of these discordant observations, the difference between the CoaguCheck S and laboratory INR was

One of the most difficult and time-consuming aspects of building compartmental models of single neurons is assigning values to free parameters to make models match experimental data. Automated parameter-search methods potentially represent a more rapid and less labor-intensive alternative to choosing parameters manually. Here we compare the performance of four different parameter-search methods on several single-neuron models. The methods compared are conjugate-gradient descent, genetic algorithms, simulated annealing, and stochastic search. Each method has been tested on five different neuronal models ranging from simple models with between 3 and 15 parameters to a realistic pyramidal cell model with 23 parameters. The results demonstrate that genetic algorithms and simulated annealing are generally the most effective methods. Simulated annealing was overwhelmingly the most effective method for simple models with small numbers of parameters, but the genetic algorithm method was equally effective for more complex models with larger numbers of parameters. The discussion considers possible explanations for these results and makes several specific recommendations for the use of parameter searches on neuronal models.

Computational modeling is being used increasingly in neuroscience. In deriving such models, inference issues such as model selection, model complexity, and model comparison must be addressed constantly. In this article we present briefly the Bayesian approach to inference. Under a simple set of commonsense axioms, there exists essentially a unique way of reasoning under uncertainty by assigning a degree of confidence to any hypothesis or model, given the available data and prior information. Such degrees of confidence must obey all the rules governing probabilities and can be updated accordingly as more data becomes available. While the Bayesian methodology can be applied to any type of model, as an example we outline its use for an important, and increasingly standard, class of models in computational neuroscience--compartmental models of single neurons. Inference issues are particularly relevant for these models: their parameter spaces are typically very large, neurophysiological and neuroanatomical data are still sparse, and probabilistic aspects are often ignored. As a tutorial, we demonstrate the Bayesian approach on a class of one-compartment models with varying numbers of conductances. We then apply Bayesian methods on a compartmental model of a real neuron to determine the optimal amount of noise to add to the model to give it a level of spike time variability comparable to that found in the real cell.

Coupled oscillator models use a single phase variable to approximate the voltage oscillation of each neuron during repetitive firing where the behavior of the model depends on the connectivity and the interaction function chosen to describe the coupling. We introduce a network model consisting of a continuum of these oscillators that includes the effects of spatially decaying coupling and axonal delay. We derive equations for determining the stability of solutions and analyze the network behavior for two different interaction functions. The first is a sine function, and the second is derived from a compartmental model of a pyramidal cell. In both cases, the system of coupled neural oscillators can undergo a bifurcation from synchronous oscillations to waves. The change in qualitative behavior is due to the axonal delay, which causes distant connections to encourage a phase shift between cells. We suggest that this mechanism could contribute to the behavior observed in several neurobiological systems.

Pain is difficult and sometimes frustrating to treat, even though new devices and new approaches have been developed in recent years. Pain varies tremendously from one patient to the next, and there are also some studies suggesting that the intensity of pain varies according to time of day. In animal experiments, a relationship between the reaction to pain and the rhythmicity of plasma endorphin concentrations was suggested because reactions to pain (such as jumping from a hot plate) were in phase with plasma endorphin levels: latencies were longest and plasma levels were highest during the resting period of rodents. In human studies, pain induced experimentally was reported to be maximal in the morning, or in the afternoon or at night. These divergent findings may be due to methodological differences, as pain was produced by different methods, many parameters were used to quantify pain intensity, and the psychological aspect of pain was rarely considered by authors. A circadian pattern of pain was found in patients suffering from pain produced by different diseases. For instance, highest toothache intensity occurred in the morning, while biliary colic, migraine, and intractable pain were highest at night. Patients with rheumatoid arthritis reported peak pain early in the morning, while those with osteoarthritis of the knee indicated that the maximal pain occurred at the end of the day. The effectiveness of opioids appears also to vary according to time of day, but large differences in the time of peak and low effects were found. Investigators found that peak pain intensity and narcotic demands occurred early in the morning, while others found maximal pain at the end of the day. Pain is a complex phenomenon and efforts should be made to standardize the methods used in studies and to describe accurately the diseases causing pain because the patterns of pain may be specific to each clinical situation. Further research should be aimed at characterizing the chronobiology of pain in different experimental and clinical situations and to determine when the analgesic drugs are producing maximal effectiveness. This information is needed before clinicians can be persuaded to use chronopharmacological data when they prescribe analgesic drugs to their patients.

In this pilot randomized, double-blind, cross-over study, the effectiveness and safety of hydromorphone administration by continuous subcutaneous (s.c.) infusion (mode A) and by continuous basal rate s.c. infusion + PCA (mode B) were compared in 8 cancer patients. Patients experimented with each infusion mode during 48 h. Statistical analysis was performed on data collected in 7 patients during 36 h from 22:00 h on day 1 to 10:00 h on day 3 and from 22:00 h on day 3 to 10:00 h on day 5. Mean hydromorphone dose +/- S.D. was 56.6 +/- 30.1 and 40.4 +/- 24.5 mg/36 h for modes A and B, respectively. There was no statistically significant difference observed in mean pain intensity, but the absence of significant difference may be related to the small sample size and high individual variability. Both methods provided adequate overall pain control in most patients. However, a large interindividual variation was detected. Indeed, some patients reported in the subjective questionnaire that they felt marked discomfort during hydromorphone administration with mode B. Only 2 patients chose mode B at the end of the study, but it was interesting to note that those 2 patients were the youngest of the group. This study demonstrated the effectiveness and safety of both modes of hydromorphone administration. The data suggest that it may be possible to identify particular cancer patients which can really benefit from an association of a basal rate infusion and PCA for opiate administration.

Treatment with 10(-5) M retinoic acid causes loss of anchorage-independent growth in src-transformed RR1022 cells but not in ras-transformed KNRK cells. In an effort to elucidate the mechanisms underlying this difference, we investigated the effect of RA on phospholipid turnover and PKC activity in these two cell lines. 10(-5) M RA treatment caused a drastic inhibition of 32P incorporation into PI and PA and a large increase in 32P incorporation into PC in RR1022 cells. Similar treatment of KNRK cells yielded no change in PC or PA labelling and a much smaller decrease in PI labelling. Furthermore, 10(-5) M RA treatment causes a large decrease in PKC activity in RR1022 cells (35% of control) but only a small decrease in KNRK cells (78% of control). We suggest that these effects are part of an altered signal transduction pathway which mediates the differential effects of RA on anchorage-independent growth in these two cell lines.