A scoping review of theories, models and frameworks used or proposed to evaluate knowledge mobilization strategies.

BACKGROUND: Evaluating knowledge mobilization strategies (KMb) presents challenges for organizations seeking to understand their impact to improve KMb effectiveness. Moreover, the large number of theories, models, and frameworks (TMFs) available can be confusing for users. Therefore, the purpose of this scoping review was to identify and describe the characteristics of TMFs that have been used or proposed in the literature to evaluate KMb strategies. METHODS: A scoping review methodology was used. Articles were identified through searches in electronic databases, previous reviews and reference lists of included articles. Titles, abstracts and full texts were screened in duplicate. Data were charted using a piloted data charting form. Data extracted included study characteristics, KMb characteristics, and TMFs used or proposed for KMb evaluation. An adapted version of Nilsen (Implement Sci 10:53, 2015) taxonomy and the Expert Recommendations for Implementing Change (ERIC) taxonomy (Powell et al. in Implement Sci 10:21, 2015) guided data synthesis. RESULTS: Of the 4763 search results, 505 were retrieved, and 88 articles were eligible for review. These consisted of 40 theoretical articles (45.5%), 44 empirical studies (50.0%) and four protocols (4.5%). The majority were published after 2010 (n = 70, 79.5%) and were health related (n = 71, 80.7%). Half of the studied KMb strategies were implemented in only four countries: Canada, Australia, the United States and the United Kingdom (n = 42, 47.7%). One-third used existing TMFs (n = 28, 31.8%). According to the adapted Nilsen taxonomy, process models (n = 34, 38.6%) and evaluation frameworks (n = 28, 31.8%) were the two most frequent types of TMFs used or proposed to evaluate KMb. According to the ERIC taxonomy, activities to "train and educate stakeholders" (n = 46, 52.3%) were the most common, followed by activities to "develop stakeholder interrelationships" (n = 23, 26.1%). Analysis of the TMFs identified revealed relevant factors of interest for the evaluation of KMb strategies, classified into four dimensions: context, process, effects and impacts. CONCLUSIONS: This scoping review provides an overview of the many KMb TMFs used or proposed. The results provide insight into potential dimensions and components to be considered when assessing KMb strategies.

Production and use of rapid responses during the COVID-19 pandemic in Quebec (Canada): perspectives from evidence synthesis producers and decision makers.

BACKGROUND: The COVID-19 pandemic has required evidence to be made available more rapidly than usual, in order to meet the needs of decision makers in a timely manner. These exceptional circumstances have caused significant challenges for organizations and teams responsible for evidence synthesis. They had to adapt to provide rapid responses to support decision-making. This study aimed to document (1) the challenges and adaptations made to produce rapid responses during the pandemic, (2) their perceived usefulness, reported use and factors influencing their use and (3) the methodological adaptations made to produce rapid responses. METHODS: A qualitative study was conducted in 2021 with eight organizations in the health and social services system in Quebec (Canada), including three institutes with a provincial mandate. Data collection included focus groups (n = 9 groups in 8 organizations with 64 participants), interviews with decision makers (n = 12), and a document analysis of COVID-19 rapid responses (n = 128). A thematic analysis of qualitative data (objectives 1 and 2) and a descriptive analysis of documents (objective 3) were conducted. RESULTS: The results highlight the teams and organizations' agility to deal with the many challenges encountered during the pandemic (e.g., increased their workloads, adoption of new technological tools or work processes, improved collaboration, development of scientific monitoring, adaptation of evidence synthesis methodologies and products). The challenge of balancing rigor and speed was reported by teams and organizations. When available at the right time, rapid responses have been reported as a useful tool for informing or justifying decisions in a context of uncertainty. Several factors that may influence their use were identified (e.g., clearly identify needs, interactions with producers, perceived rigor and credibility, precise and feasible recommendations). Certain trends in the methodological approaches used to speed up the evidence synthesis process were identified. CONCLUSIONS: This study documented rapid responses producers' experiences during the COVID-19 pandemic in Quebec, and decision makers who requested, consulted, or used these products. Potential areas of improvements are identified such as reinforce coordination, improve communication loops, clarify guidelines or methodological benchmarks, and enhance utility of rapid response products for decision makers.

Use of an expert elicitation methodology to compare welfare impacts of two approaches for blood sampling European badgers (Meles meles) in the field.

In the UK and Republic of Ireland, the European badger (Meles meles) is considered the most significant wildlife reservoir of the bacterium Mycobacterium bovis, the cause of bovine tuberculosis (bTB). To expand options for bTB surveillance and disease control, the Animal and Plant Health Agency developed a bespoke physical restraint cage to facilitate collection of a small blood sample from a restrained, conscious badger in the field. A key step, prior to pursuing operational deployment of the novel restraint cage, was an assessment of the relative welfare impacts of the approach. We used an established welfare assessment model to elicit expert opinion during two workshops to compare the impacts of the restraint cage approach with the only current alternative for obtaining blood samples from badgers in the field, which involves administration of a general anaesthetic. Eleven panellists participated in the workshops, comprising experts in the fields of wildlife biology, animal welfare science, badger capture and sampling, and veterinary science. Both approaches were assessed to have negative welfare impacts, although in neither case were overall welfare scores higher than intermediate, never exceeding 5-6 out of a possible 8. Based on our assessments, the restraint cage approach is no worse for welfare compared to using general anaesthesia and possibly has a lower overall negative impact on badger welfare. Our results can be used to integrate consideration of badger welfare alongside other factors, including financial cost and efficiency, when selecting a field method for blood sampling free-living badgers.

Analyse d'une infrastructure québécoise de transfert de connaissances en autisme : le RNETSA.

INTRODUCTION: Many Knowledge Translation (KT) networks have been set up to support the improvement of research-based practices. However despite the deployment of KT networks, there is little empirical data on how they work. The Réseau national d’expertise en trouble du spectre de l’autisme (RNETSA) is the result of a ministerial initiative. OBJECTIVE AND METHOD: Its mission is to promote the evolution of autism practices and services in the education, early childhood, and health and social services sectors. The purpose of this article is to analyze the governance structure and KT strategy of the RNETSA in terms of its legitimacy. The study was based on a case study design combining a literature review and interviews. RESULTS: The results highlight the key components of 1) the governance structure (e.g., identification of a common need, formalization of bodies, allocation of resources) and 2) the KT strategy (e.g., knowledge dissemination, collaborations, increasing participation in activities). The discussion addresses a number of building blocks that could help strengthen the network’s legitimacy with a view to bringing it closer to its purpose. CONCLUSIONS: RNETSA has demonstrated a strong capacity to ensure its legitimacy in the autism KT ecosystem. The potential to influence public policy in the field of autism is also a key feature of RNETSA. To improve knowledge of RNETSA’s legitimacy, an evaluation of the effects of its KT activities would be necessary.

Clinical features, biochemistry, and HLA-DRB1 status in youth-onset type 1 diabetes in Mali.

OBJECTIVE: Limited information is available regarding youth-onset diabetes in Mali. We investigated demographic, clinical, biochemical, and genetic features in new diabetes cases in children and adolescents. RESEARCH DESIGN AND METHODS: The study was conducted at Hôpital du Mali in Bamako. A total of 132 recently-diagnosed cases <21 years were enrolled. Demographic characteristics, clinical information, biochemical parameters (blood glucose, HbA1c, C-peptide, glutamic acid decarboxylase-65 (GAD-65) and islet antigen-2 (IA2) autoantibodies) were assessed. DNA was genotyped for HLA-DRB1 using high-resolution genotyping technology. RESULTS: A total of 130 cases were clinically diagnosed as type 1 diabetes (T1D), one with type 2 diabetes (T2D), and one with secondary diabetes. A total of 66 (50.8%) T1D cases were males and 64 (49.2%) females, with a mean age at diagnosis of 13.8 ± 4.4 years (range 0.8-20.7 years) peak onset of 15 years. 58 (44.6%) presented in diabetic ketoacidosis; with 28 (21.5%) IA2 positive, 76 (58.5%) GAD-65 positive, and 15 (11.5%) positive for both autoantibodies. HLA was also genotyped in 195 controls without diabetes. HLA-DRB1 genotyping of controls and 98 T1D cases revealed that DRB1*03:01, DRB1*04:05, and DRB1*09:01 alleles were predisposing for T1D (odds ratios [ORs]: 2.82, 14.76, and 3.48, p-values: 9.68E-5, 2.26E-10, and 8.36E-4, respectively), while DRB1*15:03 was protective (OR = 0.27; p-value = 1.73E-3). No significant differences were observed between T1D cases with and without GAD-65 and IA2 autoantibodies. Interestingly, mean C-peptide was 3.6 ± 2.7 ng/ml (1.2 ± 0.9 nmol/L) in T1D cases at diagnosis. CONCLUSIONS: C-peptide values were higher than expected in those diagnosed as T1D and autoantibody rates lower than in European populations. It is quite possible that some cases have an atypical form of T1D, ketosis-prone T2D, or youth-onset T2D. This study will help guide assessment and individual management of Malian diabetes cases, potentially enabling healthier outcomes.

Clinical features, biochemistry, and HLA-DRB1 status in youth-onset type 1 diabetes in Sudan.

OBJECTIVE: To further understand clinical and biochemical features, and HLA-DRB1 genotypes, in new cases of diabetes in Sudanese children and adolescents. RESEARCH DESIGN AND METHODS: Demographic characteristics, clinical information, and biochemical parameters (blood glucose, HbA1c, C-peptide, autoantibodies against glutamic acid decarboxylase 65 [GADA] and insulinoma-associated protein-2 [IA-2A], and HLA-DRB1) were assessed in 99 individuals <18 years, recently (<18 months) clinically diagnosed with T1D. HLA-DRB1 genotypes for 56 of these Arab individuals with T1D were compared to a mixed control group of 198 healthy Arab (75%) and African (25%) individuals without T1D. RESULTS: Mean ± SD age at diagnosis was 10.1 ± 4.3 years (range 0.7-17.6 years) with mode at 9-12 years. A female preponderance was observed. Fifty-two individuals (55.3%) presented in diabetic ketoacidosis (DKA). Mean ± SD serum fasting C-peptide values were 0.22 ± 0.25 nmol/L (0.66±0.74 ng/ml). 31.3% were autoantibody negative, 53.4% were GADA positive, 27.2% were IA-2A positive, with 12.1% positive for both autoantibodies. Association analysis compared to 198 controls of similar ethnic origin revealed strong locus association with HLA-DRB1 (p < 2.4 × 10-14 ). Five HLA-DRB1 alleles exhibited significant T1D association: three alleles (DRB1*03:01, DRB1*04:02, and DRB1*04:05) were positively associated, while three (DRB1*10:01, DRB1*15:02, and DRB1*15:03) were protective. DRB1*03:01 had the strongest association (odds ratio = 5.04, p = 1.7 × 10-10 ). CONCLUSIONS: Young Sudanese individuals with T1D generally have similar characteristics to reported European-origin T1D populations. However, they have higher rates of DKA and slightly lower autoantibody rates than reported European-origin populations, and a particularly strong association with HLA-DRB1*03:01.

Implementation of an intersectoral outreach and community nursing care intervention with refugees in Quebec: A protocol study.

AIM: To establish and assess an intersectoral local network focused on the roles of registered nurses and primary healthcare nurse practitioners to ensure the continuity of care and service pathways for refugees in Quebec. DESIGN: Developmental evaluation with a mixed methodology. METHODS: The qualitative component will include: (1) a document review; (2) observations of participants during meetings of different governance structures; (3) semi-structured interviews with key actors (n = 40; 20/neighbourhood interventions); and (4) focus groups with end users of the services (refugees) (n = 4; 6 to 8 participants per group). The quantitative component will be based on: (1) a data sheet on health and social interventions for refugees users filled in by registered nurses, primary healthcare nurse practitioners and physicians and (2) data analysis of the clinical-administrative database since 2012. This study received funding in June 2019 and Research Ethics Committee approval was granted in July 2020. DISCUSSION: In Quebec, refugee vulnerability is exacerbated by the lack of integration of existing resources and the lack of access to care and continuity of services. To address these issues, an integrated local network for refugees must be developed. Additionally, we will explore the role of registered nurses and their collaboration with primary healthcare nurse practitioners. IMPACT: This study will provide recommendations on how to optimize the scopes of practice of registered nurses and primary healthcare nurse practitioners, adapt care and services and develop a local intersectoral network to better meet the complex needs of refugees. It will evaluate the use and the appreciation of new services for targeted populations (neighbourhoods and refugees) and aim to improve the accessibility, continuity and user experience of all health services for those populations.

Barriers and Facilitators to Implementing Community Outreach Work, and Inter-professional Collaboration with Regional Partners.

Community outreach workers support individuals in accessing the health and community services they require through various forms of proximity approaches. Even though community outreach has been available in the province of Quebec (Canada) for the past 40 years, it is still difficult to implement and sustain, especially with families of young children. The aim of this study was to document barriers and facilitators to implementing community outreach practices, and to describe how such workers collaborate with sectoral (e.g. health care) and inter-sectoral (e.g. municipalities, community organizations, schools) partners. We performed a content analysis on 55 scientific and grey literature documents, and transcriptions of 24 individual interviews and 3 focus groups with stakeholders including parents, community outreach workers, health care employees, and inter-sectoral partners. This study reveals four categories of barriers and facilitators to the implementation of community outreach work (i.e. organizational factors, nature of the work and worker-related factors, family-related factors, external factors). With regards to collaboration, community outreach workers deal with various partners. Good inter-professional collaboration is achieved through positive interactions and communication, shared or co-developed activities for the families, co-intervention with families, and strategies to enhance role awareness and inter-sectoral meetings. Results highlighted that many factors interact and can either influence, positively or negatively, the opportunity to implement community outreach work. The collaborative practices identified may help to maximize facilitators and overcome barriers. Advocacy and a better understanding of how to integrate community outreach work within health services while maintaining the workers' flexibility are needed to sustain this practice.

Predominance of DR3 in Somali children with type 1 diabetes in the twin cities, Minnesota.

BACKGROUND: Minnesota is home to the largest Somali population in USA, and pediatric diabetes teams are seeing increasing numbers of Somali children with diabetes. OBJECTIVE: To assess the immune basis of diabetes in Somali children in the Twin Cities, Minnesota. METHODS: A total of 31 Somali children ≤19 yr were treated for type 1 diabetes (T1D) at the University of Minnesota Masonic Children's Hospital and Children's Hospitals and Clinics of Minnesota underwent analysis of human leukocyte antigen (HLA) alleles (n = 30) and diabetes autoantibodies [glutamic acid decarboxylase (GAD65), islet antigen 2 (IA-2), zinc transporter 8 (ZnT8); n = 31]. HLA alleles were analyzed in 49 Somalis without diabetes (controls). Anti-transglutaminase autoantibodies (TGA) for celiac disease were also measured. RESULTS: In Somali children with T1D aged 13.5 ± 5 yr (35% female, disease duration 6.5 ± 3.6 yr), the most common HLA allele was DRB1*03:01 (93%, compared with 45% of Somali controls), followed by DRB1*13:02 (27%). There was a relatively low frequency of DR4 (13%). Controls showed a similar pattern. All 31 participants were positive for at least one diabetes autoantibody. Insulin antibodies were positive in 84% (all were on insulin). Excluding insulin antibodies, 23 (74%) subjects tested positive for at least one other diabetes autoantibody; 32% had 1 autoantibody, 32% had 2 autoantibodies, and 10% had 3 autoantibodies. GAD65 autoantibodies were found in 56% of subjects, IA-2 in 29%, and ZnT8 in 26%. Four (13%) were TGA positive. CONCLUSION: The autoantibody and HLA profiles of Somali children with diabetes are consistent with autoimmune diabetes. Their HLA profile is unique with an exceptionally high prevalence of DRB1*03:01 allele and relative paucity of DR4 alleles compared with African Americans with T1D.

Hypomethylation within gene promoter regions and type 1 diabetes in discordant monozygotic twins.

Genetic susceptibility to type 1 diabetes (T1D) is well supported by epidemiologic evidence; however, disease risk cannot be entirely explained by established genetic variants identified so far. This study addresses the question of whether epigenetic modification of the inherited DNA sequence may contribute to T1D susceptibility. Using the Infinium HumanMethylation450 BeadChip array (450k), a total of seven long-term disease-discordant monozygotic (MZ) twin pairs and five pairs of HLA-identical, disease-discordant non-twin siblings (NTS) were examined for associations between DNA methylation (DNAm) and T1D. Strong evidence for global hypomethylation of CpG sites within promoter regions in MZ twins with TID compared to twins without T1D was observed. DNA methylation data were then grouped into three categories of CpG sites for further analysis, including those within: 1) the major histocompatibility complex (MHC) region, 2) non-MHC genes with reported T1D association through genome wide association studies (GWAS), and 3) the epigenome, or remainder of sites that did not include MHC and T1D associated genes. Initial results showed modest methylation differences between discordant MZ twins for the MHC region and T1D-associated CpG sites, BACH2, INS-IGF2, and CLEC16A (DNAm difference range: 2.2%-5.0%). In the epigenome CpG set, the greatest methylation differences were observed in MAGI2, FANCC, and PCDHB16, (DNAm difference range: 6.9%-16.1%). These findings were not observed in the HLA-identical NTS pairs. Targeted pyrosequencing of five candidate CpG loci identified using the 450k array in the original discordant MZ twins produced similar results using control DNA samples, indicating strong agreement between the two DNA methylation profiling platforms. However, findings for the top five candidate CpG loci were not replicated in six additional T1D-discordant MZ twin pairs. Our results indicate global DNA hypomethylation within gene promoter regions may contribute to T1D; however, findings do not support the involvement of large DNAm differences at single CpG sites alone in T1D.

Evaluation of the Effectiveness of Suicide.ca, Quebec's Digital Suicide Prevention Strategy Platform: Cross-Sectional Descriptive Study.

BACKGROUND: In 2017, the Quebec government assigned the Association québécoise de prévention du suicide (AQPS) to develop a digital suicide prevention strategy (DSPS). The AQPS responded by creating a centralized website that provides information on suicide and mental health, identifies at-risk individuals on the internet, and offers direct crisis intervention support via chat and text. OBJECTIVE: This study aims to evaluate the effectiveness of suicide.ca, Quebec's DSPS platform. METHODS: This study used a cross-sectional descriptive design. The study population comprised internet users from Quebec, Canada, who visited the suicide.ca platform between October 2020 and October 2021. Various data sources, such as Google Analytics, Firebase Console, and Customer Relation Management data, were analyzed to document the use of the platform. To understand the profile of suicide.ca users, frequency analyses were conducted using data from the self-assessment module questionnaires, the intervention service's triage questionnaire, and the counselors' intervention reports. The effectiveness of the platform's promotional activities on social media was assessed by examining traffic peaks. Google Analytics was used to evaluate the effectiveness of AQPS' strategy for identifying at-risk internet users. The impact of the intervention service was evaluated through an analysis of counselors' intervention reports and postintervention survey results. RESULTS: The platform received traffic from a diverse range of sources, with promotional efforts on social media directly contributing to the increased traffic. The requirement of a user account posed a barrier to the use of the mobile app, and a triage question that involved personal information led to a substantial number of dropouts during the intervention service triage. AdWords campaigns and fact sheets addressing suicide risk factors played a crucial role in driving traffic to the platform. With regard to the profile of suicide.ca users, the findings revealed that the platform engaged individuals with diverse levels of suicidal risk. Notably, users of the chat service displayed a higher suicide risk than those who used the self-assessment module. Crisis chat counselors reported a positive impact on approximately half of the contacts, and overall, intervention service users expressed satisfaction with the support they received. CONCLUSIONS: A centralized digital platform can be used to implement a DSPS, effectively reaching the general population, individuals with risk factors for suicide, and those facing suicidal issues.

Implementing a mental health app library in primary care: A feasibility study.

Confronted with a wide range of digital health tools (DHT), professionals and patients need guidance to use these tools correctly and optimize health management. In the fall of 2020, a DHT library developed by Quebec-based company TherAppX was implemented in 22 institutions. The library was designed to enable healthcare professionals to use DHT in clinical care. The purpose of the current study was to assess the feasibility of implementing the library, including user experience, changes in DHT recommendation habits, and factors that helped or hindered the implementation process. A multi-methods design focusing on secondary use of quantitative data collected by TherAppX and semi-structured interviews with users was employed. While the quantitative analyses indicated infrequent use of the library, qualitative analyses highlighted several factors that hindered its implementation, including certain library and user characteristics and the unprecedented context of the COVID-19 pandemic. Nevertheless, the quantitative analyses confirmed interest in DHT and their usefulness during follow-ups. The results revealed a marginally significant pre-post changes in the frequency with which DHT were recommended. This study helped identify areas for improvements and indicates that further evaluation is needed. Future implementations would benefit from ensuring optimal conditions for a successful implementation.

Musculoskeletal disorder (MSD) prevention practices by nurses working in health care settings: Facilitators and barriers to implementation.

The incidence of musculoskeletal disorders (MSD) in the healthcare professional population is concerning. In particular, the high incidence of back injuries is an issue for nurses. Although many MSD prevention initiatives are being implemented, these practices are not succeeding in reducing MSDs. Why are these efforts struggling to close the gap between knowledge and practice? This article aims to report on individual and organizational factors that may influence nurses' implementation of MSD prevention practices. A survey was sent to nurses in the Quebec health and social services network. A total of 399 questionnaires were completed and analyzed. The results revealed that nurses have the required knowledge on MSD prevention practices, but have difficulty applying them in their professional context. It would appear that successful implementation of MSD prevention practices relies mainly on organizational factors, including management support, organizational culture, feedback mechanisms, and training that is adapted to the work environment.

[Déterminants du succès d'une démarche provinciale d'usage optimal des antipsychotiques chez les résidents en soins de longue durée selon les acteurs clés impliqués dans l'implantation].

Le Québec présente le taux de prescriptions d'antipsychotiques le plus élevé chez les personnes âgées de 65 ans et plus au Canada. La démarche « Optimiser les pratiques, les usages, les soins et les services - antipsychotiques ¼ (OPUS-AP) vise à pallier cet enjeu. Étant donné ses premiers résultats prometteurs, notre étude visait à identifier les déterminants de son succès. Elle repose sur un devis d'étude de cas regroupant une analyse documentaire et 21 entrevues auprès d'acteurs clés impliqués dans l'implantation. Les résultats mettent en lumière cinq déterminants centraux : 1) une démarche intégrée, collaborative et probante; 2) des communications et des réseaux au service de la démarche; 3) un climat d'implantation favorable aux changements; 4) un engagement et une implication des parties prenantes; et 5) une stratégie d'application des connaissances intégrée et appuyée. Des défis et recommandations pour assurer la pérennisation et la mise à l'échelle d'OPUS-AP et inspirer des démarches similaires sont identifiés.

[An innovative process for sustaining and scaling up a school-based mental health promotion and anxiety prevention programs: The example of the HORS-PISTE program]. / Processus novateur pour favoriser la pérennisation et la mise à l'échelle de programmes de prévention de l'anxiété à l'école : l'exemple du programme HORS-PISTE.

Context Anxiety disorders are among the most prevalent psychopathologies for children and adolescents in Quebec. The prevalence of anxiety disorders is very high and has been affecting a growing number of young people for the past 10 years. It is possible to observe an increased number of anxiety prevention programs for young people around the world. However, some authors point out that they are rarely faithfully implemented, sustained, and scaled up in several schools. Based on implementation science, this HORS-PISTE program was developed to address these important issues by preventing anxiety in Quebec high school students. Implemented in more than 100 schools, the program is now part of Action 4.3 (Promote the deployment of the HORS-PISTE program) of the new interdepartmental Action Plan on Mental Health of the Government of Quebec (2022). Purpose This article aims to describe how the Knowledge-to-Action (KTA) framework, derived of implementation science, was used to design, implement, sustain, evaluate, and scale up the HORS-PISTE program. This framework proposes a cyclical process in seven phases. Method A multi-method and multi-stakeholder approach was conducted with a grant from the Public Health Agency of Canada's Mental Health Promotion Innovation Fund, which has been supporting 20 innovative projects across Canada since 2019. It includes a pre-post evaluation protocol consisting of validated questionnaires, surveys (administered to students, parents, and teachers), semi-structured logbooks completed by program facilitators and implementation review meetings in each school. The different cycles of the program development, implementation and evaluation are discussed through the KTA framework phases. Results From 2017 to 2021, this methodology made it possible to evaluate and readjust the program each year to promote its adaptation and prepare its scaling up. This article highlights the data collected and analyzed in relation to the seven phases of the KTA framework. Conclusion This article demonstrates how implementation science can support designers of anxiety prevention programs who are concerned by scaling up and sustaining their programs. Issues in combining the scientific rigor of evaluation with the reality of the field are also raised.

High-density SNP screening of the major histocompatibility complex in systemic lupus erythematosus demonstrates strong evidence for independent susceptibility regions.

A substantial genetic contribution to systemic lupus erythematosus (SLE) risk is conferred by major histocompatibility complex (MHC) gene(s) on chromosome 6p21. Previous studies in SLE have lacked statistical power and genetic resolution to fully define MHC influences. We characterized 1,610 Caucasian SLE cases and 1,470 parents for 1,974 MHC SNPs, the highly polymorphic HLA-DRB1 locus, and a panel of ancestry informative markers. Single-marker analyses revealed strong signals for SNPs within several MHC regions, as well as with HLA-DRB1 (global p = 9.99 x 10(-16)). The most strongly associated DRB1 alleles were: *0301 (odds ratio, OR = 2.21, p = 2.53 x 10(-12)), *1401 (OR = 0.50, p = 0.0002), and *1501 (OR = 1.39, p = 0.0032). The MHC region SNP demonstrating the strongest evidence of association with SLE was rs3117103, with OR = 2.44 and p = 2.80 x 10(-13). Conditional haplotype and stepwise logistic regression analyses identified strong evidence for association between SLE and the extended class I, class I, class III, class II, and the extended class II MHC regions. Sequential removal of SLE-associated DRB1 haplotypes revealed independent effects due to variation within OR2H2 (extended class I, rs362521, p = 0.006), CREBL1 (class III, rs8283, p = 0.01), and DQB2 (class II, rs7769979, p = 0.003, and rs10947345, p = 0.0004). Further, conditional haplotype analyses demonstrated that variation within MICB (class I, rs3828903, p = 0.006) also contributes to SLE risk independent of HLA-DRB1*0301. Our results for the first time delineate with high resolution several MHC regions with independent contributions to SLE risk. We provide a list of candidate variants based on biologic and functional considerations that may be causally related to SLE risk and warrant further investigation.

Promoting advance planning for health care and research among older adults: a randomized controlled trial.

BACKGROUND: Family members are often required to act as substitute decision-makers when health care or research participation decisions must be made for an incapacitated relative. Yet most families are unable to accurately predict older adult preferences regarding future health care and willingness to engage in research studies. Discussion and documentation of preferences could improve proxies' abilities to decide for their loved ones. This trial assesses the efficacy of an advance planning intervention in improving the accuracy of substitute decision-making and increasing the frequency of documented preferences for health care and research. It also investigates the financial impact on the healthcare system of improving substitute decision-making. METHODS/DESIGN: Dyads (n = 240) comprising an older adult and his/her self-selected proxy are randomly allocated to the experimental or control group, after stratification for type of designated proxy and self-report of prior documentation of healthcare preferences. At baseline, clinical and research vignettes are used to elicit older adult preferences and assess the ability of their proxy to predict those preferences. Responses are elicited under four health states, ranging from the subject's current health state to severe dementia. For each state, we estimated the public costs of the healthcare services that would typically be provided to a patient under these scenarios. Experimental dyads are visited at home, twice, by a specially trained facilitator who communicates the dyad-specific results of the concordance assessment, helps older adults convey their wishes to their proxies, and offers assistance in completing a guide entitled My Preferences that we designed specifically for that purpose. In between these meetings, experimental dyads attend a group information session about My Preferences. Control dyads attend three monthly workshops aimed at promoting healthy behaviors. Concordance assessments are repeated at the end of the intervention and 6 months later to assess improvement in predictive accuracy and cost savings, if any. Copies of completed guides are made at the time of these assessments. DISCUSSION: This study will determine whether the tested intervention guides proxies in making decisions that concur with those of older adults, motivates the latter to record their wishes in writing, and yields savings for the healthcare system. TRIAL REGISTRATION: ISRCTN89993391.

[A Portrait of Generalized Anxiety Symptoms in a Sample of High School Students: The Importance of Prevention, Screening and Intervention]. / Portrait des symptômes d'anxiété généralisée chez les élèves du secondaire : l'importance de la prévention, du dépistage et de l'intervention.

Anxiety disorders are among the most prevalent psychopathologies in children and adolescents around the world. They affect their personal, family, school and social functioning. Although symptoms of generalized anxiety disorder (GAD) are among the most commonly observed symptoms in adolescence, relatively little is known about the most important risk factors. Objectives The purpose of the present study was therefore 1) to document the prevalence of the central feature of GAD, excessive worrying, in high school students aged 12 to 17 years, by identifying the percentage of students reporting low, medium, and high levels of symptoms, 2) to identify key sociodemographic characteristics associated with high symptom level, and 3) to identify individual and family risk factors associated with high symptom level and estimate their relative contribution. Method A total of 8689 Quebec high school students (55.9% girls) participated in the study. The average age of these students was 14.34 years (SD=1.52). A k-means cluster analysis was first performed to create three categories based on the symptoms of generalized anxiety presented by the participants (low, medium, high). Multinomial logistic regression analyzes were then performed to identify the variables that best predict membership in these different categories. Results The results showed that 35.1% of the students reported a low level of symptoms, 40.2% reported an average level of symptoms, while 24.7% reported a high level of symptoms. Girls and adolescents in higher grades were more likely to report high levels of symptoms. Several factors were also identified as increasing the risk of being in the high generalized anxiety symptoms category compared to the average generalized anxiety symptoms and low generalized anxiety symptoms categories. These include fear of negative evaluation by others, perfectionism, depressed feelings, negative problem orientation and cognitive avoidance. Conclusion This study supports previous research showing that girls are at greater risk of developing generalized anxiety disorder. It also highlights the multidimensional aspect of the problem, by identifying the most important risk factors. Ultimately, this better understanding of the factors involved will allow us to better identify the targets to prioritize in the prevention of generalized anxiety disorders in adolescence.

Implementation conditions leading to the scale-up of an innovation involving the optimal use of antipsychotics in long-term care centers: The Optimizing Practices, Use, Care and Services-Antipsychotics (OPUS-AP) program.

BACKGROUND: Antipsychotics are often used for the first-line management of behavioral and psychological symptoms of dementia despite their limited efficacy and the risk of serious adverse drug events, compounded with disregard for guidelines recommending prioritizing non-pharmacological interventions. Some innovative interventions promote the deprescription of antipsychotics in long term care (LTC) settings. OBJECTIVE: The objective of this article is to present the conditions leading to the scale-up of an innovative program on the appropriate use of antipsychotics in LTC centers. METHODS: The Optimizing Practices, Use, Care and Services-Antipsychotics (OPUS-AP) program is a mixed-method project that aims to improve LTC residents' care through increased knowledge and competency among staff, resident-centered approaches, nonpharmacologic interventions, and by deprescribing antipsychotics when appropriate. This article consists of a qualitative study focused on exploring the implementation conditions of the OPUS-AP program. This study was carried out in an integrated health area of Québec. It consisted of 46 semi-structured interviews with staff members and managers involved in the implementation of OPUS-AP. The qualitative data analysis was inspired by a realistic evaluation approach, which shed light on the causal chain between context, mechanisms, and perceived effects. RESULTS: This study identified certain conditions conducive to scaling up the OPUS-AP program: an integrated, collaborative and evidence-based approach; communications in support of the process; stakeholder engagement at the strategic, tactical and operational levels; an implementation climate conducive to change; and an integrated knowledge translation strategy. CONCLUSION: Despite evidence of clinical efficacy, deprescribing programs require great deal of scaling up efforts. Hence, this study underscores the need to further examine conditions for scaling up medication usage programs in real life contexts.

[The Development Process of the New Quebec Digital Suicide Prevention Strategy: Suicide.ca]. / Processus d'élaboration de la nouvelle Stratégie québécoise numérique en prévention du suicide : Suicide.ca.

In Quebec, nearly 3 persons still take their own lives every day, even though this number has been declining since 2000. Several institutional and community actors are involved in suicide prevention and several initiatives have contributed to the reduction of suicide rates. Despite this hard work, additional efforts are needed to intensify service offers and resource access to better reach people at risk of suicide not reached by actual services. For many years, several countries have been implementing digital technologies to reach them. In Quebec, there were delays in adoption of digital technologies for suicide prevention. In this context, the Health and Social services Ministry mandated Association québécoise de prévention du suicide (AQPS) to develop a Digital Strategy for Suicide Prevention (DSPS). From the beginning, AQPS wanted to anchor DSPS's development in a decision-making process based on scientific, contextual and experiential evidence. A process, derived from implementation science, was therefore put in place to actualize this intent. Implementation science is defined as the science of implementing programs in real-world settings. It is recognized as contributing to the successful implementation of new programs while promoting a rigorous evaluation of their impacts and outcomes. Objectives This article aims to: 1) present the process that was put in place to facilitate DSPS design, implementation, and evaluation; and 2) describe the DSPS action model and the DSPS. Method The Knowledge to Action (KTA) framework is central to the design, implementation, and evaluation of DSPS. This framework proposes a cyclical process in 7 iterative phases, each with its own methodological aspects and data collections Results The results section illustrates the concrete actions taken at each phase of the KTA process and the highlights that emerge from the analysis of the data collected. This section also presents the DSPS. Conclusion Optimal conditions to promote the implementation of DSPS, its use and its sustainability have been put in place. The current implementation and evaluation of this implementation and its impacts will allow to assess the capacity of DSPS to achieve its main objectives: to provide information about suicide, to identify suicidal individuals, to increase the visibility of resources, and to offer help to suicidal individuals who respond less to traditional resources.