Characteristics of knowledge translation theories, models and frameworks for health technology reassessment: expert perspectives through a qualitative exploration.

BACKGROUND: Health Technology Reassessment (HTR) is a process that systematically assesses technologies that are currently used in the health care system. The process results in four outputs: increase use or decrease use, no change, or de-adoption of a technology. Implementation of these outputs remains a challenge. The Knowledge Translation (KT) field enables to transfer/translate knowledge into practice. KT could help with implementation of HTR outputs. This study sought to identify which characteristics of KT theories, models, and frameworks could be useful, specifically for decreased use or de-adoption of a technology. METHODS: A qualitative descriptive approach was used to ascertain the perspectives of international KT and HTR experts on the characteristics of KT theories, models, and frameworks for decreased use or de-adoption of a technology. One-to-one semi-structured interviews were conducted from September to December 2019. Interviews were audio recorded and transcribed verbatim. Themes and sub-themes were deduced from the data through framework analysis using five distinctive steps: familiarization, identifying an analytic framework, indexing, charting, mapping and interpretation. Themes and sub-themes were also mapped to existing KT theories, models, and frameworks. RESULTS: Thirteen experts from Canada, United States, United Kingdom, Australia, Germany, Spain, and Sweden participated in the study. Three themes emerged that illustrated the ideal traits: principles that were foundational for HTR, levers of change, and steps for knowledge to action. Principles included evidence-based, high usability, patient-centered, and ability to apply to the micro, meso, macro levels. Levers of change were characterized as positive, neutral, or negative influences for changing behaviour for HTR. Steps for knowledge to action included: build the case for HTR, adapt research knowledge, assess context, select interventions, and assess impact. Of the KT theories, models, and frameworks that were mapped, the Consolidated Framework for Implementation Research had most of the characteristics, except ability to apply to micro, meso, macro levels. CONCLUSIONS: Characteristics that need to be considered within a KT theory, model, and framework for implementing HTR outputs have been identified. Consideration of these characteristics may guide users to select relevant KT theories, models, and frameworks to apply to HTR projects.

Return on Investment of the Primary Health Care Integrated Geriatric Services Initiative Implementation.

BACKGROUND: Since June 2017, the Primary Health Care Integrated Geriatric Services Initiative (PHC IGSI) has been implemented in Alberta, Canada to, among other aims, reduce costs of unplanned health service utilization while maximizing the utilization of available community resources to support people living with dementia living in communities. AIM OF THE STUDY: We performed an economic evaluation of this initiative to inform policy regarding sustainability, scale up and spread. METHODS: We used a cohort design together with a difference-in-difference approach and a propensity score matching technique to calculate impacts of the intervention on patient's health service utilization, including inpatient, outpatient and physician services, as well as prescription drugs. We then used a decision tree to compare between benefits and costs of the intervention and reported net benefits (NB) and return on investment ratios (ROI). We used a health system perspective and a time horizon of 1 year. Both deterministic and probabilistic sensitivity analyses were performed for the uncertainty of parameters. We analyzed real-world data extracted from the Alberta Health Administrative Databases. All costs/savings were inflated to 2019 CAD (CAD 1 \sim = USD 0.75) using the Canadian Consumer Price Index. RESULTS: The intervention reduced the use of hospital (inpatient, emergency, and outpatient) services by increasing the use of community services (physician and prescription drug). As hospital services are expensive, the PHC IGSI community intervention resulted in a NB from CAD 554 to 4,046 per patient-year for the health system, and a ROI from 1.3 to 3.1 meaning that every CAD invested in PHC IGSI would bring CAD 1.3 to 3.1 in return. The probability of PHC IGSI to be cost-saving was 56.4% to 69.3%. IMPLICATIONS FOR HEALTH CARE PROVISION AND USE: The PHC IGSI is cost-effective in Alberta. IMPLICATIONS FOR HEALTH POLICY: The savings would be larger if the initiative is sustained, scaled up and spread because of not only a reduced cost of intervention in the sustainability phase, but also because of the increased number of patients that would be impacted. IMPLICATIONS FOR FURTHER RESEARCH: Future studies taking a societal perspective to also include costs for families and health and social sectors at the community level, would be desirable. Additionally, future works to determine how wellbeing is impacted by the PHC IGSI as vertical and horizontal integration interventions are implemented at the community level, are essential to undertake. Finally, in addition to people living with dementia, the PHC IGSI also supports people living in the community with frailty and other geriatric syndromes, therefore, the cost-savings estimated in this study are likely underestimated.

Human T-cell leukemia virus type 1 Gag domains have distinct RNA-binding specificities with implications for RNA packaging and dimerization.

Human T-cell leukemia virus type 1 (HTLV-1) is the first retrovirus that has conclusively been shown to cause human diseases. In HIV-1, specific interactions between the nucleocapsid (NC) domain of the Gag protein and genomic RNA (gRNA) mediate gRNA dimerization and selective packaging; however, the mechanism for gRNA packaging in HTLV-1, a deltaretrovirus, is unclear. In other deltaretroviruses, the matrix (MA) and NC domains of Gag are both involved in gRNA packaging, but MA binds nucleic acids with higher affinity and has more robust chaperone activity, suggesting that this domain may play a primary role. Here, we show that the MA domain of HTLV-1, but not the NC domain, binds short hairpin RNAs derived from the putative gRNA packaging signal. RNA probing of the HTLV-1 5' leader and cross-linking studies revealed that the primer-binding site and a region within the putative packaging signal form stable hairpins that interact with MA. In addition to a previously identified palindromic dimerization initiation site (DIS), we identified a new DIS in HTLV-1 gRNA and found that both palindromic sequences bind specifically the NC domain. Surprisingly, a mutant partially defective in dimer formation in vitro exhibited a significant increase in RNA packaging into HTLV-1-like particles, suggesting that efficient RNA dimerization may not be strictly required for RNA packaging in HTLV-1. Moreover, the lifecycle of HTLV-1 and other deltaretroviruses may be characterized by NC and MA functions that are distinct from those of the corresponding HIV-1 proteins, but together provide the functions required for viral replication.

Barriers and facilitators to diagnosing and managing apathy in Parkinson's disease: a qualitative study.

BACKGROUND: Apathy is a prominent non-motor symptom in Parkinson's disease (PD). People with apathy show a lack of emotion, passion, and motivation. Between 17 and 70% of persons with PD have apathy; the extreme heterogeneity in these estimates is due to limited heterogeneous knowledge concerning how to diagnose PD. The lack of a widely utilized diagnostic process limits understandings on how to treat and manage apathy in PD. A scoping review of apathy in PD identified only one qualitative study investigating this symptom. It was our objective to assess perceived barriers and facilitators to diagnosing, treating, and managing apathy in PD, as described by key stakeholders. METHODS: This research applied qualitative methodology, utilizing focus groups and interviews with health care practitioners (HCPs), persons with PD, and caregivers. Evidence gathered from a scoping review on apathy in PD informed discussions that took place with participants. Data collection and analysis was conducted using framework analysis, applying the Theoretical Domains Framework and Behaviour Change Wheel. RESULTS: Eleven HCPs and five persons with PD/caregivers participated. Themes included interdisciplinary teams and communication with family to facilitate diagnosis and treatment, and the use of education and increased awareness of apathy to facilitate management. Themes surrounding barriers included lack of initiative and motivation to maintain treatment plans, and a lack of evidence for apathy specific interventions. While a key barrier identified was the lack of information HCPs have access to, persons with PD and caregivers would prefer to receive a diagnosis of apathy even with limited management methods. Thus, education and awareness were noted as two of the most important facilitators, overall. CONCLUSION: These findings suggest that diagnosing, treating, and managing apathy in PD requires interdisciplinary teams, that include family and caregivers. We identified that where HCPs perceive lack of knowledge as a barrier to diagnosis, persons with PD and caregivers find being given a diagnosis facilitates understanding. These findings highlight the importance of qualitative research involving persons with PD and apathy, caregivers, and HCPs who aid in management of this symptom. Barriers reported suggest future research must aim to identify apathy specific treatments, both pharmacologic and non-pharmacologic.

Classification schemes for knowledge translation interventions: a practical resource for researchers.

BACKGROUND: As implementation science advances, the number of interventions to promote the translation of evidence into healthcare, health systems, or health policy is growing. Accordingly, classification schemes for these knowledge translation (KT) interventions have emerged. A recent scoping review identified 51 classification schemes of KT interventions to integrate evidence into healthcare practice; however, the review did not evaluate the quality of the classification schemes or provide detailed information to assist researchers in selecting a scheme for their context and purpose. This study aimed to further examine and assess the quality of these classification schemes of KT interventions, and provide information to aid researchers when selecting a classification scheme. METHODS: We abstracted the following information from each of the original 51 classification scheme articles: authors' objectives; purpose of the scheme and field of application; socioecologic level (individual, organizational, community, system); adaptability (broad versus specific); target group (patients, providers, policy-makers), intent (policy, education, practice), and purpose (dissemination versus implementation). Two reviewers independently evaluated the methodological quality of the development of each classification scheme using an adapted version of the AGREE II tool. Based on these assessments, two independent reviewers reached consensus about whether to recommend each scheme for researcher use, or not. RESULTS: Of the 51 original classification schemes, we excluded seven that were not specific classification schemes, not accessible or duplicates. Of the remaining 44 classification schemes, nine were not recommended. Of the 35 recommended classification schemes, ten focused on behaviour change and six focused on population health. Many schemes (n = 29) addressed practice considerations. Fewer schemes addressed educational or policy objectives. Twenty-five classification schemes had broad applicability, six were specific, and four had elements of both. Twenty-three schemes targeted health providers, nine targeted both patients and providers and one targeted policy-makers. Most classification schemes were intended for implementation rather than dissemination. CONCLUSIONS: Thirty-five classification schemes of KT interventions were developed and reported with sufficient rigour to be recommended for use by researchers interested in KT in healthcare. Our additional categorization and quality analysis will aid in selecting suitable classification schemes for research initiatives in the field of implementation science.

Facilitators and barriers of change toward an elder-friendly surgical environment: perspectives of clinician stakeholder groups.

BACKGROUND: Current acute care surgical practices do not focus on the unique needs of older adults. Adverse outcomes in older patients result from a complex interrelationship between baseline vulnerability and insults experienced during hospitalization. The purpose of this study is to assess the organizational readiness and the barriers and facilitators for the implementation of elder-friendly interventions in the acute care of unplanned abdominal surgery patients. METHODS: This cross-sectional mixed methods study included a convenience sample of clinician stakeholder groups. Eight focus groups were conducted with 33 surgical team members including: 10 health care aides, 6 licensed practical nurses, 6 registered nurses, 4 nurse managers and 7 surgeons, to identify barriers and facilitators to the implementation of an elder-friendly surgical unit. Audio recordings of the focus groups were transcribed verbatim and analysed using interpretive description techniques. Transcripts were coded along with explanatory memos to generate a detailed description of participant experiences. Themes were identified followed by refining the codes. Participants also completed the Organizational Readiness for Implementing Change questionnaire. Differences in organizational readiness scores across clinician stakeholder groups were assessed using Kruskal-Wallice tests. Mann-Whitney tests (Bonferroni's corrections for multiple comparisons) were conducted to assess pair-wise relationships. RESULTS: The focus group data were conceptualized to represent facilitators and barriers to change at two levels of care delivery. Readiness to change at the organizational level was evident in five categories that reflected the barriers and facilitators to implementing an elder-friendly surgical unit. These included education, environment, staffing, policies and other research projects. At the individual level barriers and facilitators were apparent in staff members' acceptance of new roles and duties with other staff, family and patients. Examples of these included communication, teamwork and leadership. The mean change commitment and change efficacy scores on the Organizational Readiness for Implementing Change Questionnaire were 3.7 (0.8) and 3.5 (0.9) respectively. No statistically significant differences were detected between the stakeholder groups. CONCLUSIONS: Staff are interested in contributing to improved care for elderly surgical patients; however, opportunities were identified to enhance facilitators and reduce barriers in advance of implementing the elder-friendly surgical unit intervention.

Drivers of COVID-19 Outcomes in Long-Term Care Facilities Using Multi-Level Analysis: A Systematic Review.

This study aimed to identify the individual, organizational, and environmental factors which contributed to COVID-19-related outcomes in long-term care facilities (LTCFs). A systematic review was conducted to summarize and synthesize empirical studies using a multi-level analysis approach to address the identified influential factors. Five databases were searched on 23 May 2023. To be included in the review, studies had to be published in peer-reviewed journals or as grey literature containing relevant statistical data. The Joanna Briggs Institute critical appraisal tool was employed to assess the methodological quality of each article included in this study. Of 2137 citations identified after exclusions, 99 records met the inclusion criteria. The predominant individual, organizational, and environmental factors that were most frequently found associated with the COVID-19 outbreak comprised older age, higher dependency level; lower staffing levels and lower star and subset domain ratings for the facility; and occupancy metrics and co-occurrences of outbreaks in counties and communities where the LTCFs were located, respectively. The primary individual, organizational, and environmental factors frequently linked to COVID-19-related deaths comprised age, and male sex; higher percentages of racial and ethnic minorities in LTCFs, as well as ownership types (including private, for-profit, and chain membership); and higher occupancy metrics and LTCF's size and bed capacity, respectively. Unfolding the risk factors collectively may mitigate the risk of outbreaks and pandemic-related mortality in LTCFs during future endemic and pandemics through developing and improving interventions that address those significant factors.

"We could have used a lot more of this before ": A qualitative study understanding barriers and facilitators to implementing a provincial PPE safety coach program during the COVID-19 pandemic.

BACKGROUND: A Provincial PPE Safety Coach Program was introduced to support appropriate use of personal protective equipment by health care workers. The objective was to understand barriers and facilitators to implementation. METHODS: A qualitative study was conducted mid-2021. Participants were recruited using a purposive sampling strategy. Interviews were conducted using a guide informed by the Theoretical Domains Framework and Consolidated Framework for Implementation Research. Analysis was conducted using the Theoretical Domains Framework. RESULTS: Prominent domains identified by staff were "social influences and skills", "environmental context and resources", "social/professional role and identity", "emotion", and "belief of consequences". Prominent domains identified by safety coaches were "knowledge", "social/professional role and identity", "environmental context and resources", and "memory". Only "environmental context and resources" and "social/professional role and identity" were similar. The main facilitators were fear of COVID-19 and leadership commitment, while the main barriers were lack of clarity and balancing the role. DISCUSSION: Understanding the local context of a health care environment influenced the success of safety coaches. The role allowed individuals to develop leadership skills and help staff improve their perceived competence in using personal protective equipment. CONCLUSIONS: Safety coaches were well received. Influencing factors provide a basis for strategies to embed this approach throughout a health care system.

Concept mapping applied to the intersection between older adults' outdoor walking and the built and social environments.

OBJECTIVE: For older adults, the ability to navigate walking routes in the outdoor environment allows them to remain active and socially engaged, facilitating community participation and independence. In order to enhance outdoor walking, it is important to understand the interaction of older adults within their local environments and the influence of broader stakeholder priorities that impact these environments. Thus, we aimed to synthesize perspectives from stakeholders to identify elements of the built and social environments that influence older adults' ability to walk outdoors. METHOD: We applied a concept mapping approach with the input of diverse stakeholders (N=75) from British Columbia, Canada in 2012. RESULTS: A seven-cluster map best represented areas that influence older adults' outdoor walking. Priority areas identified included sidewalks, crosswalks, and neighborhood features. CONCLUSION: Individual perceptions and elements of the built and social environments intersect to influence walking behaviors, although targeted studies that address this area are needed.

A framework for stakeholder identification in concept mapping and health research: a novel process and its application to older adult mobility and the built environment.

BACKGROUND: Stakeholders, as originally defined in theory, are groups or individual who can affect or are affected by an issue. Stakeholders are an important source of information in health research, providing critical perspectives and new insights on the complex determinants of health. The intersection of built and social environments with older adult mobility is an area of research that is fundamentally interdisciplinary and would benefit from a better understanding of stakeholder perspectives. Although a rich body of literature surrounds stakeholder theory, a systematic process for identifying health stakeholders in practice does not exist. This paper presents a framework of stakeholders related to older adult mobility and the built environment, and further outlines a process for systematically identifying stakeholders that can be applied in other health contexts, with a particular emphasis on concept mapping research. METHODS: Informed by gaps in the relevant literature we developed a framework for identifying and categorizing health stakeholders. The framework was created through a novel iterative process of stakeholder identification and categorization. The development entailed a literature search to identify stakeholder categories, representation of identified stakeholders in a visual chart, and correspondence with expert informants to obtain practice-based insight. RESULTS: The three-step, iterative creation process progressed from identifying stakeholder categories, to identifying specific stakeholder groups and soliciting feedback from expert informants. The result was a stakeholder framework comprised of seven categories with detailed sub-groups. The main categories of stakeholders were, (1) the Public, (2) Policy makers and governments, (3) Research community, (4) Practitioners and professionals, (5) Health and social service providers, (6) Civil society organizations, and (7) Private business. CONCLUSIONS: Stakeholders related to older adult mobility and the built environment span many disciplines and realms of practice. Researchers studying this issue may use the detailed stakeholder framework process we present to identify participants for future projects. Health researchers pursuing stakeholder-based projects in other contexts are encouraged to incorporate this process of stakeholder identification and categorization to ensure systematic consideration of relevant perspectives in their work.

Cultural Knowledge in Context - People Aged 50 Years and Over Make Sense of a First Fracture and Osteoporosis.

Catch a Break (CaB) is a secondary fracture prevention program that uses medical understandings of osteoporosis to assess first fractures and determine appropriateness for secondary fracture prevention. In this study, we interviewed CaB program participants to identify the understandings that patients themselves used to make sense of first fractures and the osteoporosis suggestion as cause. Semi-structured interviews were conducted with female and male participants of the CaB program in Canada. An interpretive practice approach was used to analyze the data. A random sample of 20 individuals, 12 women, and eight men all aged 50 years and over participated. First fractures were produced as meaningful in the context of osteoporosis only for seniors of very advanced age, and for people of any age with poor nutrition. The trauma events that led to a first fracture were produced as meaningful only if perceived as accidents, and having an active lifestyle was produced as beneficial only for mental health and well-being unrelated to osteoporosis. Cultural knowledge shapes, but does not determine, how individuals make sense of their health and illness experiences. Risk prevention program designers should include patients on the design team and be more aware of the presumptive knowledge used to identify individuals at risk of disease.

Human Retrovirus Genomic RNA Packaging.

Two non-covalently linked copies of the retrovirus genome are specifically recruited to the site of virus particle assembly and packaged into released particles. Retroviral RNA packaging requires RNA export of the unspliced genomic RNA from the nucleus, translocation of the genome to virus assembly sites, and specific interaction with Gag, the main viral structural protein. While some aspects of the RNA packaging process are understood, many others remain poorly understood. In this review, we provide an update on recent advancements in understanding the mechanism of RNA packaging for retroviruses that cause disease in humans, i.e., HIV-1, HIV-2, and HTLV-1, as well as advances in the understanding of the details of genomic RNA nuclear export, genome translocation to virus assembly sites, and genomic RNA dimerization.

Supporting Rehabilitation of Rural Patients Receiving Total Knee Arthroplasty Through Physical Activity: Perceptions of Stakeholder Groups.

OBJECTIVE: To identify how patients with osteoarthritis waiting for and recovering from total knee arthroplasty (TKA) conceptualized and participated in physical activity behaviors in their rural setting and to gather perceptions of health care professionals and rehabilitation decision-makers on the feasibility of a remotely led physical activity coaching intervention. METHODS: Using a qualitative descriptive study, we collected data from three stakeholder groups: patients waiting for or recovering from TKA (interviews), health professionals delivering a physical activity intervention to patients in the recovering cohort (focus group), and rehabilitation leaders involved in decision-making at the local or provincial level (interviews). RESULTS: A total of 38 individuals provided their perspectives (25 patients, five health professionals, eight decision-makers). Patients waiting for and recovering from surgery described the attributes of their rural environment that supported and restricted their ability to participate in physical activities. Patients recovering from TKA appreciated support for goal-setting and problem-solving during their rehabilitation. Health care professionals and decision-makers commented on the benefits of the program's innovative use of relatively simple technology to support remotely delivered, personalized rehabilitation in rural settings. CONCLUSION: This study adds to the limited voice of and about patients living with osteoarthritis who reside in rural settings and identifies facilitators and barriers to TKA rehabilitation in this population. Our findings highlight that it is important to consider the local context and the resources available to patients as they navigate living well with osteoarthritis.

Molecular Determinants of Human T-cell Leukemia Virus Type 1 Gag Targeting to the Plasma Membrane for Assembly.

Assembly of human T-cell leukemia virus type 1 (HTLV-1) particles is initiated by the trafficking of virally encoded Gag polyproteins to the inner leaflet of the plasma membrane (PM). Gag-PM interactions are mediated by the matrix (MA) domain, which contains a myristoyl group (myr) and a basic patch formed by lysine and arginine residues. For many retroviruses, Gag-PM interactions are mediated by phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2]; however, previous studies suggested that HTLV-1 Gag-PM interactions and therefore virus assembly are less dependent on PI(4,5)P2. We have recently shown that PI(4,5)P2 binds directly to HTLV-1 unmyristoylated MA [myr(-)MA] and that myr(-)MA binding to membranes is significantly enhanced by inclusion of phosphatidylserine (PS) and PI(4,5)P2. Herein, we employed structural, biophysical, biochemical, mutagenesis, and cell-based assays to identify residues involved in MA-membrane interactions. Our data revealed that the lysine-rich motif (Lys47, Lys48, and Lys51) constitutes the primary PI(4,5)P2-binding site. Furthermore, we show that arginine residues 3, 7, 14 and 17 located in the unstructured N-terminus are essential for MA binding to membranes containing PS and/or PI(4,5)P2. Substitution of lysine and arginine residues severely attenuated virus-like particle production, but only the lysine residues could be clearly correlated with reduced PM binding. These results support a mechanism by which HTLV-1 Gag targeting to the PM is mediated by a trio engagement of the myr group, Arg-rich and Lys-rich motifs. These findings advance our understanding of a key step in retroviral particle assembly.

Post-discharge management following hip fracture--get you back to B4: a parallel group, randomized controlled trial study protocol.

BACKGROUND: Fall-related hip fractures result in significant personal and societal consequences; importantly, up to half of older adults with hip fracture never regain their previous level of mobility. Strategies of follow-up care for older adults after fracture have improved investigation for osteoporosis; but managing bone health alone is not enough. Prevention of fractures requires management of both bone health and falls risk factors (including the contributing role of cognition, balance and continence) to improve outcomes. METHODS/DESIGN: This is a parallel group, pragmatic randomized controlled trial to test the effectiveness of a post-fracture clinic compared with usual care on mobility for older adults following their hospitalization for hip fracture. Participants randomized to the intervention will attend a fracture follow-up clinic where a geriatrician and physiotherapist will assess and manage their mobility and other health issues. Depending on needs identified at the clinical assessment, participants may receive individualized and group-based outpatient physiotherapy, and a home exercise program. Our primary objective is to assess the effectiveness of a novel post-discharge fracture management strategy on the mobility of older adults after hip fracture. We will enrol 130 older adults (65 years+) who have sustained a hip fracture in the previous three months, and were admitted to hospital from home and are expected to be discharged home. We will exclude older adults who prior to the fracture were: unable to walk 10 meters; diagnosed with dementia and/or significant comorbidities that would preclude their participation in the clinical service. Eligible participants will be randomly assigned to the Intervention or Usual Care groups by remote allocation. Treatment allocation will be concealed; investigators, measurement team and primary data analysts will be blinded to group allocation. Our primary outcome is mobility, operationalized as the Short Physical Performance Battery at 12 months. Secondary outcomes include frailty, rehospitalizations, falls risk factors, quality of life, as well as physical activity and sedentary behaviour. We will conduct an economic evaluation to determine health related costs in the first year, and a process evaluation to ascertain the acceptance of the program by older adults, as well as clinicians and staff within the clinic. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov: NCT01254942.

Identifying what matters most for the health of older adults in Alberta: results from a James Lind Alliance Research Priority Setting Partnership.

BACKGROUND: As the number of older adults continues to increase, addressing their health becomes increasingly important for both the population and the health care system. The aim of this priority setting partnership was to use direct engagement with older adults, caregivers and health care providers to identify and prioritize the most important topics on the health of older adults that should be addressed by future research. METHODS: We followed the James Lind Alliance method. We conducted an initial online and paper survey from Jan. 22 to May 2, 2018, with older adults in Alberta aged 65 years and older to identify what respondents saw as being most important for the health of older adults. We formed responses into summary questions and checked them against existing evidence. We administered a second survey (July 3 to Aug. 2, 2018) to shortlist summary questions and held an in-person workshop (Aug. 30, 2018) to rank the list through discussion and shared decision-making. RESULTS: We recruited 670 participants (32.7% older adults, 19.7% caregivers, 46.9% health and social care workers) in the initial survey to tell us what topics on the health of older adults mattered most to them. Over 3000 responses generated 101 summary questions, of which only 4 were completely answered by existing evidence. The second prioritization survey was completed by 232 participants (28.4% older adults, 24.6% care partners, 47.0% health and social care workers) to produce a shortlist of 22 high priority questions. Twenty-two attendees participated in the summary workshop to create a prioritized list of 10 questions for future research that address aspects of the health system, provision of care and living well in older adulthood. INTERPRETATION: Older adults, caregivers and clinicians collectively produced a prioritized list of questions that matter most to older adults' health in Alberta. Provincial researchers and research funders should consider these unmet knowledge needs of end-users in future endeavours.

Identification of knowledge translation theories, models or frameworks suitable for health technology reassessment: a survey of international experts.

OBJECTIVE: Health technology reassessment (HTR) is a field focused on managing a technology throughout its life cycle for optimal use. The process results in one of four possible recommendations: increase use, decrease use, no change or complete withdrawal of the technology. However, implementation of these recommendations has been challenging. This paper explores knowledge translation (KT) theories, models and frameworks (TMFs) and their suitability for implementation of HTR recommendations. DESIGN: Cross-sectional survey. PARTICIPANTS: Purposeful sampling of international KT and HTR experts was administered between January and March 2019. METHODS: Sixteen full-spectrum KT TMFs were rated by the experts as 'yes', 'partially yes' or 'no' on six criteria: familiarity, logical consistency/plausibility, degree of specificity, accessibility, ease of use and HTR suitability. Consensus was determined as a rating of ≥70% responding 'yes'. Descriptive statistics and manifest content analysis were conducted on open-ended comments. RESULTS: Eleven HTR and 11 KT experts from Canada, USA, UK, Australia, Germany, Spain, Italy and Sweden participated. Of the 16 KT TMFs, none received ≥70% rating. When ratings of 'yes' and 'partially yes' were combined, the Consolidated Framework for Implementation Research was considered the most suitable KT TMF by both KT and HTR experts (86%). One additional KT TMF was selected by KT experts: Knowledge to Action framework. HTR experts selected two additional KT TMFs: Co-KT framework and Plan-Do-Study-Act cycle. Experts identified three key characteristics of a KT TMF that may be important to consider: practicality, guidance on implementation and KT TMF adaptability. CONCLUSIONS: Despite not reaching an overall ≥70% rating on any of the KT TMFs, experts identified four KT TMFs suitable for HTR. Users may apply these KT TMFs in the implementation of HTR recommendations. In addition, KT TMF characteristics relevant to the field of HTR need to be explored further.

Effect of a multimethod quality improvement intervention on antipsychotic medication use among residents of long-term care.

BACKGROUND: Antipsychotic medications are used to address neuropsychiatric symptoms associated with dementia. Evidence suggests that among older adults with dementia, their harms outweigh their benefits. A quality improvement initiative was conducted to address inappropriate antipsychotic medication use in long-term care (LTC) in the province of Alberta. METHODS: We conducted a multimethod evaluation of the provincial implementation of the project in 170 LTC sites over a 3-year project period incorporating a quasi-experimental before-after design. Using a three-component intervention of education and audit and feedback delivered in a learning workshop innovation collaborative format, local LTC teams were supported to reduce the number of residents receiving antipsychotic medications in the absence of a documented indication. Project resources were preferentially allocated to supporting sites with the highest baseline antipsychotic medication use. Changes in antipsychotic medication use, associated clinical and economic outcomes, and the effects of the project on LTC staff, physicians, leaders and administrators, and family members of LTC residents were assessed at the conclusion of the implementation phase. RESULTS: The province-wide initiative was delivered with a 75% implementation fidelity. Inappropriate antipsychotic medication use declined from 26.8% to 21.1%. The decrease was achieved without unintended consequences in other outcomes including physical restraint use or aggressive behaviours. The project was more expensive but resulted in less inappropriate use of antipsychotics than the pre-project period (incremental cost per inappropriate antipsychotic avoided of $5 678.71). Accounts from family, organisational leaders, and LTC staff were supportive of the project activities and outcomes. CONCLUSION: This quality improvement initiative was successfully delivered across an entire delivery arm of the continuing care sector. Quality of care in LTC was improved.

Structural Insights into the Mechanism of Human T-cell Leukemia Virus Type 1 Gag Targeting to the Plasma Membrane for Assembly.

Retroviral Gag targeting to the plasma membrane (PM) for assembly is mediated by the N-terminal matrix (MA) domain. For many retroviruses, Gag-PM interaction is dependent on phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2). However, it has been shown that for human T-cell leukemia virus type 1 (HTLV-1), Gag binding to membranes is less dependent on PI(4,5)P2 than HIV-1, suggesting that other factors may modulate Gag assembly. To elucidate the mechanism by which HTLV-1 Gag binds to the PM, we employed NMR techniques to determine the structure of unmyristoylated MA (myr(-)MA) and to characterize its interactions with lipids and liposomes. The MA structure consists of four α-helices and unstructured N- and C-termini. We show that myr(-)MA binds to PI(4,5)P2 via the polar head and that binding to inositol phosphates (IPs) is significantly enhanced by increasing the number of phosphate groups on the inositol ring, indicating that the MA-IP binding is governed by charge-charge interactions. The IP binding site was mapped to a well-defined basic patch formed by lysine and arginine residues. Using an NMR-based liposome binding assay, we show that PI(4,5)P2and phosphatidylserine enhance myr(-)MA binding in a synergistic fashion. Confocal microscopy data revealed formation of puncta on the PM of Gag expressing cells. However, G2A-Gag mutant, lacking myristoylation, is diffuse and cytoplasmic. These results suggest that although myr(-)MA binds to membranes, myristoylation appears to be key for formation of HTLV-1 Gag puncta on the PM. Altogether, these findings advance our understanding of a key mechanism in retroviral assembly.