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Abstract Background The Good Life with osteoArthritis: Denmark (GLA:D™), an evidence-based education and exercise program designed for conservative management of knee and hip osteoarthritis (OA), has been shown to benefit participants by reducing pain, improving function, and quality of life. Standardized reporting in the GLA:D databases enabled the measurement of self-reported and performance-based outcomes. There is a paucity of qualitative research on the participants’ perceptions of this program, and it is important to understand whether participants’ perceptions of the benefits of the program align with reported quantitative findings. Methods We conducted semi-structured telephone interviews with individuals who participated in the GLA:D program from January 2017 to December 2018 in Alberta, Canada. Data were analyzed using an interpretive description approach and thematic analysis to identify emergent themes and sub-themes associated with participants perceived benefits of the GLA:D program. We analyzed the data using NVivo Pro software. Member checking and bracketing were used to ensure the rigour of the analysis. Results 30 participants were interviewed (70% female, 57% rural, 73% knee OA). Most participants felt the program positively benefited them. Two themes emerged from the analysis: wellness and self-efficacy. Participants felt the program benefited their wellness, particularly with regard to pain relief, and improvements in mobility, strength, and overall well-being. Participants felt the program benefited them by promoting a sense of self-efficacy through improving the confidence to perform exercise and routine activities, as well as awareness, and motivation to manage their OA symptoms. Twenty percent of participants felt no benefits from the program due to experiencing increased pain and feeling their OA was too severe to participate. Discussion The GLA:D program was viewed as beneficial to most participants, this study also identified factors (e.g., severe OA, extreme pain) as to why some participants did not experience meaningful improvements. Early intervention with the GLA:D program prior to individuals experiencing severe OA could help increase the number of participants who experience benefits from their participation. Conclusion As the GLA:D program expands across jurisdictions, providers of the program may consider recruitment earlier in disease progression and targeting those with mild and moderate OA.

Several barriers exist in Alberta, Canada to providing accurate and accessible diagnoses for patients presenting with acute knee injuries and chronic knee problems. In efforts to improve quality of care for these patients, an evidence-informed clinical decision-making tool was developed. Forty-five expert panelists were purposively chosen to represent stakeholder groups, various expertise, and each of Alberta Health Services’ 5 geographical health regions. A systematic rapid review and modified Delphi approach were executed with the intention of developing standardized clinical decision-making processes for acute knee injuries, atraumatic/overuse conditions, knee arthritis, and degenerative meniscus. Standardized criteria for screening, history-taking, physical examination, diagnostic imaging, timelines, and treatment were developed. This tool standardizes and optimizes assessment and diagnosis of acute knee injuries and chronic knee problems in Alberta. This project was a highly collaborative, province-wide effort led by Alberta Health Services’ Bone and Joint Health Strategic Clinical Network (BJH SCN) and the Alberta Bone and Joint Health Institute (ABJHI).

Background During COVID-19 healthcare systems had to make concessions to make room for the surge of COVID-19 patients requiring hospital and intensive care. Postponing surgeries was a common strategy; however, it is unclear how surgical care was delivered during this time of constraint. The objective of this study was to understand how surgical care was delivered and prioritized during the COVID-19 pandemic response. Methods This was an environmental scan following the Canadian Agency for Drugs and Technologies in Health methodology. This study was conducted in Canada; a universal, publicly funded healthcare system. Evidence sources on policies pertaining to the provision of surgical care between January 2020 and October 2022 were obtained from ministries of health, health services agencies and publicly funded hospitals across all 10 provinces and three territories. We synthesized the evidence sources using framework analysis. Results We identified 205 evidence sources that described six themes about the provision of surgical care during the COVID-19 pandemic: the cycle of postponement and resumption; guidelines for triaging and prioritizing surgical cases; Infection Prevention and Control (IPAC), and safety measures for surgical care during COVID-19, patient-centred care, and looking forward (recovery planning, leadership, and decision-making). Conclusion This study provides a comprehensive understanding of how surgical care was disrupted and innovated during COVID-19 which can inform future strategies for providing effective and efficient surgical care during times of healthcare constraint.

IntroductionThe Good Life with osteoArthritis: Denmark (GLA:DTM) is an evidence-based program designed for individuals with symptomatic hip and knee osteoarthritis (OA). This program has reported improvement in pain, quality of life and self-efficacy, as well as delays in joint replacement surgery for adults with moderate to severe hip or knee OA. Evaluations of GLA:DTM implementation in several countries have focused on effectiveness, training, and feasibility of the program primarily from the provider perspective. Our objective was to examine how the GLA:DTM program was perceived and experienced by individuals with hip and knee OA to inform on-going program refinement and implementation.MethodsThirty semi-structured telephone interviews were conducted with participants who completed the GLA:DTM program in Alberta. An interpretive description approach was used to frame the study and thematic analysis was used to code the data and identify emergent themes and sub-themes associated with participants' experience and perception of the GLA:DTM program.ResultsMost participants had a positive experience of the GLA:DTM program and particularly enjoyed the group format, although some participants felt the group format prevented one-on-one support from providers. Three emergent themes related to acceptability were identified: accessible, adaptable, and supportive. Participants found the program to be accessible in terms of location, cost, and scheduling. They also felt the program was adaptable and allowed for individual attention and translatability into other settings. Finally, most participants found the group format to be motivating and fostered connections between participants.ConclusionThe GLA:DTM program was perceived as acceptable by most participants, yet the group format may not be useful for all individuals living with OA. Recommended improvements included adapting screening to identify those suited for the group format, providing program access earlier in the disease progression trajectory, modifying educational content based on participants' knowledge of OA and finally, providing refresher sessions after program completion.

Objectives: Delays in access to specialty care and elective hip and knee total joint replacement (TJR) surgery remain a major concern among patients with osteoarthritis (OA) in Canada. Centralized intake systems as a wait time management strategy in the face of resource constraints can increase access and patient flow through the system but are not standard practice. We examine how wait time management strategies for the assessment and triaging referrals in a centralized intake system can inform quality improvement initiatives. Design: We developed a discrete-event simulation model using all referrals to the Edmonton Bone and Joint Centre centralized intake system from 2012 to 2016 for the base case model. We assessed the combined effect of three wait time management strategies: improved prioritization, improved sorting through screening, and increased conservative management. Outcomes were measured in terms of patient flow and wait times. Results: The screener sees more patient referrals (7094 compared to 6922), and the number of patients who proceed to surgery is reduced by 282 patients (4%) in the wait time management scenario compared to the base case model. Wait times from referral to surgery are reduced by 54 days for surgical patients. Furthermore, urgent surgical patients experienced lower wait times in all stages of care than non-urgent patients, with wait times from referral to surgery reduced by 86 days. Conclusions: Triaging processes addressing prioritization, screening and conservative management of non-surgical patients can improve patient flow and significantly reduce patient wait times in a centralized intake process for TJR.

Objectives Timely access to rheumatologists remains a challenge in Alberta, a Canadian province with vast rural areas, whereas rheumatologists are primarily clustered in metro areas. To address the goal of timely and equitable access to rheumatoid arthritis (RA) care, health planners require information at the regional and local level to determine the RA prevalence and the associated health care needs. Methods Using Alberta Health administrative databases, we identified RA‐prevalent cases (April 1, 2015‐March 31, 2016) on the basis of a validated case definition. Age‐ and sex‐standardized prevalence rates per 1000 population members and the standardized rates ratio (SRR) were calculated. We applied Global Moran’s I and Gi* hotspot analysis using three different weight matrices to explore the geospatial pattern of RA prevalence in Alberta. Results Among 38 350 RA cases (68% female; n = 26 236), the prevalence rate was 11.81 cases per 1000 population members (95% confidence interval [CI] 11.80‐11.81) after age and sex standardization. Approximately 60% of RA cases resided in metro (Calgary and Edmonton) and moderate metro areas. The highest rate was observed in rural areas (14.46; 95% CI 14.45‐14.47; SRR 1.28), compared with the lowest in metro areas (10.69; 95% CI 10.68‐10.69; SRR 0.82). The RA prevalence across local geographic areas ranged from 4.7 to 30.6 cases. The Global Moran’s I index was 0.15 using three different matrices (z‐score 3.96‐4.24). We identified 10 hotspots in the south and north rural areas and 18 cold spots in metro and moderate metro Calgary. Conclusion The findings highlight notable rural–urban variation in RA prevalence in Alberta. Our findings can inform strategies aimed at reducing geographic disparities by targeting areas with high health care needs.

Objectives Hospitals introducing the National Surgical Quality Improvement Program (NSQIP) face implementation challenges. To understand the work of embedding NSQIP into routine practice, we explored interactions between contextual factors and the work among implementation teams at the individual, team and organisational level to illuminate how to support and sustain NSQIP implementation.Design Qualitative interpretative study using thematic analysis.Setting Five contextually diverse hospital sites in Alberta, Canada, for in-depth interviewing and four additional hospitals for observation of NSQIP meetings.Participants 9 Surgeon and Anaesthesiologist Champions; 6 Surgical Clinical Reviewers; 4 Directors and 1 Surgical Site Manager; 3 Operating Room Managers; 3 Quality Improvement Consultants; 1 Surgeon and 1 Provincial NSQIP Lead.Methods To capture context, process and the dynamic interplay between the two, we integrated the Consolidated Framework for Implementation Research (CFIR) and Normalisation Process Theory (NPT) to guide data collection and analysis. 28 individual semi-structured interviews with key informants and observations with field notes of 10 NSQIP meetings were conducted. Data were coded deductively and inductively and analysed thematically.Results Key findings informed by CFIR describe the impact of Provincial Collaboratives, leadership support and resources to support NSQIP work. Key findings illuminated by NPT highlight how teams overcame mistrust in NSQIP through relationship building, creating formative spaces to inform collective understandings of NSQIP and inviting feedback from professional groups to cocreate quality improvement solutions. This approach led to increased engagement with NSQIP data and encouraged shifts in conversations within and between nursing and physician groups from problems to solutions based.Conclusions The work the teams did to implement and sustain NSQIP highlights the need for time and resources to develop shared understandings of work processes, reorganise themselves to work together and understand how to help others in the surgical community interpret and value using NSQIP to improve care.

Objectives To understand how surgical services have been reorganised during and following public health emergencies, particularly the first wave of the COVID-19 pandemic, and the consequences for patients, healthcare providers and healthcare systems.Design A rapid scoping review.Setting We searched the MEDLINE, Embase and grey literature sources for documents and press releases from governments and surgical organisations or associations.Participants Studies examining surgical service delivery during public health emergencies including COVID-19, and the impact on patients, providers and healthcare systems were included.Primary and secondary outcome measures Primary outcomes were strategies implemented for the reorganisation of surgical services. Secondary were the impacts of reorganisation and resuming surgical services, such as: adverse events (including morbidity and mortality), primary care and emergency department visits, length of hospital and ICU stay, and changes to surgical waitlists.Results One hundred and thirty-two studies were included in this review; 111 described reorganisation of surgical services, 55 described the consequences of reorganising surgical services; and 6 reported actions taken to rebuild surgical capacity in public health emergencies. Reorganisations of surgical services were grouped under six domains: case selection/triage, personal protective equipment (PPE) regulations and practice, workforce composition and deployment, outpatient and inpatient patient care, resident and fellow education, and the hospital or clinical environment. Service reorganisations led to large reductions in non-urgent surgical volumes, increases in surgical wait times and impacted medical training (ie, reduced case involvement) and patient outcomes (eg, increases in pain). Strategies for rebuilding surgical capacity were scarce but focused on the availability of staff, PPE and patient readiness for surgery as key factors to consider before resuming services.Conclusions Reorganisation of surgical services in response to public health emergencies appears to be context dependent and has far-reaching consequences that must be better understood in order to optimise future health system responses to public health emergencies.

Introduction: The wait times crisis for hip and knee total joint replacement surgery has been a significant health care issue in Alberta and across Canada. Significant resource and financial efforts have been put forward to reduce wait times for surgery as a means of treating patients with osteoarthritis (OA), but the gains achieved were not sustained. Objective: To effectively address wait time issues, an alternative perspective on this problem is presented – that the wait times are an immediate problem for those needing surgery, but are also a symptom of the bigger issue of an inability of health care systems in Canada to address the needs of individuals with early OA with first-line treatment protocols. Discussion: In considering this more comprehensive understanding of the overall OA management problem, encapsulated by the concept of an “osteoarthritis funnel”, we outline potential approaches for a solution on a systemic level that integrates services delivery, health care resource allocation and conceptualization of OA in research activities. It also emphasizes the need for a more effective and relevant program of research to address this complex problem that requires unique solutions. Conclusions: New approaches and understanding are needed to address integrated implementation of effective first-line treatments for newly diagnosed osteoarthritis to prevent the expanding demand for joint replacement surgery. While the focus here is on the Canadian perspective, the need to develop and implement better first-line treatments for those with early OA and those at risk for development of OA is not unique to Canada.

ABSTRACTMycoplasma genitalium is fastidious to culture, and its detection in human clinical specimens relies mainly on molecular methods. Phenotypic determination of antibiotic susceptibility for this bacterium is not a timely or feasible option for most clinical laboratories. This study sought to determine whether next-generation sequencing technologies can effectively be employed in determining genetic mutations associated with drug resistance in M. genitalium samples collected in Aptima Hologic tubes and possibly integrating them into viable workflows in public health laboratories. Following analysis by a custom-designed bioinformatics pipeline, at least one mutation/sample has been identified in 94/98 specimens in at least one of seven loci (macrolides: rrl, rplD, rplV; fluoroquinolones: parC, parE, gyrA, gyrB) described previously to be connected to antibiotic resistance. This method identified a total of 469 single nucleotide polymorphisms (SNPs) (452 mutations): 134 of 23S rRNA SNPs and 318 amino acid mutations: 114 substitutions and 204 synonymous; the turnaround time (sample to analyzed sequence) was typically 3 days. The assays and workflows described in this work demonstrated that the determination of a drug resistance profile for macrolides and fluoroquinolones of M. genitalium samples by using next-generation sequencing in clinical samples is a feasible approach that can be implemented in clinical laboratories, following thorough and extensive validation studies.IMPORTANCEThe mechanisms of drug resistance in Mycoplasma genitalium are complex and involve several genetic loci. The molecular methods for accurately characterizing resistance to fluoroquinolones and macrolides in this organism are often not available or approved for patient use and do not cover all genetic determinants. To this end, we propose a next-generation sequencing-based method with a turnaround time of 3 days that includes the investigation of all drug resistance loci of M. genitalium. Following adaptation, validation, and verification for routine clinical use, assays based on this method may yield molecular results that can be used to guide proper treatment regimens and for surveillance of drug resistance in the general population.

Rapid and early identification of Streptococcus pneumoniae from positive blood cultures is crucial for the management of patients with bloodstream infections (BSI). Many identification systems in microbiology laboratories have difficulty differentiating S. pneumoniae from other closely related species in the Streptococcus mitis group. To overcome this limitation, we developed a rapid workflow in our laboratory combining direct MALDI-TOF MS identification with the Immulex S. pneumoniae Omni test (SSI Diagnostica, Denmark) for rapid detection of S. pneumoniae directly from positive blood cultures. The workflow was evaluated using 51 Streptococcus isolates. Compared to conventional biochemical testing, our new workflow demonstrates 100 % specificity and sensitivity for the detection and differentiation of S. pneumoniae from other closely related species. Our new workflow is accurate, cost-effective, and can easily be implemented in microbiology laboratories that already perform direct MALDI-TOF identification from positive blood cultures to improve the management of patients with invasive pneumococcal disease. Importance: Invasive pneumococcal disease remains a major public health problem worldwide. Reducing the time to identify Streptococcus pneumoniae in positive blood cultures allows patients to be treated sooner with more targeted and effective antibiotics. We evaluated a two-step protocol where positive blood cultures are first tested directly by MALDI-TOF MS and any samples containing Streptococcus species are tested by Immulex S. pneumoniae Omni test to both detect and differentiate S. pneumoniae from other closely related Streptococcus species. Our study results showed 100 % sensitivity and specificity, and a much faster turn-around time than conventional methods.

Objectives: To implement evidence-based urinalysis (UA) reflex criteria and to evaluate the impact of the intervention on reducing unnecessary antibiotic usage. Methods: A prospective intervention study was conducted on 4130 urine samples that were subjected to UA during March to May 2020. Results were analyzed in order to evaluate the effectiveness of newly implemented evidence-based criteria in predicting positive urine cultures. The intervention involved implementing evidence-based UA reflex criteria to ensure a high predictive value of the UA reflex parameters. Multivariable logistic regression was utilized to evaluate the effectiveness of these UA parameters in predicting positive urine cultures and to assess the impact of the new UA criteria on antibiotic usage. Results: A total of 4130 patient samples were included in the study; 60.1% (n = 2484) were from female patients and 39.9% (n = 1646) were from male patients. The total number of negative urine reflex samples was 3116, which accounted for 75.4% of the total UA reflex samples. In contrast, 24.6% of the urine reflex samples (n = 1014) returned positive UA results and were reflexed to urine culture. Among the urine samples that were cultured, 9% (n = 91) were negative urine cultures, while 91.0% (n = 923) were positive urine cultures. Chi-square analysis indicated highly statistically significant associations between the combination parameters of (≥5 white blood cells (WBCs) and positive nitrite) and positive urine cultures (Chi-square = 516.428, p < 0.001) and (≥5 WBCs and moderate or large esterase) and positive urine cultures (Chi-square = 503.387, p < 0.001). Additionally, Chi-square analysis indicated a highly statistically significant association between the combination parameters of (≥5 WBCs and ≥1 bacteria) and positive urine cultures (Chi-square = 434.806, p < 0.001). The statistical analysis showed that the implementation of evidence-based UA reflex criteria significantly decreased the number of urine cultures performed and potentially decreased the number of patients inappropriately treated with antibiotics from 45.1% to 9%. Conclusions: In conclusion, ≥5 WBCs and positive nitrite yielded the highest positive predictive value of 98.00% and showed a highly significant association with positive urine cultures. It was observed that the new UA reflex criteria are highly effective in predicting positive urine cultures, thus potentially resulting in the reduction of unnecessary antibiotic usage.

Objective The objective of the study was to estimate the incidence and prevalence of rheumatoid arthritis (RA) in Alberta using administrative health data. Methods We identified RA cases in patients 16 years and older by applying a national case definition to linked administrative health data (ie, hospital discharge abstract records, physician claims, and health insurance registry records) using a unique personal identifier. Incidence and prevalence are reported for the 2015‐2016 fiscal year and a trend analysis from 2011‐2012 to 2015‐2016. Incidence and prevalence estimates were standardized using the 2011 Canadian census population. Results In 2015‐2016, the overall crude incidence was 0.74 [95% confidence interval (CI): 0.71‐0.77] per 1000 and crude prevalence was 1.08% (95% CI: 1.07‐1.09). The women‐to‐men crude incidence and prevalence sex ratios were 2.04 and 2.19, respectively. People aged 65 to 79 years had the highest incidence of RA, and the highest prevalence was observed among those 80 years and older. From 2011‐2012 to 2015‐2016, the overall age‐standardized incidence decreased [0.97 (95% CI: 0.94‐1.01) to 0.79 (95% CI: 0.76‐0.82) per 1000], whereas age‐standardized prevalence remained constant [1.17 (95% CI: 1.15‐1.18) to 1.18 (95% CI: 1.17‐1.19)]. Conclusion In Alberta, there was a decreasing trend in RA incidence over the study period, whereas prevalence was stable. These estimates, combined with clinical data, will be used to measure system performance for quality improvement and to inform simulation modeling for planning the expected demand for health services for patients living with RA.

The C29197T mutation is one of 4 point mutations known to cause N-gene target failure (NGTF) in the Xpert Xpress SARS-CoV-2 and Xpert Omni SARS-CoV-2 assays from Cepheid (Sunnyvale, CA). We describe a high local prevalence in January of 8.5% (CI 4.9-14.2%) for the C29197T mutation, which was over 3-fold higher than the prevalence estimated statewide in California during the same time frame, 2.5% (CI 2.1-2.8%). Using phylogenetic analysis, we discovered that this increase in prevalence was due, at least in part, to a disproportionately large infection cluster of unknown origin. This study emphasizes the importance of sequencing at the local jurisdictional level and demonstrates the impact that regional variation can have when assessing risk due to point mutations that impact clinical test performance. It also reinforces the need for diligent reporting of abnormal test results by clinical laboratories, especially during Emergency Use Authorization (EUA) periods, as additional information is gathered about the target organism and the performance of EUA-authorized tests over time.

ABSTRACT IMPACT: Development of our animal model of moyamoya will provide a meaningful assessment of therapeutic efficacy of interventions applicable to the clinical setting. OBJECTIVES/GOALS: Moyamoya is a cerebrovascular condition with progressive stenosis of the internal carotid arteries (ICA) and formation of abnormal vascular collaterals at the base of the brain, all of which result in ischemic and hemorrhagic strokes. We aim to develop a needed animal model of this condition in order to develop new therapeutics. METHODS/STUDY POPULATION: Male and female C57Bl/6J mice (4 months old) underwent surgery for the unilateral placement of a microcoil (0.16 mm ID) onto the proximal ICA or sham control. After 30 and 60 days (N = 6-8/time point), the brain blood vessels were examined for changes in diameter, number of anastomoses, and development of new collaterals using DiI stain. Brain tissue was examined for micro-hemorrhages using Prussian blue stain, and cross-sections of blood vessels were examined for intimal thickening using H&E and smooth muscle actin. Expression of vascular endothelial growth factor (VEGF), which is associated with angiogenesis and moyamoya syndrome, was quantified by qPCR. Blood samples were also analyzed for inflammatory biomarkers using ELISA. RESULTS/ANTICIPATED RESULTS: Within 30 days, the distal ICA and anterior cerebral artery (ACA) had significantly decreased diameters at the Circle of Willis, with an initial decrease in the number of cortical anastomoses. Histology demonstrated smaller lumen diameter and alterations to in the various layers of the blood vessels, indicating intimal thickening and stenosis of the affected blood vessels. There was also a significant increase in the number of intracranial micro-bleeds, suggesting a compromised vascular integrity. This may be due, in part, to a significant upregulation in VEGF gene expression within the striatum, a region of hemorrhagic occurrence in moyamoya patients. DISCUSSION/SIGNIFICANCE OF FINDINGS: We report the development of an animal model with vasculopathies that mimic those observed in patients with moyamoya syndrome. With further characterization, this animal model will have a positive impact as a meaningful assessment of therapeutic efficacy of interventions applicable to the clinical setting.

It is important to discover novel antimalarial pharmacophores because of the widespread emergence of Plasmodium falciparum isolates resistant to the available drugs. Secondary metabolites derived from microbes associated with marine invertebrates are a valuable resource for the discovery of novel drug leads. However, the potential of marine microbes as a source of antimalarials has not been explored. We investigated the promise of marine microorganisms for the production of antimalarial activities by testing 2365 diverse microbial extracts using phenotypic screening of a multidrug resistant chloroquine resistant P. falciparum strain. We conducted counter screening against mammalian cells for the 317 active extracts that exhibited more than 70% inhibition at 1 µg/mL. The screen identified 17 potent bioactive leads from a broad range of taxa. Our results establish that the marine microbiome is a rich source of antiplasmodial compounds that warrants in depth exploration.

Perlecan Domain V (DV) promotes brain angiogenesis by inducing VEGF release from brain endothelial cells (BECs) following stroke. In this study, we define the specific mechanism of DV interaction with the α(5)β(1) integrin, identify the downstream signal transduction pathway, and further investigate the functional significance of resultant VEGF release. Interestingly, we found that the LG3 portion of DV, which has been suggested to possess most of DV's angio-modulatory activity outside of the brain, binds poorly to α(5)β(1) and induces less BEC proliferation compared to full length DV. Additionally, we implicate DV's DGR sequence as an important element for the interaction of DV with α(5)β(1). Furthermore, we investigated the importance of AKT and ERK signaling in DV-induced VEGF expression and secretion. We show that DV increases the phosphorylation of ERK, which leads to subsequent activation and stabilization of eIF4E and HIF-1α. Inhibition of ERK activity by U0126 suppressed DV-induced expression and secretion of VEGR in BECs. While DV was capable of phosphorylating AKT we show that AKT phosphorylation does not play a role in DV's induction of VEGF expression or secretion using two separate inhibitors, LY294002 and Akt IV. Lastly, we demonstrate that VEGF activity is critical for DV increases in BEC proliferation, as well as angiogenesis in a BEC-neuronal co-culture system. Collectively, our findings expand our understanding of DV's mechanism of action on BECs, and further support its potential as a novel stroke therapy.