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Background: Less than one third of research evidence is translated into policy or practice. Knowledge translation requires effective dissemination, adoption and finally implementation. These three stages are equally important, however, existing knowledge translation models and frameworks provide little and disparate information about the steps and activities required for effective dissemination., Objective: This study aimed to empirically develop a consolidated framework of evidence-based steps and activities for disseminating research evidence., Methods: We identified models and frameworks from a scoping review and dissemination and implementation webtool. We synthesised them into a prototype dissemination framework. Models and frameworks were eligible to inform steps in our framework if they fulfilled at least one of three elements of dissemination: intending to generate awareness of a message, incorporates targeting an audience: tailoring communication. An initial coding framework was created to organise data into dissemination steps. Drawing on 'co-approach' principles, authors of the included models and frameworks (dissemination experts) and health service researchers (end users) were invited to test and refine the prototype framework at a workshop., Results: From 48 models and frameworks reviewed, only 32 fulfilled one or more of the three dissemination elements. The initial coding framework, upon refinement, yielded the Guide to Disseminating Research (GuiDiR) comprising five steps. 1) Identify target audiences and dissemination partners. 2) Engage with dissemination partners. 3) Identify barriers and enablers to dissemination. 4) Create dissemination messages. 5) Disseminate and evaluate. Multiple activities were identified for each step and no single model or framework represents all steps and activities in GuiDiR., Conclusions: GuiDiR unifies dissemination components from knowledge translation models and frameworks and harmonises language into a format accessible to non-experts. It outlines for researchers, funders and practitioners the expected structure of dissemination and details the activities for executing an evidence-based dissemination strategy., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024. Published by Elsevier Inc.)

Competing Interests: Dr Tsuyuki has received investigator-initiated arm’s length research grants from Merck, Pfizer, AstraZeneca, and Sanofi. He has been a speaker/consultant for Merck, Emergent Biosolutions, and Shoppers Drug Mart/Loblaw Companies Limited. Dr Rader has been a consultant for Bristol-Meyers Squibb, Cytokinetics, Idorsia, Medtronic, and ReCor Medical.

Objective: The objective of this scoping review is to understand the current body of knowledge regarding deprescribing in adults aged 60 and over in acute care settings, including the deprescribing activities that are being undertaken, and the feasibility, challenges, and outcomes of the practice., Introduction: Polypharmacy is prevalent amongst older adults, despite risks to patients. Much of the existing research on deprescribing has occurred in the outpatient context, with recent research emerging on the unique opportunity that acute care may provide., Inclusion Criteria: This review will include deprescribing in adults aged 60 and older in acute care. It will consider deprescribing occurring during inpatient admission and at the time of discharge from hospital., Methods: The JBI method for scoping reviews will guide this review. A search of MEDLINE (Ovid), Scopus, Web of Science, CINAHL (EBSCOhost), Embase (Ovid), and the Cochrane Database will be undertaken from inception to present with no language restrictions. Qualitative, quantitative, and mixed method studies, clinical practice guidelines, and opinion papers will be considered for inclusion. Systematic reviews and scoping reviews will be excluded. Google Scholar and a general Google search will be conducted for gray literature. Two reviewers will assess articles for inclusion and any disagreements will be discussed and resolved by discussion or a third reviewer, if required. Findings will be presented in the scoping review using a narrative approach with supporting quantitative data in a tabular format according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews checklist (PRISMA-ScR)., Review Registration: Open Science Framework https://osf.io/pb7aw/., Competing Interests: The authors declare no conflicts of interest, (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc. on Behalf of JBI.)

Importance: Major gaps in the delivery of appropriate oral anticoagulation therapy (OAC) exist, leaving a large proportion of persons with atrial fibrillation (AF) unnecessarily at risk for stroke and its sequalae., Objective: To investigate whether pharmacist-led OAC prescription can increase the delivery of stroke risk reduction therapy in individuals with AF., Design, Setting, and Participants: This prospective, open-label, patient-level randomized clinical trial of early vs delayed pharmacist intervention from January 1, 2019, to December 31, 2022, was performed in 27 community pharmacies in Alberta, Canada. Pharmacists identified patients 65 years or older with 1 additional stroke risk factor and known, untreated AF (OAC nonprescription or OAC suboptimal dosing) or performed screening using a 30-second single-lead electrocardiogram to detect previously unrecognized AF. Patients with undertreated or newly diagnosed AF eligible for OAC therapy were considered to have actionable AF. Data were analyzed from April 3 to November 30, 2023., Interventions: In the early intervention group, pharmacists prescribed OAC using guideline-based algorithms with follow-up visits at 1 and 3 months. In the delayed intervention group, which served as the usual care control, the primary care physician (PCP) was sent a notification of actionable AF along with a medication list (both enhancement over usual care). After 3 months, patients without OAC optimization in the control group underwent delayed pharmacist intervention., Main Outcomes and Measures: The primary outcome was the difference in the rate of guideline-concordant OAC use in the 2 groups at 3-month follow-up ascertained by a research pharmacist blinded to treatment allocation., Results: Eighty patients were enrolled with actionable AF (9 [11.3%] newly diagnosed in 235 individuals screened). The mean (SD) age was 79.7 (7.4) years, and 45 patients (56.3%) were female. The median CHADS2 (congestive heart failure, hypertension, age, diabetes, and stroke or transient ischemic attack) score was 2 (IQR, 2-3). Seventy patients completed follow-up. Guideline-concordant OAC use at 3 months occurred in 36 of 39 patients (92.3%) in the early intervention group vs 23 of 41 (56.1%) in the control group (P < .001), with an absolute increase of 34% and number needed to treat of 3. Of the 23 patients who received appropriate OAC prescription in the control group, the PCP called the pharmacist for prescribing advice in 6 patients., Conclusions and Relevance: This randomized clinical trial found that pharmacist OAC prescription is a potentially high-yield opportunity to effectively close gaps in the delivery of stroke risk reduction therapy for AF. Scalability and sustainability of pharmacist OAC prescription will require larger trials demonstrating effectiveness and safety., Trial Registration: ClinicalTrials.gov Identifier: NCT03126214.

Objectives: Our aim in this work was to 1) explore barriers and enablers to patient and health-care provider (HCP) behaviours related to sick-day medication guidance (SDMG), 2) identify theory-informed strategies to advise SDMG intervention design, and 3) obtain perspectives on an eHealth tool for this purpose., Methods: A qualitative descriptive study using qualitative conventional content analysis was undertaken. Interviews and focus groups were held with patients and HCPs from January 2021 to April 2022. Data were analyzed using the Behaviour Change Wheel and Theoretical Domains Framework to inform intervention design., Results: Forty-eight people (20 patients, 13 pharmacists, 12 family physicians, and 3 nurse practitioners) participated in this study. Three interventions were designed to address the identified barriers and enablers: 1) prescriptions provided by a community-based care provider, 2) pharmacists adding a label to at-risk medications, and 3) built-in prompts for prescribing and dispensing software. Most participants accepted the concept of an eHealth tool and identified pharmacists as the ideal point-of-care provider. Challenges for an eHealth tool were raised, including credibility, privacy of data, medical liability, clinician remuneration and workload impact, and equitable access to use of the tool., Conclusions: Patients and HCPs endorsed non-technology and eHealth innovations as strategies to aid in the delivery of SDMG. These findings can guide the design of future theory-informed SDMG interventions., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Importance: We designed an online educational program for primary care health care providers, the Hypertension Canada Professional Certification Program (HC-PCP), based upon its 2020 guidelines., Objective: The objective was to determine the effect of the HC-PCP, taken by pharmacists, on systolic blood pressure (BP) in patients with poorly controlled hypertension., Design: Stepped wedge cluster randomized trial (unit of randomization was the pharmacy)., Participants: Patients with poorly controlled hypertension (BP >140/90 mmHg or >130/80 mmHg [diabetes]) in community pharmacies in Alberta, Canada, were recruited by their pharmacist., Intervention: Pharmacists completed the HC-PCP program, then provided care to their patients with poorly controlled hypertension according to what they learned in the course., Control: Pharmacists were given a copy of the Hypertension Canada guidelines and provided their usual care to their patients prior to undertaking the HC-PCP later., Main Outcome and Measure: The primary outcome was a difference in change in systolic BP at 3 months between groups, while the secondary outcome was patient satisfaction with using the Consultation Satisfaction Questionnaire., Results: We enrolled 890 patients from 59 pharmacies (including 104 pharmacists). Using a linear mixed-effect model with BP reduction as the dependent variable and independent variables of treatment allocation, baseline BP, site effect and patient effect, the intervention was associated with a 4.76 mmHg (95% confidence interval, 2.02-7.50, p < 0.0001) systolic BP reduction at 3 months. Patient satisfaction with using the Consultation Satisfaction Questionnaire was high at 75.9 (/90)., Conclusion and Relevance: Most educational programs are not evaluated at the patient care level. The HC-PCP taken by pharmacists resulted in a 4.76 mmHg systolic BP reduction in their patients over 3 months. This would have major implications for public health, reducing heart disease, stroke and kidney failure., Competing Interests: RTT is a paid Editor-in-Chief of the Canadian Pharmacists Journal. He has received investigator-initiated grants from Merck, AstraZeneca, Pfizer and Sanofi. The remaining authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this article., (© The Author(s) 2024.)

Background: Human papillomavirus (HPV) immunization can prevent cancers, but uptake has been incomplete (and worse with the COVID-19 pandemic). Dental clinicians already screen for oral cancers, many of which are caused by HPV, and could identify vaccination candidates, but this requires a case-finding strategy., Objective: The purpose of this study was (1) to develop and test a case-finding approach to identify patients who were candidates for HPV vaccinations, (2) to test an HPV vaccination intervention by dental professionals on vaccination uptake., Methods: Design: Prospective, non-randomized feasibility case finding study with a 4-week enrollment period and a 6 week follow up period in general dental offices.Setting: Two general and non-commercial dentistry offices in Edmonton, Alberta Canada.Subjects: Consecutive scheduled (non-emergent) patients who met the Health Canada criteria for HPV vaccination: immunocompetent males and females aged 9-45 years and those who are immunocompromised. Consent for the discussion was obtained from each subject or parent.Intervention: Scheduled dental patients meeting the inclusion criteria were flagged by a research assistant who reviewed the appointment schedule each week for 4 weeks. For these subjects, dental clinicians (dentists and dental hygienists) used our Dental Dialogue Tool to discuss HPV vaccination and answer questions. Participating patients who consented to receive the HPV vaccine were given a prescription by the attending dentist and were directed to follow-up with a local pharmacy to have the vaccine administered. Each participant that was provided with an HPV prescription was contacted after 6 weeks to identify if they received the first dose of vaccine.Outcomes: Yield of our case-finding strategy and receipt of a patient's first HPV vaccine dose during 6 weeks post vaccine prescription., Results: Our case-finding strategy assessed 656 scheduled patients over 4 weeks. From this screening,179 (a case-finding yield of 20.4 %), were candidates for HPV vaccine discussion. Forty-three of these 179 patients (24 %) were already vaccinated.. Two patients (1.1 %) did not consent to be spoken with and 134 (74.8 %) consented to the HPV vaccine discussion.. Forty-eight of 134 patients (35.8 %) of patients accepted a prescription from the dentist after speaking with the dental clinician. Ultimately, 8/48 (16 %) (patients received their first dose of the HPV vaccine by the 6 week of follow-up call. However, this is only 4.5 % (8/177) of those patients who did consent for the discussion of HPV cancers and vaccination from their dentist., Conclusion: We demonstrated that case-finding for HPV vaccine candidates in general dental offices was feasible, with a reasonable yield. While the dental dialogue tool was described as a great resource to explain the facts and answer questions, very few patients were vaccinated after 6 weeks of follow-up. Further work is necessary to sharpen the intervention, perhaps including follow-up discussions with the dental clinicians., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr Ross Tsuyuki reports financial support was provided by Merck Canada. Dr Cheryl Cable reports a relationship with Merck & Co Inc that includes: consulting or advisory and speaking and lecture fees. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Background: Cisplatin is associated with acute kidney injury (AKI) and electrolyte abnormalities. Urine tissue inhibitor of metalloproteinase 2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP-7) may be early cisplatin-AKI biomarkers., Methods: We conducted a 12-site prospective cohort study with pediatric patients treated with cisplatin (May 2013-December 2017). Blood and urine (measured for TIMP-2, IGFBP-7) were collected pre-cisplatin, 24-h post-cisplatin, and near hospital discharge during the first or second cisplatin cycle (early visit (EV)) and during second-to-last or last cisplatin cycle (late visit (LV))., Primary Outcome: serum creatinine (SCr)-defined AKI (≥ stage 1)., Results: At EV (median (interquartile (IQR)) age: 6 (2-12) years; 78 (50%) female), 46/156 (29%) developed AKI; at LV, 22/127 (17%) experienced AKI. At EV, TIMP-2, IGFBP-7, and TIMP-2*IGFBP-7 pre-cisplatin infusion concentrations were significantly higher in participants with vs. those without AKI. At EV and LV, biomarker concentrations were significantly lower in participants with vs. those without AKI at post-infusion and near-hospital discharge. Biomarker values normalized to urine creatinine were higher in patients with AKI compared to without (LV post-infusion, median (IQR): TIMP-2*IGFBP-7: 0.28 (0.08-0.56) vs. 0.04 (0.02-0.12) (ng/mg creatinine) 2 /1000; P < .001). At EV, pre-infusion biomarker concentrations had the highest area under the curves (AUC) (range: 0.61-0.62) for AKI diagnosis; at LV, biomarkers measured post-infusion and near discharge yielded the highest AUCs (range: 0.64-0.70)., Conclusions: TIMP-2*IGFBP-7 were poor to modest at detecting AKI post-cisplatin. Additional studies are needed to determine whether raw biomarker values or biomarker values normalized to urinary creatinine are more strongly associated with patient outcomes. A higher resolution version of the Graphical abstract is available as Supplementary information., (© 2023. The Author(s), under exclusive licence to International Pediatric Nephrology Association.)

Background: High blood pressure (BP) is a leading cause of cardiovascular and stroke-related events. Office-based BP measurement has declined in recent years due to the COVID-19 pandemic, which may have resulted in higher rates of undetected and uncontrolled hypertension. To gain a better idea of adult BP levels in Newfoundland and Labrador, we engaged community pharmacists in BP screening on World Hypertension Day., Methods: Data collection and BP screening occurred on May 17, 2022. Pharmacists and pharmacy students collected 3 seated BP readings from participants, using an automated device. The average of readings 2 and 3 was used to estimate BP, with elevated BP defined as ≥ 140/90 mm Hg, or ≥ 130/80 mm Hg for individuals with diabetes. Data on participant demographics, access to primary care, medical history, and antihypertensive use were also collected. Data analysis included descriptive statistics and logistic regression techniques., Results: A total of 460 participants were included in the analysis. The mean age was 56.3 years (standard deviation: 16.95); 63.3% (n = 291) were female; and 43.7% (n = 201) reported having hypertension. Elevated BP was identified in 27% (n = 123). Of those with elevated BP, 41.5% (n = 51) had no history of diagnosed hypertension. Age, sex, and diabetes were statistically significant predictors of elevated BP in the multivariable model., Conclusions: A large proportion of participants in our study had elevated BP. Targeted measures are needed to improve the detection, treatment, and control of high BP in Newfoundland and Labrador. Community pharmacists can support BP care., (© 2023 The Authors.)

Introduction: Despite the importance of timing of nerve surgery after peripheral nerve injury, optimal timing of intervention has not been clearly delineated. The goal of this study is to explore factors that may have a significant impact on clinical outcomes of severe peripheral nerve injury that requires reconstruction with nerve transfer or graft., Materials and Methods: Adult patients who underwent peripheral nerve transfer or grafting in Alberta were reviewed. Clustered multivariable logistic regression analysis was used to examine the association of time to surgery, type of nerve repair, and patient characteristics on strength outcomes. Cox proportional hazard regression analysis model was used to examine factors correlated with increased time to surgery., Results: Of the 163 patients identified, the median time to surgery was 212 days. For every week of delay, the adjusted odds of achieving Medical Research Council strength grade ≥ 3 decreases by 3%. An increase in preinjury comorbidities was associated with longer overall time to surgery (aHR 0.84, 95% CI 0.74-0.95). Referrals made by surgeons were associated with a shorter time to surgery compared to general practitioners (aHR 1.87, 95% CI 1.14-3.06). In patients treated with nerve transfer, the adjusted odds of achieving antigravity strength was 388% compared to nerve grafting; while the adjusted odds decreased by 65% if the injury sustained had a pre-ganglionic injury component., Conclusion: Mitigating delays in surgical intervention is crucial to optimizing outcomes. The nature of initial nerve injury and surgical reconstructive techniques are additional important factors that impact postoperative outcomes.

Importance: Pharmacist-led interventions can significantly improve blood pressure (BP) control. The long-term cost-effectiveness of pharmacist-prescribing interventions implemented on a large scale in the US remains unclear., Objective: To estimate the cost-effectiveness of implementing a pharmacist-prescribing intervention to improve BP control in the US., Design, Setting, and Participants: This economic evaluation included a 5-state Markov model based on the pharmacist-prescribing intervention used in The Alberta Clinical Trial in Optimizing Hypertension (or RxACTION) (2009 to 2013). In the trial, control group patients received an active intervention, including a BP wallet card, education, and usual care. Data were analyzed from January to June 2023., Main Outcomes and Measures: Cardiovascular (CV) events, end-stage kidney disease events, life years, quality-adjusted life years (QALYs), lifetime costs, and lifetime incremental cost-effectiveness ratio (ICER). CV risk was calculated using Framingham risk equations. Costs were based on the reimbursement rate for level 1 encounters, medication costs from published literature, and event costs from national surveys and pricing data sets. Quality of life was determined using a published catalog of EQ-5D utility values. One-way sensitivity analyses were used to assess alternative reimbursement values, a reduced time horizon of 5 years, alternative assumptions for BP reduction, and the assumption of no benefit to the intervention after 10 years. The model was expanded to the US population to estimate population-level cost and health impacts., Results: Assumed demographics were mean (SD) age, 64 (12.5) years, 121 (49%) male, and a mean (SD) baseline BP of 150/84 (13.9/11.5) mm Hg. Over a 30-year time horizon, the pharmacist-prescribing intervention yielded 2100 fewer cases of CV disease and 8 fewer cases of kidney disease per 10 000 patients. The intervention was also associated with 0.34 (2.5th-97.5th percentiles, 0.23-0.45) additional life years and 0.62 (2.5th-97.5th percentiles, 0.53-0.73) additional QALYs. The cost savings were $10 162 (2.5th-97.5th percentiles, $6636-$13 581) per person due to fewer CV events with the pharmacist-prescribing intervention, even after the cost of the visits and medication adjustments. The intervention continued to produce benefits in more conservative analyses despite increased costs as the ICER ranged from $2093 to $24 076. At the population level, a 50% intervention uptake was associated with a $1.137 trillion in cost savings and would save an estimated 30.2 million life years over 30 years., Conclusion and Relevance: These findings suggest that a pharmacist-prescribing intervention to improve BP control may provide high economic value. The necessary tools and resources are readily available to implement pharmacist-prescribing interventions across the US; however, reimbursement limitations remain a barrier.

Background: Measurement of home blood pressure is an important tool for the management of hypertension. However, the validity of home devices is of concern. The Recommended Blood Pressure Devices Program of Hypertension Canada reviews and recommends blood pressure devices using international validation standards. We sought to determine the proportion of Hypertension Canada-recommended devices available for purchase in pharmacies and online., Methods: We visited 16 community pharmacies in the Edmonton area to record the blood pressure devices they sold. We also reviewed the 50 most popular devices from online retailers (Amazon, Walmart, Best Buy, and Canadian Tire). All devices were referenced against the Recommended Blood Pressure Device Program of Hypertension Canada (www.hypertension.ca/bpdevices) to determine if the models were recommended., Results: We reviewed 170 devices. Of those sold in pharmacies, 61 of 68 (89.7%) were Hypertension Canada-recommended devices, whereas online retailers had only 46 of 102 (45.1%) recommended devices; P < 0.001., Conclusions: Most blood pressure devices sold in pharmacies are Hypertension Canada recommended, in contrast to less than one-half from online retailers. The lack of validation of many home blood pressure devices could have important clinical implications, leading to over- or undertreatment of hypertension. Clinicians should advise patients on the importance of home blood pressure device validation and direct them to resources such as Hypertension Canada (https://hypertension.ca/public/recommended-devices) for guidance., (© 2023 The Authors.)

Introduction: People with chronic medical conditions often take medications that improve long-term outcomes but which can be harmful during acute illness. Guidelines recommend that healthcare providers offer instructions to temporarily stop these medications when patients are sick (i.e., sick days). We describe the experiences of patients managing sick days and of healthcare providers providing sick day guidance to their patients., Methods: We undertook a qualitative descriptive study. We purposively sampled patients and healthcare providers from across Canada. Adult patients were eligible if they took at least two medications for diabetes, heart disease, high blood pressure and/or kidney disease. Healthcare providers were eligible if they were practising in a community setting with at least 1 year of experience. Data were collected using virtual focus groups and individual phone interviews conducted in English. Team members analyzed transcripts using conventional content analysis., Results: We interviewed 48 participants (20 patients and 28 healthcare providers). Most patients were between 50 and 64 years of age and identified their health status as 'good'. Most healthcare providers were between 45 and 54 years of age and the majority practised as pharmacists in urban areas. We identified three overarching themes that summarize the experiences of patients and healthcare providers, largely suggesting a broad spectrum in approaches to managing sick days: Individualized Communication, Tailored Sick Day Practices, and Variation in Knowledge of Sick Day Practices and Relevant Resources., Conclusion: It is important to understand the perspectives of both patients and healthcare providers with respect to the management of sick days. This understanding can be used to improve care and outcomes for people living with chronic conditions during sick days., Patient or Public Contribution: Two patient partners were involved from proposal development to the dissemination of our findings, including manuscript development. Both patient partners took part in team meetings and contributed to team decision-making. Patient partners also participated in data analysis by reviewing codes and theme development. Furthermore, patients living with various chronic conditions and healthcare providers participated in focus groups and individual interviews., (© 2023 The Authors. Health Expectations published by John Wiley & Sons Ltd.)

Background: Community pharmacists were the face of the health response to the unprecedented COVID-19 pandemic. Their pivotal role during the pandemic has been widely recognized, as they adapted to continue to provide a higher level of care to their patients., Objective: The objective of this study was to gain a deeper understanding of frontline pharmacists' lived experiences of the COVID-19 pandemic and its impact on their roles., Methods: Photovoice, a visual research method that uses participant-generated photographs to articulate their experiences, was used with semi-structured interviews to explore pharmacists' lived experiences. Frontline community pharmacists who provided direct patient care during the COVID-19 pandemic in Alberta, Canada were recruited. Participants were asked to provide 3-5 photos that reflected on how they see themselves as a pharmacist and/or represents what they do as a pharmacist. Data analysis incorporated content, thematic and visual analysis and was facilitated using NVivo software. A published conceptual framework model was used as the foundation of the analysis with care taken to include new concepts. Ethics approval was obtained from the University of Alberta health research ethics board., Results: Interviews were conducted with 21 participants and they 71 photos. This study advanced the conceptual framework model presented in a scoping review, of what was made visible (pharmacists' information, public health, and medication management roles) and what was invisible but made visible by the pandemic (pharmacists' leadership roles). It was revealed through the reflective nature of this study the important leadership role pharmacists have in their communities., Conclusions: This study highlighted the work of community pharmacists responding to the COVID-19 pandemic through their information, public health, medication management, and leadership roles. Their experiences also made visible the cost their work had on them as they did more to adapt and continually respond as the pandemic evolved. Pharmacists recognized their role as leaders in their practice and communities., Competing Interests: Declaration of competing interest RTT receives consulting fees from Shoppers Drug Mart and Emergent BioSolutions and is a paid Editor-in-Chief of the Canadian Pharmacists Journal. He has received investigator-initiated grants from Merck and Sanofi. The remaining authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this article., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: One in eight people with heart disease has poor medication adherence that, in part, is related to copayment costs. This study tested whether eliminating copayments for high-value medications among low-income older adults at high cardiovascular risk would improve clinical outcomes., Methods: This randomized 2×2 factorial trial studied 2 distinct interventions in Alberta, Canada: eliminating copayments for high-value preventive medications and a self-management education and support program (reported separately). The findings for the first intervention, which waived the usual 30% copayment on 15 medication classes commonly used to reduce cardiovascular events, compared with usual copayment, is reported here. The primary outcome was the composite of death, myocardial infarction, stroke, coronary revascularization, and cardiovascular-related hospitalizations over a 3-year follow-up. Rates of the primary outcome and its components were compared using negative binomial regression. Secondary outcomes included quality of life (Euroqol 5-dimension index score), medication adherence, and overall health care costs., Results: A total of 4761 individuals were randomized and followed for a median of 36 months. There was no evidence of statistical interaction ( P =0.99) or of a synergistic effect between the 2 interventions in the factorial trial with respect to the primary outcome, which allowed us to evaluate the effect of each intervention separately. The rate of the primary outcome was not reduced by copayment elimination, (521 versus 533 events, incidence rate ratio 0.84 [95% CI, 0.66-1.07], P =0.162). The incidence rate ratio for nonfatal myocardial infarction, nonfatal stroke, and cardiovascular death (0.97 [95% CI, 0.67-1.39]), death (0.94 [95% CI, 0.80 to 1.11]), and cardiovascular-related hospitalizations (0.78 [95% CI, 0.57 to 1.06]) did not differ between groups. No significant between-group changes in quality of life over time were observed (mean difference, 0.012 [95% CI, -0.006 to 0.030], P =0.19). The proportion of participants who were adherent to statins was 0.72 versus 0.69 for the copayment elimination versus usual copayment groups, respectively (mean difference, 0.03 [95% CI, 0.006-0.06], P =0.016). Overall adjusted health care costs did not differ ($3575 [95% CI, -605 to 7168], P =0.098)., Conclusions: In low-income adults at high cardiovascular risk, eliminating copayments (average, $35/mo) did not improve clinical outcomes or reduce health care costs, despite a modest improvement in adherence to medications., Registration: URL: https://www., Clinicaltrials: gov; Unique identifier: NCT02579655., Competing Interests: Disclosures M.T. has received honoraria for lectures not related to the topic of the current article from AstraZeneca and received honoraria donated to charity. C.M. is an employee of Alberta Health, presently in the capacity of Assistant Deputy Minister of the Pharmaceutical Branch. R.T.T. is a consultant for Shoppers Drug Mart and Emergent Biosolutions. R.T.T. has received investigator-initiated arms-length grants from Merck, Sanofi, AstraZeneca, and Pfizer. The other authors report no conflicts.

Background: Self-management education and support (SMES) interventions have modest effects on intermediate outcomes for those at risk of cardiovascular disease, but few studies have measured or demonstrated an effect on clinical end points. Advertising for commercial products is known to influence behavior, but advertising principles are not typically incorporated into SMES design., Methods: This randomized trial studied the effect of a novel tailored SMES program designed by an advertising firm among a population of older adults with low income at high cardiovascular risk in Alberta, Canada. The intervention included health promotion messaging from a fictitious "peer" and facilitated relay of clinical information to patients' primary care provider and pharmacist. The primary outcome was the composite of death, myocardial infarction, stroke, coronary revascularization, and hospitalizations for cardiovascular-related ambulatory care-sensitive conditions. Rates of the primary outcome and its components were compared using negative binomial regression. Secondary outcomes included quality of life (EQ-5D [EuroQoL 5-dimension] index score), medication adherence, and overall health care costs., Results: We randomized 4761 individuals, with a mean age of 74.4 years, of whom 46.8% were female. There was no evidence of statistical interaction ( P =0.99) or of a synergistic effect between the 2 interventions in the factorial trial with respect to the primary outcome, which allowed us to evaluate the effect of each intervention separately. Over a median follow-up time of 36 months, the rate of the primary outcome was lower in the group that received SMES compared with the control group (incidence rate ratio, 0.78 [95% CI, 0.61 to 1.00]; P =0.047). No significant between-group changes in quality of life over time were observed (mean difference, 0.0001 [95% CI, -0.018 to 0.018]; P =0.99). The proportion of participants who were adherent to medications was not different between the 2 groups ( P =0.199 for statins and P =0.754 for angiotensin-converting enzyme inhibitors/angiotensin receptor blockers). Overall adjusted health care costs did not differ between those receiving SMES and the control group ($2015 [95% CI, -$1953 to $5985]; P =0.320)., Conclusions: For older adults with low income, a tailored SMES program using advertising principles reduced the rate of clinical outcomes compared with usual care. The mechanisms of improvement are unclear and further studies are required., Registration: URL: https://www., Clinicaltrials: gov; Unique identifier: NCT02579655., Competing Interests: Disclosures Dr Tonelli has received honoraria for lectures not related to the topic of the current article from AstraZeneca and received honoraria donated to charity. C. Mitchell is an employee of Alberta Health, currently in the capacity of assistant deputy minister of the pharmaceutical branch. Dr Tsuyuki is a consultant for Shoppers Drug Mart and Emergent Biosolutions. He has received investigator-initiated arms-length grants from Merck, Sanofi, AstraZeneca, and Pfizer. Dr Pannu is president and chief executive officer of Emergence Creative.

Background: Few studies describe acute kidney injury (AKI) burden during paediatric cisplatin therapy and post-cisplatin kidney outcomes. We determined risk factors for and rate of (1) AKI during cisplatin therapy, (2) chronic kidney disease (CKD) and hypertension 2-6 months post-cisplatin, and (3) whether AKI is associated with 2-6-month outcomes., Methods: This prospective cohort study enrolled children (aged < 18 years at cancer diagnosis) treated with cisplatin from twelve Canadian hospitals. AKI during cisplatin therapy (primary exposure) was defined based on Kidney Disease: Improving Global Outcomes (KDIGO) serum creatinine criteria (≥ stage one). Severe electrolyte abnormalities (secondary exposure) included ≥ grade three hypophosphatemia, hypokalemia, or hypomagnesemia (National Cancer Institute Common Terminology Criteria for Adverse Events v4.0). CKD was albuminuria or decreased kidney function for age (KDIGO guidelines). Hypertension was defined based on the 2017 American Academy of Pediatrics guidelines., Results: Of 159 children (median [interquartile range [IQR]] age: 6 [2-12] years), 73/159 (46%) participants developed AKI and 55/159 (35%) experienced severe electrolyte abnormalities during cisplatin therapy. At median [IQR] 90 [76-110] days post-cisplatin, 53/119 (45%) had CKD and 18/128 (14%) developed hypertension. In multivariable analyses, AKI was not associated with 2-6-month CKD or hypertension. Severe electrolyte abnormalities during cisplatin were associated with having 2-6-month CKD or hypertension (adjusted odds ratio (AdjOR) [95% CI]: 2.65 [1.04-6.74]). Having both AKI and severe electrolyte abnormalities was associated with 2-6-month hypertension (AdjOR [95% CI]: 3.64 [1.05-12.62])., Conclusions: Severe electrolyte abnormalities were associated with kidney outcomes. Cisplatin dose optimization to reduce toxicity and clear post-cisplatin kidney follow-up guidelines are needed. A higher resolution version of the Graphical abstract is available as Supplementary information., (© 2022. The Author(s), under exclusive licence to International Pediatric Nephrology Association.)

Rationale & Objective: Sick day medication guidance (SDMG) involves withholding or adjusting specific medications in the setting of acute illnesses that could contribute to complications such as hypotension, acute kidney injury (AKI), or hypoglycemia. We sought to achieve consensus among clinical experts on recommendations for SDMG that could be studied in future intervention studies., Study Design: A modified Delphi process following guidelines for conducting and reporting Delphi studies., Setting & Participants: An international group of clinicians with expertise relevant to SDMG was recruited through purposive and snowball sampling. A scoping review of the literature was presented, followed by 3 sequential rounds of development, refinement, and voting on recommendations. Meetings were held virtually and structured to allow the participants to provide their input and rapidly prioritize and refine ideas., Outcome: Opinions of participants were measured as the percentage who agreed with each recommendation, whereas consensus was defined as >75% agreement., Analytical Approach: Quantitative data were summarized using counts and percentages. A qualitative content analysis was performed to capture the context of the discussion around recommendations and any additional considerations brought forward by participants., Results: The final panel included 26 clinician participants from 4 countries and 10 clinical disciplines. Participants reached a consensus on 42 specific recommendations: 5 regarding the signs and symptoms accompanying volume depletion that should trigger SDMG; 6 regarding signs that should prompt urgent contact with a health care provider (including a reduced level of consciousness, severe vomiting, low blood pressure, presence of ketones, tachycardia, and fever); and 14 related to scenarios and strategies for patient self-management (including frequent glucose monitoring, checking ketones, fluid intake, and consumption of food to prevent hypoglycemia). There was consensus that renin-angiotensin system inhibitors, diuretics, nonsteroidal anti-inflammatory drugs, sodium/glucose cotransporter 2 inhibitors, and metformin should be temporarily stopped. Participants recommended that insulin, sulfonylureas, and meglitinides be held only if blood glucose was low and that basal and bolus insulin be increased by 10%-20% if blood glucose was elevated. There was consensus on 6 recommendations related to the resumption of medications within 24-48 hours of the resolution of symptoms and the presence of normal patterns of eating and drinking., Limitations: Participants were from high-income countries, predominantly Canada. Findings may not be generalizable to implementation in other settings., Conclusions: A multidisciplinary panel of clinicians reached a consensus on recommendations for SDMG in the presence of signs and symptoms of volume depletion, as well as self-management strategies and medication instructions in this setting. These recommendations may inform the design of future trials of SDMG strategies., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Type 2 myocardial infarction (T2MI) occurs when myocardial oxygen demand exceeds myocardial oxygen supply. T2MIs occur more frequently and have worse outcomes compared to Type 1 myocardial infarction caused by an acute plaque rupture. No clinical trial evidence is available to guide pharmacological therapies in this high-risk population., Methods: The Rivaroxaban in Type 2 Myocardial Infarction (R2MI) trial (NCT04838808) was a trainee-led, pragmatic, pilot study that randomised patients with a T2MI to either rivaroxaban 2.5 mg twice daily or placebo. The trial was stopped early due to low recruitment. Investigators explored the challenges of conducting the trial in this population. This was supplemented by a retrospective chart review of 10,000 consecutive troponin assays undertaken during the study period., Results: Over a 1-year period, 276 patients with T2MI were screened for inclusion of which only 7 (2.5%) were randomised in the trial. Study investigators identified trial design and participant population factors that limited recruitment. These included: heterogeneity of patient presentation, poor clinical prognosis, and lack of dedicated non-trainee study personnel. The major limitation to recruitment was the frequency of identified exclusion criterion. The retrospective chart review identified 1715 patients with an elevated high-sensitivity troponin level, of which 916 (53%) were adjudicated to be related to T2MI. Of these, 94.5% possessed an exclusion criterion for the trial., Conclusion: Patients with a T2MI are challenging to recruit into clinical trials involving oral anticoagulation. Future studies should account for only ∼1 in every 20 screened individuals being a candidate for study recruitment., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:All authors declare no conflict of interest. This work was funded from a competitive research grant competition – the CCS-Bayer Cardiovascular Research Award which was awarded to Pishoy Gouda. The sponsor had no input in the design or conduct of the study., (© 2023 The Authors.)

Background Because the impact of changes in how outpatient care was delivered during the COVID-19 pandemic is uncertain, we designed this study to examine the frequency and type of outpatient visits between March 1, 2019 to February 29, 2020 (prepandemic) and from March 1, 2020 to February 28, 2021 (pandemic) and specifically compared outcomes after virtual versus in-person outpatient visits during the pandemic. Methods and Results Population-based retrospective cohort study of all 3.8 million adults in Alberta, Canada. We examined all physician visits and 30- and 90-day outcomes, with a focus on those adults with the cardiovascular ambulatory-care sensitive conditions heart failure, hypertension, and diabetes. Our primary outcome was emergency department visit or hospitalization, evaluated using survival analysis accounting for competing risk of death. Although in-person outpatient visits decreased by 38.9% in the year after March 1, 2020 (10 142 184 versus 16 592 599 in the prior year), the introduction of virtual visits (7 152 147; 41.4% of total) meant that total outpatient visits increased by 4.1% in the first year of the pandemic for Albertan adults. Outpatient visit frequency (albeit 41.4% virtual, 58.6% in-person) and prescribing patterns were stable in the first year after pandemic onset for patients with the cardiovascular ambulatory-care sensitive conditions we examined, but laboratory test frequency declined by 20% (serum creatinine) to 47% (glycosylated hemoglobin). In the first year of the pandemic, virtual outpatient visits were associated with fewer subsequent emergency department visits or hospitalizations (compared with in-person visits) for patients with heart failure (adjusted hazard ratio [aHR], 0.90 [95% CI, 0.85-0.96] at 30 days and 0.96 [95% CI, 0.92-1.00] at 90 days), hypertension (aHR, 0.88 [95% CI, 0.85-0.91] and 0.93 [95% CI, 0.91-0.95] at 30 and 90 days), or diabetes (aHR, 0.90 [95% CI, 0.87-0.93] and 0.93 [95% CI, 0.91-0.95] at 30 and 90 days). Conclusions The adoption and rapid uptake of virtual outpatient care during the COVID-19 pandemic did not negatively impact frequency of follow-up, prescribing, or short-term outcomes, and could have potentially positively impacted some of these for adults with heart failure, diabetes, or hypertension in a setting where there was an active reimbursement policy for virtual visits. Given declines in laboratory monitoring and screening activities, further research is needed to evaluate whether long-term outcomes will differ.

Background: Multiple sclerosis (MS) is a chronic disease affecting multiple functional aspects of patients' lives. Depression and anxiety are common amongst persons with MS (PwMS). There has been an interest in utilizing patient-reported outcome measures (PROMs) to capture and systematically assess patient's perceptions of their MS experience in addition to other clinical measures, but PROMs are not usually collected in routine clinical practice. Therefore, this study aims to systematically incorporate periodic electronically administered PROMs into the care of PwMS to evaluate its effects on depression and anxiety., Methods: A randomized controlled trial will be conducted with patients allocated 1:1 to either intervention or conservative treatment groups. Patients in the intervention group will complete PROMs at the start of the study and then every 6 months for 1 year, in addition to having their MS healthcare provider prompted to view their scores. The conservative treatment group will complete PROMs at the start of the study and again after 12 months, and their neurologist will not be able to view their scores. For both groups, pre-determined critical PROM scores will trigger an alert to the patient's MS provider. The difference in change in Hospital Anxiety and Depression Scale score between the intervention and conservative treatment groups at 12 months will be the primary outcome, along with difference in Consultation Satisfaction Questionnaire and CollaboRATE scores at 12 months, and proportion and type of healthcare provider intervention/alerts initiated by different PROMs as secondary outcomes., Discussion: This study will determine the feasibility of utilizing PROMs on an interval basis and its effects on the psychological well-being of PwMS. Findings of this study will provide evidence on use of PROMs in future MS clinical practice., Trial Registration: This trial is registered at the National Institutes of Health United States National Library of Medicine, ClinicalTrials.gov NCT04979546 . Registered on July 28, 2021., (© 2023. The Author(s).)

Background: The use of topical vancomycin in the reduction of sternal wound infection (SWI) risk has become a point of contention. The earlier literature consists of observational studies and 1 unblinded trial. Hence, the objective of this study was to assess whether vancomycin reduces the incidence of SWI in a double-blind randomized controlled trial., Methods: Patients were randomized 1:1 to either vancomycin-soaked (vancomycin) or saline-soaked (control) sponges. The sponges were applied once the sternum was opened and were removed just before sternal closure. Patients were followed up at 3 months and at 1 year postoperatively to determine the incidence of SWI in each group. Results were analyzed according to the modified intention-to-treat principle., Results: This study assessed 1038 patients for eligibility and enrolled 1037 patients. There were 517 patients randomized to the vancomycin group and 520 patients randomized to the control group. Analysis was performed on 1021 patients. At 3 months postoperatively, there was no significant difference in the incidence of SWI between the vancomycin and control groups (2.7% vs 4.1%; P = .23). There was also no significant difference between the vancomycin and control groups in the risk of superficial, deep, and organ-space infections. Similar findings were observed 1 year postoperatively. The most common organism isolated was coagulase-negative Staphylococcus., Conclusions: The use of vancomycin applied to the sternum during cardiac surgery does not reduce the incidence of SWI., (Copyright © 2022 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

As the leading risk for death, population control of increased blood pressure represents a major challenge for all countries of the Americas. In the early 1990's, Canada had a hypertension control rate of 13%. The control rate increased to 68% in 2010, accompanied by a sharp decline in cardiovascular disease. The unprecedented improvement in hypertension control started around the year 2000 when a comprehensive program to implement annually updated hypertension treatment recommendations started. The program included a comprehensive monitoring system for hypertension control. After 2011, there was a marked decrease in emphasis on implementation and evaluation and the hypertension control rate declined, driven by a reduction in control in women from 69% to 49%. A coalition of health and scientific organizations formed in 2011 with a priority to develop advocacy positions for dietary policies to prevent and control hypertension. By 2015, the positions were adopted by most federal political parties, but implementation has been slow. This manuscript reviews key success factors and learnings. Some key success factors included having broad representation on the program steering committee, multidisciplinary engagement with substantive primary care involvement, unbiased up to date credible recommendations, development and active adaptation of education resources based on field experience, extensive implementation of primary care resources, annual review of the program and hypertension indicators and developing and emphasizing the few interventions important for hypertension control. Learnings included the need for having strong national and provincial government engagement and support, and retaining primary care organizations and clinicians in the implementation and evaluation.

Background: The assessment of the implementation process of a clinical intervention in a community pharmacy setting can reveal useful insights for future implementation efforts., Objective: We aimed to examine the implementation of a community pharmacist-led prospective registry and practice tool (R x ING, Epidemiology Research Coordinating Center and the University of Alberta) designed to reduce cardiovascular risk among patients with diabetes and to assess how the participating pharmacists could be supported at each of these stages., Methods: Semistructured interviews were conducted developed using the Exploration, Preparation, Implementation, Sustainment (EPIS) framework. The EPIS framework was used to evaluate the implementation of an online, guideline-driven tool (R x ING tool) designed to help pharmacists implement and document the care of patients with diabetes by a group of community pharmacies located in Alberta, Canada., Results: In relation to the preparation phase, responses focused more on suitability of the work environments and less on workflow adjustment. With regard to the implementation stage, participants mentioned that often the pharmacy manager or owner received the training to operate the R x ING tool, complicating their ability to engage in regular patient recruitment and follow-up. Most pharmacies did not have specific goals relating to patient recruitment and retention. Concerns hindering sustainability of the evidence-based practice centered around the time-consuming online documentation process and patient retention. Finally, innovation factors identified from the pharmacists' responses were related to patient recruitment and streamlining the documentation process., Conclusions: This study identified 17 key recommendations that should be considered when designing and implementing future community pharmacy-led projects. In particular, providing assistance and training to pharmacies on-site, specific planning for program roll-out, identifying participating staff who have the time to engage with the program, and troubleshooting how to best integrate programs in normal workflow processes are some key recommendations., (Copyright © 2022 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.)

Background: Care for People with Multiple Sclerosis (PwMS) is increasingly complex, requiring innovations in care. Canada has high rates of MS; it is challenging for general neurologists to optimally care for PwMS with busy office practices. The aim of this study was to evaluate the effects of add-on Nurse Practitioner (NP)-led care for PwMS on depression and anxiety (Hospital Anxiety and Depression Scale, HADS), compared to usual care (community neurologist, family physician)., Methods: PwMS followed by community neurologists were randomized to add-on NP-led or Usual care for 6 months. Primary outcome was the change in HADS at 3 months. Secondary outcomes were HADS (6 months), EQ5D, MSIF, CAREQOL-MS, at 3 and 6 months, and Consultant Satisfaction Survey (6 months)., Results: We recruited 248 participants; 228 completed the trial (NP-led care arm n = 120, Usual care arm n = 108). There were no significant baseline differences between groups. Study subjects were highly educated (71.05%), working full-time (41.23%), living independently (68.86%), with mean age of 47.32 (11.09), mean EDSS 2.53 (SD 2.06), mean duration since MS diagnosis 12.18 years (SD 8.82) and 85% had relapsing remitting MS. Mean change in HADS depression (3 months) was: -0.41 (SD 2.81) NP-led care group vs 1.11 (2.98) Usual care group p = 0.001, sustained at 6 months; for anxiety, - 0.32 (2.73) NP-led care group vs 0.42 (2.82) Usual care group, p = 0.059. Other secondary outcomes were not significantly different. There was no difference in satisfaction of care in the NP-led care arm (63.83 (5.63)) vs Usual care (62.82 (5.45)), p = 0.194)., Conclusion: Add-on NP-led care improved depression compared to usual neurologist care and 3 and 6 months in PwMS, and there was no difference in satisfaction with care. Further research is needed to explore how NPs could enrich care provided for PwMS in healthcare settings., Trial Registration: Retrospectively registered on clinicaltrials.gov ( ClinicalTrials.gov Identifier: NCT04388592 , 14/05/2020)., (© 2022. The Author(s).)

Rationale & Objective: Sick day medication guidance has been promoted to prevent adverse events for people with chronic conditions. Our aim was to summarize the existing sick day medication guidance and the evidence base for the effectiveness of interventions for implementing this guidance., Study Design: Scoping review of quantitative and qualitative studies., Setting & Population: Sick day medication guidance for people with chronic conditions including diabetes mellitus, kidney diseases, and cardiovascular diseases., Selection Criteria for Studies: A search of 6 bibliographic databases (Ovid MEDLINE, Ovid Embase, CINAHL, Scopus, Web of Science Core Collection, and Cochrane Library [via Wiley]) and a comprehensive gray literature search were completed in June 2021., Data Extraction: Intervention and study characteristics were extracted using standardized tools., Analytical Approach: Data were summarized descriptively, and our approach observed the Preferred Reporting Items for Systematic Reviews and Meta-analyses extension for scoping reviews., Results: The literature search identified 2,308 documents, which were screened against the eligibility criteria, leading to 74 documents that were included. The majority of the identified documents (n = 55) were guidelines or educational resources. Of the 19 primary research studies identified, 10 studies described an intervention, with only 2 examining the effect of sick day medication guidance interventions within clinical care and no studies reporting beneficial effects on clinical outcomes. Most documents (n = 58) included guidance specific to patients with diabetes mellitus, with fewer including guidance for patients with chronic kidney disease (n = 9) or heart failure (n = 2)., Limitations: Risk of bias was not assessed., Conclusions: Many resources promoting sick day medication guidance have been developed; however, there is very little empirical evidence for the effectiveness of current approaches in implementing sick day medication guidance into practice. Recommendations for the use of sick day medication guidance will require further research to develop consistent, understandable, and usable approaches for its implementation within self-management strategies as well as empirical studies to demonstrate the effectiveness of these interventions., (© 2022 The Authors.)

Introduction: Hypertension management remains a major public health challenge in primary care. Innovative interventions to improve blood pressure (BP) control are needed. One approach is through community-based models of care with the involvement of pharmacists and other non-physician healthcare professionals. Our objective is to systematically review the evidence of the impact of pharmacist care alone or in collaboration with other healthcare professionals on BP among hypertensive outpatients compared with usual care. Because these interventions can be complex, with various components, the effect size may differ between the type of interventions. One major focus of our study will be to assess carefully the heterogeneity in the effects of these interventions to identify which ones work best in a given healthcare setting., Methods and Analysis: Systematic searches of the Medical Literature Analysis and Retrieval System Online (MEDLINE), Excerpta Medica (Embase) and Central Register of Controlled Trials (CENTRAL) databases will be conducted. Randomised controlled trials assessing the effect of pharmacist interventions on BP among outpatients will be included. Examples for pharmacist interventions are patient education, feedback to physician and medication management. The outcome will be the change in BP or BP at follow-up or BP control. Results will be synthesised descriptively and, if appropriate, will be pooled across studies to perform meta-analyses. If feasible, we will also perform a network meta-analysis to compare interventions that have not been compared directly head-to-head by using indirect evidence. Heterogeneity in the effect will be evaluated through prespecified subgroup and stratified analyses, accounting notably for the type and intensity of interventions, patients' characteristics and healthcare setting., Ethics and Dissemination: Ethical approval is not required as the results will be drawn from currently available published literature. Outcomes of the review will be shared through peer-reviewed journal and used for implementation policy., Prospero Registration Number: CRD42021279751., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Canada has one of the highest rates of multiple sclerosis (MS) in the world. Treatments and supports for people with MS (PwMS) have become increasingly complex, requiring individualized and adaptive care. Specialized NPs provide advanced skills to those with complex medical conditions, with potential to enhance the health, functioning, and quality of life for PwMS. This study aims to determine the effect of a Nurse Practitioner (NP) on depression and anxiety levels in PwMS., Methods: We will perform a parallel randomized controlled trial. PwMS who are followed by general private-practice neurologists will be randomly assigned to the intervention group (NP-led care) or the 'usual care' control group (general neurologist or family physician and registered nurse support). In the intervention group, the NP will assess and provide care to the MS patient and their caregiver at a baseline visit, with 3-month and 6-month follow-up visits. PwMS in the control group will receive usual care provided by their community neurologists or family physicians with the standard assistance provided by registered nurses experienced in MS care. The primary outcome will be the difference in change in the patient's anxiety and depression scores as measured by the validated Hospital Anxiety and Depression Scale (HADS) questionnaire at 3 months. Secondary outcomes will include difference in change in HADS at 6 months; Modified Fatigue Impact Scale scores (MSIF) at 3 and 6 months; EQ-5D scores at 3 and 6 months; caregiver health-related quality of life in MS measures (CAREQOL-MS) at 3 and 6 months; number of visits and phone calls to healthcare professionals recorded by patient, and satisfaction with NP-led care vs usual care measured by the validated Consultant Satisfaction Questionnaire., Discussion: Findings from this study will contribute to exploring benefits of advanced nursing practitioner interventions for PwMS followed by general neurologists and family physicians in a community setting. It will provide evidence of the benefits of NP-led care for PwMS and offer an alternative healthcare resource for management of MS., Trial Registration: ClinicalTrials.gov Pro00069595 . Retrospectively registered on June 26, 2020. Protocol version: January 2017, version 1., (© 2021. The Author(s).)

Background: Few studies have described associations between the AKI biomarkers urinary neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) with AKI in cisplatin-treated children. We aimed to describe excretion patterns of urine NGAL and KIM-1 and associations with AKI in children receiving cisplatin., Methods: Participants ( n =159) were enrolled between 2013 and 2017 in a prospective cohort study conducted in 12 Canadian pediatric hospitals. Participants were evaluated at early cisplatin infusions (at first or second cisplatin cycle) and late cisplatin infusions (last or second-to-last cycle). Urine NGAL and KIM-1 were measured ( 1 ) pre-cisplatin infusion, ( 2 ) post-infusion (morning after), and ( 3 ) at hospital discharge at early and late cisplatin infusions. Primary outcome: AKI defined by serum creatinine rise within 10 days post-cisplatin, on the basis of Kidney Disease Improving Global Outcomes guidelines criteria (stage 1 or higher)., Results: Of 159 children, 156 (median [interquartile range (IQR)] age: 5.8 [2.4-12.0] years; 78 [50%] female) had biomarker data available at early cisplatin infusions and 127 had data at late infusions. Forty six of the 156 (29%) and 22 of the 127 (17%) children developed AKI within 10 days of cisplatin administration after early and late infusions, respectively. Urine NGAL and KIM-1 concentrations were significantly higher in patients with versus without AKI (near hospital discharge of late cisplatin infusion, median [IQR] NGAL levels were 76.1 [10.0-232.7] versus 14.9 [5.4-29.7] ng/mg creatinine; KIM-1 levels were 4415 [2083-9077] versus 1049 [358-3326] pg/mg creatinine; P <0.01). These markers modestly discriminated for AKI (area under receiver operating characteristic curve [AUC-ROC] range: NGAL, 0.56-0.72; KIM-1, 0.48-0.75). Biomarker concentrations were higher and better discriminated for AKI at late cisplatin infusions (AUC-ROC range, 0.54-0.75) versus early infusions (AUC-ROC range, 0.48-0.65)., Conclusions: Urine NGAL and KIM-1 were modest at discriminating for cisplatin-associated AKI. Further research is needed to determine clinical utility and applicability of these markers and associations with late kidney outcomes., Competing Interests: T.D. Blydt-Hansen reports having ownership interest in Apple, Hydrogenics, and Royal Bank of Canada; receiving honoraria from Astellas Canada; receiving research funding from Astellas Canada, Canadian Institutes of Health Research, Child and Family Research Institute, Children’s Hospital of Manitoba Research Institute, and Transplant Research Foundation of BC; having consultancy agreements with Astellas Canada, Horizon Canada, Novartis, and Ricordati; and serving as a scientific advisor for or member of BC Transplant, Canadian National Transplant Research Program, International Pediatric Transplant Association (council member), and North American Pediatric Transplant and Collaborative Studies. B.C. Carleton reports serving as a scientific advisor for or member of AEVI Genomic Medicine, United Health Group Pharmacogenomics (on the advisory committee); having consultancy agreements with Dynacare Specialized Diagnostics; receiving research funding from Dynacare Specialized Diagnostics (ended in June 2021) and grants from federal and provincial agencies; and having other interests/relationships with Rare Disease Society. P. Devarajan reports having consultancy agreements with Alnylam, Dicerna, Natera, and Reata; being a coinventor on patents for the use of NGAL as a biomarker of kidney injury; and serving on speakers bureaus for BioPorto Inc., Natera, and Reata. M. Pinsk reports having consultancy agreements with Canadian Agency for Drugs and Technologies in Health (as consultant); serving as an expert witness for legal consultations (multiple); and having other interests/relationships with Canadian Society of Nephrology, International Pediatric Nephrology Association, and Medical Council of Canada. K. R. Schultz reports having consultancy agreements with AVM Biotech, Celgene/Juno, Jazz, and Medpace; receiving honoraria from Bristol Myers Squibb (BMS), Celegene, and Jazz; serving on the data safety monitoring boards for BMS/Juno and Medpace; and serving as a scientific advisor or membership of Jazz. R.T. Tsuyuki reports receiving research funding from AstraZeneca, Merck Canada Inc., and Sanofi; serving as the editor-in-chief for Canadian Pharmacists Journal, and as president, chair, and on the board of directors for Hypertension Canada; receiving honoraria from Emergent Biosolutions and Merck Canada Inc.; and having consultancy agreements with Emergent Biosolutions and Shoppers Drug Mart. M. Zappitelli reports having consultancy agreements with BioPorto Inc., CytoPheryx Inc., and Eloxx Pharmaceuticals; receiving honoraria from Bioporto Inc. and Eloxx Pharmaceuticals; and having other interests/relationships with Canadian Pediatric Nephrologists Association, Canadian Society of Nephrology, and Kidney Foundation of Canada. All remaining authors have nothing to disclose., (Copyright © 2022 by the American Society of Nephrology.)