Re-Purposing the Ordering of Routine Laboratory Tests in Hospitalized Medical Patients (RePORT): protocol for a multicenter stepped-wedge cluster randomised trial to evaluate the impact of a multicomponent intervention bundle to reduce laboratory test over-utilization.

BACKGROUND: Laboratory test overuse in hospitals is a form of healthcare waste that also harms patients. Developing and evaluating interventions to reduce this form of healthcare waste is critical. We detail the protocol for our study which aims to implement and evaluate the impact of an evidence-based, multicomponent intervention bundle on repetitive use of routine laboratory testing in hospitalized medical patients across adult hospitals in the province of British Columbia, Canada. METHODS: We have designed a stepped-wedge cluster randomized trial to assess the impact of a multicomponent intervention bundle across 16 hospitals in the province of British Columbia in Canada. We will use the Knowledge to Action cycle to guide implementation and the RE-AIM framework to guide evaluation of the intervention bundle. The primary outcome will be the number of routine laboratory tests ordered per patient-day in the intervention versus control periods. Secondary outcome measures will assess implementation fidelity, number of all common laboratory tests used, impact on healthcare costs, and safety outcomes. The study will include patients admitted to adult medical wards (internal medicine or family medicine) and healthcare providers working in these wards within the participating hospitals. After a baseline period of 24 weeks, we will conduct a 16-week pilot at one hospital site. A new cluster (containing approximately 2-3 hospitals) will receive the intervention every 12 weeks. We will evaluate the sustainability of implementation at 24 weeks post implementation of the final cluster. Using intention to treat, we will use generalized linear mixed models for analysis to evaluate the impact of the intervention on outcomes. DISCUSSION: The study builds upon a multicomponent intervention bundle that has previously demonstrated effectiveness. The elements of the intervention bundle are easily adaptable to other settings, facilitating future adoption in wider contexts. The study outputs are expected to have a positive impact as they will reduce usage of repetitive laboratory tests and provide empirically supported measures and tools for accomplishing this work. TRIAL REGISTRATION: This study was prospectively registered on April 8, 2024, via ClinicalTrials.gov Protocols Registration and Results System (NCT06359587). https://classic. CLINICALTRIALS: gov/ct2/show/NCT06359587?term=NCT06359587&recrs=ab&draw=2&rank=1.

The impact of the COVID-19 pandemic on transfers between long-term care and emergency departments across Alberta.

BACKGROUND: Long-term care (LTC) was overwhelmingly impacted by COVID-19 and unnecessary transfer to emergency departments (ED) can have negative health outcomes. This study aimed to explore how the COVID-19 pandemic impacted LTC to ED transfers and hospitalizations, utilization of community paramedics and facilitated conversations between LTC and ED physicians during the first four waves of the pandemic in Alberta, Canada. METHODS: In this retrospective population-based study, administrative databases were linked to identify episodes of care for LTC residents who resided in facilities in Alberta, Canada. This study included data from January 1, 2018 to December 31, 2021 to capture outcomes prior to the onset of the pandemic and across the first four waves. Individuals were included if they visited an emergency department, received care from a community paramedic or whose care involved a facilitated conversation between LTC and ED physicians during this time period. RESULTS: Transfers to ED and hospitalizations from LTC have been gradually declining since 2018 with a sharp decline seen during wave 1 of the pandemic that was greatest in the lowest-priority triage classification (CTAS 5). Community paramedic visits were highest during the first two waves of the pandemic before declining in subsequent waves; facilitated calls between LTC and ED physicians increased during the waves. CONCLUSIONS: There was a reduction in number of transfers from LTC to EDs and in hospitalizations during the first four waves of the pandemic. This was supported by increased conversations between LTC and ED physicians, but was not associated with increased community paramedic visits. Additional work is needed to explore how programs such as community paramedics and facilitated conversations between LTC and ED providers can help to reduce unnecessary transfers to hospital.

Multicentre implementation of a quality improvement initiative to reduce delirium in adult intensive care units: An interrupted time series analysis.

PURPOSE: The ABCDEF bundle may improve delirium outcomes among intensive care unit (ICU) patients, however population-based studies are lacking. In this study we evaluated effects of a quality improvement initiative based on the ABCDEF bundle in adult ICUs in Alberta, Canada. MATERIAL AND METHODS: We conducted a pre-post, registry-based clinical trial, analysed using interrupted time series methodology. Outcomes were examined via segmented linear regression using mixed effects models. The main data source was a population-based electronic health record. RESULTS: 44,405 consecutive admissions (38,400 unique patients) admitted to 15 general medical/surgical and/or neurologic adult ICUs between 2014 and 2019 were included. The proportion of delirium days per ICU increased from 30.24% to 35.31% during the pre-intervention period. After intervention implementation it decreased significantly (bimonthly decrease of 0.34%, 95%CI 0.18-0.50%, p < 0.01) from 33.48% (95%CI 29.64-37.31%) in 2017 to 28.74% (95%CI 25.22-32.26%) in 2019. The proportion of sedation days using midazolam demonstrated an immediate decrease of 7.58% (95%CI 4.00-11.16%). There were no significant changes in duration of invasive ventilation, proportion of partial coma days, ICU mortality, or potential adverse events. CONCLUSIONS: An ABCDEF delirium initiative was implemented on a population-basis within adult ICUs and was successful at reducing the prevalence of delirium.

Effectiveness of Bio-K+ for the prevention of Clostridioides difficile infection: Stepped-wedge cluster-randomized controlled trial.

OBJECTIVE: To evaluate the impact of administering probiotics to prevent Clostridioides difficile infection (CDI) among patients receiving therapeutic antibiotics. DESIGN: Stepped-wedge cluster-randomized trial between September 1, 2016, and August 31, 2019. SETTING: This study was conducted in 4 acute-care hospitals across an integrated health region. PATIENTS: Hospitalized patients, aged ≥55 years. METHODS: Patients were given 2 probiotic capsules daily (Bio-K+, Laval, Quebec, Canada), containing 50 billion colony-forming units of Lactobacillus acidophilus CL1285, L. casei LBC80R, and L. rhamnosus CLR2. We measured hospital-acquired CDI (HA-CDI) and the number of positive C. difficile tests per 10,000 patient days as well as adherence to administration of Bio-K+ within 48 and 72 hours of antibiotic administration. Mixed-effects generalized linear models, adjusted for influenza admissions and facility characteristics, were used to evaluate the impact of the intervention on outcomes. RESULTS: Overall adherence of Bio-K+ administration ranged from 76.9% to 84.6% when stratified by facility and periods. Rates of adherence to administration within 48 and 72 hours of antibiotic treatment were 60.2% -71.4% and 66.7%-75.8%, respectively. In the adjusted analysis, there was no change in HA-CDI (incidence rate ratio [IRR], 0.92; 95% confidence interval [CI], 0.68-1.23) or C. difficile positivity rate (IRR, 1.05; 95% CI, 0.89-1.24). Discharged patients may not have received a complete course of Bio-K+. Our hospitals had a low baseline incidence of HA-CDI. Patients who did not receive Bio-K+ may have differential risks of acquiring CDI, introducing selection bias. CONCLUSIONS: Hospitals considering probiotics as a primary prevention strategy should consider the baseline incidence of HA-CDI in their population and timing of probiotics relative to the start of antimicrobial administration.

Implementation strategies for hospital-based probiotic administration in a stepped-wedge cluster randomized trial design for preventing hospital-acquired Clostridioides difficile infection.

BACKGROUND: Clostridioides difficile infection (CDI) is associated with considerable morbidity and mortality in hospitalized patients, especially among older adults. Probiotics have been evaluated to prevent hospital-acquired (HA) CDI in patients who are receiving systemic antibiotics, but the implementation of timely probiotic administration remains a challenge. We evaluated methods for effective probiotic implementation across a large health region as part of a study to assess the real-world effectiveness of a probiotic to prevent HA-CDI (Prevent CDI-55 +). METHODS: We used a stepped-wedge cluster-randomized controlled trial across four acute-care adult hospitals (n = 2,490 beds) to implement the use of the probiotic Bio-K + ® (Lactobacillus acidophilus CL1285®, L. casei LBC80R® and L. rhamnosus CLR2®; Laval, Quebec, Canada) in patients 55 years and older receiving systemic antimicrobials. The multifaceted probiotic implementation strategy included electronic clinical decision support, local site champions, and both health care provider and patient educational interventions. Focus groups were conducted during study implementation to identify ongoing barriers and facilitators to probiotic implementation, guiding needed adaptations of the implementation strategy. Focus groups were thematically analyzed using the Theoretical Domains Framework and the Consolidated Framework of Implementation Research. RESULTS: A total of 340 education sessions with over 1,800 key partners and participants occurred before and during implementation in each of the four hospitals. Site champions were identified for each included hospital, and both electronic clinical decision support and printed educational resources were available to health care providers and patients. A total of 15 individuals participated in 2 focus group and 7 interviews. Key barriers identified from the focus groups resulted in adaptation of the electronic clinical decision support and the addition of nursing education related to probiotic administration. As a result of modifying implementation strategies for identified behaviour change barriers, probiotic adherence rates were from 66.7 to 75.8% at 72 h of starting antibiotic therapy across the four participating acute care hospitals. CONCLUSIONS: Use of a barrier-targeted multifaceted approach, including electronic clinical decision support, education, focus groups to guide the adaptation of the implementation plan, and local site champions, resulted in a high probiotic adherence rate in the Prevent CDI-55 + study.

Physician Variation and the Impact of Payment Model in Cardiac Imaging.

BACKGROUND: The influence of fee-for-service reimbursement on cardiac imaging has not been compared with other payment models. Furthermore, variation in ordering practices is not well understood. METHODS AND RESULTS: This retrospective, population-based cohort study using linked administrative data from Alberta, Canada included adults with chronic heart disease (atrial fibrillation, coronary artery disease, and heart failure) seen by cardiac specialists for a new outpatient consultation April 2012 to December 2018. Generalized linear mixed-effects models estimated the association of payment model (including the ability to bill to interpret imaging tests) and the use of cardiac imaging and quantified variation in cardiac imaging. Among 31 685 adults seen by 308 physicians at 136 sites, patients received an observed mean of 0.67 (95% CI, 0.67-0.68) imaging tests per consultation. After adjustment, patients seeing fee-for-service physicians had 2.07 (95% CI, 1.68-2.54) and fee-for-service physicians with ability to interpret had 2.87 (95% CI, 2.16-3.81) times the rate of receiving a test than those seeing salaried physicians. Measured patient, physician, and site effects accounted for 31% of imaging variation and, following adjustment, reduced unexplained site-level variation 40% and physician-level variation 29%. CONCLUSIONS: We identified substantial variation in the use of outpatient cardiac imaging related to physician and site factors. Physician payment models have a significant association with imaging use. Our results raise concern that payment models may influence cardiac imaging practice. Similar methods could be applied to identify the source and magnitude of variation in other health care processes and outcomes.

Machine learning risk estimation and prediction of death in continuing care facilities using administrative data.

In this study, we aimed to identify the factors that were associated with mortality among continuing care residents in Alberta, during the coronavirus disease 2019 (COVID-19) pandemic. We achieved this by leveraging and linking various administrative datasets together. Then, we examined pre-processing methods in terms of prediction performance. Finally, we developed several machine learning models and compared the results of these models in terms of performance. We conducted a retrospective cohort study of all continuing care residents in Alberta, Canada, from March 1, 2020, to March 31, 2021. We used a univariable and a multivariable logistic regression (LR) model to identify predictive factors of 60-day all-cause mortality by estimating odds ratios (ORs) with a 95% confidence interval. To determine the best sensitivity-specificity cut-off point, the Youden index was employed. We developed several machine learning models to determine the best model regarding performance. In this cohort study, increased age, male sex, symptoms, previous admissions, and some specific comorbidities were associated with increased mortality. Machine learning and pre-processing approaches offer a potentially valuable method for improving risk prediction for mortality, but more work is needed to show improvement beyond standard risk factors.

AI-powered assessment of biomarkers for growth prediction of abdominal aortic aneurysms.

Objective: The purpose of this study was to employ biomechanics-based biomarkers to locally characterize abdominal aortic aneurysm (AAA) tissue and investigate their relation to local aortic growth by means of an artificial intelligence model. Methods: The study focused on a population of 36 patients with AAAs undergoing serial monitoring with electrocardiogram-gated multiphase computed tomography angiography acquisitions. The geometries of the aortic lumen and wall were reconstructed from the baseline scans and used for the baseline assessment of regional aortic weakness with three functional biomarkers, time-averaged wall-shear stress, in vivo principal strain, and intra-luminal thrombus thickness. The biomarkers were encoded as regional averages on axial and circumferential sections perpendicularly to the aortic centerline. Local diametric growth was obtained as difference in diameter between baseline and follow-up at the level of each axial section. An artificial intelligence model was developed to predict accelerated aneurysmal growth with the Extra Trees algorithm used as a binary classifier where the positive class represented regions that grew more than 2.5 mm/year. Additional clinical biomarkers, such as maximum aortic diameter at baseline, were also investigated as predictors of growth. Results: The area under the curve for the constructed receiver operating characteristic curve for the Extra Trees classifier showed a very good performance in predicting relevant aortic growth (area under the curve = 0.92), with the three biomechanics-based functional biomarkers being objectively selected as the main predictors of growth. Conclusions: The use of features based on the functional and local characterization of the aortic tissue resulted in a superior performance in terms of growth prediction when compared with models based on geometrical assessments. With rapid growth linked to increasing risk for patients with AAAs, the ability to access functional information related to tissue weakening and disease progression at baseline has the potential to support early clinical decisions and improve disease management.

Association of co-morbidity with acute stroke mortality by age and time since stroke: A population-based study.

OBJECTIVE: To examine whether the association of co-morbidity with mortality after acute stroke is influenced by stroke type, age, sex, or time since stroke. MATERIALS AND METHODS: We conducted a province-wide population-based study using linked administrative databases to identify all admissions for acute stroke between 2007-2018 in Alberta, Canada. We used Cox proportional hazard models to determine the association of severe co-morbidity based on the Charlson Co-morbidity Index with 1-year mortality after stroke, assessing for effect modification by stroke type, age, and sex, and with adjustment for estimated stroke severity, comprehensive stroke centre care, hypertension, atrial fibrillation, and year of study. We used a piecewise model to analyze the impact of co-morbidity across four time periods. RESULTS: We had 28,672 patients in our final cohort (87.8% ischemic stroke). The hazard of mortality with severe co-morbidity was higher for individuals with ischemic stroke (adjusted hazard ratio [aHR] 2.20, 95% CI 2.07-2.32) compared to those with intracerebral hemorrhage (aHR 1.70, 95% CI 1.51-1.92; pint<0.001), and higher in individuals under age 75 (aHR 3.20, 95% CI 2.90-3.53) compared to age ≥75 (aHR 1.93, 95% CI 1.82-2.05, pint<0.001). There was no interaction by sex. The hazard ratio increased in a graded fashion at younger ages and was higher after the first 30 days of acute stroke. CONCLUSION: There was a stronger association between co-morbidity and mortality at younger age and in the subacute phase of stroke. Further research is needed to determine the reason for these findings and identify ways to improve outcomes among those with stroke and co-morbid conditions at young age.

Mortality and risk factors for ruptured abdominal aortic aneurysm after repair endovascular (rARE).

Objective: The aim of this study was to characterize risk factors for infrarenal abdominal aortic aneurysm rupture after endovascular repair (rARE) and evaluate 30-day mortality in comparison to primary ruptured abdominal aortic aneurysm (rAAA). Methods: A retrospective review of all adult patients with rAAA at a single tertiary university care center between February 11, 2006, and December 31, 2018, was performed. A total of 267 patients with rAAA were identified, 11 of whom had rARE. Descriptive statistics were applied due to the small sample size. Results: Overall 30-day mortality was similar between primary rAAA and rARE (31.5% vs 27.3%); however, patients with rARE were more likely to receive palliative care (3.9% vs 18.2%). Mortality of patients who underwent operative intervention was 11.1% for rARE and 28.7% for primary rAAA at 30 days. All patients had an endoleak at the time of rupture. Type 1 and type 3 endoleaks resulting in direct aortic sac pressurization were the primary cause of rARE (9 of 11 patients); however, rupture occurred in two patients with only a type 2 endoleak. There was no sac expansion at the time of rupture in four of 11 patients with rARE. Four of 11 patients were lost to follow-up prior to rARE. Conclusions: rARE is an uncommon complication following EVAR and contributes to late aneurysm-related mortality following endovascular repair. Although the 30-day mortality rate was similar for rARE and primary rAAA, larger series are required to determine which patients with rARE will benefit from intervention. The presence of endoleak and sac expansion may alert surgeons to increased risk of rARE; however, a subset of patients with rARE did not have sac expansion or surveillance imaging on follow-up. Loss to lifelong imaging surveillance remains a risk factor for rARE.

Repurposing the Ordering of Routine Laboratory Tests in Hospitalised Medical Patients (RePORT): results of a cluster randomised stepped-wedge quality improvement study.

BACKGROUND: Low-value use of laboratory tests is a global challenge. Our objective was to evaluate an intervention bundle to reduce repetitive use of routine laboratory testing in hospitalised patients. METHODS: We used a stepped-wedge design to implement an intervention bundle across eight medical units. Our intervention included educational tools and social comparison reports followed by peer-facilitated report discussion sessions. The study spanned October 2020-June 2021, divided into control, feasibility testing, intervention and a follow-up period. The primary outcomes were the number and costs of routine laboratory tests ordered per patient-day. We used generalised linear mixed models, and analyses were by intention to treat. RESULTS: We included a total of 125 854 patient-days. Patient groups were similar in age, sex, Charlson Comorbidity Index and length of stay during the control, intervention and follow-up periods. From the control to the follow-up period, there was a 14% (incidence rate ratio (IRR)=0.86, 95% CI 0.79 to 0.92) overall reduction in ordering of routine tests with the intervention, along with a 14% (ß coefficient=-0.14, 95% CI -0.07 to -0.21) reduction in costs of routine testing. This amounted to a total cost savings of $C1.15 per patient-day. There was also a 15% (IRR=0.85, 95% CI 0.79, 0.92) reduction in ordering of all common tests with the intervention and a 20% (IRR=1.20, 95% CI 1.10 to 1.30) increase in routine test-free patient-days. No worsening was noted in patient safety endpoints with the intervention. CONCLUSIONS: A multifaceted intervention bundle using education and facilitated multilevel social comparison was associated with a safe and effective reduction in use of routine daily laboratory testing in hospitals. Further research is needed to understand how system-level interventions may increase this effect and which intervention elements are necessary to sustain results.

Buprenorphine/naloxone initiation and referral as a quality improvement intervention for patients who live with opioid use disorder: quantitative evaluation of provincial spread to 107 rural and urban Alberta emergency departments.

OBJECTIVES: Opioid use disorder is a major public health concern that accounts for a high number of potential years of life lost. Buprenorphine/naloxone is a recommended treatment for opioid use disorder that can be started in the emergency department (ED). We developed an ED-based program to initiate buprenorphine/naloxone for eligible patients who live with opioid use disorder, and to provide unscheduled, next-day follow-up referrals to an opioid use disorder treatment clinic (in person or virtual) for continuing patient care throughout Alberta. METHODS: In this quality improvement initiative, we supported local ED teams to offer buprenorphine/naloxone to eligible patients presenting to the ED with suspected opioid use disorder and refer these patients for follow-up care. Process, outcome, and balancing measures were evaluated over the first 2 years of the initiative (May 15, 2018-May 15, 2020). RESULTS: The program was implemented at 107 sites across Alberta during our evaluation period. Buprenorphine/naloxone initiations in the ED increased post-intervention at most sites with baseline data available (11 of 13), and most patients (67%) continued to fill an opioid agonist prescription at 180 days post-ED visit. Of the 572 referrals recorded at clinics, 271 (47%) attended their first follow-up visit. Safety events were reported in ten initiations and were all categorized as no harm to minimal harm. CONCLUSIONS: A standardized provincial approach to initiating buprenorphine/naloxone in the ED for patients living with opioid use disorder was spread to 107 sites with dedicated program support staff and adjustment to local contexts. Similar quality improvement approaches may benefit other jurisdictions.

ABSTRAIT: OBJECTIFS: Le trouble lié à la consommation d'opioïdes est une préoccupation majeure en santé publique qui explique le nombre élevé d'années potentielles de vie perdues. La buprénorphine/naloxone est un traitement recommandé pour le trouble lié à l'utilisation d'opioïdes qui peut être commencé au service des urgences (SU). Nous avons mis au point un programme axé sur les urgences pour commencer la buprénorphine/naloxone pour les patients éligibles qui vivent avec un trouble lié à l'utilisation d'opioïdes, et pour fournir suivis des cas référés le jour suivant vers une clinique de soins des troubles liés à l'utilisation d'opioïdes (sur place ou virtuelle) pour les soins continus aux patients partout en Alberta. MéTHODES: Dans le cadre de cette initiative d'amélioration de la qualité, nous avons aidé les équipes locales de SU à offrir la buprénorphine/naloxone aux patients admissibles qui se présentent à la SU avec un trouble présumé de consommation d'opioïdes et à les diriger vers des soins de suivi. Le processus, les résultats et les mesures d'équilibre ont été évalués au cours des deux premières années de l'initiative (du 15 mai 2018 au 15 mai 2020). RéSULTATS: Le programme a été mis en œuvre dans 107 sites en Alberta pendant notre période d'évaluation. Les initiations à la buprénorphine/naloxone à l'urgence ont augmenté après l'intervention dans la plus grande partie de sites pour lesquels des données de référence étaient disponibles (11 sur 13), et la plupart des patients (67 %) ont continué de remplir une ordonnance d'agonistes opioïdes 180 jours après la visite à l'urgence. Sur les 572 renvois enregistrés aux cliniques, 271 (47 %) ont assisté à leur première visite de suivi. Des événements liés à la sécurité ont été signalés dans 10 initiatives et ont tous été classés comme n'ayant causé aucun conséquences à des conséquences minimes. CONCLUSIONS: Une approche provinciale standardisé de lancement de la buprénorphine/naloxone à l'urgence pour les patients atteints d'un trouble lié à la consommation d'opioïdes a été diffusée à 107 sites à l'aide de soutien aux programmes spécialisé et des ajustements aux contextes locaux. Des approches semblables d'amélioration de la qualité pourraient profiter à d'autres juridictions.

Alberta Collaborative Quality Improvement Strategies to Improve Outcomes of Moderate and Late Preterm Infants (ABC-QI) Trial: a protocol for a multicentre, stepped-wedge cluster randomized trial.

BACKGROUND: Evidence-based Practice for Improving Quality (EPIQ) is a collaborative quality improvement method adopted by the Canadian Neonatal Network that led to decreased mortality and morbidity in very preterm neonates. The Alberta Collaborative Quality Improvement Strategies to Improve Outcomes of Moderate and Late Preterm Infants (ABC-QI) Trial aims to evaluate the impact of EPIQ collaborative quality improvement strategies in moderate and late preterm neonates in Alberta, Canada. METHODS: In a 4-year, multicentre, stepped-wedge cluster randomized trial involving 12 neonatal intensive care units (NICUs), we will collect baseline data with the current practices in the first year (all NICUs in the control arm). Four NICUs will transition to the intervention arm at the end of each year, with 1 year of follow-up after the last group transitions to the intervention arm. Neonates born at 32 + 0 to 36 + 6 weeks' gestation with primary admission to NICUs or postpartum units will be included. The intervention includes implementation of respiratory and nutritional care bundles using EPIQ strategies, including quality improvement team building, quality improvement education, bundle implementation, quality improvement mentoring and collaborative networking. The primary outcome is length of hospital stay; secondary outcomes include health care costs and short-term clinical outcomes. Neonatal intensive care unit staff will complete a survey in the first year to assess quality improvement culture in each unit, and a sample will be interviewed 1 year after implementation in each unit to evaluate the implementation process. INTERPRETATION: The ABC-QI Trial will assess whether collaborative quality improvement strategies affect length of stay in moderate and late preterm neonates. It will provide detailed population-based data to support future research, benchmarking and quality improvement. TRIAL REGISTRATION: ClinicalTrials.gov, no. NCT05231200.

The unrestricted global effort to complete the COOL trial.

BACKGROUND: Severe complicated intra-abdominal sepsis (SCIAS) has an increasing incidence with mortality rates over 80% in some settings. Mortality typically results from disruption of the gastrointestinal tract, progressive and self-perpetuating bio-mediator generation, systemic inflammation, and multiple organ failure. A further therapeutic option may be open abdomen (OA) management with negative peritoneal pressure therapy (NPPT) to remove inflammatory ascites and attenuate the systemic damage from SCIAS, although there are definite risks of leaving the abdomen open whenever it might possibly be closed. This potential therapeutic paradigm is the rationale being assessed in the Closed Or Open after Laparotomy (COOL trial) ( https://clinicaltrials.gov/ct2/show/NCT03163095 ). Initially, the COOL trial received Industry sponsorship; however, this funding mandated the use of a specific trademarked and expensive NPPT device in half of the patients allocated to the intervention (open) arm. In August 2022, the 3 M/Acelity Corporation without consultation but within the terms of the contract canceled the financial support of the trial. Although creating financial difficulty, there is now no restriction on specific NPPT devices and removing a cost-prohibitive intervention creates an opportunity to expand the COOL trial to a truly global basis. This document describes the evolution of the COOL trial, with a focus on future opportunities for global growth of the study. METHODS: The COOL trial is the largest prospective randomized controlled trial examining the random allocation of SCIAS patients intra-operatively to either formal closure of the fascia or the use of the OA with an application of an NPPT dressing. Patients are eligible if they have free uncontained intraperitoneal contamination and physiologic derangements exemplified by septic shock OR severely adverse predicted clinical outcomes. The primary outcome is intended to definitively inform global practice by conclusively evaluating 90-day survival. Initial recruitment has been lower than hoped but satisfactory, and the COOL steering committee and trial investigators intend with increased global support to continue enrollment until recruitment ensures a definitive answer. DISCUSSION: OA is mandated in many cases of SCIAS such as the risk of abdominal compartment syndrome associated with closure, or a planned second look as for example part of "damage control"; however, improved source control (locally and systemically) is the most uncertain indication for an OA. The COOL trial seeks to expand potential sites and proceed with the evaluation of NPPT agnostic to device, to properly examine the hypothesis that this treatment attenuates systemic damage and improves survival. This approach will not affect internal validity and should improve the external validity of any observed results of the intervention. TRIAL REGISTRATION: National Institutes of Health ( https://clinicaltrials.gov/ct2/show/NCT03163095 ).

Patient appropriateness for total knee arthroplasty and predicted probability of a good outcome.

OBJECTIVES: One-fifth of total knee arthroplasty (TKA) recipients experience a suboptimal outcome. Incorporation of patients' preferences in TKA assessment may improve outcomes. We determined the discriminant ability of preoperative measures of TKA need, readiness/willingness and expectations for a good TKA outcome. METHODS: In patients with knee osteoarthritis (OA) undergoing primary TKA, we preoperatively assessed TKA need (Western Ontario-McMaster Universities OA Index (WOMAC) Pain Score and Knee injury and Osteoarthritis Outcome Score (KOOS) function, arthritis coping), health status, readiness (Patient Acceptable Symptom State, depressive symptoms), willingness (definitely yes-yes/no) and expectations (outcomes deemed 'very important'). A good outcome was defined as symptom improvement (met Outcome Measures in Rheumatology and Osteoarthritis Research Society International (OMERACT-OARSI) responder criteria) and satisfaction with results 1 year post TKA. Using logistic regression, we assessed independent outcome predictors, model discrimination (area under the receiver operating characteristic curve, AUC) and the predicted probability of a good outcome for different need, readiness/willingness and expectations scenarios. RESULTS: Of 1,053 TKA recipients (mean age 66.9 years (SD 8.8); 58.6% women), 78.1% achieved a good outcome. With TKA need alone (WOMAC pain subscale, KOOS physical function short-form), model discrimination was good (AUC 0.67, 95% CI 0.63 to 0.71). Inclusion of readiness/willingness, depressive symptoms and expectations regarding kneeling, stair climbing, well-being and performing recreational activities improved discrimination (p=0.01; optimism corrected AUC 0.70, 0.66-0.74). The predicted probability of a good outcome ranged from 44.4% (33.9-55.5) to 92.4% (88.4-95.1) depending on level of TKA need, readiness/willingness, depressive symptoms and surgical expectations. CONCLUSIONS: Although external validation is required, our findings suggest that incorporation of patients' TKA readiness, willingness and expectations in TKA decision-making may improve the proportion of recipients that experience a good outcome.

Self-Management Support Using Advertising Principles for Older Adults With Low Income at High Cardiovascular Risk: A Randomized Controlled Trial.

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.

Eliminating Medication Copayments for Low-Income Older Adults at High Cardiovascular Risk: A Randomized Controlled Trial.

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.

Investigating Associations Between Access to Rheumatology Care, Treatment, Continuous Care, and Healthcare Utilization and Costs Among Older Individuals With Rheumatoid Arthritis.

OBJECTIVE: To examine the association between rheumatologist access, early treatment, and ongoing care of older-onset rheumatoid arthritis (RA) and healthcare utilization and costs following diagnosis. METHODS: We analyzed data from a population-based inception cohort of individuals aged > 65 years with RA in Ontario, Canada, diagnosed between 2002 and 2014 with follow-up to 2019. We assessed 4 performance measures in the first 4 years following diagnosis, including access to rheumatology care, yearly follow-up, timely treatment, and ongoing treatment with a disease-modifying antirheumatic drug. We examined annual healthcare utilization, mean direct healthcare costs, and whether the performance measures were associated with costs in year 5. RESULTS: A total of 13,293 individuals met inclusion criteria. The mean age was 73.7 (SD 5.7) years and 68% were female. Total mean direct healthcare cost per individual increased annually and was CAD $13,929 in year 5. All 4 performance measures were met for 35% of individuals. In multivariable analyses, costs for not meeting access to rheumatology care and timely treatment performance measures were 20% (95% CI 8-32) and 6% (95% CI 1-12) higher, respectively, than where those measures were met. The main driver of cost savings among individuals meeting all 4 performance measures were from lower complex continuing care, home care, and long-term care costs, as well as fewer hospitalizations and emergency visits. CONCLUSION: Access to rheumatologists for RA diagnosis, timely treatment, and ongoing care are associated with lower total healthcare costs at 5 years. Investments in improving access to care may be associated with long-term health system savings.

Barriers to Care for Poststroke Visual Deficits in Alberta, Canada.

Poststroke visual impairment (VI) negatively affects rehabilitation potential and quality of life for stroke survivors. In this cross-sectional observational study, stroke survivors and providers were surveyed to quantify perspectives regarding care for poststroke VI in Alberta, Canada (n = 46 survivors; n = 87 providers). Few patients (35%) felt prepared to cope with VI at the time of discharge from acute stroke and inpatient rehabilitation settings. Less than 25% of stroke survivors, and <16% of providers, felt referral processes were adequate. 95.2% of providers and 82% of stroke survivors advocated for a provincial clinical pathway to improve care quality for poststroke VI.

Impact of lifetime lactation on the risk and duration of frequent vasomotor symptoms: A longitudinal dose-response analysis.

OBJECTIVE: To examine the association between lifetime lactation and risk and duration of frequent vasomotor symptoms (VMS). DESIGN: Prospective cohort. SETTING: USA, 1995-2008. SAMPLE: 2356 parous midlife women in the Study of Women's Health Across the Nation. METHODS: Lifetime lactation was defined as the duration of breastfeeding across all births in months. We used generalised estimating equations to analyse risk of frequent VMS and Cox regression to analyse duration of frequent VMS in years. MAIN OUTCOME MEASURES: Frequent VMS (hot flashes and night sweats) were measured annually for 10 years, defined as occurring ≥6 days in the past 2 weeks. RESULTS: Overall, 57.1% of women reported hot flashes and 43.0% reported night sweats during follow-up. Lifetime lactation was inversely associated with hot flashes plateauing at 12 months of breastfeeding (6 months: adjusted odds ratio [AOR] 0.85, 95% confidence interval (CI) 0.75-0.96; 12 months: AOR 0.78, 95% CI 0.65-0.93) and was inversely associated with night sweats in a downward linear fashion (6 months: AOR 0.93, 95% CI 0.81-1.08; 18 months: AOR 0.82, 95% CI 0.67-1.02; 30 months: AOR 0.73, 95% CI 0.56-0.97). Lifetime lactation was associated with shorter duration of hot flashes and night sweats in a quadratic (bell-shaped) fashion. The association was strongest at 12-18 months of breastfeeding and significant for hot flashes (6 months: adjusted hazard ratio [AHR] 1.35, 95% CI 1.11-1.65; 18 months: AHR 1.54, 95% CI 1.16-2.03; 30 months: AHR 1.18, 95% CI 0.83-1.68). CONCLUSIONS: Longer lifetime lactation is associated with decreased risk and duration of frequent VMS.