An Innovative Approach to Determine Programmed Intermittent Epidural Bolus Pump Settings for Labor Analgesia: A Randomized Controlled Trial.

BACKGROUND: Three settings are required on a programmed intermittent epidural bolus (PIEB) pump for labor analgesia: the PIEB next bolus (PIEBnb), PIEB interval (PIEBi), and PIEB volume (PIEBv). The ideal settings for these parameters are still unknown. We hypothesized a mathematical modeling tool, response surface methodology (RSM), could estimate 3 PIEB pump parameters while balancing 3 clinically important patient outcomes simultaneously. The study objective was to use RSM to estimate PIEB settings (PIEBnb, PIEBi, and PIEBv) while maximizing maternal satisfaction, minimizing the need for clinician-administered boluses, and optimizing the ratio of delivered/requested patient-controlled epidural analgesia (PCEA) boluses simultaneously. METHODS: With institutional ethics approval, a double-blind randomized trial was completed in a tertiary care labor and delivery center. Nulliparous, English-speaking American Society of Anesthesiologists (ASA) physical status II patients aged 18 to 45 years at full term, single gestation in vertex presentation, in spontaneous labor and ≤7 cm cervical dilation were included. Patients with comorbidities, contraindications to neuraxial analgesia, using chronic analgesics, <152 cm, or body mass index (BMI) >45 kg/m2 were excluded. After informed consent, labor analgesia was initiated using 10 mL ropivacaine 0.2% with 10 µg/mL fentanyl solution and PCEA (volume 6 mL every 10 minutes). Patients were randomized to predetermined PIEB settings. RSM identified 3 pump settings that represented a stationary point that best maximized or minimized 3 outcomes simultaneously: PCEA ratio (a ratio closest to 1), clinician bolus (optimal is 0), and maternal satisfaction (visual analog scale, 0-100, ideal response is ≥90). RESULTS: Of 287 potential participants, 192 did not meet inclusion criteria or declined to participate, and 26 were withdrawn, leaving 69 patients for study inclusion. Using RSM, the suggested PIEB settings for all the primary study outcomes were as follows: PIEBnb = 29.4 minutes, PIEBi = 59.8 minutes, and PIEBv = 6.2 mL. These PIEB settings corresponded to the following clinical outcomes: maternal satisfaction at 93.9%, PCEA ratio at 0.77, and need for clinician bolus at 0.29. The dermatome sensory score was between T10 and T5 in 89% of the patients. The median lowest Bromage score was 4. CONCLUSIONS: This novel study used a mathematical model to estimate PIEB pump settings while simultaneously maximizing 3 clinical outcomes. Equally weighted clinical outcomes prevent maximal outcome optimization and may not reflect patient priorities. Future studies or quality improvement endeavors could use RSM methodology to estimate PIEB pump settings targeting optimal values for a single clinical outcome of determined importance to parturients.

Novel inflammatory mediator profile observed during pediatric heart surgery with cardiopulmonary bypass and continuous ultrafiltration.

BACKGROUND: Cardiopulmonary bypass (CPB) is associated with systemic inflammation, featuring increased levels of circulating pro-inflammatory cytokines. Intra-operative ultrafiltration extracts fluid and inflammatory factors potentially dampening inflammation-related organ dysfunction and enhancing post-operative recovery. This study aimed to define the impact of continuous subzero-balance ultrafiltration (SBUF) on circulating levels of major inflammatory mediators. METHODS: Twenty pediatric patients undergoing cardiac surgery, CPB and SBUF were prospectively enrolled. Blood samples were collected prior to CPB initiation (Pre-CPB Plasma) and immediately before weaning off CPB (End-CPB Plasma). Ultrafiltrate effluent samples were also collected at the End-CPB time-point (End-CPB Effluent). The concentrations of thirty-nine inflammatory factors were assessed and sieving coefficients were calculated. RESULTS: A profound increase in inflammatory cytokines and activated complement products were noted in plasma following CBP. Twenty-two inflammatory mediators were detected in the ultrafiltrate effluent. Novel mediators removed by ultrafiltration included cytokines IL1-Ra, IL-2, IL-12, IL-17A, IL-33, TRAIL, GM-CSF, ET-1, and the chemokines CCL2, CCL3, CCL4, CXCL1, CXCL2 and CXCL10. Mediator extraction by SBUF was significantly associated with molecular mass < 66 kDa (Chi2 statistic = 18.8, Chi2 with Yates' correction = 16.0, p < 0.0001). There was a moderate negative linear correlation between molecular mass and sieving coefficient (Spearman R = - 0.45 and p = 0.02). Notably, the anti-inflammatory cytokine IL-10 was not efficiently extracted by SBUF. CONCLUSIONS: CPB is associated with a burden of circulating inflammatory mediators, and SBUF selectively extracts twenty of these pro-inflammatory factors while preserving the key anti-inflammatory regulator IL-10. Ultrafiltration could potentially function as an immunomodulatory therapy during pediatric cardiac surgery. Trial registration ClinicalTrials.gov, NCT05154864. Registered retrospectively on December 13, 2021. https://clinicaltrials.gov/ct2/show/record/NCT05154864 .

Validation of Ultrasound Dating Protocols Using Data From Twins Conceived Through In Vitro Fertilization in Nova Scotia: A Retrospective Cohort Study.

OBJECTIVES: Clinical practice guidelines recommend determining gestational age (GA) for twin pregnancies using the fetal crown rump length (CRL) of the larger fetus. This study investigated whether the CRL of the larger or smaller fetus at 11-14 weeks best predicted in vitro fertilization (IVF) assigned GA. METHODS: A retrospective cohort study of twin pregnancies conceived by IVF ± intracytoplasmic sperm injection, 2004-2022, generated GA estimations for each co-twin CRL at the 11-14 week ultrasound, to determine which fetus (smaller or larger) more consistently predicted IVF-assigned GA. Monoamniotic twins and twins with known structural or vascular abnormalities were excluded. Paired t tests evaluated the ability of CRL to predict GA, and logistic regression evaluated the predictive ability of each of the co-twin groups with increasing size differences. Statistical significance was set at P < 0.05. RESULTS: Viewpoint 6 identified 359 eligible twin pairs. CRL was closest with the smaller fetus (0.38 days); CRL for both the smaller (95% CI 0.16-0.61) and the larger (2.25 days, 95% CI 2.04-2.46) fetus showed deviation from IVF-assigned GA. As the absolute difference between the small and large fetus increased, the ultrasound-estimated GA of the smaller fetus was still consistently closer to IVF-assigned GA. CONCLUSIONS: In this selected population of twins with known GA, the CRL of the smaller fetus more accurately predicted IVF-assigned GA even with increasing differences in fetal size. These findings provide important information for appropriately dating pregnancies to facilitate adherence to national guidelines to monitor for pregnancy complications, and plan frequency and type of fetal surveillance, as well as timing of delivery.

Needs and expectations for artificial intelligence in emergency medicine according to Canadian physicians.

BACKGROUND: Artificial Intelligence (AI) is recognized by emergency physicians (EPs) as an important technology that will affect clinical practice. Several AI-tools have already been developed to aid care delivery in emergency medicine (EM). However, many EM tools appear to have been developed without a cross-disciplinary needs assessment, making it difficult to understand their broader importance to general-practice. Clinician surveys about AI tools have been conducted within other medical specialties to help guide future design. This study aims to understand the needs of Canadian EPs for the apt use of AI-based tools. METHODS: A national cross-sectional, two-stage, mixed-method electronic survey of Canadian EPs was conducted from January-May 2022. The survey includes demographic and physician practice-pattern data, clinicians' current use and perceptions of AI, and individual rankings of which EM work-activities most benefit from AI. RESULTS: The primary outcome is a ranked list of high-priority AI-tools for EM that physicians want translated into general use within the next 10 years. When ranking specific AI examples, 'automated charting/report generation', 'clinical prediction rules' and 'monitoring vitals with early-warning detection' were the top items. When ranking by physician work-activities, 'AI-tools for documentation', 'AI-tools for computer use' and 'AI-tools for triaging patients' were the top items. For secondary outcomes, EPs indicated AI was 'likely' (43.1%) or 'extremely likely' (43.7%) to be able to complete the task of 'documentation' and indicated either 'a-great-deal' (32.8%) or 'quite-a-bit' (39.7%) of potential for AI in EM. Further, EPs were either 'strongly' (48.5%) or 'somewhat' (39.8%) interested in AI for EM. CONCLUSIONS: Physician input on the design of AI is essential to ensure the uptake of this technology. Translation of AI-tools to facilitate documentation is considered a high-priority, and respondents had high confidence that AI could facilitate this task. This study will guide future directions regarding the use of AI for EM and help direct efforts to address prevailing technology-translation barriers such as access to high-quality application-specific data and developing reporting guidelines for specific AI-applications. With a prioritized list of high-need AI applications, decision-makers can develop focused strategies to address these larger obstacles.

The Prevalence of Pregnancy-Specific Perinatal Anxiety in Nova Scotia.

OBJECTIVES: Pregnancy-Specific Perinatal Anxiety (PSPA) is an understudied mental health condition of pregnancy that may affect maternal-fetal health outcomes. The purpose of this study was to determine the prevalence of PSPA among pregnant women in the province of Nova Scotia, Canada, as well as the factors associated with it. METHODS: A sample of 90 pregnant women provided data on PSPA symptomology and demographic co-variables via a self-report online survey. The prevalence of PSPA in the sample was calculated and bivariate statistics and binomial logistic regression were conducted to assess the relationship between the presence of PSPA and the independent variables. RESULTS: The prevalence of PSPA in our sample was 17.8%. Smoking during pregnancy and a pre-pregnancy diagnosis of anxiety were significantly associated with meeting the criteria for PSPA (p = 0.008 and p = 0.013, respectively) and strongly predicted the presence of PSPA (odds ratio 8.54 and 3.44, respectively). CONCLUSIONS FOR PRACTICE: A significant proportion of participants in our sample experienced symptoms consistent with a diagnosis of PSPA. This underscores the importance of further research on PSPA as a unique phenomenon in pregnant women, and the impact it may have on fetal and maternal health outcomes. A greater clinical emphasis should be placed on screening for and treating mental health conditions of pregnancy, including PSPA.

Anxiety in pregnancy affects maternal, fetal, and child health outcomes. A distinction ­ in terms of definition and diagnostic criteria ­ exists between generalized anxiety disorder (GAD) affecting pregnant women and pregnancy-specific perinatal anxiety (PSPA). The latter is a condition that has been identified as affecting pregnant women uniquely and with distinct clinical impact, but few studies have made effort to distinguish it from GAD when studying its prevalence and impact on health. This study examines the prevalence of PSPA exclusively and the variables associated with it to provide insight on the importance of this distinct clinical phenomena.

Exploring the health care utilization of children and youth in the care of child welfare: a retrospective matched cohort study.

BACKGROUND: Children and youth whose lives intersect with child welfare systems are amongst the most vulnerable paediatric populations. Despite the increased rates of chronic conditions, these children and youth often experience unmet health care needs. OBJECTIVES: To examine patterns of health care utilization from birth for children and youth in the care of a child welfare authority. METHODS: This retrospective matched cohort design study examined children/youth aged 0-18 who had visited a paediatric tertiary care facility from 2016 April 1 to 2017 March 31 and had "social worker" documented as their guardian. A control cohort was matched based on age and sex. Primary outcomes of interest included primary health care, emergency, outpatient, and inpatient visits. Visits for immunizations, physiological development, well-baby checks, mental health, and oral health were also examined. RESULTS: A total of 200 cases and 200 controls were included in our cohort. No statistically significant differences were found between primary care visits, well-baby checks, inpatient admissions, outpatient mental health visits, or immunizations for children in care in comparison to their controls. There was a significant difference in oral health visits, lack of physiological development, and emergency department visits for children in care when compared to their controls. CONCLUSIONS: Our study revealed disparities in health care utilization amongst children in the care of child welfare in comparison to those who are not, highlighting the need for improved practice, policy, and research initiatives. A collaborative data collection/sharing system is needed to identify and track the health care of this vulnerable population.

Children and youth whose lives intersect with child welfare systems are amongst the most vulnerable pediatric populations. Despite the increased rates of chronic health conditions, these children and youth often experience unmet health care needs. Using a retrospective matched cohort design, we sought to examine patterns of health care utilization from birth to age 18 for children and youth in the care of a child welfare authority in comparison to children/youth who were not in the care of child welfare. No statistically significant differences were found between primary care visits, well-baby checks, inpatient admissions, outpatient mental health visits, or immunizations for children in care when compared to their counterparts not in care. There was a significantly higher number of oral health visits, physiological development concerns, and emergency department visits for children in care when compared to their controls. Our study revealed differences in health care use amongst children in the care of a child welfare in comparison to those who are not, highlighting the need for improved practice, policy and research initiatives. A collaborative data collection and sharing system is needed to help accurately identify and track the health care use of this vulnerable population.

Aspirin or Rivaroxaban for VTE Prophylaxis after Hip or Knee Arthroplasty.

BACKGROUND: Clinical trials and meta-analyses have suggested that aspirin may be effective for the prevention of venous thromboembolism (proximal deep-vein thrombosis or pulmonary embolism) after total hip or total knee arthroplasty, but comparisons with direct oral anticoagulants are lacking for prophylaxis beyond hospital discharge. METHODS: We performed a multicenter, double-blind, randomized, controlled trial involving patients who were undergoing total hip or knee arthroplasty. All the patients received once-daily oral rivaroxaban (10 mg) until postoperative day 5 and then were randomly assigned to continue rivaroxaban or switch to aspirin (81 mg daily) for an additional 9 days after total knee arthroplasty or for 30 days after total hip arthroplasty. Patients were followed for 90 days for symptomatic venous thromboembolism (the primary effectiveness outcome) and bleeding complications, including major or clinically relevant nonmajor bleeding (the primary safety outcome). RESULTS: A total of 3424 patients (1804 undergoing total hip arthroplasty and 1620 undergoing total knee arthroplasty) were enrolled in the trial. Venous thromboembolism occurred in 11 of 1707 patients (0.64%) in the aspirin group and in 12 of 1717 patients (0.70%) in the rivaroxaban group (difference, 0.06 percentage points; 95% confidence interval [CI], -0.55 to 0.66; P<0.001 for noninferiority and P=0.84 for superiority). Major bleeding complications occurred in 8 patients (0.47%) in the aspirin group and in 5 (0.29%) in the rivaroxaban group (difference, 0.18 percentage points; 95% CI, -0.65 to 0.29; P=0.42). Clinically important bleeding occurred in 22 patients (1.29%) in the aspirin group and in 17 (0.99%) in the rivaroxaban group (difference, 0.30 percentage points; 95% CI, -1.07 to 0.47; P=0.43). CONCLUSIONS: Among patients who received 5 days of rivaroxaban prophylaxis after total hip or total knee arthroplasty, extended prophylaxis with aspirin was not significantly different from rivaroxaban in the prevention of symptomatic venous thromboembolism. (Funded by the Canadian Institutes of Health Research; ClinicalTrials.gov number, NCT01720108 .).

Children's Sleep During COVID-19: How Sleep Influences Surviving and Thriving in Families.

OBJECTIVE: The COVID-19 pandemic has the potential to disrupt the lives of families and may have implications for children with existing sleep problems. As such, we aimed to: (1) characterize sleep changes during the COVID-19 pandemic in children who had previously been identified as having sleep problems, (2) identify factors contributing to sleep changes due to COVID-19 safety measures, and (3) understand parents' and children's needs to support sleep during the pandemic. METHODS: Eighty-five Canadian parents with children aged 4-14 years participated in this explanatory sequential, mixed-methods study using an online survey of children's and parents' sleep, with a subset of 16 parents, selected based on changes in their children's sleep, participating in semi-structured interviews. Families had previously participated in the Better Nights, Better Days (BNBD) randomized controlled trial. RESULTS: While some parents perceived their child's sleep quality improved during the COVID-19 pandemic (14.1%, n = 12), many parents perceived their child's sleep had worsened (40.0%, n = 34). Parents attributed children's worsened sleep to increased screen time, anxiety, and decreased exercise. Findings from semi-structured interviews highlighted the effect of disrupted routines on sleep and stress, and that stress reciprocally influenced children's and parents' sleep. CONCLUSIONS: The sleep of many Canadian children was affected by the first wave of the COVID-19 pandemic, with the disruption of routines influencing children's sleep. eHealth interventions, such as BNBD with modifications that address the COVID-19 context, could help families address these challenges.

Concordance of actigraphy with polysomnography in children with and without attention-deficit/hyperactivity disorder.

This study sought to: (1) compare actigraphy-derived estimated sleep variables to the same variables based on the gold-standard of sleep assessment, polysomnography; (2) examine whether the correlations between the measures differ between children with attention-deficit/hyperactivity disorder and typically developing children; and (3) determine whether these correlations are altered when children with attention-deficit/hyperactivity disorder are treated with medication. Participants (24 attention-deficit/hyperactivity disorder; 24 typically developing), aged 6-12 years, completed a 1-week baseline assessment of typical sleep and daytime functioning. Following the baseline week, participants in the attention-deficit/hyperactivity disorder group completed a 4-week blinded randomized control trial of methylphenidate hydrochloride, including a 2-week placebo and 2-week methylphenidate hydrochloride treatment period. At the end of each observation (typically developing: baseline; attention-deficit/hyperactivity disorder: baseline, placebo and methylphenidate hydrochloride treatment), all participants were invited to a sleep research laboratory, where overnight polysomnography and actigraphy were recorded concurrently. Findings from intra-class correlations and Bland-Altman plots were consistent. Actigraphy was found to provide good estimates (e.g. intra-class correlations >0.61) of polysomnography results for sleep duration for all groups and conditions, as well as for sleep-onset latency and sleep efficiency for the typically developing group and attention-deficit/hyperactivity disorder group while on medication, but not for the attention-deficit/hyperactivity disorder group during baseline or placebo. Based on the Bland-Altman plots, actigraphy tended to underestimate for sleep duration (8.6-18.5 min), sleep efficiency (5.6-9.3%) and sleep-onset latency, except for attention-deficit/hyperactivity disorder during placebo in which actigraphy overestimated (-2.1 to 6.3 min). The results of the current study highlight the importance of utilizing a multimodal approach to sleep assessment in children with attention-deficit/hyperactivity disorder.

What type of rural? Assessing the variations in life expectancy at birth at small area-level for a small population province using classes of locally defined settlement types.

BACKGROUND: Although efforts have been made to articulate rural-urban health inequalities in recent years, results have been inconsistent due to different geographical scales used in these studies. Small-area level investigations of health inequalities will likely show more detailed pictures of health inequalities among diverse rural communities, but they are difficult to conduct, particularly in a small population region. The objectives of this study were: 1) to compare life expectancy at birth for females and males across small-areas classified by locally defined settlement types for a small province in Canada; 2) to assess whether any of the settlement types explains variations in life expectancy over and above the extent of socioeconomic disadvantage and social isolation; and 3) to examine variations in life expectancies within a (larger) area unit used as the basis of health inequality investigations in previous studies. METHODS: Seven settlement types were determined for the 'community' units based on population per-kilometre-road density and settlement forms. Mean life expectancies at birth for both genders were compared by settlement type, both for the entire province and within the Halifax Regional Municipality--the province's only census designated metropolitan area, but also contains rural settlements. Linear regression analyses were conducted to assess the statistical associations between life expectancy and the settlement types, adjusting for indicators of community-level deprivation. RESULTS: While types of communities considered as 'rural' generally had lower life expectancy for both genders, the effects of living in any settlement type were attenuated once adjusted for socioeconomic deprivation and social isolation. An exception was the village and settlement cluster type, which had additionally negative effects on health for females. There were some variations observed within the Halifax Regional Municipality, suggesting the importance of further investigating a variety of health and disease outcomes at smaller area-levels than those employed in previous studies. CONCLUSIONS: This paper highlighted the importance of further articulating the differences in the characteristics of rural at finer area-levels and the differential influence they may have on health. Further efforts are desirable to overcome various data challenges in order to extend the investigation of health inequalities to hard-to-study provinces.

A randomized placebo-controlled trial of two doses of pregabalin for postoperative analgesia in patients undergoing abdominal hysterectomy.

PURPOSE: Acute pain after open abdominal hysterectomy limits the function of patients in the postoperative period, but data regarding the analgesic efficacy of a low dose of pregabalin (75 or 150 mg) have been conflicting. This study was performed to determine if a low dose of pregabalin could decrease postoperative opioid use following abdominal hysterectomy when compared with placebo. METHODS: American Society of Anesthesiologists I-II patients older than 18 yr and scheduled for open elective abdominal hysterectomy were recruited for participation and randomized to one of three groups: pregabalin 75 mg (P75), pregabalin 150 mg (P150), or placebo. The study drug was administered two hours prior to surgery and 12 hr following the initial dose. Anesthetic technique and postoperative analgesia were standardized. Postoperative pain was managed using patient-controlled analgesia with morphine. Pain at rest and movement as well as nausea were assessed with an 11-point numeric rating scale. RESULTS: One hundred and one patients were recruited, and 89 patients completed the study. Mean (SD) cumulative morphine consumption at 24 hr postoperatively was 54.0 (26.2) mg for the placebo group, 53.1 (22.7) mg for the P75 group, and 44.3 (20.9) mg for the P150 group. Independent Student's t tests indicated no difference between the placebo group and either the P75 group (95% confidence interval [CI]: -11.75 to 13.44; P = 0.8937) or the P150 group (95% CI: -2.74 to 22.15; P = 0.1238). CONCLUSIONS: At the doses used in this study, pregabalin treatment may not be effective in reducing opioid use up to 24 hr postoperatively following abdominal hysterectomy. This trial was registered at www.ClinicalTrials.gov : NCT00781131.

Aspirin versus low-molecular-weight heparin for extended venous thromboembolism prophylaxis after total hip arthroplasty: a randomized trial.

BACKGROUND: The role of aspirin in thromboprophylaxis after total hip arthroplasty (THA) is controversial. OBJECTIVE: To compare extended prophylaxis with aspirin and dalteparin for prevention of symptomatic venous thromboembolism (VTE) after THA. DESIGN: Multicenter randomized, controlled trial with a noninferiority design based on a minimal clinically important difference of 2.0%. Randomization was electronically generated; patients were assigned to a treatment group through a Web-based program. Patients, physicians, study coordinators, health care team members, outcome adjudicators, and data analysts were blinded to interventions. (Current Controlled Trials: ISRCTN11902170). SETTING: 12 tertiary care orthopedic referral centers in Canada. PATIENTS: 778 patients who had elective unilateral THA between 2007 and 2010. INTERVENTION: After an initial 10 days of dalteparin prophylaxis after elective THA, patients were randomly assigned to 28 days of dalteparin (n = 400) or aspirin (n = 386). MEASUREMENTS: Symptomatic VTE confirmed by objective testing (primary efficacy outcome) and bleeding. RESULTS: Five of 398 patients (1.3%) randomly assigned to dalteparin and 1 of 380 (0.3%) randomly assigned to aspirin had VTE (absolute difference, 1.0 percentage point [95% CI, -0.5 to 2.5 percentage points]). Aspirin was noninferior (P < 0.001) but not superior (P = 0.22) to dalteparin. Clinically significant bleeding occurred in 5 patients (1.3%) receiving dalteparin and 2 (0.5%) receiving aspirin. The absolute between-group difference in a composite of all VTE and clinically significant bleeding events was 1.7 percentage points (CI, -0.3 to 3.8 percentage points; P = 0.091) in favor of aspirin. LIMITATION: The study was halted prematurely because of difficulty with patient recruitment. CONCLUSION: Extended prophylaxis for 28 days with aspirin was noninferior to and as safe as dalteparin for the prevention of VTE after THA in patients who initially received dalteparin for 10 days. Given its low cost and greater convenience, aspirin may be considered a reasonable alternative for extended thromboprophylaxis after THA. PRIMARY FUNDING SOURCE: Canadian Institutes of Health Research.

An eHealth Program for Insomnia in Children With Neurodevelopmental Disorders (Better Nights, Better Days): Protocol for an Economic Evaluation of a Randomized Controlled Trial.

BACKGROUND: Children with neurodevelopmental disorders have a high risk of sleep disturbances, with insomnia being the most common sleep disorder (ie, chronic and frequent difficulties with going and staying asleep). Insomnia adversely affects the well-being of these children and their caregivers. Pediatric sleep experts recommend behavioral interventions as the first-line treatment option for children. Better Nights, Better Days for Children with Neurodevelopmental Disorders (BNBD-NDD) is a 5-session eHealth behavioral intervention delivered to parents to improve outcomes (eg, Pediatric Quality of Life Inventory [PedsQL]) for their children (ages 4-12 years) with insomnia and who have a diagnosis of mild to moderate attention-deficit/hyperactivity disorder, autism spectrum disorder, cerebral palsy, or fetal alcohol spectrum disorder. If cost-effective, BNBD-NDD can be a scalable intervention that provides value to an underserved population. OBJECTIVE: This protocol outlines an economic evaluation conducted alongside the BNBD-NDD randomized controlled trial (RCT) that aims to assess its costs, efficacy, and cost-effectiveness compared to usual care. METHODS: The BNBD-NDD RCT evaluates the impacts of the intervention on children's sleep and quality of life, as well as parents' daytime functioning and psychosocial health. Parent participants were randomized to the BNBD-NDD treatment or to usual care. The economic evaluation assesses outcomes at baseline and 8 months later, which include the PedsQL as the primary measure. Quality of life outcomes facilitate the comparison of competing interventions across different populations and medical conditions. Cost items include the BNBD-NDD intervention and parent-reported usage of private and publicly funded resources for their children's insomnia. The economic evaluation involves a reference case cost-effectiveness analysis to examine the incremental cost of BNBD-NDD per units gained in the PedsQL from the family payer perspective and a cost-consequence analysis from a societal perspective. These analyses will be conducted over an 8-month time horizon. RESULTS: Research funding was obtained from the Kids Brain Health Network in 2015. Ethics were approved by the IWK Health Research Ethics Board and the University of Calgary Conjoint Health Research Ethics Board in January 2019 and June 2022, respectively. The BNBD-NDD RCT data collection commenced in June 2019 and ended in April 2022. The RCT data are currently being analyzed, and data relevant to the economic analysis will be analyzed concurrently. CONCLUSIONS: To our knowledge, this will be the first economic evaluation of an eHealth intervention for insomnia in children with neurodevelopmental disorders. This evaluation's findings can inform users and stakeholders regarding the costs and benefits of BNBD-NDD. TRIAL REGISTRATION: ClinicalTrial.gov NCT02694003; https://clinicaltrials.gov/study/NCT02694003. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/46735.

Relationship Between Time-Varying Achieved High-Density Lipoprotein Cholesterol and Risk of Coronary Events Depends on Haptoglobin Phenotype Within the ACCORD Lipid Study.

Background The Hp (haptoglobin)2-2 phenotype (~40% of people) is associated with dysfunctional high-density lipoprotein (HDL) that is heavily oxidized in hyperglycemia, which may explain why raising HDL-cholesterol (HDL-C) does not reliably prevent coronary artery disease (CAD) in diabetes. Methods and Results In this observational study using longitudinal data from the ACCORD (Action to Control Cardiovascular Risk in Diabetes) lipid trial, time-varying (achieved) HDL-C updated at 4, 8, and 12 months, and annually thereafter over a mean of 4.7 years, was analyzed in relation to risk of CAD and secondary outcomes using Cox proportional hazards regression with time-varying covariables among participants with (n=1781) and without (n=3191) the Hp2-2 phenotype. HDL-C did not differ between the phenotypes throughout the study. Having low HDL-C (<40 mg/dL for male participants and <50 mg/dL for female participants) was associated with a greater risk of CAD compared with non-low HDL-C among participants with the non-Hp2-2 phenotype (hazard ratio [HR], 1.48 [95% CI, 1.18-1.87]) but not among the Hp2-2 phenotype (HR, 0.97 [95% CI, 0.70-1.35]; P interaction=0.03). Similarly, an inverse relationship was observed between HDL-C quintiles and CAD risk among participants without the Hp2-2 phenotype, whereas no significant inverse relationship was observed among participants with the Hp2-2 phenotype (P interaction=0.38). Among the Hp2-2 phenotype group, having low HDL-C was associated with higher risk of CVD mortality (HR, 2.09 [95% CI, 1.05-4.13]), and compared with the lowest HDL-C quintile, higher quintiles were associated with lower risk of CVD mortality and congestive heart failure. Conclusions Hp phenotype modified the association between HDL-C and risk of CAD in the ACCORD lipid study, suggesting that HDL dysfunction in the Hp2-2 phenotype may hinder CAD-protective properties of HDL-C.

Environmental Correlates of Physical Activity, Sedentary Behavior, and Self-Rated Health in Chronic Obstructive Pulmonary Disease.

PURPOSE: Physical activity (PA) predicts important health outcomes in chronic obstructive pulmonary disease (COPD). In the general population, environmental factors have the potential to influence PA; however, data are limited in this clinical population. Therefore, we sought to investigate associations between the environment and PA, sedentary behavior, and self-rated health in COPD. METHODS: Sociodemographic, PA, sedentary behavior, and self-rated health data were collected from a prospective cohort of 418 individuals with COPD (65% female; 58 ± 8 yr), while environmental data were drawn from a national environmental data repository and individually matched to participant postal code. Environmental variables included social and material deprivation, urban form index, surrounding greenness, and air quality (concentrations of air pollution for fine particles, nitrogen dioxide, ozone, and sulphur dioxide). Logistic and multivariate linear regression models were used to investigate the strongest environmental predictors. RESULTS: The models showed a statistically significant negative correlation between PA level and ozone pollution (P = .023; adjusted OR = 0.85: 95% CI, 0.74-0.98). Urban form index was also significantly associated with sedentary behavior (ß = 0.113; t value = 1.71; P = .011). Self-rated health was significantly positively correlated with PA level (P = .006; adjusted OR = 2.22: 95% CI, 1.25-3.94), and significantly inversely correlated with sedentary behavior (ß = -0.159; t value =-2.42; P = .016). CONCLUSION: These new data may identify barriers to PA and assist clinicians in the prescription of exercise for individuals living with COPD.

Haptoglobin Phenotype Modifies the Effect of Fenofibrate on Risk of Coronary Event: ACCORD Lipid Trial.

OBJECTIVE: The haptoglobin (Hp)2-2 phenotype (∼35-40% of people) is associated with increased oxidation and dysfunctional HDL in hyperglycemia and may explain why drugs designed to pharmacologically raise HDL cholesterol and lower triglycerides have not reliably prevented cardiovascular disease in diabetes. We aimed to determine whether the effect of adding fenofibrate versus placebo to simvastatin on the risk of coronary artery disease (CAD) events depends on Hp phenotype in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) lipid trial. RESEARCH DESIGN AND METHODS: Cox proportional hazards regression models quantified the relationship between fenofibrate therapy and CAD events in the ACCORD lipid trial in participants with the Hp2-2 phenotype (n = 1,795) separately from those without (n = 3,201). RESULTS: Fenofibrate therapy successfully lowered the risk of CAD events in participants without the Hp2-2 phenotype (multivariable adjusted hazard ratio 0.74 [95% CI 0.60-0.90] compared with no fenofibrate therapy) but not in participants with the Hp2-2 phenotype (1.16 [0.87-1.56]; P interaction = 0.009). Subgroup analyses revealed that this protective effect of fenofibrate against CAD events among the non-Hp2-2 phenotype group was pronounced in participants with severe dyslipidemia (P interaction = 0.01) and in males (P interaction = 0.02) with an increased CAD risk from fenofibrate treatment observed in females with the Hp2-2 phenotype (P interaction = 0.002). CONCLUSIONS: The effect of fenofibrate added to simvastatin on risk of CAD events depends on Hp phenotype in the ACCORD lipid trial.

Cardiovascular Outcomes in Nova Scotia During the Early Phase of the COVID-19 Pandemic.

BACKGROUND: This study sought to determine the impact of the COVID-19 pandemic response to healthcare delivery on outcomes in patients with cardiovascular disease. METHODS: This is a population-based cohort study performed in the province of Nova Scotia, Canada (population 979,499), between the pre-COVID (March 1, 2017-March 16, 2020) and in-COVID (March 17, 2020-December 31, 2020) periods. Adult patients (age ≥ 18 years) with new-onset or existing cardiovascular disease were included for comparison between periods. The main outcome measures included the following: cardiovascular emergency department visits or hospitalizations, mortality, and out-of-hospital cardiac arrest. RESULTS: In the first month of the in-COVID period, emergency department visits (n = 51,750) for cardiac symptoms decreased by 20.8% (95% confidence interval [CI] 14.0%-27.0%, P < 0.001). Cardiovascular hospitalizations (n = 20,609) declined by 48.1% (95% CI 40.4% to 54.9%, P < 0.001). The in-hospital mortality rate increased in patients with cardiovascular admissions in secondary care institutions by 55.1% (95% CI 10.1%-118%, P = 0.013). A decline of 20.4%-44.0% occurred in cardiovascular surgical/interventional procedures. The number of out-of-hospital cardiac arrests (n = 5528) increased from a monthly mean of 115 ± 15 to 136 ± 14, beginning in May 2020. Mortality for ambulatory patients awaiting cardiac intervention (n = 14,083) increased from 0.16% (n = 12,501) to 2.49% (n = 361) in the in-COVID period (P < 0.0001). CONCLUSIONS: This study demonstrates increased cardiovascular morbidity and mortality during restrictions maintained during the COVID-19 period, in an area with a low burden of COVID-19. As the healthcare system recovers or enters subsequent waves of COVID-19, these findings should inform communication to the public regarding cardiovascular symptoms, and policy for delivery of cardiovascular care.

CONTEXTE: Cette étude visait à déterminer les répercussions de la réponse à la pandémie de COVID-19 sur la prestation des soins de santé et son incidence sur les résultats obtenus par les patients atteints d'une maladie cardiovasculaire. MÉTHODOLOGIE: Il s'agit d'une étude de cohorte représentative de la population réalisée dans la province de la Nouvelle-Écosse, au Canada (population de 979 499 habitants), entre la période précédant le début de la pandémie de COVID-19 (du 1er mars 2017 au 16 mars 2020) et la période de pandémie (du 17 mars 2020 au 31 décembre 2020). Des patients adultes (âge ≥ 18 ans) atteints d'une maladie cardiovasculaire préexistante ou d'apparition récente ont été inclus pour la comparaison entre les périodes. Les principaux paramètres d'évaluation comprenaient les visites ou hospitalisations dans un service d'urgences cardiovasculaires, la mortalité et l'arrêt cardiaque en milieu extrahospitalier. RÉSULTATS: Au cours du premier mois de la période de pandémie, les visites aux services des urgences (n = 51 750) pour des symptômes cardiaques ont diminué de 20,8 % (intervalle de confiance [IC] à 95 % : 14,0 % ­ 27,0 %, p < 0,001). Les hospitalisations en raison d'un événement cardiovasculaire (n = 20 609) ont décliné de 48,1 % (IC à 95 % : 40,4 % ­ 54,9 %, p < 0,001). Le taux de mortalité hospitalière parmi les patients admis dans des établissements de soins secondaires a augmenté de 55,1 % (IC à 95 % : 10,1 % ­ 118 %, p = 0,013). Une baisse de 20,4 à 44,0 % du nombre d'interventions chirurgicales ou interventionnelles visant à prendre en charge un événement cardiovasculaire a également été enregistrée. Le nombre d'arrêts cardiaques survenus en milieu extrahospitalier (n = 5 528) est passé d'une moyenne mensuelle de 115 ± 15 à 136 ± 14, à compter de mai 2020. La mortalité des patients ambulatoires en attente d'une intervention cardiaque (n = 14 083) a augmenté, passant de 0,16 % (n = 12 501) à 2,49 % (n = 361) pendant la période de pandémie (p < 0,0001). CONCLUSIONS: Cette étude révèle une augmentation de la morbidité et de la mortalité cardiovasculaires durant le maintien des restrictions liées à la COVID-19 dans une région où le fardeau associé à cette maladie est faible. À mesure que le système de santé se rétablit ou affronte les vagues subséquentes de COVID-19, ces résultats devraient éclairer les communications au public concernant les symptômes cardiovasculaires et orienter la politique de prestation de soins cardiovasculaires.

Prediction of Hospitalizations in Systemic Lupus Erythematosus Using the Systemic Lupus International Collaborating Clinics Frailty Index.

OBJECTIVE: The Systemic Lupus International Collaborating Clinics (SLICC) frailty index (FI) predicts mortality and damage accrual in systemic lupus erythematosus (SLE), but its association with hospitalizations has not been described. Our objective was to estimate the association of baseline SLICC-FI values with future hospitalizations in the SLICC inception cohort. METHODS: Baseline SLICC-FI scores were calculated. The number and duration of inpatient hospitalizations during follow-up were recorded. Negative binomial regression was used to estimate the association between baseline SLICC-FI values and the rate of hospitalizations per patient-year of follow-up. Linear regression was used to estimate the association of baseline SLICC-FI scores with the proportion of follow-up time spent in the hospital. Multivariable models were adjusted for relevant baseline characteristics. RESULTS: The 1,549 patients with SLE eligible for this analysis were mostly female (88.7%), with a mean ± SD age of 35.7 ± 13.3 years and a median disease duration of 1.2 years (interquartile range 0.9-1.5) at baseline. Mean ± SD baseline SLICC-FI was 0.17 ± 0.08. During mean ± SD follow-up of 7.2 ± 3.7 years, 614 patients (39.6%) experienced 1,570 hospitalizations. Higher baseline SLICC-FI values (per 0.05 increment) were associated with more frequent hospitalizations during follow-up, with an incidence rate ratio of 1.21 (95% confidence interval [95% CI] 1.13-1.30) after adjustment for baseline age, sex, glucocorticoid use, immunosuppressive use, ethnicity/location, SLE Disease Activity Index 2000 score, SLICC/American College of Rheumatology Damage Index score, and disease duration. Among patients with ≥1 hospitalization, higher baseline SLICC-FI values predicted a greater proportion of follow-up time spent hospitalized (relative rate 1.09 [95% CI 1.02-1.16]). CONCLUSION: The SLICC-FI predicts future hospitalizations among incident SLE patients, further supporting the SLICC-FI as a valid health measure in SLE.

The utilization of antidepressants and benzodiazepines among people with major depression in Canada.

OBJECTIVE: Although clinical guidelines recommend monotherapy with antidepressants (ADs) for major depression, polypharmacy with benzodiazepines (BDZs) remains an issue. Risks associated with such treatments include tolerance and dependence, among others. We assessed the prevalence and determinants of AD and BDZ utilization among Canadians who experienced a major depressive episode (MDE) in the previous 12 months, and determined the association of seeing a psychiatrist on the utilization of ADs and BDZs. METHOD: Data were drawn from the 2002 Canadian Community Health Survey: Health and Well-Being, a nationally representative sample of Canadians aged 15 years and older. Descriptive statistics quantified utilization, while logistic regression identified factors associated with utilization, such as sociodemographic characteristics or type of physician seen. Sampling weights and bootstrap variance estimations were used for all analysis. RESULTS: The overall prevalence of AD and BDZ utilization was 49.3% of respondents who experienced an MDE in the past 12 months and reported AD use. Key determinants of utilization were younger age and unemployment in the past week (OR 2.6; P < 0.001). Being seen by a psychiatrist increased utilization (OR 2.5; P < 0.001), possibly because psychiatrists were seeing patients with severe depression. CONCLUSION: A large proportion of people with past-year MDEs utilized ADs and BDZs. It is unclear how much of this is appropriate given that evidence-based clinical guidelines recommend monotherapy with ADs in the treatment of major depression.