Cost-Effectiveness of a Quality Improvement Initiative for the Clinical Management of Children with Newly Diagnosed Immune Thrombocytopenia.

OBJECTIVE: To assess the cost-effectiveness of an evidence-informed institutional protocol for physicians that encouraged management of children with newly diagnosed immune thrombocytopenia (ITP) with observation over active therapy, where appropriate. STUDY DESIGN: We conducted a probabilistic cost-effectiveness analysis from an institutional perspective using a decision tree with a 1 year time horizon. Patient-level data were retrospectively ascertained for children diagnosed in pre-protocol (2007-2009) and post-protocol (2013-2018) time periods. ITP resolution was defined as achieving a sustained platelet count of >100 × 103/µL at 9-12 months after diagnosis. Outpatient care and inpatient costs were obtained from the institution and provincial sources. Intervention costs accounted for quality improvement initiative preparation and staff physician training. Incremental costs, incremental effects, and CIs were calculated from 10 000 model iterations. RESULTS: Forty-eight patients were followed for 1 year in the pre-protocol period and 84 in the post-protocol period. After protocol implementation, an average cost savings per child managed of $2055 (95% CI: $656, $3890) Canadian Dollars was observed, as was a higher proportion of resolved ITP cases. The implementation strategy remained less costly and more effective in 99.7% of model iterations. CONCLUSIONS: Implementation of an evidence-informed institutional protocol to guide physicians toward increased uptake of observation over active therapy when managing children with newly diagnosed ITP resulted in significant cost savings on a per case basis, even after accounting for training-related costs. Though the long-term cost implications regarding the sustainability of the intervention are not yet known, it is anticipated that continued institutional savings could occur.

A Cost Analysis of Pulse Oximetry as a Determinant in the Decision to Admit Infants With Mild to Moderate Bronchiolitis.

OBJECTIVES: A previous randomized controlled trial showed that artificially elevating the pulse oximetry display resulted in fewer hospitalizations with no worse outcomes. This suggests that management decisions based mainly on pulse oximetry may unnecessarily increase health care costs. This study assessed the incremental cost of altered relative to true oximetry in infants with mild to moderate bronchiolitis. METHODS: A cost analysis was undertaken from the health care system and societal perspectives using patient-level data from the randomized controlled trial, with a 5-day time horizon after emergency department visit. Infants aged 4 weeks to 12 months with mild to moderate bronchiolitis were randomized to pulse oximetry measurements with true or altered saturation values displayed by artificially increasing saturation 3% points above true values. Direct and indirect health care costs were measured. Sensitivity analyses were performed to assess parameter uncertainty. RESULTS: From the health care system perspective, the average cost per patient was Can $1155 for altered oximetry and $1967 for true oximetry, with a net savings of $812. From a societal perspective, the average cost per patient was $1559 for altered oximetry and $2473 for true oximetry, with a net savings of $914. Probabilistic analyses demonstrated that altered oximetry remained the less costly study group, with an average savings of $810 (95% confidence interval, $748-$872) from the health care system perspective and $910 (95% confidence interval, $848-$973) from the societal system perspective. CONCLUSIONS: Reliance on oximetry as a major determinant in the decision to hospitalize infants with mild to moderate bronchiolitis is associated with significantly greater costs.

Recruitment of adolescents with suicidal ideation in the emergency department: lessons from a randomized controlled pilot trial of a youth suicide prevention intervention.

BACKGROUND: Emergency Departments (EDs) are a first point-of-contact for many youth with mental health and suicidality concerns and can serve as an effective recruitment source for randomized controlled trials (RCTs) of mental health interventions. However, recruitment in acute care settings is impeded by several challenges. This pilot RCT of a youth suicide prevention intervention recruited adolescents aged 12 to 17 years presenting to a pediatric hospital ED with suicide related behaviors. METHODS: Recruitment barriers were identified during the initial study recruitment period and included: the time of day of ED presentations, challenges inherent to study presentation, engagement and participation during an acute presentation, challenges approaching and enrolling acutely suicidal patients and families, ED environmental factors, and youth and parental concerns regarding the study. We calculated the average recruitment productivity for published trials of adolescent suicide prevention strategies which included the ED as a recruitment site in order to compare our recruitment productivity. RESULTS: In response to identified barriers, an enhanced ED-centered recruitment strategy was developed to address low recruitment rate, specifically (i) engaging a wider network of ED and outpatient psychiatry staff (ii) dissemination of study pamphlets across multiple areas of the ED and relevant outpatient clinics. Following implementation of the enhanced recruitment strategy, the pre-post recruitment productivity, a ratio of patients screened to patients randomized, was computed. A total of 120 patients were approached for participation, 89 (74.2%) were screened and 45 (37.5%) were consented for the study from March 2018 to April 2019. The screening to randomization ratio for the study period prior to the introduction of the enhanced recruitment strategies was 3:1, which decreased to 1.8:1 following the implementation of enhanced recruitment strategies. The ratio for the total recruitment period was 2.1:1. This was lower than the average ratio of 3.2:1 for published trials. CONCLUSIONS: EDs are feasible sites for participant recruitment in RCTs examining new interventions for acute mental health problems, including suicidality. Engaging multi-disciplinary ED staff to support recruitment for such studies, proactively addressing anticipated concerns, and creating a robust recruitment pathway that includes approach at outpatient appointments can optimize recruitment. TRIAL REGISTRATION: ClinicalTrials.gov : NCT03488602 , retrospectively registered April 4, 2018.

A suicide prevention strategy for youth presenting to the emergency department with suicide related behaviour: protocol for a randomized controlled trial.

BACKGROUND: Suicide is a leading cause of death among adolescents in North America. Youth who present to the Emergency Department (ED) with acute suicidality are at increased risk for eventual death by suicide, thereby presenting an opportunity for secondary prevention of suicide. The current study evaluates the effectiveness of a standardized individual and family-based suicidal behaviour risk reduction intervention targeting adolescents at high-risk for suicide. METHODS: A randomized controlled trial (RCT) will be conducted to evaluate the effectiveness of a manualized youth- and family- based suicide prevention strategy (SPS) as compared with case navigation (NAV) among adolescents aged 12 to 18 years of age who present to the ED with acute suicidal ideation (SI) or suicide risk behaviours (SRB). We will recruit 128 participants and compare psychiatric symptoms including SI/SRB, family communication, and functional impairment at baseline and follow-ups (post-intervention [6 weeks], 24 weeks). The primary outcome is change in suicidal ideation measured with the Suicide Ideation Questionnaire- Junior. SRBs are measured with the Suicide Behaviour Questionnaire. Secondary outcomes are change in depressive and anxious symptoms measured with semi-structured psychiatric interview and Screen for Child Anxiety Related Disorders; acute mental health crises measured by urgent medical (including ED) visits; family communication measured with Conflict Behaviour Questionnaire, functional impairment measured by Columbia Impairment Scale; cost effectiveness, and fidelity of implementation measured by audio recording and fidelity checklist. DISCUSSION: Results of this study will inform a larger multi-centre RCT that will include both community and academic hospitals in urban and rural settings. Study results will be shared at international psychiatry and emergency medicine meetings, in local rounds, and via publication in academic journals and clinician-oriented newsletters. If effective, the intervention may provide a brief, scalable, and transportable treatment program that may be implemented in a variety of settings, including those in which access to children's mental health care services is challenging. TRIAL REGISTRATION: ClinicalTrials.gov: NCT03488602, retrospectively registered April 4, 2018.

Quetiapine Excretion Into Human Breast Milk.

BACKGROUND: Risk assessment of the use of quetiapine during breastfeeding is challenging owing to a paucity of data. METHODS: A pharmacokinetic study was conducted in lactating women who were taking quetiapine. The primary endpoint was to determine quetiapine concentration profiles in milk and estimated infant exposure levels. Multiple milk and a single blood quetiapine concentrations were determined using a highly sensitive liquid chromatography with tandem mass spectroscopy method. RESULTS: Nine subjects receiving fast-release quetiapine (mean dose, 41 mg/d) were analyzed at steady state. The mean milk/plasma drug concentration ratio at 2-hour postdose was 0.47 (SD, 0.50; range, 0.13-1.67). The mean milk concentration of each patient was 5.7 ng/mL (SD, 4.5; range, 1.4-13.9 ng/mL). The mean infant quetiapine dose via milk per body weight relative to weight-adjusted maternal dose was 0.16 % (SD, 0.08; range, 0.04%-0.35%). CONCLUSIONS: Infant exposure levels to quetiapine via milk are predicted to be very small.

Patterns and factors associated with low adherence to psychotropic medications during pregnancy--a cross-sectional, multinational web-based study.

BACKGROUND: No previous studies have explored how closely women follow their psychotropic drug regimens during pregnancy. This study aimed to explore patterns of and factors associated with low adherence to psychotropic medication during pregnancy. METHODS: Multinational web-based study was performed in 18 countries in Europe, North America, and Australia. Uniform data collection was ensured via an electronic questionnaire. Pregnant women were eligible to participate. Adherence was measured via the 8-item Morisky Medication Adherence Scale (MMAS-8). The Beliefs about Prescribed Medicines Questionnaire (BMQ-specific), the Edinburgh Postnatal Depression Scale (EPDS), and a numeric rating scale were utilized to measure women's beliefs, depressive symptoms, and antidepressant risk perception, respectively. Participants reporting use of psychotropic medication during pregnancy (n = 160) were included in the analysis. RESULTS: On the basis of the MMAS-8, 78 of 160 women (48.8%, 95% CI: 41.1-56.4%) demonstrated low adherence during pregnancy. The rates of low adherence were 51.3% for medication for anxiety, 47.2% for depression, and 42.9% for other psychiatric disorders. Smoking during pregnancy, elevated antidepressant risk perception (risk≥6), and depressive symptoms were associated with a significant 3.9-, 2.3-, and 2.5-fold increased likelihood of low medication adherence, respectively. Women on psychotropic polytherapy were less likely to demonstrate low adherence. The belief that the benefit of pharmacotherapy outweighed the risks positively correlated (r = .282) with higher medication adherence. CONCLUSIONS: Approximately one of two pregnant women using psychotropic medication demonstrated low adherence in pregnancy. Life-style factors, risk perception, depressive symptoms, and individual beliefs are important factors related to adherence to psychotropic medication in pregnancy.

Exposure to nitrofurantoin during early pregnancy and congenital malformations: a systematic review and meta-analysis.

OBJECTIVE: Because of an increased resistance of urinary pathogens to penicillin derivatives, nitrofurantoin is commonly used as an alternative in treating urinary tract infection because a wide range of both Gram negative and positive organisms are sensitive to it. The safety of the fetus after exposure to nitrofurantoin remains controversial. METHODS: We conducted a systematic review and meta-analysis to evaluate the fetal safety of nitrofurantoin. We searched Medline, EMBASE, references from published reports, and meeting abstracts for relevant studies. Articles were included in the review if they were human studies, reported pregnancy outcomes, reported the use of nitrofurantoin in the first trimester of pregnancy, and included a comparator group of unexposed pregnancies. The primary outcome was the rate of major malformations; secondary outcomes were rates of craniosynostosis, cleft lip or palate defects, cardiovascular defects, and hypoplastic left heart syndrome. RESULTS: Eight studies reporting on 91 115 exposed cases and 1 578 745 unexposed controls were included in the primary meta-analysis examining the risk of major malformation. Five cohort studies reported on 9275 exposed and 1 491 933 unexposed infants, resulting in an overall RR of 1.01 (95% CI 0.81 to 1.26); however, three case-control studies with a total of 39 268 cases of major malformations and 129 394 controls gave an overall OR of 1.22 (95% CI 1.02 to 1.45). No increased risk for cardiovascular malformations, oral cleft, or craniosynostosis was identified. For assessing risk of hypoplastic left heart syndrome, only three articles were eligible; these demonstrated an OR of 3.07 (95% CI 1.59 to 5.93). CONCLUSION: While no association was found between fetal exposure to nitrofurantoin and major malformation in cohort studies, there was a slight but significant teratogenic risk in case-control studies, which are more sensitive to adverse effects.

Objectif : Compte tenu de la résistance accrue des pathogènes urinaires aux dérivés de la pénicilline, la nitrofurantoïne est couramment utilisée à titre de solution de rechange pour la prise en charge de l'infection des voies urinaires, et ce, en raison de la vaste gamme des organismes tant Gram négatifs que Gram positifs qui y sont sensibles. L'innocuité de l'exposition du fœtus à la nitrofurantoïne demeure controversée. Méthodes : Nous avons mené une analyse systématique et une méta-analyse afin d'évaluer l'innocuité fœtale de la nitrofurantoïne. Nous avons mené des recherches dans Medline, EMBASE, les références de rapports publiés et des résumés de réunion en vue d'en tirer les études pertinentes. Les articles ont été inclus dans l'analyse s'il s'agissait d'études menées chez l'homme, s'ils faisaient état des issues de grossesse, s'ils traitaient de l'utilisation de nitrofurantoïne au cours du premier trimestre de grossesse et s'ils comprenaient un groupe témoin de grossesses non exposées. Le taux de malformations majeures constituait le critère d'évaluation principal; les taux de craniosynostose, de fente labiale ou palatine, d'anomalies cardiovasculaires et d'hypoplasie du cœur gauche constituaient les critères d'évaluation secondaires. Résultats : Huit études couvrant un total de 91 115 cas exposés et de 1 578 745 témoins non exposés ont été incluses dans la méta-analyse primaire examinant le risque de malformation majeure. Cinq études de cohorte se sont penchées sur 9 275 nouveau-nés exposés et sur 1 491 933 nouveau-nés non exposés, le tout donnant lieu à un RR global de 1,01 (IC à 95 %, 0,81 - 1,26); toutefois, trois études cas-témoins s'étant penchées sur un total de 39 268 cas de malformations majeures et de 129 394 cas témoins ont donné lieu à un RC global de 1,22 (IC à 95 %, 1,02 - 1,45). Aucune hausse du risque de malformations cardiovasculaires, de fente orale ou de craniosynostose n'a été identifiée. Pour ce qui est de l'évaluation du risque d'hypoplasie du cœur gauche, seuls trois articles étaient admissibles; ces articles ont donné lieu à un RC de 3,07 (IC à 95 %, 1,59 - 5,93). Conclusion : Bien qu'aucune association n'ait été constatée entre l'exposition du fœtus à la nitrofurantoïne et la manifestation de malformations majeures dans le cadre d'études de cohorte, un risque léger mais significatif de tératogénicité a été constaté dans le cadre d'études cas-témoins (lesquelles sont plus sensibles aux effets indésirables).

The fetal safety of fluoxetine: a systematic review and meta-analysis.

OBJECTIVE: Fluoxetine is the selective serotonin reuptake inhibitor (SSRI) with the longest clinical use. Published reports regarding its fetal safety are contradictory. We aimed to establish the fetal safety of the drug. METHODS: We performed a systematic review of the literature, searching PubMed, Medline, and Embase from inception to August 31, 2012, for cohort and case-control studies in which women were exposed to fluoxetine during the first trimester and compared outcomes with those of unexposed control subjects. RESULTS: Twenty-one studies met the inclusion criteria. The odds ratio for major malformations associated with maternal fluoxetine use in cohort studies was 1.12 (95% CI 0.98 to 1.28). The studies included were homogeneous. Fifteen cohort studies evaluated cardiac malformations and yielded an overall odds ratio of 1.6 (95% CI 1.31 to 1.95). These studies also were homogeneous. In contrast, two case-control studies assessing cardiac malformations yielded a combined odds ratio of 0.63 (95% CI 0.39 to 1.03). CONCLUSION: The apparent increased risk of fetal cardiac malformations associated with maternal use of fluoxetine has recently been shown also in depressed women who deferred SSRI therapy in pregnancy, and therefore most probably reflects an ascertainment bias. Overall, women who are treated with fluoxetine during the first trimester of pregnancy do not appear to have an increased risk of major fetal malformations.

Objectif : La fluoxétine est l'inhibiteur spécifique du recaptage de la sérotonine (ISRS) qui compte la plus longue période d'utilisation clinique. Les rapports publiés qui traitent de son innocuité fœtale sont contradictoires. Nous avons cherché à établir son innocuité fœtale. Méthodes : Nous avons mené une analyse systématique de la littérature en menant des recherches dans PubMed, Medline et Embase, des débuts jusqu'au 31 août 2012, afin d'en tirer les études de cohorte et les études cas-témoins dans le cadre desquelles des femmes ont été exposées à la fluoxétine au cours du premier trimestre; nous avons par la suite comparé les issues constatées chez ces femmes aux issues qu'ont connues les témoins non exposés. Résultats : Vingt et une études ont satisfait aux critères d'inclusion. Dans le cadre des études de cohorte, le rapport de cotes en ce qui concerne les malformations majeures qui sont associées à l'utilisation maternelle de fluoxétine était de 1,12 (IC à 95 %, 0,98 - 1,28). Les études incluses étaient homogènes. Quinze études de cohorte ont évalué les malformations cardiaques et ont généré un rapport de cotes global de 1,6 (IC à 95 %, 1,31 - 1,95). Ces études ont également été homogènes. En revanche, deux études cas-témoins évaluant les malformations cardiaques ont généré un rapport de cotes combiné de 0,63 (IC à 95 %, 0,39 - 1,03). Conclusion : La hausse apparente du risque de malformations cardiaques fœtales qui est associée à l'utilisation maternelle de fluoxétine a récemment été également démontrée chez les femmes déprimées qui ont suspendu leur traitement aux ISRS pendant la grossesse, ce qui reflète fort probablement la présence d'un biais de constatation. Règle générale, les femmes qui sont traitées à la fluoxétine au cours du premier trimestre de grossesse ne semblent pas être exposées à un risque accru de malformations fœtales majeures.

Randomized controlled trial evaluating a virtual parenting intervention for young children at risk of obesity: study protocol for Parenting Addressing Early Years Intervention with Coaching Visits in Toronto (PARENT) trial.

BACKGROUND: The prevalence of overweight (15%) and obesity (6%) in children under 5 years of age in Canada are high, and young children with overweight and obesity are at increased risk of the development of chronic disease(s) in adulthood. Prior research has demonstrated very few published trials on effective obesity prevention interventions in young children at risk of obesity, within primary healthcare settings. The aim of this study is to determine if 18-48-month-old children at risk for obesity, who are randomized to receive the Parents Together program (i.e., intervention group), have reduced body mass index z-score (zBMI), compared to those not receiving the intervention, at a 12-month follow-up. Secondary clinical outcomes between the intervention and control groups will be compared at 12 months. METHODS: A pragmatic, parallel group, 1:1, superiority, randomized control trial (RCT) through the TARGetKids! Practice Based Research Network will be conducted. Young children (ages 18-48 months) who are at increased risk for childhood obesity will be invited to participate. Parents who are enrolled in the intervention group will participate in eight weekly group sessions and 4-5 coaching visits, facilitated by a trained public health nurse. Children and parents who are enrolled in the control group will receive the usual health care. The primary outcome will be compared between intervention arms using an analysis of covariance (ANCOVA). Feasibility and acceptability will be assessed by parent focus groups and interviews, and fidelity to the intervention will be measured using nurse-completed checklists. A cost-effectiveness analysis (CEA) will be conducted. DISCUSSION: This study will aim to reflect the social, cultural, and geographic diversity of children in primary care in Toronto, Ontario, represented by an innovative collaboration among applied child health researchers, community health researchers, and primary care providers (i.e., pediatricians and family physicians in three different models of primary care). Clinical and implementation outcomes will be used to inform future research to test this intervention in a larger number, and diverse practices across diverse geographic settings in Ontario. TRIAL REGISTRATION: ClinicalTrials.gov NCT03219697. Registered on June 27, 2017.

Effectiveness of Structured Care Coordination for Children With Medical Complexity: The Complex Care for Kids Ontario (CCKO) Randomized Clinical Trial.

Importance: Children with medical complexity (CMC) have chronic conditions and high health needs and may experience fragmented care. Objective: To compare the effectiveness of a structured complex care program, Complex Care for Kids Ontario (CCKO), with usual care. Design, Setting, and Participants: This randomized clinical trial used a waitlist variation for randomizing patients from 12 complex care clinics in Ontario, Canada, over 2 years. The study was conducted from December 2016 to June 2021. Participants were identified based on complex care clinic referral and randomly allocated into an intervention group, seen at the next available clinic appointment, or a control group that was placed on a waitlist to receive the intervention after 12 months. Intervention: Assignment of a nurse practitioner-pediatrician dyad partnering with families in a structured complex care clinic to provide intensive care coordination and comprehensive plans of care. Main Outcomes and Measures: Co-primary outcomes, assessed at baseline and at 6, 12, and 24 months postrandomization, were service delivery indicators from the Family Experiences With Coordination of Care that scored (1) coordination of care among health care professionals, (2) coordination of care between health care professionals and families, and (3) utility of care planning tools. Secondary outcomes included child and parent health outcomes and child health care system utilization and cost. Results: Of 144 participants randomized, 141 had complete health administrative data, and 139 had complete baseline surveys. The median (IQR) age of the participants was 29 months (9-102); 83 (60%) were male. At 12 months, scores for utility of care planning tools improved in the intervention group compared with the waitlist group (adjusted odds ratio, 9.3; 95% CI, 3.9-21.9; P < .001), with no difference between groups for the other 2 co-primary outcomes. There were no group differences for secondary outcomes of child outcomes, parent outcomes, and health care system utilization and cost. At 24 months, when both groups were receiving the intervention, no primary outcome differences were observed. Total health care costs in the second year were lower for the intervention group (median, CAD$17 891; IQR, 6098-61 346; vs CAD$37 524; IQR, 9338-119 547 [US $13 415; IQR, 4572-45 998; vs US $28 136; IQR, 7002-89 637]; P = .01). Conclusions and Relevance: The CCKO program improved the perceived utility of care planning tools but not other outcomes at 1 year. Extended evaluation periods may be helpful in assessing pediatric complex care interventions. Trial Registration: ClinicalTrials.gov Identifier: NCT02928757.

Immediate versus delayed sequential bilateral cataract surgery in children: a cost-effectiveness analysis.

BACKGROUND/AIMS: Children with bilateral cataracts may undergo immediate sequential bilateral cataract surgery (ISBCS), which involves surgery on both eyes during the same general anaesthesia, or delayed sequential bilateral cataract surgery (DSBCS), which involves operating on each eye on separate days and requires a second anaesthesia. ISBCS is viewed with caution because of the risk of bilateral endophthalmitis. Proponents of ISBCS emphasise that the incidence of serious complications is low and is outweighed by benefits such as avoidance of multiple anaesthesia, faster visual rehabilitation and potential for decreased costs. However, there is a paucity of literature regarding the cost-effectiveness of ISBCS in children. We conducted a cost-effectiveness analysis to determine whether ISBCS is more cost-effective than DSBCS from the societal and health system perspectives in Ontario, Canada, which has a universal, single-payer system. METHODS: A retrospective analysis of children who underwent ISBCS or DSBCS at a tertiary referral paediatric hospital was conducted. A decision tree was constructed using TreeAge Pro 2018 software. Clear visual axis was the measure of effectiveness. A time horizon of 8 weeks postoperatively was adopted. Both direct and indirect costs were included. RESULTS: Fifty-three children were included, 37 in the ISBCS group and 16 in the DSBCS group. ISBCS and DSBCS were equally effective. ISBCS resulted in cost-savings of $3,776 (95% CI:-$4,641 to $12,578) CAD, per patient, from the societal perspective and $2,200 (95% CI:-$5,615 to $10,373) CAD per patient from the health system perspective. CONCLUSION: ISBCS was less costly than DSBCS from both societal and health system perspectives while being equally effective.

The Transitions to Long-term In Home Ventilator Engagement Study (Transitions to LIVE): study protocol for a pragmatic randomized controlled trial.

BACKGROUND OVERVIEW AND RATIONALE: We co-developed a multi-component virtual care solution (TtLIVE) for the home mechanical ventilation (HMV) population using the aTouchAway™ platform (Aetonix). The TtLIVE intervention includes (1) virtual home visits; (2) customizable care plans; (3) clinical workflows that incorporate reminders, completion of symptom profiles, and tele-monitoring; and (4) digitally secure communication via messaging, audio, and video calls; (5) Resource library including print and audiovisual material. OBJECTIVES AND BRIEF METHODS: Our primary objective is to evaluate the TtLIVE intervention compared to a usual care control group using an eight-center, pragmatic, parallel-group single-blind (outcome assessors) randomized controlled trial. Eligible patients are children and adults newly transitioning to HMV in Ontario, Canada. Our target sample size is 440 participants (220 each arm). Our co-primary outcomes are a number of emergency department (ED) visits in the 12 months after randomization and change in family caregiver (FC) reported Pearlin Mastery Scale score from baseline to 12 months. Secondary outcomes also measured in the 12 months post randomization include healthcare utilization measured using a hybrid Ambulatory Home Care Record (AHCR-hybrid), FC burden using the Zarit Burden Interview, and health-related quality of life using the EQ-5D. In addition, we will conduct a cost-utility analysis over a 1-year time horizon and measure process outcomes including healthcare provider time using the Care Coordination Measurement Tool. We will use qualitative interviews in a subset of study participants to understand acceptability, barriers, and facilitators to the TtLIVE intervention. We will administer the Family Experiences with Care Coordination (FECC) to interview participants. We will use Poisson regression for a number of ED visits at 12 months. We will use linear regression for the Pearlin Mastery scale score at 12 months. We will adjust for the baseline score to estimate the effect of the intervention on the primary outcomes. Analysis of secondary outcomes will employ regression, causal, and linear mixed modeling. Primary analysis will follow intention-to-treat principles. We have Research Ethics Board approval from SickKids, Children's Hospital Eastern Ontario, McMaster Children's Hospital, Children's Hospital-London Health Sciences, Sunnybrook Hospital, London Health Sciences, West Park Healthcare Centre, and Ottawa Hospital. DISCUSSION: This pragmatic randomized controlled single-blind trial will determine the effectiveness and cost-effectiveness of the TtLIVE virtual care solution compared to usual care while providing important data on patient and family experience, as well as process measures such as healthcare provider time to deliver the intervention. TRIAL REGISTRATION: ClinicalTrials.gov NCT04180722 . Registered on November 27, 2019.

Cost-effectiveness of Intermittent vs Continuous Pulse Oximetry Monitoring in Infants Hospitalized With Stabilized Bronchiolitis.

Importance: Pulse oximetry is a noninvasive technology that is integral to the supportive care of hospitalized infants with bronchiolitis. A multicenter, randomized trial comparing the effectiveness of intermittent vs continuous pulse oximetry found similar length of hospital stay and safety outcomes, and greater nursing satisfaction, with intermittent monitoring. Objectives: To evaluate the cost-effectiveness of intermittent vs continuous pulse oximetry in hospitalized infants with stabilized bronchiolitis. Design, Setting, and Participants: An economic evaluation concurrent with a randomized trial in community and tertiary children's hospitals in Ontario, Canada, was conducted using a probabilistic analysis. Patients were enrolled from November 1, 2016, to May 31, 2019. Data included infants aged 4 weeks to 24 months hospitalized with bronchiolitis, with or without supplemental oxygen, after stabilization. The cost-effectiveness analysis adopted a societal and health care system perspective and a time horizon from hospitalization to 15 days post-discharge. Patient level direct health care costs and indirect costs were included. Health resource use, costs, and clinical outcomes were obtained from trial data. Publicly available pricing resources were used to supplement costs. Ranges for sensitivity analysis were based on 95% confidence intervals of the trial data. All costs were reported in 2021 Canadian dollars. Interventions: Intermittent (every 4 hours) vs continuous pulse oximetry using an oxygen saturation target of 90% or higher. Main Outcomes and Measures: Costs and incremental costs. Results: Trial data from 229 infants (median [IQR] age, 4.0 [2.2-8.5] months; 136 boys [59.4%], 93 girls [40.6%]) were included. Mean societal costs per patient were $6879 (95% CI, $3393 to $12 317) in the intermittent and $7428 (95% CI, $1743 to $25 011) in the continuous group with a mean incremental cost of -$548 (95% CI, -$18 486 to $8105). Mean health care system costs per patient were $4195 (95% CI, $1191 to $9461) in the intermittent and $4716 (95% CI, $335 to $22 093) in the continuous group (incremental cost, -$520; 95% CI, -$18 286 to $7358). The mean effect measure of length of stay was similar between the 2 groups: 37.4 hours (95% CI, 1.0 to 137.7 hours) in the intermittent group and 38.5 hours (95% CI, 0 to 237.1 hours) in the continuous group. One-way sensitivity analyses on all variables revealed that the findings were robust and the incremental costs were not sensitive to the uncertainty within the defined ranges. Conclusions and Relevance: In this prospective economic evaluation study, we found that costs were similar for intermittent and continuous pulse oximetry considering societal and health care perspectives. Given that clinical outcomes between monitoring strategies are comparable and that other practice considerations favor intermittent monitoring, these findings provide additional information that support the use of intermittent monitoring in hospitalized infants with stabilized bronchiolitis.

Implementing a Care Coordination Strategy for Children with Medical Complexity in Ontario, Canada: A Process Evaluation.

Introduction: A provincial strategy to expand care coordination and integration of care for children with medical complexity (CMC) was launched in Ontario, Canada in 2015. A process evaluation of the roll-out examined the processes, mechanisms of impact, and contextual factors affecting the implementation of the Complex Care for Kids Ontario (CCKO) intervention strategy. Methods: This process evaluation was conducted and analyzed according to the United Kingdom Medical Research Council (UK-MRC) process evaluation framework. To evaluate the implementation of the CCKO intervention, a multi-method study design was used, including semi-structured interviews with 38 key informants and 10 families of CMC involved in CCKO. To further understand implementation details across regional sites, provincial-level implementation plans, and process documents were reviewed. Discussion: Strengths of CCKO included novel collaborations and partnerships between complex care teams, community partners and regional sites. Issues relating to communication and coordination across care sectors created challenges to holistic care coordination objectives. Provincial system fragmentation limited the ability of CCKO to provide seamless care coordination due to the multiple care sectors involved. Conclusion: This study adds to the understanding of the processes involved in a population-level care coordination intervention for CMC. Lessons learned through CCKO can help facilitate reproducibility and necessary adjustments of the intervention in different settings.

Managing Obesity in Young Children: A Multiple Methods Study Assessing Feasibility, Acceptability, and Implementation of a Multicomponent, Family-Based Intervention.

Background: We developed a multicomponent, family-based intervention for young children with obesity consisting of parent group sessions, home nursing visits, and multidisciplinary clinical encounters. Our objective was to assess intervention feasibility, acceptability, and implementation. Methods: From 2017 to 2020, we conducted a multiple methods study in the obesity management clinic at a tertiary children's hospital (Toronto, Canada). We included 1-6 year olds with a body mass index ≥97th percentile and their parents; we also included health care providers (HCPs) who delivered the intervention. To assess feasibility, we performed a pilot randomized controlled trial (RCT) comparing the intervention to usual care. To explore acceptability, we conducted parent focus groups. To explore implementation, we examined contextual factors with HCPs using the Consolidated Framework for Implementation Research. Results: There was a high level of ineligibility (n = 34/61) for the pilot RCT. Over 21 months, 11 parent-child dyads were recruited; of 6 randomized to the intervention, 3 did not participate in group sessions or home visits. In focus groups, themes identified by parents (n = 8) related to information provided at referral; fit between the intervention and patient needs; parental gains from participating in the intervention; and feasibility of group sessions. HCPs (n = 10) identified contextual factors that were positively and negatively associated with intervention implementation. Conclusions: We encountered challenges related to intervention feasibility, acceptability, and implementation. Lessons learned from this study will inform the next iteration of our intervention and are relevant to intervention development and implementation for young children with obesity. Clinical Trial Registration number: NCT03219658.

Prevalence, Cost, and Variation in Cost of Pediatric Hospitalizations in Ontario, Canada.

Importance: Identifying conditions that could be prioritized for research based on health care system burden is important for developing a research agenda for the care of hospitalized children. However, existing prioritization studies are decades old or do not include data from both pediatric and general hospitals. Objective: To assess the prevalence, cost, and variation in cost of pediatric hospitalizations at all general and pediatric hospitals in Ontario, Canada, with the aim of identifying conditions that could be prioritized for future research. Design, Setting, and Participants: This population-based cross-sectional study used health administrative data from 165 general and pediatric hospitals in Ontario, Canada. Children younger than 18 years with an inpatient hospital encounter between April 1, 2014, and March 31, 2019, were included. Main Outcomes and Measures: Condition-specific prevalence, cost of pediatric hospitalizations, and condition-specific variation in cost per inpatient encounter across hospitals. Variation in cost was evaluated using (1) intraclass correlation coefficient (ICC) and (2) number of outlier hospitals. Costs were adjusted for inflation to 2018 US dollars. Results: Overall, 627 314 inpatient hospital encounters (44.8% among children younger than 30 days and 53.0% among boys) at 165 hospitals (157 general and 8 pediatric) costing $3.3 billion were identified. A total of 408 003 hospitalizations (65.0%) and $1.4 billion (43.8%) in total costs occurred at general hospitals. Among the 50 most prevalent and 50 most costly conditions (of 68 total conditions), the top 10 highest-cost conditions accounted for 55.5% of all costs and 48.6% of all encounters. The conditions with highest prevalence and cost included low birth weight (86.2 per 1000 encounters; $676.3 million), preterm newborn (38.0 per 1000 encounters; $137.4 million), major depressive disorder (20.7 per 1000 encounters; $78.3 million), pneumonia (27.3 per 1000 encounters; $71.6 million), other perinatal conditions (68.0 per 1000 encounters; $65.8 million), bronchiolitis (25.4 per 1000 encounters; $54.6 million), and neonatal hyperbilirubinemia (47.9 per 1000 encounters; $46.7 million). The highest variation in cost per encounter among the most costly medical conditions was observed for 2 mental health conditions (other mental health disorders [ICC, 0.28] and anxiety disorders [ICC, 0.19]) and 3 newborn conditions (intrauterine hypoxia and birth asphyxia [ICC, 0.27], other perinatal conditions [ICC, 0.17], and surfactant deficiency disorder [ICC, 0.17]). Conclusions and Relevance: This population-based cross-sectional study of hospitalized children identified several newborn and mental health conditions as having the highest prevalence, cost, and variation in cost across hospitals. Findings of this study can be used to develop a research agenda for the care of hospitalized children that includes general hospitals and to ultimately build a more substantial evidence base and improve patient outcomes.

Outcome following high-dose methotrexate in pregnancies misdiagnosed as ectopic.

OBJECTIVE: The objective of this study was to report the outcomes of intrauterine pregnancies misdiagnosed as ectopic and exposed to methotrexate, a major teratogen. STUDY DESIGN: We report the outcomes of all subjects who sought consultation after exposure to high-dose methotrexate to induce abortion in presumed ectopic pregnancies, which were later identified as viable intrauterine pregnancies by 3 North American Teratology Information Services between 2002 and 2010. RESULTS: Eight women with normal, desired pregnancies were administered high-dose methotrexate in the first trimester because of presumed, misdiagnosed ectopic pregnancies. All pregnancies resulted in catastrophic outcomes. Two pregnancies resulted in severely malformed newborns with methotrexate embryopathy; 3 women miscarried shortly after exposure, and in 3 the erroneous diagnosis led the physicians to advise and perform surgical termination. CONCLUSION: Erroneous diagnosis of intrauterine pregnancies as ectopic with subsequent first-trimester exposure to methotrexate may result in the birth of severely malformed babies or fetal demise.

Safety of insulin glargine use in pregnancy: a systematic review and meta-analysis.

BACKGROUND: The prevalence of diabetes in women of childbearing age is increasing. As such, the number of pregnancies complicated by diabetes will inevitably increase. New insulin analogues such as the long-acting analogue insulin glargine may represent beneficial treatment options in pregnancy by ensuring that patients achieve excellent glycemic control without risk of maternal hypoglycemia. OBJECTIVE: To determine the fetal safety of insulin glargine use in the treatment of diabetes in pregnancy compared with NPH insulin therapy. METHODS: A systematic review and meta-analysis was performed of all original human studies that reported neonatal outcomes among women with pregestational or gestational diabetes who were managed with either insulin glargine or NPH insulin during pregnancy. A systematic literature search was conducted using MEDLINE, EMBASE, CINAHL, the Cochrane Central Register for Controlled Trials database, and Web of Science from 1980 to June 1, 2010. Outcomes included large size for gestational age, macrosomia, neonatal hypoglycemia, neonatal intensive care unit admissions, birth trauma, congenital anomalies, preterm delivery, perinatal mortality, respiratory distress, and hyperbilirubinemia. Relative risk ratios and weighted mean differences were computed with 95% confidence intervals. RESULTS: Eight studies reporting on a total of 702 women with pregestational or gestational diabetes in pregnancy treated with either insulin glargine (n = 331) or NPH insulin (n = 371) met the inclusion criteria. There were no statistically significant differences in the occurrence of fetal outcomes studied with the use of insulin glargine compared to NPH insulin. CONCLUSIONS: No evidence has been documented for increased adverse fetal outcomes with the use of insulin glargine in pregnancy compared to the use of NPH insulin. These results increase the choices for women requiring basal insulin therapy in pregnancy.

The fetal safety of benzodiazepines: an updated meta-analysis.

Benzodiazepines are commonly used by women of reproductive age, and hence many pregnant women are exposed to them. An updated meta-analysis of their fetal safety synthesized nine studies with over one million pregnancies, yielding an odds ratio of 1.07 (95% CI 0.91 to 1.25). While benzodiazepines do not appear to increase teratogenic risk in general, case-controls suggest a twofold increased risk of oral cleft.

Cost-effectiveness of preferred fluids versus electrolytes in pediatric gastroenteritis.

BACKGROUND: While electrolyte maintenance solution is recommended and commonly used in pediatric gastroenteritis, it can be more costly and less palatable than preferred fluids such as apple juice. OBJECTIVE: To assess the incremental cost-effectiveness of apple juice/preferred fluids versus electrolyte maintenance solution in reducing treatment failures in children in an emergency department from societal and health care perspectives. METHODS: A probabilistic cost-effectiveness analysis was performed using clinical trial and chart data. All intervention, and direct and indirect costs were included, with a 14-day time horizon. Cost-effectiveness was examined by calculating the difference in mean number of treatment failures and mean cost/patient between treatment groups. The probabilistic point estimate and 95% confidence intervals for incremental costs and incremental effectiveness were determined. RESULTS: The apple juice strategy was less costly than electrolytes with average per child savings of CAD $171 (95% CI $22 to $1097) from a societal perspective, and $147 (95% CI $23 to $1056) from a health care perspective. There were 0.08 fewer treatment failures per child (95% CI - 0.15 to - 0.02). The higher electrolyte maintenance solution cost was due to more frequent hospitalizations, ongoing care, and greater lost parental productivity due to additional medical visits. CONCLUSION: Apple juice/preferred fluids strategy was dominant over electrolytes in the treatment of children with minimal dehydration secondary to acute gastroenteritis as this option yielded fewer treatment failures and a lower societal cost. Given the high prevalence of acute gastroenteritis, this approach may result in significant cost savings while leading to improved clinical outcomes.

RéSUMé: CONTEXTE: Bien que la solution de maintien des électrolytes soit recommandée et couramment utilisée dans les gastro-entérites pédiatriques, elle peut être plus coûteuse et moins agréable au goût que les liquides préférés tels que le jus de pomme. OBJECTIF: Évaluer le rapport coût-efficacité supplémentaire du jus de pomme/des liquides préférés par rapport à des électrolytes pour réduire les échecs de traitement chez les enfants dans un service d'urgence, du point de vue de la société et des soins de santé. LES MéTHODES: Une analyse probabiliste de la rentabilité a été réalisée en utilisant les données des essais cliniques et des dossiers. Tous les coûts d'intervention, directs et indirects, ont été inclus, avec un horizon temporel de 14 jours. La rentabilité a été examinée en calculant la différence du nombre moyen d'échecs de traitement et du coût/patient moyen entre les groupes de traitement. L'estimation ponctuelle probabiliste et les intervalles de confiance à 95% pour les coûts différentiels et l'efficacité différentielle ont été déterminés. RéSULTATS: La stratégie du jus de pomme était moins coûteuse que les électrolytes, avec des économies moyennes par enfant de 171 $ CAD (IC à 95 % : 22 $ à 1097 $) du point de vue sociétal et de 147 $ (IC à 95 % : 23 $ à 1056 $) du point de vue des soins de santé. Il y a eu 0,08 échec de traitement en moins par enfant (IC 95 % : -0,15 à -0,02). Le coût plus élevé des électrolytes est dû à des hospitalisations plus fréquentes, à des soins continus et à une plus grande perte de productivité des parents en raison de visites médicales supplémentaires. CONCLUSION: La stratégie du jus de pomme/des liquides préférés a été dominante sur les électrolytes dans le traitement des enfants présentant une déshydratation minimale secondaire à une gastro-entérite aiguë, car cette option a permis de réduire les échecs du traitement et le coût pour la société. Compte tenu de la prévalence élevée de la gastro-entérite aiguë, cette approche peut entraîner des économies de coûts significatives tout en améliorant les résultats cliniques.