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.

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.

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.

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.

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.

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.

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.

Erratum.

[This corrects the article DOI: 10.1093/jcag/gwz045.][This corrects the article DOI: 10.1093/jcag/gwz045.].

A Cost-Utility Analysis of Switching from Reference to Biosimilar Infliximab Compared to Maintaining Reference Infliximab in Adult Patients with Crohn's Disease.

BACKGROUND AND AIMS: Lower-cost biosimilar infliximab may address affordability concerns in the treatment of adults with Crohn's disease (CD), however, evidence regarding the cost-effectiveness of switching from reference to biosimilar is warranted. The aim of this research was to assess the incremental cost of switching from treatment with reference infliximab to biosimilar compared with maintaining reference infliximab in adults with CD per quality-adjusted life year (QALY) gained. METHODS: A probabilistic cohort Markov model with 8-week cycle lengths was constructed to estimate the incremental costs and effects of switching over a 5-year time horizon from a public payer perspective. Base-case clinical inputs were obtained from NOR-SWITCH subgroup analyses and other published trials. Costs were obtained from Canadian sources. A total of 10,000 simulations were run. Sensitivity analysis was used to test the robustness of the results to variations in uncertain parameters. RESULTS: Switching to biosimilar infliximab was less costly but also less effective with incremental savings of $46,194 (95% confidence interval [CI]: $42,420, $50,455) and a loss in QALYs of -0.13 (95% CI: -0.16, -0.07). Eighty-three per cent of the simulations demonstrated incremental cost savings and an incremental loss of effectiveness. The model was sensitive to differences in rates of disease worsening between reference and biosimilar infliximab. CONCLUSIONS: While biosimilar infliximab is associated with incremental savings for patients on maintenance therapy who are switched from reference infliximab, funding decision makers must decide whether a small loss of effectiveness is justified. Further evidence will help to inform reimbursement policy.

Protocol for a cost-utility analysis of neurostimulation and intensive camp-based therapy for children with perinatal stroke and hemiparesis based on a multicentre clinical trial.

INTRODUCTION: Perinatal stroke leads to cerebral palsy (CP) and lifelong disability for thousands of Canadian children. Hemiparesis, referring to impaired functionality in one side of the body, is a common complication of perinatal stroke. Standard long-term care for hemiparetic CP focuses on rehabilitation therapies. Early research suggests that patients with hemiparesis may benefit from adjunctive neuromodulation treatments such as transcranial direct current stimulation (tDCS). tDCS uses electric current to stimulate targeted areas of the brain non-invasively, potentially enhancing the effects of motor learning therapies. This protocol describes an economic evaluation to be conducted alongside a randomised controlled trial (RCT) to assess the incremental cost of tDCS added to a camp-based therapy compared with camp-based therapy alone per quality-adjusted life year (QALY) gained in children with hemiparetic CP. METHODS AND ANALYSIS: The Stimulation for Perinatal Stroke Optimising Recovery Trajectories (SPORT) trial is a multicentre RCT evaluating tDCS added to a 2-week camp-based therapy for children aged 6-18 years with perinatal ischaemic stroke and disabling hemiparetic CP affecting the upper limb. Outcomes are assessed at baseline, 1 week, 2 months and 6 months following intervention. Cost and quality of life data are collected at baseline and 6 months and results will be used to conduct a cost-utility analysis (CUA). The evaluation will be conducted from the perspectives of the public healthcare system and society. The CUA will be conducted over a 6-month time horizon. ETHICS AND DISSEMINATION: Ethical approval for the SPORT trial and the associated economic evaluation has been given by the research ethics boards at each of the study sites. The findings of the economic evaluation will be submitted for publication in a peer reviewed academic journal and submitted for presentation at conference. TRIAL REGISTRATION NUMBER: NCT03216837; Post-results.

Time Driven Activity Based Costing of Management Pathways for Vesicoureteral Reflux.

INTRODUCTION: The approach to the management of vesicoureteral reflux remains variable despite being a common pediatric diagnosis, which makes costing unpredictable. The aim of our study is to employ time driven activity based costing to characterize institutional costs of 3 management pathways for vesicoureteral reflux. METHODS: We developed process maps for vesicoureteral reflux management based on practice guidelines applicable to a hypothetical female patient with vesicoureteral reflux index with grade 3 unilateral reflux without bowel bladder dysfunction at our institution. The costs of 3 management pathways were described, including watch and wait, minimally invasive endoscopic surgery with dextranomer/hyaluronic acid and open re-implantation surgery. Costs for each pathway were calculated using the capacity cost rate ($/minute) for institutional resources and time estimates of resource use captured through direct observation and electronic medical record data. Clinical outcomes such as the breakthrough urinary tract infections or renal scarring were not addressed in this cost description. RESULTS: A substantial range of total costs ($CAD) was observed for all pathways including watch and wait ($1,683.58 to $2,041.12), minimally invasive endoscopic surgery ($2,616.35 to $4,012.89) and open re-implantation surgery ($3,317.76 to $3,924.82). Total costs for a single dimercaptosuccinic acid scan accounted for 8% to 15% of any pathway's overall costs. Material costs for voiding cystourethrogram imaging and endoscopic surgery were high at 59% and 64% to 76% of their individual total costs, respectively. For open re-implantation surgery, high costs were attributable to the longer use of operating room space and inpatient postoperative stay. CONCLUSIONS: Time driven activity based costing demonstrates significant cost variability in vesicoureteral reflux treatment modalities and identified local cost drivers to target. Results from this study may be used to inform future cost-effectiveness analyses.

Process Evaluation of a Hub-and-Spoke Model to Deliver Coordinated Care for Children with Medical Complexity across Ontario: Facilitators, Barriers and Lessons Learned.

BACKGROUND: Complex Care for Kids Ontario (CCKO) is a multi-year strategy aimed at expanding a hub-and-spoke model to deliver coordinated care for children with medical complexity (CMC) across Ontario. OBJECTIVE: This paper aims to identify the facilitators, barriers and lessons learned from the implementation of the Ontario CCKO strategy. METHOD: Alongside an outcome evaluation of the CCKO strategy, we conducted a process evaluation to understand the implementation context, process and mechanisms. Semi-structured interviews were conducted with 38 healthcare leaders, clinicians and support staff from four regions involved in CCKO care delivery and/or governance. RESULTS: Facilitators to CCKO implementation were sustained engagement of system-wide stakeholders, inter-organizational partnerships, knowledge sharing and family engagement. Barriers to CCKO implementation were resources and funding, fragmentation of care, aligning perspectives between providers and clinical staff recruitment and retention. CONCLUSION: A flexible approach is required to implement a complex, multi-centre policy strategy. Other jurisdictions considering such a model of care delivery would benefit from attention to contextual variations in implementation setting, building cross-sector engagement and buy-in, and offering continuous support for modifications to the intervention as and when required.