Are Generative Pretrained Transformer 4 Responses to Developmental Dysplasia of the Hip Clinical Scenarios Universal? An International Review.

OBJECTIVE: There is increasing interest in applying artificial intelligence chatbots like generative pretrained transformer 4 (GPT-4) in the medical field. This study aimed to explore the universality of GPT-4 responses to simulated clinical scenarios of developmental dysplasia of the hip (DDH) across diverse global settings. METHODS: Seventeen international experts with more than 15 years of experience in pediatric orthopaedics were selected for the evaluation panel. Eight simulated DDH clinical scenarios were created, covering 4 key areas: (1) initial evaluation and diagnosis, (2) initial examination and treatment, (3) nursing care and follow-up, and (4) prognosis and rehabilitation planning. Each scenario was completed independently in a new GPT-4 session. Interrater reliability was assessed using Fleiss kappa, and the quality, relevance, and applicability of GPT-4 responses were analyzed using median scores and interquartile ranges. Following scoring, experts met in ZOOM sessions to generate Regional Consensus Assessment Scores, which were intended to represent a consistent regional assessment of the use of the GPT-4 in pediatric orthopaedic care. RESULTS: GPT-4's responses to the 8 clinical DDH scenarios received performance scores ranging from 44.3% to 98.9% of the 88-point maximum. The Fleiss kappa statistic of 0.113 (P = 0.001) indicated low agreement among experts in their ratings. When assessing the responses' quality, relevance, and applicability, the median scores were 3, with interquartile ranges of 3 to 4, 3 to 4, and 2 to 3, respectively. Significant differences were noted in the prognosis and rehabilitation domain scores (P < 0.05 for all). Regional consensus scores were 75 for Africa, 74 for Asia, 73 for India, 80 for Europe, and 65 for North America, with the Kruskal-Wallis test highlighting significant disparities between these regions (P = 0.034). CONCLUSIONS: This study demonstrates the promise of GPT-4 in pediatric orthopaedic care, particularly in supporting preliminary DDH assessments and guiding treatment strategies for specialist care. However, effective integration of GPT-4 into clinical practice will require adaptation to specific regional health care contexts, highlighting the importance of a nuanced approach to health technology adaptation. LEVEL OF EVIDENCE: Level IV.

Routine ultrasound screening for hip dysplasia in children with clubfoot is not supported.

PURPOSE: Despite the existence of guidelines for screening for developmental dysplasia of the hip (DDH), there remains controversy regarding the need for routine ultrasound screening for DDH in patients with clubfoot due to an unclear correlation between the two conditions. The purpose of this study is to determine whether ultrasound screening for DDH in this population improved the diagnostic accuracy of DDH over standard assessment for patient risk factors and physical exam. METHODS: This is a retrospective cross-sectional review of infants diagnosed with idiopathic clubfoot who underwent hip ultrasounds to assess for DDH as identified by keyword search in an institutional radiological database at a tertiary care paediatric hospital. Patient demographics, risk factors for DDH, physical exam findings, and ultrasound results were recorded. RESULTS: Of the 120 patients who met the inclusion criteria between 2003 and 2018, 8 had hip dysplasia confirmed on ultrasound (6.7%). All these patients either had known risk factors for hip dysplasia or had an abnormal physical exam finding suggestive of hip instability or dislocation as performed by an orthopaedic surgeon on their initial consultation. CONCLUSION: A detailed history to determine risk factors and a thorough physical exam are adequate to determine the need for hip ultrasound in infants with idiopathic clubfoot. Routine ultrasound screening of all patients with clubfoot is likely unnecessary and may pose a significant burden on the health care system.

Maternal exposure to metals and time-to-pregnancy: The MIREC cohort study.

OBJECTIVE: To study the association between maternal exposure to arsenic, cadmium, lead, manganese and mercury, time-to-pregnancy (TTP) and infertility. DESIGN: Pregnancy-based retrospective TTP cohort study. SETTING: Hospitals and clinics from ten cities across Canada. POPULATION: A total of 1784 pregnant women. METHODS: Concentrations of arsenic, cadmium, lead, manganese and mercury were measured in maternal whole blood during the first trimester of pregnancy as a proxy of preconception exposure. Discrete-time Cox proportional hazards models generated fecundability odds ratios (FOR) for the association between metals and TTP. Logistic regression generated odds ratios (OR) for the association between metals and infertility. Models were adjusted for maternal age, pre-pregnancy body mass index, education, income, recruitment site and plasma lipids. MAIN OUTCOME MEASURES: TTP was self-reported as the number of months of unprotected intercourse to become pregnant. Infertility was defined as TTP longer than 12 months. RESULTS: A total of 1784 women were eligible for the analysis. Mean ± SD maternal age and gestational age at interview were 32.2 ± 5.0 years, and 11.6 ± 1.6 weeks, respectively. Exposure to arsenic, cadmium, manganese or mercury was not associated with TTP or infertility. Increments of one standard deviation of lead concentrations resulted in a shorter TTP (adjusted FOR 1.09, 95% CI 1.02-1.16); however, the association was not linear when exposure was modelled in tertiles. CONCLUSION: Blood concentrations of metals at typical levels of exposure among Canadian pregnant women were not associated with TTP or infertility. Further studies are needed to assess the role of lead, if any, on TTP.

Using in vitro data to derive acceptable exposure levels: A case study on PBDE developmental neurotoxicity.

BACKGROUND: Current acceptable chemical exposure levels (e.g., tolerable daily intake) are mainly based on animal experiments, which are costly, time-consuming, considered non-ethical by many, and may poorly predict adverse outcomes in humans. OBJECTIVE: To evaluate a method using human in vitro data and biological modeling to calculate an acceptable exposure level through a case study on 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) developmental neurotoxicity (DNT). METHODS: We reviewed the literature on in vitro assays studying BDE-47-induced DNT. Using the most sensitive endpoint, we derived a point of departure using a mass-balance in vitro disposition model and benchmark dose modeling for a 5% response (BMC05) in cells. We subsequently used a pharmacokinetic model of gestation and lactation to estimate administered equivalent doses leading to four different metrics of child brain concentration (i.e., average prenatal, average postnatal, average overall, and maximum concentration) equal to the point of departure. The administered equivalent doses were translated into tolerable daily intakes using uncertainty factors. Finally, we calculated biomonitoring equivalents for maternal serum and compared them to published epidemiological studies of DNT. RESULTS: We calculated a BMC05 of 164 µg/kg of cells for BDE-47 induced alteration of differentiation in neural progenitor cells. We estimated administered equivalent doses of 0.925-3.767 µg/kg/day in mothers, and tolerable daily intakes of 0.009-0.038 µg/kg/day (composite uncertainty factor: 100). The lowest derived biomonitoring equivalent was 19.75 ng/g lipids, which was consistent with reported median (0.9-23 ng/g lipids) and geometric mean (7.02-26.9 ng/g lipids) maternal serum concentrations from epidemiological studies. CONCLUSION: This case study supports using in vitro data and biological modeling as a viable alternative to animal testing to derive acceptable exposure levels.

Density and proximity of oil and gas wells and concentrations of trace elements in urine, hair, nails and tap water samples from pregnant individuals living in Northeastern British Columbia.

BACKGROUND: Oil and gas exploitation can release several contaminants in the environment, including trace elements, with potentially deleterious effects on exposed pregnant individuals and their developing fetus. Currently, there is limited data on pregnant individuals' exposure to contaminants associated with oil and gas activity. OBJECTIVES: We aimed to 1)measure concentrations of trace elements in biological and tap water samples collected from pregnant individuals participating in the EXPERIVA study; 2)compare with reference populations and health-based guidance values; 3)assess correlations across matrices; and 4)evaluate associations with the density/proximity of oil and gas wells. METHODS: We collected tap water, hair, nails, and repeated urine samples from 85pregnant individuals, and measured concentrations of 21trace elements. We calculated oil and gas well density/proximity (Inverse Distance Weighting [IDW]) for 4buffer sizes (2.5 km, 5 km, 10 km, no buffer). We performed Spearman's rank correlation analyses to assess the correlations across elements and matrices. We used multiple linear regression models to evaluate the associations between IDWs and concentrations. RESULTS: Some study participants had urinary trace element concentrations exceeding the 95th percentile of reference values; 75% of participants for V, 29% for Co, 22% for Ba, and 20% for Mn. For a given trace element, correlation coefficients ranged from -0.23 to 0.65 across matrices; correlations with tap water concentrations were strongest for hair, followed by nails, and urine. Positive (e.g., Cu, Cr, Sr, U, Ga, Ba, Al, Cd) and negative (e.g., Fe) associations were observed between IDW metrics and the concentrations of certain trace elements in water, hair, and nails. SIGNIFICANCE: Our results suggest that pregnant individuals living in an area of oil and gas activity may be more exposed to certain trace elements (e.g., Mn, Sr, Co, Ba) than the general population. Association with density/proximity of wells remains unclear.

Comparing patient-reported outcomes of the Oxford Ankle and Foot Questionnaire in children with clubfoot from two different geographic and cultural environments: a cohort study in India and Canada.

PURPOSE: The purpose of this study is to compare the results of the Oxford Ankle and Foot Questionnaire (OxAFQ) in children with clubfoot in Canada and India to assess its ability to predict outcomes and capture patient experiences in different cultural contexts. METHODS: This is a retrospective study of children with clubfoot in India and Canada who completed the OxAFQ. Statistical analyses were implemented on registry-collected data to test for independent predictors of poor outcomes and compare scores between countries, among children and their parents, and in Canada where relapse data was collected and the effect of a relapse on scores. RESULTS: A total of 361 children were included. The mean Indian OxAFQ scores were higher (p < 0.001) in all domains. Pirani score, tenotomy, laterality, and age at presentation were found to be predictive of outcomes between the sites (p < 0.05). OxAFQ scores decreased after relapse for children in Canada (p < 0.05). Canadian children were found to generally have lower OxAFQ scores in all domains compared to their parents (n = 95; Z = -3.178, -3.493, -3.353, and -3.635 for physical, school and play, emotion, and footwear, respectively; p < 0.001). Indian parents and children showed no significant differences in their scores. CONCLUSIONS: A difference was observed in scores between both sites, suggesting there may be differences in how these populations assess personal health outcomes. These findings support the need for cultural validity of patient-reported outcome measures.

The Evolution of Sinus Tarsi Syndrome-What Is the Underlying Pathology?-A Critical Review.

Background and Objectives: Sinus tarsi syndrome (STS) is defined as pain located at the lateral opening of the tarsal sinus. The exact etiology of sinus tarsi syndrome is not completely understood. Some do not believe it to be a true pathology. This review aims to clarify the definition of sinus tarsi syndrome to better understand the underlying pathologies. We further propose an algorithm to evaluate sinus tarsi pain and provide advice for consecutive treatment options. Design: This is a narrative review. By searching PubMed, the available current literature was reviewed. Articles were critically analyzed to determine the pathoanatomy, biomechanics, and etiology of sinus tarsi pain. Algorithms for clinical evaluation, diagnosis, and treatment were also recorded. Finally, the authors approach to evaluating and treating sinus tarsi pain was included in this review. Results: Reviewing the available literature, STS seems to be a catch-all phrase used to describe any pain in this anatomic region. Many causes of sinus tarsi pain were listed, including impingement, subtalar instability, and many other pathologies around the ankle. Conclusions: A thorough evaluation of patients presenting with pain in the sinus tarsi or instability of the hindfoot is essential to determining the underlying cause. When the cause of pain is still not clear after clinical exam and radiologic assessment, subtalar arthroscopy can be helpful as both a diagnostic and treatment tool. We propose that the term of STS should be avoided and that a more accurate diagnosis be used when possible. Once a diagnosis is made, appropriate treatment can be initiated.

Cohort profile update: The Canadian Maternal-Infant Research on Environmental Chemicals Child Development study (MIREC-CD PLUS).

BACKGROUND: The pan-Canadian Maternal-Infant Research on Environmental Chemicals (MIREC) study was established to determine whether maternal environmental chemical exposures were associated with adverse pregnancy outcomes in 2001 pregnant women. OBJECTIVES: The MIREC-Child Development (CD PLUS) study followed this cohort with the goal of assessing the potential effects of prenatal exposures on anthropometry and neurodevelopment in early childhood. POPULATION: MIREC families with children between the ages of 15 months and 5 years who had agreed to be contacted for future research (n = 1459) were invited to participate in MIREC-CD PLUS which combines data collected from an online Maternal Self-Administered Questionnaire with biomonitoring and neurodevelopment data collected from two in-person visits. PRELIMINARY RESULTS: Between April 2013 and March 2015, 803 children participated in the Biomonitoring visit where we collected anthropometric measures, blood, and urine from the children. The Behavioural Assessment System for Children-2, Behaviour Rating Inventory of Executive Function, MacArthur-Bates Communicative Development Inventories and the Communication subscale of the Adaptive Behaviour Scale from the Bayley Scales of Infant and Toddler Development-III are available on close to 900 children. There were 610 singleton children who completed in-person visits for neurodevelopment assessments including the Social Responsiveness Scale, Wechsler Preschool Primary Scale of Intelligence-III and NEuroPSYchological assessments (NEPSY). Currently, we are following the cohort into early adolescence to measure the impact of early life exposures on endocrine and metabolic function (MIREC-ENDO). CONCLUSIONS: Data collection for the MIREC-CD PLUS study is complete and analysis of the data continues. We are now extending the follow-up of the cohort into adolescence to measure the impact of early life exposures on endocrine and metabolic function (MIREC-ENDO). MIREC-CD PLUS is limited by loss to follow-up and the fact that mothers are predominately of higher socioeconomic status and 'White' ethnicity, which limits our generalizability. However, the depth of biomonitoring and clinical measures in MIREC provides a platform to examine associations of prenatal, infancy and childhood exposures with child growth and development.

Childhood exposure to pyrethroids and neurodevelopment in Canadian preschoolers.

BACKGROUND: Pyrethroid insecticides are used both residentially and agriculturally and their toxicity targets the nervous system of insects. They might also interfere with development and function of the human brain. A few epidemiological studies suggest that exposure to pyrethroids may be associated with neurobehavioral problems in children but there is little data on potential associations with cognitive outcomes. Furthermore, many studies showed that the neurotoxic effects of several pesticides are modified by sex, hence, considerations of potential sex-differences are important to investigate. OBJECTIVE: To study the cross-sectional association between urinary levels of pyrethroid metabolites and neurodevelopment, including neurobehavioral and cognitive outcomes, in preschool-age children, and to examine whether sex might modify these associations. METHODS: We used data from a follow-up examination of the Maternal-Infant Research on Environmental Chemicals (MIREC), the MIREC Child Development study (MIREC-CD Plus) on children at age 3-4 years living in 6 Canadian cities. For each participant, we collected a urine sample for measurements of pyrethroids metabolites (cis-DBCA, cis-DCCA, trans-DCCA, 3-PBA, 4-F-3-PBA). We assessed neurodevelopment with the Wechsler Primary and Preschool Scale of Intelligence-III (WPPSI-III) and two scales of the Behavior Rating Inventory of Executive Function-Preschool (BRIEF-P). Parents reported children's behavior using the Behavior Assessment System for Children-2 (BASC-2) and the Social Responsiveness Scale-2 (SRS-2). We examined associations between children's urinary pyrethroid metabolite concentrations and neurodevelopmental scores with multiple linear regression models, adjusting for confounders, in boys and girls separately. RESULTS: The study included 179 children (mean age: 3.2 y, range 2.8-4.0). The detection frequencies were high for most pyrethroid metabolites (83-100%), but lower for 4-F-3-PBA (36%). Higher concentrations of cis-DBCA were significantly associated with lower verbal, performance and full-scale IQ scores in boys (e.g., for a 2-fold increase in cis-DBCA, ß = -2.0; 95% CI: -3.4, -0.6 for full-scale IQ). In girls, the only metabolite associated with cognitive scores was 3-PBA, which was associated with lower verbal IQ scores (ß = -1.3, 95% CI: -2.6, -0.1). For neurobehavioral outcomes in boys, there were associations between poorer BASC-2 Adaptive Skills scores with higher concentrations of cis-DCCA (ß = -1.6, 95% CI: -2.3, -0.9), trans-DCCA (ß = -1.5, 95% CI: -2.2, -0.8), 3-PBA (ß = -1.7, 95% CI: -2.5, -0.9), and sum of pyrethroid metabolites (ß = -1.8, 95% CI: -2.6, -0.9). In girls, we observed a significant association between higher concentration of cis-DCCA and better BASC-2 Adaptive Skills score (ß = 1.0; 95% CI, 0.2, 1.8), but not with other urinary pyrethroids metabolites. Scores on the SRS-2 and BRIEF-P were not associated with pyrethroid metabolites. CONCLUSION: There were associations between some pyrethroid pesticide metabolites and indicators of neurodevelopmental disorder, especially among boys. These associations are in agreement with previous studies and could suggest that exposure to pyrethroid pesticides represents a risk of potential toxicity for the cognitive development of children, and a risk for behavioral development. However, the cross-sectional nature of this study limits causal inferences.

Outcomes of paediatric septic arthritis patients: rates of re-admission, re-operation, and unplanned emergency room visits after discharge.

PURPOSE: This study is aimed at determining the rates and predictors of re-operation and re-admission in children with septic arthritis treated at an institution without routine clinical practice guidelines. METHODS: This is a retrospective cohort study of patients less than 18 years old who underwent surgery for septic arthritis between January 1, 2009, and January 1, 2019, at a single tertiary-care paediatric institution. Uni- and multivariate analysis was performed to identify any risk factors associated with re-operation or unplanned visits to the emergency department after hospital admission compared to patients who had an uncomplicated post-operative course. RESULTS: One hundred and forty-four patients were included. The mean age was five years (range 1 month-17 years), and the most commonly affected joint was the hip. The re-admission rate was 1% (n = 2), and the re-operation rate was 8% (n = 12). Twenty percent of patients (n = 29) had unplanned presentations to the emergency department (ED) after discharge. Discharge CRP level was not significantly higher in patients with unplanned presentations to the ED or re-operation. Positive joint fluid culture and infection of any other joint than the hip increased the likelihood of re-operation. Patients who had septic arthritis of the hip were more likely to have an unplanned ED presentation. CONCLUSIONS: Rates of re-admission and re-operation were similar to literature despite lack of a standardized treatment pathway or discharge protocol. Outcomes of pediatric septic arthritis did not correlate with discharge CRP level. There was a high rate of unplanned ED visits after discharge.

Measurement of 24 phthalate metabolites in 1st trimester urine samples: The MIREC study.

Phthalates are non-persistent chemicals measured as metabolites in urine. Over time, new metabolites have been identified. In the original Maternal-Infant Research on Environmental Chemicals (MIREC) study (2008-2011), we measured 11 phthalate metabolites in first trimester urine samples. The goal of the present study was to develop a method to measure new metabolites, to increase the sensitivity for some previously measured metabolites, and to measure these new metabolites in biobanked urine samples from MIREC participants. Using Ultra Performance Liquid Chromatography with a tandem mass spectrometer, we developed a method to measure 24 metabolites from 10 different parent phthalates. Chromatographic interpretation of some of the di-iso-decyl phthalate metabolites (mono-(2-propyl-6oxoheptyl) phthalate (MOiDP), mono-(2,7-methyl-7-carboxyheptyl) phthalate (MCiNP), mono-(2-propyl-6-hydroxy-heptyl) phthalate (MHiDP)) and di-iso-nonyl phthalate metabolites (mono(oxo-isononyl) phthalate (MOiNP), mono(carboxy-isooctyl) phthalate (MCiOP), mono(hydroxy-isononyl) phthalate (MHiNP) and mono-isononyl phthalate (MiNP)) was challenging as these are complex isomeric mixtures. To validate and confirm our quantitation peaks, an assay using a high-resolution detection technique was developed on a Quadrupole Time-of-Flight (QToF) system. This system has a mass resolution of at least 0.005 amu, compared to 0.5 amu for the MS/MS detector. Using the QToF system, the distinction between an isomer and possible interference was achieved with the use of the exact mass. In about 1800 MIREC samples, mono-cyclo-hexyl phthalate (MCHP), mono-(7-carboxy-n-heptyl) phthalate (MCHpP), mono-iso-decyl phthalate (MiDP), and mono-n-octyl phthalate (MnOP) were rarely detected, while detection of MMP was improved. MCiOP, MiNP and MCiNP had to be reported semi-quantitatively. Given the complexity of isomeric mixtures of some phthalates, researchers must be careful in their determination of the analytes and the approach used in their quantification when generating biomonitoring data. This study produced biomonitoring data for a large population of pregnant people that can be used in risk assessment of phthalates. Future work will examine associations with birth and child outcomes.

Hemiepiphysiodesis for juvenile hallux valgus deformity: A systematic review.

BACKGROUND: Among the numerous surgical interventions for correcting hallux valgus deformity in skeletally immature patients, hemiepiphysiodesis is a simple technique with a low complication rate yet its effectiveness remains unclear. This systematic review evaluates hemiepiphysiodesis of the first metatarsal for treating juvenile hallux valgus (JHV) deformities with respect to radiological outcomes, postoperative clinical outcomes, and postoperative complications. METHODS: EMBASE, MEDLINE, PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), and Cumulative Index to Nursing and Allied Health Literature (CINAHL) database were searched from inception to September 15th, 2022, for studies investigating hemiepephysiodesis for JHV and its effect on clinical and radiological outcomes. The search, data extraction and methodologic assessment were performed in duplicate for all included studies. RESULTS: Six studies out of 488 with a total of 147 feet in 85 patients were included in the final qualitative synthesis. The American Orthopaedic Foot & Ankle Society hallux metatarsophalangeal interphalangeal scale (AOFAS Hallux MTP-IP scale) was used in two studies. The mean pooled preoperative score was 62.2 ± 8.9 and improved to 88.6 ± 4.8 postoperatively in 33 patients. All six studies reported significant improvement in the hallux valgus angle (HVA) from mean preoperative angle of 29.2° ± 3.7-23.8° ± 4.5° postoperatively, while the intermetatarsal angle (IMA) preoperative and postoperative means corrected from 13.9° ± 1.1-11.4° ± 1.2°, respectively. Out of 147 feet, 21 (14.2%) had reported complications including recurrence and need for revision surgery. CONCLUSION: This systematic review confirms that hemiepiphysiodesis of the first metatarsal in patients with JHV has improved clinical and radiological outcomes. LEVEL OF EVIDENCE: Level IV, Systematic review.

Computerized Cognitive Test Batteries for Children and Adolescents-A Scoping Review of Tools For Lab- and Web-Based Settings From 2000 to 2021.

OBJECTIVE: Cognitive functioning is essential to well-being. Since cognitive difficulties are common in many disorders, their early identification is critical, notably during childhood and adolescence. This scoping review aims to provide a comprehensive literature overview of computerized cognitive test batteries (CCTB) that have been developed and used in children and adolescents over the past 22 years and to evaluate their psychometric properties. METHOD: Among 3192 records identified from three databases (PubMed, PsycNET, and Web of Science) between 2000 and 2021, 564 peer-reviewed articles conducted in children and adolescents aged 3 to 18 years met inclusion criteria. Twenty main CCTBs were identified and further reviewed following PRISMA guidelines. Relevant study details (sample information, topic, location, setting, norms, and psychometrics) were extracted, as well as administration and instrument characteristics for the main CCTBs. RESULTS: Findings suggest that CCTB use varies according to age, location, and topic, with eight tools accounting for 85% of studies, and the Cambridge Neuropsychological Test Automated Battery (CANTAB) being most frequently used. Few instruments were applied in web-based settings or include social cognition tasks. Only 13% of studies reported psychometric properties. CONCLUSIONS: Over the past two decades, a high number of computerized cognitive batteries have been developed. Among these, more validation studies are needed, particularly across diverse cultural contexts. This review offers a comprehensive synthesis of CCTBs to aid both researchers and clinicians to conduct cognitive assessments in children in either a lab- or web-based setting.

Prenatal and concurrent blood mercury concentrations and associations with IQ in canadian preschool children.

BACKGROUND: Prenatal and childhood mercury (Hg) exposures have been associated with negative impacts on child neurodevelopment. It is unclear if associations persist at the low Hg exposures typical in Western countries. OBJECTIVE: To examine associations between prenatal/childhood blood Hg concentrations and child IQ in Canadian male and female children while considering the potential modifying role of prenatal fish consumption. METHODS: We analyzed data from the Maternal-Infant Research on Environmental Chemicals study. Hg was measured in first trimester (n = 527), cord (n = 430), and child (at 3-4 years of age, n = 355) blood and examined sex-stratified associations between blood Hg and children's Full Scale IQ (FSIQ), Verbal IQ (VIQ), Performance IQ (PIQ), and General Language Composite (GLC) scores (assessed with WPPSI-III). Prenatal Hg analyses were further stratified by prenatal fish consumption (low: 0-2, moderate: 3-7, or high: ≥8 times/month). RESULTS: Higher cord blood Hg concentrations were associated with lower PIQ (ß = -3.27; 95%CI: 6.44, -0.09) in male children with the lowest prenatal fish consumption. Progressively stronger positive associations were observed with PIQ in male children for moderate (ß = 1.08; 95%CI: 0.10, 2.26) and high (ß = 3.07; 95%CI: 1.95, 4.19) prenatal fish consumption. Cord blood Hg concentrations were positively associated with female children's FSIQ (ß = 1.29; 95% CI: 0.77, 1.81) and PIQ (ß = 2.01; 95% CI: 1.19, 2.83); however, when stratified only in the highest fish consumption subgroup. Among female children, higher child blood Hg concentrations were associated with an approximately 1-point increase in FSIQ, VIQ, and GLC. CONCLUSIONS: Prenatal exposure to low levels of Hg was associated with lower PIQ scores in male children with low prenatal fish intake. Positive associations between cord and child blood Hg concentrations and IQ were primarily observed in female children and may be due to beneficial effects of prenatal fish intake.

Prenatal exposure to legacy PFAS and neurodevelopment in preschool-aged Canadian children: The MIREC cohort.

BACKGROUND: Exposure to perfluoroalkyl substances (PFAS) has been shown to be neurotoxic in experimental studies, but epidemiological evidence linking prenatal PFAS exposure to child neurodevelopment is equivocal and scarce. OBJECTIVE: To quantify associations between prenatal exposure to legacy PFAS and children's intelligence (IQ) and executive functioning (EF) in a Canadian pregnancy and birth cohort and to determine if these associations differ by child sex. METHODS: We measured first-trimester plasma concentrations of perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS), and perfluorohexanesulfonic acid (PFHxS) in the Maternal-Infant Research on Environmental Chemicals (MIREC) study and assessed children's full-scale (n = 522), performance (n = 517), and verbal (n = 519) IQ using the Wechsler Preschool and Primary Scale of Intelligence (WPPSI-III). Children's working memory (n = 513) and ability to plan and organize (n = 514) were assessed using a parent-reported questionnaire, the Behavior Rating Inventory of Executive Function - Preschool Version (BRIEF-P). We quantified associations between individual log2-transformed PFAS exposure and children's IQ and EF using multiple linear regression analyses and evaluated effect modification by child sex. We also used Repeated Holdout Weighted Quantile Sum (WQS) regression models with effect modification by child sex to quantify the effect of combined exposure to all three PFAS chemicals on IQ and EF. All models were adjusted for key sociodemographic characteristics. RESULTS: Geometric mean plasma concentrations (IQR) for PFOA, PFOS and PFHxS were 1.68 (1.10-2.50), 4.97 (3.20-6.20) and 1.09 (0.67-1.60) µg/L respectively. We found evidence of effect modification by child sex in all models examining performance IQ (p < .01). Specifically, every doubling of PFOA, PFOS, and or PFHxS was inversely associated with performance IQ, but only in males (PFOA: B = -2.80, 95% CI: -4.92, -0.68; PFOS: B = -2.64, 95% CI: -4.77, -0.52; PFHxS: B = -2.92, 95% CI: -4.72, -1.12). Similarly, every quartile increase in the WQS index was associated with poorer performance IQ in males (B = -3.16, 95% CI: -4.90, -1.43), with PFHxS contributing the largest weight to the index. In contrast, no significant association was found for females (B = 0.63, 95% CI: -0.99, 2.26). No significant associations were found for EF in either males or females. CONCLUSIONS: Higher prenatal PFAS exposure was associated with lower performance IQ in males, suggesting that this association may be sex- and domain-specific.

Enhancing Postoperative Pain Management and Decreasing Hospital Length of Stay on a Pediatric Orthopedic Unit: Implementation of an Ambulatory Continuous Peripheral Nerve Block Program.

PURPOSE: Pediatric Ambulatory Continuous Peripheral Nerve Block (ACPNB) programs are a safe and effective pain management modality that can reduce patient length of stay (LOS) while ensuring optimal, multimodal pain management at home after surgery. Our institution previously solely used electronic infusion pumps to deliver local anesthetic via peripheral nerve catheters, requiring postoperative inpatient admissions for pain management. We aimed to enhance postoperative pain management and decrease hospital LOS after orthopedic foot and ankle surgery through implementation of an ACPNB program. DESIGN: An ACPNB program was developed and implemented for pediatric patients undergoing foot and ankle reconstruction surgery. METHODS: We provide a detailed description of the multidepartment collaboration led by the acute pain service (APS) and orthopedics that resulted in the development and implementation of a pediatric ACPNB program using portable, elastomeric devices for patients undergoing reconstructive foot and ankle surgery. Implementation tools, including caregiver and nursing education resources, a data collection log, a process map, and staff surveys are shared. FINDINGS: Twenty-eight patients received elastomeric devices during the 12 months of data collection. All 28 patients who required a continuous peripheral nerve block (CPNB) for pain management following foot and ankle reconstruction surgery received their block via an elastomeric device rather than an electronic hospital infusion pump. All patients and caregivers expressed positive satisfaction with pain management after hospital discharge. No patient with an elastomeric device required scheduled opioids for pain management by the end of their hospital admission. LOS on the orthopedic inpatient unit for foot and ankle surgery decreased by 58%, representing an estimated 29 days and $27,557.88 saved. A majority (96.4%) of staff survey respondents reported feeling satisfied with their overall experience working with an elastomeric device. CONCLUSIONS: The successful implementation of a pediatric ACPNB program has led to positive patient outcomes, including a significant decrease in hospital LOS and health system cost savings for this patient population.

Descriptive analysis of organophosphate ester metabolites in a pan-Canadian pregnancy cohort.

Organophosphate esters (OPEs) are widely used in numerous consumer products for their flame retardant and plasticizing properties. Despite potential widespread exposure, biomonitoring data during critical windows of development are scarce and limited to the most widely studied metabolites. We quantified urinary concentrations of multiple OPE metabolites in a vulnerable Canadian population. Using data and biobanked specimens from the Maternal-Infant Research on Environmental Chemicals (MIREC) study (2008-2011), we measured first trimester urinary concentrations of 15 OPE metabolites as well as one flame retardant metabolite and quantified associations with sociodemographic and sample collection characteristics in 1865 pregnant participants. We applied 2 different analytical methods to quantify OPEs, one using UItra-Performance Liquid Chromatography coupled to tandem mass spectrometry (UPLC-MS/MS) and the other using Atmospheric Pressure Gas Chromatography coupled to mass spectrometry (APGC-MS/MS) with sensitive limits of detection (0.008-0.1 µg/L). We modelled associations between sociodemographic and sample collection characteristics and specific gravity-standardized chemical concentrations. Six OPE metabolites were detected in the majority (68.1-97.4 %) of participants. Bis-(2-chloroethyl) hydrogen phosphate had the highest detection rate (97.4 %). Diphenyl phosphate had the highest geometric mean concentration (0.657 µg/L). Metabolites of tricresyl phosphate were detected in few participants. Associations between sociodemographic characteristics varied according to each OPE metabolite. Pre-pregnancy body mass index tended to be positively associated with OPE metabolite concentrations whereas age tended to be inversely associated with OPE concentrations. OPE concentrations were, on average, higher in urine samples collected in the summer than other seasons the winter. We present the largest biomonitoring study of OPE metabolites in pregnant people to date. These findings demonstrate widespread exposure to OPEs and their metabolites and identify subpopulations who may experience heightened exposure.

Urinary concentrations and determinants of glyphosate and glufosinate in pregnant Canadian participants in the MIREC study.

BACKGROUND: Glyphosate is the most widely applied herbicide in agriculture. Glufosinate is a broad spectrum herbicide used to manage glyphosate-resistant weeds. Despite the widespread use of these herbicides, biomonitoring data - which inform risk assessment and management - are sparse. OBJECTIVES: To identify determinants of urinary concentrations of these herbicides and their metabolites in pregnancy. METHODS: We measured urinary concentrations of glyphosate, glufosinate, and their primary metabolites aminomethylphosphonic acid (AMPA) and 3-methylphosphinicopropionic acid (3-MPPA) in a single spot urine specimen collected during the first trimester of pregnancy from the Maternal-Infant Research on Environmental Chemicals (MIREC) study. MIREC recruited about 2000 pregnant women from 10 Canadian cities between 2008 and 2011. We used UItra-Performance Liquid Chromatography coupled to tandem mass spectrometry (UPLC-MS/MS) with sensitive limits of detection to quantify analyte concentrations. We examined urinary concentrations according to maternal sociodemographics, sample collection characteristics, reported pesticide use, and consumption of fruits, vegetables, legumes, and grain products. We used ANOVA models with specific gravity-standardized chemical concentrations as the dependent variable to determine associations with maternal and sample determinants. RESULTS: Among women with biobanked urine samples (n = 1829-1854), 74% and 72% had detectable concentrations of glyphosate and AMPA, respectively. In contrast, one and six percent of women had detectable concentrations of glufosinate and 3-MPPA, respectively. The specific gravity-standardized geometric mean (95% CI) concentrations of glyphosate and AMPA were 0.112 (0.099-0.127) µg/L and 0.159 (0.147-0.172) µg/L, respectively. We observed a dose-response relationship between consumption of whole grain bread and higher urinary glyphosate concentrations. Season of urine collection and self-reported pesticide use were not associated with increased concentrations of any analyte. CONCLUSIONS: We detected glyphosate and AMPA in the majority of pregnant women from this predominantly urban Canadian cohort. Diet was a probable route of exposure.

Incidence of secondary interventions after early spica casting for diaphyseal femur fractures in young children.

BACKGROUND: Children aged 6 months to 5 years with diaphyseal femur fractures are typically treated with spica casting, as recommended by the American Association of Orthopaedic Surgeons clinical practice guideline. We aimed to determine the incidence of secondary interventions after early spica casting for femur fractures in children aged 6 years or less. METHODS: This was a retrospective cohort study of patients aged 6 years or less with diaphyseal femur fractures treated with early spica casting at a single Canadian tertiary care, level 1 trauma pediatric centre between January 2005 and May 2015. RESULTS: A total of 246 patients were included (190 boys [77.2%] and 56 girls [22.8%] with a mean age of 2.28 yr [standard deviation (SD) 1.35 yr]). Nine patients (3.7%) required early secondary interventions (cast wedging in 8 and flexible intramedullary nail fixation in 1). At last follow-up, 51 patients (20.7%) had clinically measurable limb length discrepancy (LLD) (mean 9.4 mm [SD 3-25 mm]), and 1 patient (0.4%) had mild clinical valgus deformity. Older, heavier patients with initial fracture shortening of 20 mm or more had a higher likelihood of developing a clinically measurable LLD. No patient required surgical intervention after fracture union to correct acquired LLD or angular deformity. CONCLUSION: Early spica casting for diaphyseal femoral fractures in children aged 6 years or younger had a low rate of complications and return to the operating room, Although 21% of patients had a clinically measurable LLD at last follow-up, no patient required secondary intervention after fracture union to correct acquired LLD or angular deformity. These findings have relevance for the Canadian health care system, especially during the COVID-19 pandemic.

Clinically Detected Leg Length Discrepancy in Patients With Idiopathic Clubfoot Deformity: Prevalence and Outcomes.

BACKGROUND: This study evaluates the prevalence and outcomes of patients with idiopathic clubfoot and clinically detected limb length discrepancy (LLD). METHODS: This is a retrospective cohort study of idiopathic clubfoot patients in a Research Ethics Board-approved clubfoot registry. Patients with LLD ≥0.5 cm (LLD+) were compared with those with no or <0.5 cm LLD (LLD-). LLD was determined by documented clinical examination. Exclusion criteria included nonidiopathic clubfoot deformity, <2-year follow-up, and incomplete records. RESULTS: Of the 300 patients included, 27 (9.0%) had an LLD, of whom 23 patients had a unilateral clubfoot deformity. The prevalence of LLD was 15.3% and 2.67% in unilateral and bilateral clubfoot patients, respectively. The mean LLD was 1.21 cm (0.5 to 3.5 cm, SD: 0.78 cm) in LLD+ patients, with a mean of 1.27 cm (SD: 0.79 cm) in unilateral clubfoot patients and 0.88 cm (SD: 0.75 cm) in bilateral patients. The total number of casts applied in LLD+ unilateral clubfoot patients was significantly higher than in LLD- unilateral patients (9.5 vs. 6.8 casts; P =0.015). The overall relapse rate in all patients was 30.3% and was significantly higher in the unilateral only LLD+ group [relative risk (RR)=2.89] and the total LLD+ patient cohort (RR=1.68). The risk of repeat casting for relapse was also higher in the unilateral LLD+ group (RR=2.45) and the total LLD+ group (RR=1.87). The risk of surgery for relapse was significantly higher in the unilateral LLD+ group for any surgery ( P =0.046), and most specifically for open tendo-Achilles tenotomy ( P =0.008) and tibialis anterior tendon transfer ( P =0.019). There was no correlation between the severity of LLD and Pirani score at presentation. CONCLUSIONS: LLD was present in 9% of idiopathic clubfoot patients, and most were <2 cm. There is a significantly higher risk of relapse in patients with unilateral clubfoot and LLD. The risk of surgery overall was higher in all patients with a unilateral LLD. Assessment of LLD should be routinely performed in clubfoot patients. LEVEL OF EVIDENCE: Level III.