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Abstract Background Although morbidity and mortality from coronary heart disease (CHD) are high, only a minority of acute coronary syndrome (ACS) survivors accesses an effective secondary prevention program. We aim to determine whether the previously proven CHOICE program can be replicated at multiple sites and whether ongoing reinforcement further improves risk factor modification. Methods/design Participants eligible for but not accessing standard cardiac rehabilitation will be randomly allocated to either a previously tested 3-month CHOICE program or a 30-month CHOICE program (CHOICE-plus). Both groups will participate in individualised risk factor modules of differing duration that involve choice, goal setting and telephone follow-up for three months. CHOICE-plus will also receive additional face-to-face and telephone reinforcement between three and 30 months. At one site we will recruit a randomised control group, receiving conventional care. Primary outcomes are lipid levels, blood pressure, physical activity levels and smoking rates. Secondary outcomes include readmission rates, death, the number of risk factors, other modifiable risk factors, quality of life and process evaluation measures over three years. Discussion We present the rationale and design of a multi-centre, replication study testing a modular approach for the secondary prevention of CHD following an ACS. Trial Registration [Clinical Trial Registration Number, ACTRN12608000182392]

Abstract Background Coronary heart disease (CHD) is a major cause of morbidity and mortality in Australia and it is recommended that all persons with unstable angina (UA) or myocardial infarction (MI) participate in secondary prevention as offered in cardiac rehabilitation (CR) programs. However, the majority of patients do not access standard CR and have higher baseline coronary risk and poorer knowledge of CHD than those persons due to commence CR. The objective of this study is to investigate whether a modular guided self-choice approach to secondary prevention improves coronary risk profile and knowledge in patients who do not access standard CR. Methods/Design This randomised controlled trial with one year follow-up will be conducted at a tertiary referral hospital. Participants eligible for but not accessing standard CR will be randomly allocated to either a modular or conventional care group. Modular care will involve participation in individualised modules that involve choice, goal-setting and coaching. Conventional care will involve ongoing heart disease management as directed by the participant's doctors. Both modular and conventional groups will be compared with a contemporary reference group of patients attending CR. Outcomes include measured modifiable risk factors, relative heart disease risk and knowledge of risk factors. Discussion We present the rationale and design of a randomised controlled trial testing a modular approachfor the secondary prevention of coronary heart disease following acute coronary syndrome.

Supraventricular tachycardia (SVT) is a common cardiac rhythm disturbance; it usually presents with recurrent episodes of tachycardia, which often increase in frequency and severity with time. Although SVT is usually not life-threatening, many patients suffer recurrent symptoms that have a major impact on their quality of life. The uncertain and sporadic nature of episodes of tachycardia can cause considerable anxiety - many patients curtail their lifestyle as a result, and many prefer curative treatment. SVT often terminates before presentation, and episodes may be erroneously attributed to anxiety. Sudden-onset, rapid, regular palpitations characterise SVT and, in most patients, a diagnosis can be made with a high degree of certainty from patient history alone. Repeated attempts at electrocardiographic documentation of the arrhythmia may be unnecessary. Treatment of SVT may not be necessary when the episodes are infrequent and self-terminating, and produce minimal symptoms. When episodes of tachycardia occur frequently, are prolonged or are associated with symptoms that affect quality of life, catheter ablation is the first choice of treatment; it is a low-risk procedure with a high success rate. Long-term preventive pharmacotherapy is an alternative approach in some patients. [ABSTRACT FROM AUTHOR]

To optimize the identification of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected children, specimen collection and testing method are crucial considerations. Ideally, specimen collection is easy and causes minimal discomfort, and the laboratory approach is simple, accurate, and rapid. In this prospective cohort study we evaluated the accuracy of a point-of care nucleic acid device using caregiver/patient self-collected buccal swabs. Participants were recruited in 14 Canadian tertiary care pediatric emergency departments. Children <18 years of age deemed to require SARS-CoV-2 testing were eligible. Caregivers or the patient-collected buccal swabs which were tested on the ABBOTT ID NOW. The reference standard was nasopharyngeal swab specimens collected by a healthcare provider tested via laboratory reverse transcription PCR (RT-PCR). We enrolled 2,640 study participants and 14.4% (381/2,640) were SARS-CoV-2 RT-PCR-positive. Eight percent (223/2,640) and 85.0% (2,244/2,640) were concordant test-positive and concordant test-negative, respectively. Sensitivity and specificity of the investigational approach were 58.5% [95% confidence interval (CI): 53.4, 63.5] and 99.3% (95% CI: 98.9, 99.6), respectively. Cycle threshold values were lower among concordant [median 17 (15, 21)] relative to discordant [median 30 (22, 35)] swabs ( P < 0.001). Sensitivity was greatest among children <4 years of age, when caregivers performed the swabs, among unvaccinated children, and those with shorter symptom duration. Across multiple pain measures, less pain was associated with buccal swab testing. Although accuracy of the buccal swab point-of-care SARS-CoV-2 test was good and negative agreement was excellent, sensitivity was only 58.5%. Concordance was greater among those with higher viral loads, and the approach involving buccal swabs was less painful.IMPORTANCETo optimize the identification of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected children, specimen collection and testing method are crucial considerations. Ideally, specimen collection is easy and causes minimal discomfort, and laboratory approach is simple, accurate, and rapid. We evaluated the accuracy and pain associated with buccal swab specimen collection by caregivers or children themselves who were tested using a point-of-care isothermal nucleic acid amplification SARS-CoV-2 test. This novel approach was compared to nasopharyngeal swab specimens tested using laboratory-based PCR tests. While negative agreement was excellent, positive percent agreement was less than 60%. Concordance was greater among those with higher viral loads, and thus, sensitivity is excellent when transmissibility is more likely to occur. Importantly, the approach involving buccal swabs was significantly less painful, and thus, children and their caregivers are more likely to agree to testing using such an approach.CLINICAL TRIALSRegistered at ClinicalTrials.gov (NCT05040763).

Objective: Using a double-dummy pilot randomized controlled trial design, we aimed to determine the feasibility and acceptability of comparing remote electrical neuromodulation (REN) to typical care intravenous pharmacologic interventions for the treatment of children and adolescents visiting the emergency department (ED) with migraine, and to compare parallel-group versus crossover trial designs., Background: There are limited data to guide the management of migraine in the ED. Children and adolescents are interested in neuromodulation, and specifically REN, for treatment in this setting, but there are no existing data on this approach., Methods: We employed a double-dummy, double-blind, pilot randomized controlled trial that tested two designs in two phases: a parallel-group design and a crossover design (ClinicalTrials.gov identifier: NCT05102591). The intervention arms consisted of: (i) active REN stimulation with matched normal saline placebo intravenously, and (ii) matched sham REN stimulation, intravenous metoclopramide (0.15 mg/kg, maximum 10 mg), and intravenous ketorolac (0.5 mg/kg, maximum 30 mg). Youth aged 8.0-<18.0 years visiting a Canadian tertiary care pediatric ED with migraine attacks as per criteria B-E of the International Classification of Headache Disorders third edition were eligible. Primary outcomes were focused on trial feasibility and acceptability, and preliminary efficacy and safety data were also collected., Results: A total of 34% (22/65) of those who screened eligible were enrolled. Three participants (14%) withdrew prior to receiving any study interventions. In all, 10 participants were allocated to typical care, and nine to REN. All treated participants (19/19) completed all assessments. Recruitment was higher during the parallel-group phase: 1.1 participants/month versus 0.6 participants/month, and 36% (17/47) versus 28% (five of 18) of screened eligible were enrolled in the parallel-group and crossover phases, respectively. Participants reported positive impressions of REN use in the ED, e.g., higher mean (standard deviation [SD]) levels of interest in using REN only at 3.7 (1.0) versus 2.8 (1.0) in using intravenous interventions only for a future ED visit. Participants and clinical staff reported overall positive impressions regarding the study protocol. Employing an 11-point pain numerical rating scale, the mean (SD) reduction in pain severity score was 2.1 (1.3) and 2.9 (2.9) from baseline to 1 h, and 2.4 (1.6) and 4.0 (3.5) from baseline to 2 h for REN and intravenous interventions, respectively. One participant in the typical care group and none in the REN group experienced adverse events., Conclusion: We demonstrated the feasibility and acceptability of our trial protocol and of using REN to treat youth presenting to the ED with migraine. The parallel-group design generated a higher recruitment rate than the crossover design. Our preliminary efficacy and safety data suggest that REN could be non-inferior to typical care, but we were not powered for these outcomes. Further research on REN's use in the ED setting is warranted., (© 2024 The Author(s). Headache: The Journal of Head and Face Pain published by Wiley Periodicals LLC on behalf of American Headache Society.)

Objective: To evaluate how social behaviors relate to SARS-CoV-2 test positivity across pediatric age groups., Methods: Multicenter, cross-sectional study recruiting children <18 years old tested for SARS-CoV-2 infection in emergency departments between 2020 and 2022. We used multivariate logistic regression to assess how self-reported social behaviors affect SARS-CoV-2 test positivity across four age groups. Causal mediation analysis quantified how mask-wearing and presence of an infected close contact mediated the SARS-CoV-2 risk of given behaviors., Results: Seven thousand two hundred and seventy two children were enrolled and 1457 (20.0%) tested positive for SARS-CoV-2. Attending a social gathering was associated with increased odds (aOR 1.64, 95% CI: 1.05, 2.57) of SARS-CoV-2 positivity among children aged 5-<12 years. Those attending in-person school/daycare were less likely to test positive for SARS-CoV-2 across all age categories. Attending childcare was associated with 16.3% (95% CI: -21.0%, -11.2%) and 9.0% (95% CI: -11.6%, -6.5%) reductions in the probability of testing positive for SARS-CoV-2 infection, with 53.5% (95% CI: 39.2%, 73.9%) and 22.8% (95% CI: 9.7%, 36.2%) of the effects being mediated by the presence of a close contact among <1 year and 1-<5 year age groups, respectively. Masking in public mediated the association between childcare attendance and SARS-CoV-2 positivity in children aged <1 year., Conclusions: Attending social gatherings increased the risk of SARS-CoV-2 test positivity in 5-<12-year-old children, but in-person daycare/school was associated with a reduced odds of testing positive across all ages. Settings with high public health adherence (ie, schools) reduced the risk of testing positive for SARS-CoV-2, possibly from reduced close contact with SARS-CoV-2 positive individuals., Competing Interests: Declaration of Competing Interest No conflicts of interest to disclose., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To assess the association between Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection and long-term quality of life (QoL)., Methods: Prospective cohort study with 6- and 12-months follow-up conducted in 14 Canadian institutions. Children tested for SARS-CoV-2 between August 2020 and February 2022 were eligible. QoL was measured using PedsQL-4.0, overall health status scores 6- and 12-months after testing., Results: Among SARS-CoV-2 positive and negative participants eligible for long-term follow-up, 74.8% (505/675) and 71.8% (1106/1541) at 6- and 59.0% (727/1233) and 68.1% (2520/3699) at 12-months, completed follow-up, respectively. Mean ± SD PedsQL scores did not differ between positive and negative groups; difference: -0.86 (95% CI: -2.33, 0.61) at 6- and -0.48 (95% CI: -1.6, 0.64) at 12-months, respectively. SARS-CoV-2 test-positivity was associated with higher social subscale scores. Although in bivariate analysis, overall health status at 6-months was higher among SARS-CoV-2 cases [difference: 2.16 (95% CI: 0.80, 3.53)], after adjustment for co-variates, SARS-CoV-2 infection was not independently associated with total PedsQL or overall health status at either time point. Parental perception of recovery did not differ based on SARS-CoV-2 test-status at either time point., Conclusions: SARS-CoV-2 infection was not associated with QoL, overall health status, or parental perception of recovery 6- and 12-months following infection., Competing Interests: Declaration of Competing Interest This work was supported by the Public Health Agency of Canada’s Immunization Partnership Fund (Emerging Issues Fund) and their Emerging Issues Fund (Enhanced Surveillance), and the Canadian Institute of Health Research (Operating Grant: Emerging COVID 19 Research Gaps and Priorities Funding Opportunity). SF is supported by the Alberta Children’s Hospital Foundation Professorship in Child Health and Wellness. FD is supported by the University of Calgary, Eyes High Post-Doctoral Fellowship., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Protective factors, including psychological resilience, cognitive reserve, and brain reserve, may be positively associated with recovery after pediatric mild traumatic brain injury (mTBI) but are yet to be studied concurrently. We sought to examine these factors as moderators of post-concussive symptoms (PCS) in pediatric mTBI compared with mild orthopedic injury (OI). Participants included 967 children (633 mTBI, 334 OI) aged 8-16.99 years, recruited from 5 Canadian pediatric emergency departments as part of a prospective longitudinal cohort study. At 10 days post-injury, psychological resilience was measured using the Connor-Davidson Resilience Scale and brain reserve was measured using total brain volume derived from structural magnetic resonance imaging. Cognitive reserve was measured at 3 months post-injury using IQ scores from the Wechsler Abbreviated Scale of Intelligence-Second Edition. Cognitive and somatic PCS were measured using child and parent ratings on the Health and Behavior Inventory, completed weekly for 3 months and biweekly to 6 months. Analyses involved generalized least-squares regression models using restricted cubic splines. Covariates included age at injury, sex, racialized identity, material and social deprivation, pre-injury migraine and concussion history, and retrospective pre-injury PCS. Psychological resilience moderated group differences in parent-reported PCS. At 30 days post-injury, estimated group differences in parent-reported cognitive and somatic PCS (mTBI > OI) were larger at higher (75th percentile) resilience scores ( Est = 2.25 [0.87, 3.64] and Est = 2.38 [1.76, 3.00], respectively) than at lower (25th percentile) resilience scores ( Est = 1.44 [0.01, 2.86] and Est = 2.08 [1.45, 2.71], respectively). Resilience did not moderate group differences in child-reported PCS but was negatively associated with child-reported PCS in both groups ( p s ≤ 0.001). Brain reserve (i.e., total brain volume [TBV]) also moderated group differences, but only for parent-reported somatic PCS ( p = 0.018). Group difference (mTBI > OI) at 30 days was larger at smaller (25th percentile) TBV ( Est = 2.78 [2.17, 3.38]) than at larger (75th percentile) TBV ( Est = 1.95 [1.31, 2.59]). TBV was not associated with parent-reported cognitive PCS or child-reported PCS. IQ did not moderate PCS in either group but had a significant non-linear association in both groups with child-reported somatic PCS ( p = 0.018) and parent-reported PCS ( p < 0.001), with higher PCS scores at both lower and higher IQs. These findings suggest that higher resilience predicts fewer PCS, but less strongly after mTBI than OI; greater brain reserve may reduce the effect of mTBI on somatic PCS; and cognitive reserve has an unexpected curvilinear association with PCS across injury types. The results highlight the importance of protective factors as predictors of recovery and potential targets for intervention following pediatric mTBI.

Background: Asymptomatic SARS-CoV-2 infection in children is highly prevalent but its acute and chronic implications have been minimally described., Methods: In this controlled case-ascertained household transmission study, we recruited asymptomatic children <18 years with SARS-CoV-2 nucleic acid testing performed at 12 tertiary care pediatric institutions in Canada and the United States. We attempted to recruit all test-positive children and 1 to 3 test-negative, site-matched controls. After 14 days' follow-up we assessed the clinical (ie, symptomatic) and combined (ie, test-positive, or symptomatic) secondary attack rates (SARs) among household contacts. Additionally, post-COVID-19 condition (PCC) was assessed in SARS-CoV-2-positive participating children after 90 days' follow-up., Results: A total of 111 test-positive and 256 SARS-CoV-2 test-negative asymptomatic children were enrolled between January 2021 and April 2022. After 14 days, excluding households with co-primary cases, the clinical SAR among household contacts of SARS-CoV-2-positive and -negative index children was 10.6% (19/179; 95% CI: 6.5%-16.1%) and 2.0% (13/663; 95% CI: 1.0%-3.3%), respectively (relative risk = 5.4; 95% CI: 2.7-10.7). In households with a SARS-CoV-2-positive index child, age <5 years, being pre-symptomatic (ie, developed symptoms after test), and testing positive during Omicron and Delta circulation periods (vs earlier) were associated with increased clinical and combined SARs among household contacts. Among 77 asymptomatic SARS-CoV-2-infected children with 90-day follow-up, 6 (7.8%; 95% CI: 2.9%-16.2%) reported PCC., Conclusions: Asymptomatic SARS-CoV-2-infected children, especially those <5 years, are important contributors to household transmission, with 1 in 10 exposed household contacts developing symptomatic illness within 14 days. Asymptomatic SARS-CoV-2-infected children may develop PCC., Competing Interests: Potential conflicts of interest . A. F. reports grants from the University of Calgary Eyes High Postdoctoral Fellowship and Canadian Institutes of Health Research Banting Postdoctoral Fellowship, and support for meetings and/or travel from a Trainee Travel Grant (Pediatric Academic Societies and Trainee travel grant), Alberta Children's Hospital Association, University of Calgary. L. A. reports grants from Pfizer. M. W. reports support for meetings and/or travel from US Acute Care Solutions (USACS), stock and a board of directors position for EM Device Lab. N. K. reports a leadership or fiduciary role for the Pediatric Emergency Care Applied Research, Pediatric Emergency Research Network; research funding from the National Institutes of Health (NIH), Health Resources and Services Administration (HRSA), and Patient-Centered Outcomes Research Institute (PCORI). R. M. reports royalties or licenses for Affinivax; consulting fees from GSK, Affinivax, and Merck; payment for lectures and support for meetings and/or travel from GSK; patents planned, issued, or pending for Boston Children's Hospital; being a member of the Affinivax board of directors; and stock options for Affinivax and Corner Therapeutics. S. M. M. reports grants from Sanofi, Merck, Pfizer National Minority Quality Forum (US); support for meetings and/or travel from Sanofi, Merck, GSK, Pfizer, CSL, Biosciences Association of Manitoba (BAM), and the National Minority Quality Forum (US); and participation on a Data and Safety Monitoring Board or Advisory board for Sanofi. T. A. F. reports grants from the National Heart, Lung, and Blood Institute (NHLBI) and leadership or fiduciary roles for the Society of Pediatric Research and the Pediatric Academic Societies. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Objectives: To compare symptoms and outcomes among infants aged ≤90 days tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a broad, international sample of emergency departments (EDs)., Methods: This was a secondary analysis of infants aged 0 to 90 days with suspected SARS-CoV-2 infections tested using molecular approaches and with 14-day follow-up. The parent studies were conducted at 41 EDs in 10 countries (the global Pediatric Emergency Research Network; March 2020-June 2021) and 14 EDs across Canada (Pediatric Emergency Research Canada network; August 2020-February 2022). Symptom profiles included presence and number of presenting symptoms. Clinical outcomes included hospitalization, ICU admission, and severe outcomes (a composite of intensive interventions, severe organ impairment, or death)., Results: Among 1048 infants tested for SARS-CoV-2, 1007 (96.1%) were symptomatic at presentation and 432 (41.2%) were SARS-CoV-2-positive. A systemic symptom (any of the following: Apnea, drowsiness, irritability, or lethargy) was most common and present in 646 (61.6%) infants, regardless of SARS-CoV-2 status. Although fever and upper respiratory symptoms were more common among SARS-CoV-2-positive infants, dehydration, gastrointestinal, skin, and oral symptoms, and the overall number of presenting symptoms did not differ between groups. Infants with SARS-CoV-2 infections were less likely to be hospitalized (32.9% vs 44.8%; difference -11.9% [95% confidence interval (CI) -17.9% to -6.0%]), require intensive care (1.4% vs 5.0%; difference -3.6% [95% CI -5.7% to -1.6%]), and experience severe outcomes (1.4% vs 5.4%; difference -4.0% [95% CI -6.1% to -1.9%])., Conclusions: SARS-CoV-2 infections may be difficult to differentiate from similar illnesses among the youngest infants but are generally milder. SARS-CoV-2 testing can help inform clinical management., (Copyright © 2024 by the American Academy of Pediatrics.)

Objective: To examine preinjury life events as moderators of postconcussive symptoms (PCS) and quality of life (QoL) in children with pediatric mild traumatic brain injury (mTBI) versus orthopedic injury (OI)., Methods: Participants were 633 children with mTBI and 334 with OI, ages 8-16.99, recruited from 5 pediatric emergency departments and followed for 6 months postinjury as part of a prospective cohort study. Preinjury life events were measured retrospectively using the Child and Adolescent Survey of Experiences, PCS using the Health and Behavior Inventory (HBI) and Post-Concussion Symptom Interview (PCS-I), and QoL using the Pediatric Quality of Life Inventory (PedsQL). Analyses involved longitudinal regression using restricted cubic splines, with group, positive and negative life events, and time as primary predictors. Covariates included age, sex, race, socioeconomic status, preinjury history (i.e., headache, migraine, previous concussion), and parent-rated retrospective PCS-I, HBI, and PedsQL scores., Results: PCS and QoL were worse after mTBI than OI, but group differences declined with time (all p < .001). Group differences in PCS were larger at higher levels of positive life events, which predicted lower PCS (p= .03 to p < .001) and higher QoL (p = .048) after OI but not after mTBI. Negative life events predicted worse PCS and QoL in both groups (p = .002 to p < .001)., Conclusions: Preinjury positive life events moderate outcomes after pediatric injury, with a protective effect seen in OI but not in mTBI. Negative life events are consistently associated with worse outcomes regardless of injury type., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society of Pediatric Psychology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Rationale & Objective: Atrial fibrillation (AF) and chronic kidney disease (CKD) often coexist. However, it is not known whether CKD is an independent risk factor for incident AF. Therefore, we evaluated the association between markers of CKD-estimated glomerular filtration rate (eGFR) and albuminuria-and incident AF., Study Design: Systematic review and meta-analysis of cohort studies and randomized controlled trials., Setting & Study Populations: Participants with measurement of eGFR and/or albuminuria who were not receiving dialysis., Selection Criteria for Studies: Cohort studies and randomized controlled trials were included that reported incident AF risk in adults according to eGFR and/or albuminuria., Analytical Approach: Age- or multivariate-adjusted risk ratios (RRs) for incident AF were extracted from cohort studies, and RRs for each trial were derived from event data. RRs for incident AF were pooled using random-effects models., Results: 38 studies involving 28,470,249 participants with 530,041 incident AF cases were included. Adjusted risk of incident AF was greater among participants with lower eGFR than those with higher eGFR (eGFR<60 vs≥60mL/min/1.73m 2 : RR, 1.43; 95% CI, 1.30-1.57; and eGFR<90 vs≥90mL/min/1.73m 2 : RR, 1.42; 95% CI, 1.26-1.60). Adjusted incident AF risk was greater among participants with albuminuria (any albuminuria vs no albuminuria: RR, 1.43; 95% CI, 1.25-1.63; and moderately to severely increased albuminuria vs normal to mildly increased albuminuria: RR, 1.64; 95% CI, 1.31-2.06). Subgroup analyses showed an exposure-dependent association between CKD and incident AF, with the risk increasing progressively at lower eGFR and higher albuminuria categories., Limitations: Lack of patient-level data, interaction between eGFR and albuminuria could not be evaluated, possible ascertainment bias due to variation in the methods of AF detection., Conclusions: Lower eGFR and greater albuminuria were independently associated with increased risk of incident AF. CKD should be regarded as an independent risk factor for incident AF., Plain-Language Summary: Irregular heartbeat, or atrial fibrillation (AF), is the commonest abnormal heart rhythm. AF occurs commonly in people with chronic kidney disease (CKD), and CKD is also common in people with AF. However, CKD in not widely recognized as a risk factor for new-onset or incident AF. In this research, we combined data on more than 28 million participants in 38 studies to determine whether CKD itself increases the chances of incident AF. We found that both commonly used markers of kidney disease (estimated glomerular filtration rate and albuminuria, ie, protein in the urine) were independently associated with a greater risk of incident AF. This finding suggests that CKD should be recognized as an independent risk factor for incident AF., (Copyright © 2023 National Kidney Foundation, Inc. All rights reserved.)

Advanced magnetic resonance imaging (MRI) techniques indicate that concussion (i.e., mild traumatic brain injury) disrupts brain structure and function in children. However, the functional connectivity of brain regions within global and local networks (i.e., functional connectome) is poorly understood in pediatric concussion. This prospective, longitudinal study addressed this gap using data from the largest neuroimaging study of pediatric concussion to date to study the functional connectome longitudinally after concussion as compared with mild orthopedic injury (OI). Children and adolescents ( n  = 967) 8-16.99 years with concussion or mild OI were recruited from pediatric emergency departments within 48 h post-injury. Pre-injury and 1-month post-injury symptom ratings were used to classify concussion with or without persistent symptoms based on reliable change. Subjects completed a post-acute (2-33 days) and chronic (3 or 6 months via random assignment) MRI scan. Graph theory metrics were derived from 918 resting-state functional MRI scans in 585 children (386 concussion/199 OI). Linear mixed-effects modeling was performed to assess group differences over time, correcting for multiple comparisons. Relative to OI, the global clustering coefficient was reduced at 3 months post-injury in older children with concussion and in females with concussion and persistent symptoms. Time post-injury and sex moderated group differences in local (regional) network metrics of several brain regions, including degree centrality, efficiency, and clustering coefficient of the angular gyrus, calcarine fissure, cuneus, and inferior occipital, lingual, middle occipital, post-central, and superior occipital gyrus. Relative to OI, degree centrality and nodal efficiency were reduced post-acutely, and nodal efficiency and clustering coefficient were reduced chronically after concussion (i.e., at 3 and 6 months post-injury in females; at 6 months post-injury in males). Functional network alterations were more robust and widespread chronically as opposed to post-acutely after concussion, and varied by sex, age, and symptom recovery at 1-month post-injury. Local network segregation reductions emerged globally (across the whole brain network) in older children and in females with poor recovery chronically after concussion. Reduced functioning between neighboring regions could negatively disrupt specialized information processing. Local network metric alterations were demonstrated in several posterior regions that are involved in vision and attention after concussion relative to OI. This indicates that functioning of superior parietal and occipital regions could be particularly susceptibile to the effects of concussion. Moreover, those regional alterations were especially apparent at later time periods post-injury, emerging after post-concussive symptoms resolved in most and persisted up to 6 months post-injury, and differed by biological sex. This indicates that neurobiological changes continue to occur up to 6 months after pediatric concussion, although changes emerge earlier in females than in males. Changes could reflect neural compensation mechanisms.

Importance: There is a need to understand the long-term outcomes among children infected with SARS-CoV-2., Objective: To quantify the prevalence of post-COVID-19 condition (PCC) among children tested for SARS-CoV-2 infection in pediatric emergency departments (EDs)., Design, Setting, and Participants: Multicenter, prospective cohort study at 14 Canadian tertiary pediatric EDs that are members of the Pediatric Emergency Research Canada network with 90-day, 6-month, and 12-month follow-up. Participants were children younger than 18 years who were tested for SARS-CoV-2 infection between August 2020 and February 2022. Data were analyzed from May to November 2023., Exposure: The presence of SARS-CoV-2 infection at or within 14 days of the index ED visit., Main Outcomes and Measures: Presence of symptoms and QoL reductions that meet the PCC definition. This includes any symptom with onset within 3 months of infection that is ongoing at the time of follow-up and affects everyday functioning. The outcome was quantified at 6 and 12 months following the index ED visit., Results: Among the 5147 children at 6 months (1152 with SARS-CoV-2 positive tests and 3995 with negative tests) and 5563 children at 12 months (1192 with SARS-CoV-2 positive tests and 4371 with negative tests) who had sufficient data regarding the primary outcome to enable PCC classification, the median (IQR) age was 2.0 (0.9-5.0) years, and 2956 of 5563 (53.1%) were male. At 6-month follow-up, symptoms and QoL changes consistent with the PCC definition were present in 6 of 1152 children with positive SARS-CoV-2 tests (0.52%) and 4 of 3995 children with negative SARS-CoV-2 tests (0.10%; absolute risk difference, 0.42%; 95% CI, 0.02% to 0.94%). The PCC definition was met at 12 months by 8 of 1192 children with positive SARS-CoV-2 tests (0.67%) and 7 of 4371 children with negative SARS-CoV-2 tests (0.16%; absolute risk difference, 0.51%; 95% CI, 0.06 to 1.08%). At 12 months, the median (IQR) PedsQL Generic Core Scale scores were 98.4 (90.0-100) among children with positive SARS-CoV-2 tests and 98.8 (91.7-100) among children with negative SARS-CoV-2 tests (difference, -0.3; 95% CI, -1.5 to 0.8; P = .56). Among the 8 children with SARS-CoV-2 positive tests and PCC at 12-month follow-up, children reported respiratory (7 of 8 patients [88%]), systemic (3 of 8 patients [38%]), and neurologic (1 of 8 patients [13%]) symptoms., Conclusions and Relevance: In this cohort study of children tested for SARS-CoV-2 infection in Canadian pediatric EDs, although children infected with SARS-CoV-2 reported increased chronic symptoms, few of these children developed PCC, and overall QoL did not differ from children with negative SARS-CoV-2 tests.

Background: To assist clinicians with identifying children at risk of severe outcomes, we assessed the association between laboratory findings and severe outcomes among severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected children and determined if SARS-CoV-2 test result status modified the associations., Methods: We conducted a cross-sectional analysis of participants tested for SARS-CoV-2 infection in 41 pediatric emergency departments in 10 countries. Participants were hospitalized, had laboratory testing performed, and completed 14-day follow-up. The primary objective was to assess the associations between laboratory findings and severe outcomes. The secondary objective was to determine if the SARS-CoV-2 test result modified the associations., Results: We included 1817 participants; 522 (28.7%) SARS-CoV-2 test-positive and 1295 (71.3%) test-negative. Seventy-five (14.4%) test-positive and 174 (13.4%) test-negative children experienced severe outcomes. In regression analysis, we found that among SARS-CoV-2-positive children, procalcitonin ≥0.5 ng/mL (adjusted odds ratio [aOR], 9.14; 95% CI, 2.90-28.80), ferritin >500 ng/mL (aOR, 7.95; 95% CI, 1.89-33.44), D-dimer ≥1500 ng/mL (aOR, 4.57; 95% CI, 1.12-18.68), serum glucose ≥120 mg/dL (aOR, 2.01; 95% CI, 1.06-3.81), lymphocyte count <1.0 × 10 9 /L (aOR, 3.21; 95% CI, 1.34-7.69), and platelet count <150 × 10 9 /L (aOR, 2.82; 95% CI, 1.31-6.07) were associated with severe outcomes. Evaluation of the interaction term revealed that a positive SARS-CoV-2 result increased the associations with severe outcomes for elevated procalcitonin, C-reactive protein (CRP), D-dimer, and for reduced lymphocyte and platelet counts., Conclusions: Specific laboratory parameters are associated with severe outcomes in SARS-CoV-2-infected children, and elevated serum procalcitonin, CRP, and D-dimer and low absolute lymphocyte and platelet counts were more strongly associated with severe outcomes in children testing positive compared with those testing negative., Competing Interests: Potential conflicts of interest. All authors: no reported conflicts., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: The COVID-19 pandemic had profound effects on the mental wellbeing of adolescents. We sought to evaluate pandemic-related changes in health care use for suicidal ideation, self-poisoning and self-harm., Methods: We obtained data from the Canadian Institute for Health Information on emergency department visits and hospital admissions from April 2015 to March 2022 among adolescents aged 10-18 years in Canada. We calculated the quarterly percentage of emergency department visits and hospital admissions for a composite outcome comprising suicidal ideation, self-poisoning and self-harm relative to all-cause emergency department visits and hospital admissions. We used interrupted time-series methods to compare changes in levels and trends of these outcomes between the prepandemic (Apr. 1, 2015-Mar. 1, 2020) and pandemic (Apr. 1, 2020-Mar. 31, 2022) periods., Results: The average quarterly percentage of emergency department visits for suicidal ideation, self-poisoning and self-harm relative to all-cause emergency department visits was 2.30% during the prepandemic period and 3.52% during the pandemic period. The level (0.08%, 95% confidence interval [CI] -0.79% to 0.95%) or trend (0.07% per quarter, 95% CI -0.14% to 0.28%) of this percentage did not change significantly between periods. The average quarterly percentage of hospital admissions for the composite outcome relative to all-cause admissions was 7.18% during the prepandemic period and 8.96% during the pandemic period. This percentage showed no significant change in level (-0.70%, 95% CI -1.90% to 0.50%), but did show a significantly increasing trend (0.36% per quarter; 95% 0.07% to 0.65%) during the pandemic versus prepandemic periods, specifically among females aged 10-14 years (0.76% per quarter, 95% CI 0.22% to 1.30%) and females aged 15-18 years (0.56% per quarter, 95% CI 0.31% to 0.81%)., Interpretation: The quarterly change in the percentage of hospital admissions for suicidal ideation, self-poisoning and self-harm increased among adolescent females in Canada during the first 2 years of the COVID-19 pandemic. This underscores the need to promote public health policies that mitigate the impact of the pandemic on adolescent mental health., Competing Interests: Competing interests: Naveen Poonai reports research funding from the Canadian Institutes of Health Research (CIHR) and Physicians Services Incorporated (PSI). Amanda Newton reports research funding from CIHR, the Women and Children’s Health Research Institute and Alberta Innovates. She sits on the mental health section board with the Canadian Paediatric Society. Samina Ali is a member of the scientific advisory board of the National Pain Advisory Council. Eleanor Fitzpatrick is executive chair of the IWK Research Ethics Board. Roger Zemek holds a Clinical Research Chair in Pediatric Concussion from the University of Ottawa, and receives research funding from the CIHR, Ontario Neurotrauma Foundation, PSI Foundation, CHEO Foundation, Ontario Brain Institute, National Football League, Ontario Ministry of Health, Public Health Agency of Canada, Parachute Canada and Ontario SPOR Support Unit. He sits on the board of directors for the North American Brain Injury Society in a volunteer role and is a cofounder of and minority shareholder in 360 Concussion Care, an interdisciplinary concussion clinic; no proceeds have been transferred to him. No other competing interests were declared., (© 2023 CMA Impact Inc. or its licensors.)

Background and Objectives: This prospective, longitudinal cohort study examined trajectories of brain gray matter macrostructure after pediatric mild traumatic brain injury (mTBI)., Methods: Children aged 8-16.99 years with mTBI or mild orthopedic injury (OI) were recruited from 5 pediatric emergency departments. Reliable change between preinjury and 1 month postinjury symptom ratings was used to classify mTBI with or without persistent symptoms. Children completed postacute (2-33 days) and/or chronic (3 or 6 months) postinjury T1-weighted MRI, from which macrostructural metrics were derived using automated segmentation. Linear mixed-effects models were used, with multiple comparisons correction., Results: Groups ( N = 623; 407 mTBI/216 OI; 59% male; age mean = 12.03, SD = 2.38 years) did not differ in total brain, white, or gray matter volumes or regional subcortical gray matter volumes. However, time postinjury, age at injury, and biological sex-moderated differences among symptom groups in cortical thickness of the angular gyrus, basal forebrain, calcarine cortex, gyrus rectus, medial and posterior orbital gyrus, and the subcallosal area all corrected p < 0.05. Gray matter macrostructural metrics did not differ between groups postacutely. However, cortical thinning emerged chronically after mTBI relative to OI in the angular gyrus in older children ( d [95% confidence interval] = -0.61 [-1.15 to -0.08]); and in the basal forebrain (-0.47 [-0.94 to -0.01]), subcallosal area (-0.55 [-1.01 to -0.08]), and the posterior orbital gyrus (-0.55 [-1.02 to -0.08]) in females. Cortical thinning was demonstrated for frontal and occipital regions 3 months postinjury in males with mTBI with persistent symptoms vs without persistent symptoms (-0.80 [-1.55 to -0.05] to -0.83 [-1.56 to -0.10]) and 6 months postinjury in females and younger children with mTBI with persistent symptoms relative to mTBI without persistent symptoms and OI (-1.42 [-2.29 to -0.45] to -0.91 [-1.81 to -0.01])., Discussion: These findings signal little diagnostic and prognostic utility of postacute gray matter macrostructure in pediatric mTBI. However, mTBI altered the typical course of cortical gray matter thinning up to 6 months postinjury, even after symptoms typically abate in most children. Collapsing across symptom status obscured the neurobiological heterogeneity of discrete clinical outcomes after pediatric mTBI. The results illustrate the need to examine neurobiology in relation to clinical outcomes and within a neurodevelopmental framework., (© 2023 American Academy of Neurology.)

Introduction: An increasing number of jurisdictions have legalized recreational cannabis for adult use. The subsequent availability and marketing of recreational cannabis has led to a parallel increase in rates and severity of pediatric cannabis intoxications. We explored predictors of severe outcomes in pediatric patients who presented to the emergency department with cannabis intoxication., Methods: In this prospective cohort study, we collected data on all pediatric patients (<18 years) who presented with cannabis intoxication from August 2017 through June 2020 to participating sites in the Toxicology Investigators Consortium. In cases that involved polysubstance exposure, patients were included if cannabis was a significant contributing agent. The primary outcome was a composite severe outcome endpoint, defined as an intensive care unit admission or in-hospital death. Covariates included relevant sociodemographic and exposure characteristics., Results: One hundred and thirty-eight pediatric patients (54% males, median age 14.0 years, interquartile range 3.7-16.0) presented to a participating emergency department with cannabis intoxication. Fifty-two patients (38%) were admitted to an intensive care unit, including one patient who died. In the multivariable logistic regression analysis, polysubstance ingestion (adjusted odds ratio = 16.3; 95% confidence interval: 4.6-58.3; P  < 0.001)) and cannabis edibles ingestion (adjusted odds ratio = 5.5; 95% confidence interval: 1.9-15.9; P  = 0.001) were strong independent predictors of severe outcome. In an age-stratified regression analysis, in children older than >10 years, only polysubstance abuse remained an independent predictor for the severe outcome (adjusted odds ratio 37.1; 95% confidence interval: 6.2-221.2; P  < 0.001). As all children 10 years and younger ingested edibles, a dedicated multivariable analysis could not be performed (unadjusted odds ratio 3.3; 95% confidence interval: 1.6-6.7)., Conclusions: Severe outcomes occurred for different reasons and were largely associated with the patient's age. Young children, all of whom were exposed to edibles, were at higher risk of severe outcomes. Teenagers with severe outcomes were frequently involved in polysubstance exposure, while psychosocial factors may have played a role.