Access to essential cancer medicines for children: a comparative mixed-methods analysis of availability, price, and health-system determinants in east Africa.

BACKGROUND: Access to essential childhood cancer medicines is a core determinant of childhood cancer outcomes. Available evidence, although scarce, suggests that access to these medicines is highly variable across countries, particularly in low-income and middle-income countries, where the burden of childhood cancer is greatest. To support evidence-informed national and regional policies for improved childhood cancer outcomes, we aimed to analyse access to essential childhood cancer medicines in four east African countries-Kenya, Rwanda, Tanzania, and Uganda-by determining the availability and price of these medicines and the health system determinants of access. METHODS: In this comparative analysis, we used prospective mixed-method analyses to track and analyse the availability and price of essential childhood cancer medicines, investigate contextual determinants of access to childhood cancer medicines within and across included countries, and assess the potential effects of medicine stockouts on treatment. Eight tertiary care hospitals were included, seven were public sites (Kenyatta National Hospital [KNH; Nairobi, Kenya], Jaramogi Oginga Odinga Referral and Teaching Hospital [JOORTH; Kisumu, Kenya], Moi University Teaching and Referral Hospital [MTRH; Eldoret, Kenya], Bugando Medical Centre [BMC; Mwanza, Tanzania], Muhimbili National Hospital [MNH; Dar es Salaam, Tanzania], Butaro Cancer Centre of Excellence [BCCE; Butaro Sector, Rwanda], and Uganda Cancer Institute [UCI; Kampala, Uganda]) and one was a private site (Aga Khan University Hospital [AKU; Nairobi, Kenya]). We catalogued prices and stockouts for 37 essential drugs from each of the eight study siteson the basis of 52 weeks of prospective data that was collected across sites from May 1, 2020, to Jan 31, 2022. We analysed determinants of medicine access using thematic analysis of academic literature, policy documents, and semi-structured interviews from a purposive sample of health system stakeholders. FINDINGS: Recurrent stockouts of a wide range of cytotoxic and supportive care medicines were observed across sites, with highest mean unavailability in Kenya (JOORTH; 48·5%), Rwanda (BCCE; 39·0%), and Tanzania (BMC; 32·2%). Drugs that had frequent stockouts across at least four sites included methotrexate, bleomycin, etoposide, ifosfamide, oral morphine, and allopurinol. Average median price ratio of medicines at each site was within WHO's internationally accepted threshold for efficient procurement (median price ratio ≤1·5). The effect of stockouts on treatment was noted across most sites, with the greatest potential for treatment interruptions in patients with Hodgkin lymphoma, retinoblastoma, and acute lymphocytic leukaemia. Policy prioritisation of childhood cancers, health financing and coverage, medicine procurement and supply chain management, and health system infrastructure emerged as four prominent determinants of access when the stratified purposive sample of key informants (n=64) across all four countries (Kenya n=19, Rwanda n=15, Tanzania n=13, and Uganda n=17) was interviewed. INTERPRETATION: Access to childhood cancer medicines across east Africa is marked by gaps in availability that have implications for effective treatment delivery for a range of childhood cancers. Our findings provide detailed evidence of barriers to access to childhood cancer medicine at multiple points in the pharmaceutical value chain. These data could inform national and regional policy makers to optimise cancer medicine availability and affordability as part of efforts to improve childhood cancer outcomes specific regions and internationally. FUNDING: American Childhood Cancer Organization, Childhood Cancer International, and the Friends of Cancer Patients Ameera Fund.

Viral dynamics of the SARS-CoV-2 Omicron Variant in Paediatric Patients; A prospective cohort study.

BACKGROUND: There are limited data on the viral dynamics of SARS-CoV-2 in children. Understanding viral load changes over the course of illness and duration of viral shedding may provide insight into transmission dynamics to inform public health and infection control decisions. METHODS: We conducted a prospective cohort study of children 18 years and younger with PCR confirmed SARS-CoV-2 between February 1, 2022 and March 14, 2022. SARS-CoV-2 testing occurred on daily samples for 10 days; a subset of participants completed daily rapid antigen testing (RAT). Viral RNA trajectories were described in relation to symptom onset and resolution. The associations between both time since symptom onset/resolution and non-infectious viral load were evaluated using a Cox proportional hazards model. FINDINGS: Among 101 children aged 2 to 17 years, the median time to study-defined non-infectious viral load was 5 days post symptom onset, with 75% meeting this threshold by 7 days, and 90% by 10 days. On the day of and day after symptom resolution, 43 of 87 (49%) and 52 (60%) had met the non-infectious thresholds, respectively. Of the 50 participants completing RAT, positivity at symptom onset and on the day after symptom onset was 67% (16/24) and 75% (14/20). On the first day where the non-infectious threshold was met, 61% (n = 27/44) of participant RAT results were positive. INTERPRETATION: Children often met the study-defined non-infectiousness threshold on the day after symptom resolution. RAT tests were often negative early in the course of illness and should not be relied on to exclude infection. CLINICAL TRIALS REGISTRATION: NCT05240183.

Excess weight gain in the paediatric bleeding disorders population: Impact of the COVID-19 Pandemic.

INTRODUCTION: The COVID-19 pandemic has resulted in lifestyle changes for children. The aim of this study was to evaluate the impact of the pandemic on weight/BMI in children with severe bleeding disorders. METHODS: We conducted a retrospective review of patients age 3-18 years with severe bleeding disorders on prophylactic therapy treated at SickKids Hospital (Toronto, Canada) between February 01, 2018 and March 31, 2021. We evaluated the following pre- and post-COVID variables: weight (kg), weight percentile, BMI (kg/m2 ), BMI percentile, HJHS score, and prophylactic dosing (units/kg). RESULTS: One hundred and four patients were included in the final analysis. Diagnoses were as follows:  haemophilia A (n = 92; 70.8%), haemophilia B (n = 17; 13.1%), type 3 von Willebrand disease (n = 11; 8.5%), the remainder were diagnosed with rare factor deficiencies.  Median interval time from pre-COVID measurements to latest follow-up was 12.4 months (IQR 10.32-14.52 months) during which there was a statistically significant increase in median weight percentile +5.75 centiles (from 63rd centile to 68.75th centile). There was a statistically significant increase in mean BMI of +1.03 kg/m2 (P = < .001) while median BMI percentile increased +8.82 centiles (from 53.9th centile to 62.72nd centile) and mean BMI percentile increased 3.42 centiles (from 57.5 centile to 60.9 centile). The group that gained the most weight centiles, BMI and BMI centiles were 5-14 years old. CONCLUSION: There was a trend to weight gain over the study period. More long-term data is required to evaluate the impact of this increase in weight and BMI on children with bleeding disorders.

How essential are in-person clinic visits during maintenance treatment of children with acute lymphoblastic leukemia?

BACKGROUND: Acute lymphoblastic leukemia (ALL) is the most common cancer in children. Treatment consists of an initial intensive phase of chemotherapy, followed by a prolonged period of maintenance chemotherapy intended to reduce the risk of relapse. During the COVID-19 pandemic, the need arose to identify and reduce non-essential hospital visits. OBJECTIVE: We aimed to determine which proportion of in-person clinic visits during ALL maintenance therapy was associated with a change of management based on the results of the physical examination. PATIENTS AND METHODS: Medical records of children receiving maintenance chemotherapy for B-precursor ALL between September 2019 and February 2020 were reviewed. Visits with a new finding on physical examination were divided into those where an in-person assessment was deemed essential versus not essential. Finally, we determined the proportion of essential in-person visits that resulted in a change of management. RESULTS: A total of 240 maintenance visits by 75 children were analyzed. An abnormal finding on physical examination was noted during 20 visits (8.3%). Of those, 14 (5.8%) uncovered a new finding, six (2.5%) were classified as "in-person visit essential," and among those six visits, three (1.2%) resulted in a change of patient management (one for acute otitis media, one for wheezing, and one for limp). CONCLUSION: Our findings support the evaluation of care delivery models other than in-person visits during ALL maintenance therapy. A prospective study is required to delineate criteria, benefits/risks, and families' perspectives associated with virtual care delivery and the optimal frequency of in-person visits.

UV, ozone, and COVID-19 transmission in Ontario, Canada using generalised linear models.

BACKGROUND: Quantifying the impact of environmental factors on COVID-19 transmission is crucial in preventing more cases. Ultraviolet (UV) radiation and ozone (O3) have reported antimicrobial properties but few studies have examined associations with community infectivity of COVID-19. Research suggests UV light can be preventative while the effect of O3 is contested. We sought to determine the relationship between UV, O3, and COVID-19 incidence in Ontario, Canada. METHODS: In our time series analyses, we calculated daily incidence rates and reproductive number (Rt) from 34,975 cases between January and June 2020 across 34 Ontario Public Health Units. We used generalised linear models, adjusting for potential confounders, to calculate point estimates (PE) and 95% confidence intervals (CI) for UV and O3. Analyses were further stratified by age groups and outbreaks at institutions versus community. RESULTS: We found that 1-week averaged UV was significantly associated with a 13% decrease (95% CI: 0.80-0.96) in overall COVID-19 Rt, per unit increase. A negative association with UV was also significant among community outbreaks (PE: 0.88, 95% CI: 0.81-0.96) but not institutional outbreaks (PE: 0.94, 95% CI: 0.85-1.03). A positive association of O3 with COVID-19 incidence is strongly suggested among institutional outbreak cases (PE: 1.06, 95% CI: 1.00-1.13). CONCLUSION: Our study found evidence to support the hypothesis that higher UV reduced transmission of COVID-19 and some evidence that ground-level O3 positively influenced COVID-19 transmission. Setting of infection should be strongly considered as a factor in future research. UV and O3 may explain some of COVID-19's seasonal behaviour.

Pediatric point-of-care ultrasound of optic disc elevation for increased intracranial pressure: A pilot study.

OBJECTIVE: Papilledema is often difficult to detect in children. Ocular point-of-care ultrasound (POCUS) measurement of the optic nerve sheath diameter (ONSD) is a non-invasive test for increased intracranial pressure (ICP), but no consensus exists on normal pediatric ONSD values. Detection of optic disc elevation (ODE, a component of papilledema) using POCUS has recently been qualitatively described. We sought to establish the diagnostic accuracy of different ODE cutoffs to detect increased ICP in children who underwent ocular POCUS in our pediatric emergency department (PED). METHODS: We retrospectively reviewed charts of patients ages 0-18 years who received ocular POCUS in our tertiary PED between 2011 and 2016. Patients were included if their archived POCUS examinations were deemed high-quality by a POCUS expert and they underwent ICP determination within 48 h after ocular POCUS. A blinded POCUS expert measured ODE, optic disc width at mid-height (ODWAMH), and ONSD. Receiver-operator curve analysis was performed for various cutoffs for these measurements in detecting increased ICP. RESULTS: 76 eyes from 40 patients met study criteria. 26 patients had increased ICP. The mean ODE of both eyes (ODE-B) generated the largest area under the curve (0.962, 95% CI 0.890-1). The optimal ODE-B cutoff was 0.66 mm, with a sensitivity of 96% (95% CI 79-100%) and a specificity of 93% (95% CI 79-100%). 1/40 (2.5%) of patients with ODE-B < 0.66 had increased ICP. CONCLUSIONS: ODE-B may represent the optimal ocular POCUS measurement for detecting increased ICP in children, and future prospective studies could more accurately describe the diagnostic performance of different pediatric ODE-B cutoffs.

Effect of the COVID-19 Pandemic on Patient Volumes, Acuity, and Outcomes in Pediatric Emergency Departments: A Nationwide Study.

OBJECTIVES: The aim of this study was to quantify the effect of the COVID-19 pandemic on pediatric emergency department (ED) utilization and outcomes. METHODS: This study is an interrupted-time-series observational study of children presenting to 11 Canadian tertiary-care pediatric EDs. Data were grouped into weeks in 3 study periods: prepandemic (January 1, 2018-January 27, 2020), peripandemic (January 28, 2020-March 10, 2020), and early pandemic (March 11, 2020-April 30, 2020). These periods were compared with the same time intervals in the 2 preceding calendar years. Primary outcomes were number of ED visits per week. The secondary outcomes were triage acuity, hospitalization, intensive care unit (ICU) admission, mortality, length of hospital stay, ED revisits, and visits for trauma and mental health concerns. RESULTS: There were 577,807 ED visits (median age, 4.5 years; 52.9% male). Relative to the prepandemic period, there was a reduction [-58%; 95% confidence interval (CI), -63% to -51%] in the number of ED visits during the early-pandemic period, with concomitant higher acuity. There was a concurrent increase in the proportion of ward [odds ratio (OR), 1.39; 95% CI, 1.32-1.45] and intensive care unit (OR, 1.20; 95% CI, 1.01-1.42) admissions, and trauma-related ED visits among children less than 10 years (OR, 1.51; 95% CI, 1.45-1.56). Mental health-related visits in children declined in the early-pandemic period (in <10 years, -60%; 95% CI, -67% to -51%; in children ≥10 years: -56%; 95% CI, -63% to -47%) relative to the pre-COVID-19 period. There were no differences in mortality or length of stay; however, ED revisits within 72 hours were reduced during the early-pandemic period (percent change: -55%; 95% CI, -61% to -49%; P < 0.001). CONCLUSIONS: After the declaration of the COVID-19 pandemic, dramatic reductions in pediatric ED visits occurred across Canada. Children seeking ED care were sicker, and there was an increase in trauma-related visits among children more than 10 years of age, whereas mental health visits declined during the early-pandemic period. When faced with a future pandemic, public health officials must consider the impact of the illness and the measures implemented on children's health and acute care needs.

Causes of death in pediatric neuro-oncology: the sickkids experience from 2000 to 2017.

PURPOSE: Primary benign and malignant central nervous system (CNS) tumors are the most frequent solid tumors in the pediatric age and represent the leading cause of death by cancer in children in high income countries. However, information regarding specific causes of death in this population is still limited. The objective of this work was to investigate mortality in a large cohort of children diagnosed at our institution. METHODS: We identified patients consecutively diagnosed with CNS tumor and treated at a Tertiary Care Canadian Children's Hospital between January 2000 and December 2017. Patient charts were reviewed and different variables such as tumor diagnosis, location, gender, age at diagnosis, age at death and cause of death collected. RESULTS: Of 1274 patients, 306 (24%) succumbed to their disease. Mortality rate varied significantly according to tumor subtype, ranging from 3.1% in low grade glioma (LGG) to 97.8% in diffuse intrinsic pontine glioma (DIPG). While high grade gliomas (HGG) and DIPG represented only 6.3 and 7.1% of total diagnoses respectively, together they accounted for 49.3% of total deaths (n = 151). Median time from diagnosis to death was 15 months (4 days to 15 years) and shortest for DIPG (11 months). Two hundred and ninety patients (94.8%) died as a result of the primary disease, 4 of treatment-related toxicity, two patients' deaths were unrelated to the primary disease (idiopathic encephalopathy and domestic fire) whereas 10 patients succumbed to a secondary malignancy. Of note, four of these ten patients had a confirmed underlying cancer predisposition syndrome. CONCLUSION: Disease progression is the main cause of death in children with brain tumor, while treatment related mortality is low in this series. Research should continue to focus on improving treatment strategies for patients whose prognosis remains dismal.

Bevacizumab for NF2-associated vestibular schwannomas of childhood and adolescence.

Seventeen children at six institutions with neurofibromatosis type 2 (NF2)-related vestibular schwannomas received bevacizumab. Eight of the 13 patients with initial hearing loss (61%) showed objective hearing improvement within six months of treatment. No patients showed hearing deterioration during therapy; however, only two patients showed objective radiological response. Seven of eight patients had tumor progression or worsening hearing loss upon cessation of treatment. Bevacizumab was well tolerated with no patients discontinuing therapy. Bevacizumab appears to postpone hearing loss in childhood NF2-associated vestibular schwannomas, but responses are not durable, suggesting that either longer maintenance therapy or new strategies are required.

Pap tests in the diagnosis of cervical cancer: Help or hinder?

OBJECTIVE: To evaluate the impact of pap tests on the time to diagnosis of cervical cancer. METHODS: In this population-based retrospective cohort study, Ontario women ≥21 years diagnosed with cervical cancer between 2011 and 2014 were identified and database data collected. The presence or absence of a pap test 0-2 years preceding cancer diagnosis was identified. Descriptive and modelling analyses were performed to determine the effect of pap results on cancer diagnosis. RESULTS: 2002 patients were identified, 75% received a pap test. 1250 patients had known cytology - 13% normal, 8% low-grade and 7.5% suspicious for cancer. Across all FIGO stages at diagnosis, 5-10% of cytology was low grade, 3-11.5% was positive for carcinoma and 4-41% was normal, which increased with advancing stage. For all cytology and FIGO stages (except stage 1A), OBGYNs had a significantly shorter time to diagnosis compared to family physicians. Factors increasing the odds of low-grade cytology were advanced stage (OR 4.5 (2.4-8.0), p < 0.01) and adenocarcinoma (OR 1.5 (1.1-2.1), p < 0.01). Low grade cytology resulted in the longest delay to diagnosis (p < 0.001). CONCLUSION: Pap tests are performed frequently in the 0-2 years prior to the diagnosis of cervical cancer which can result in false negative cytology and diagnostic delay in patients with advanced cancers.

Comparison of logistic regression with machine learning methods for the prediction of fetal growth abnormalities: a retrospective cohort study.

BACKGROUND: While there is increasing interest in identifying pregnancies at risk for adverse outcome, existing prediction models have not adequately assessed population-based risks, and have been based on conventional regression methods. The objective of the current study was to identify predictors of fetal growth abnormalities using logistic regression and machine learning methods, and compare diagnostic properties in a population-based sample of infants. METHODS: Data for 30,705 singleton infants born between 2009 and 2014 to mothers resident in Nova Scotia, Canada was obtained from the Nova Scotia Atlee Perinatal Database. Primary outcomes were small (SGA) and large for gestational age (LGA). Maternal characteristics pre-pregnancy and at 26 weeks were studied as predictors. Logistic regression and select machine learning methods were used to build the models, stratified by parity. Area under the curve was used to compare the models; relative importance of predictors was compared qualitatively. RESULTS: 7.9% and 13.5% of infants were SGA and LGA, respectively; 48.6% of births were to primiparous women and 51.4% were to multiparous women. Prediction of SGA and LGA was poor to fair (area under the curve 60-75%) and improved with increasing parity and pregnancy information. Smoking, previous low birthweight infant, and gestational weight gain were important predictors for SGA; pre-pregnancy body mass index, gestational weight gain, and previous macrosomic infant were the strongest predictors for LGA. CONCLUSIONS: The machine learning methods used in this study did not offer any advantage over logistic regression in the prediction of fetal growth abnormalities. Prediction accuracy for SGA and LGA based on maternal information is poor for primiparous women and fair for multiparous women.

Percentile curves for cardiometabolic disease markers in Canadian children and youth: a cross-sectional study.

BACKGROUND: The objective of this study to develop percentile curves for cardiometabolic disease markers in a population-based sample of Canadian children and youth. METHODS: The analysis used data from 6116 children and adolescents between 6 and 19 years of age who participated in the Canadian Health Measures Survey cycles 1 (2007/2009), 2 (2009/2011), and 3 (2012/2013). Total cholesterol, HDL cholesterol, and hemoglobin A1c levels as well as fasting levels of triglycerides, insulin, and homeostasis model assessment insulin resistance were measured using standardized procedures. Age- and sex-specific centiles for all markers were calculated using Cole and Green's LMS method. RESULTS: With the exception of hemoglobin A1c, all markers showed age- and sex-related differences during childhood and adolescence. CONCLUSIONS: We have developed centile curves for cardiometabolic disease markers in Canadian children and adolescents and demonstrated age and sex differences that should be considered when evaluating these markers in this age group.

Factors Associated with Trial of Labour and Mode of Delivery in Robson Group 5: A Select Group of Women With Previous Caesarean Section.

OBJECTIVE: To determine the proportion of women in Robson group 5 (RG5) who were eligible for a trial of labour after Caesarean (TOLAC) and, among eligible candidates, identify determinants of having a TOLAC and subsequent vaginal delivery (VD). METHODS: This population-based cohort study used data derived from the Nova Scotia Atlee Perinatal Database. Deliveries from 1998-2014 to women in RG5 (≥1 previous CS with a singleton term cephalic fetus) were included. Eligibility for a TOLAC was based on SOGC criteria. Multivariable logistic regression was used to identify characteristics independently associated with TOLAC and VD. The characteristics associated with VD were used in a logistic model to predict the theoretical probability of VD in women who did not have a TOLAC. RESULTS: Of the 15 111 deliveries in RG5, 75.3% were by CS. Of the 14 763 eligible women, 5488 (37.2%) had a TOLAC, of which 3739 (68.1%) resulted in VD. Predictors of VD included high area-level income and either a CS without labour or a spontaneous VD in the preceding pregnancy. While mode of previous delivery also predicted TOLAC among eligible women, high area-level income was associated with reduced odds of TOLAC. The probability of VD in women who did not undergo TOLAC was estimated to be 47.1%, and the lowest CS rate attainable in RG5 was estimated at 46.3%. CONCLUSIONS: Sociodemographic factors such as income and previous mode of delivery were associated with the rates of TOLAC and subsequent VD in eligible women, and suggest that the Caesarean section rate in RG5 could be safely reduced.

Birth Weight for Gestational Age, Anthropometric Measures, and Cardiovascular Disease Markers in Children.

OBJECTIVE: To examine the association of birth weight for gestational age with anthropometric measures and cardiometabolic markers in a population-based sample of Canadian children. STUDY DESIGN: The study used data from 2016 children aged 6-12 years from the first 2 cycles of the Canadian Health Measures Survey, a population-based survey of Canadian residents. The main exposure was birth weight for gestational age (small [SGA], large [LGA], and appropriate for gestational age [AGA]). The outcomes were anthropometric measures, blood pressure, and laboratory cardiovascular disease markers. The association between the exposure and the outcomes was examined using multiple regression. Analyses were weighted to account for the complex sampling design and for nonresponse. RESULTS: SGA infants had lower and LGA infants had higher z scores for anthropometric measures compared with the AGA group but most differences were not statistically significant. There were no differences between the SGA or LGA infants and the AGA group in blood pressure or individual cardiometabolic markers but SGA infants were significantly less likely to have elevated levels of 3 or more components of the metabolic syndrome compared with their AGA peers. CONCLUSIONS: Former SGA and LGA infants have lower (SGA) and higher (LGA) body mass index and waist circumference, respectively, than their AGA peers. The known long-term increased cardiovascular disease risk among SGA or LGA infants was not reflected in the blood pressure and laboratory measurements at age 6-12 years.

Improving inpatient paediatric de-labelling of allergies to beta-lactams: a quality improvement study.

OBJECTIVE: To evaluate the implementation of an antimicrobial stewardship programme-led inpatient beta-lactam allergy de-labelling programme using a direct oral provocation test (OPT). DESIGN: One-year quality improvement study using a before-after design. SETTING: Free-standing tertiary care paediatric hospital. PATIENTS: Patients with a reported beta-lactam allergy admitted to the paediatric medicine inpatient unit. INTERVENTIONS: Following standardised assessment and risk stratification of reported symptoms, patients with a low-risk history were offered an OPT. Beta-lactam allergy labels were removed if a reported history was considered non-allergic or after successful OPT. MAIN OUTCOME MEASURES: Removal of inappropriate beta-lactam allergy labels. RESULTS: 80 patients with 85 reported beta-lactam allergies were assessed. Median age was 8.1 years (IQR 4.8-12.9) and 34 (42%) were female. The majority (n=55, 69%) had an underlying medical condition. Amoxicillin was the most reported allergy (n=25, 29%). Reported reactions were primarily dermatological (n=65, 77%). Half of participants (n=40) were ineligible for OPT, with equal proportions due to clinical reasons or the nature of the reported reaction. Of the 40 eligible patients, 28 patients (70%) were de-labelled either by history alone (n=10) or OPT (n=18). All OPTs were successful. De-labelling allowed five additional patients (11% of those receiving antibiotics) to receive the preferred beta-lactam. Including patients who were subsequently assessed in the allergy clinic, almost half of all evaluated patients were de-labelled (n=37, 46%). CONCLUSIONS: An antimicrobial stewardship programme-led programme using a direct OPT was feasible and safe for expanding beta-lactam allergy de-labelling to paediatric patients admitted to the paediatric medicine inpatient unit.

Rise in the incidence of severe pediatric blepharokeratoconjunctivitis during the COVID-19 pandemic.

Severe blepharokeratoconjunctivitis (BKC) is associated with vision loss and ocular morbidity; hence, early diagnosis and treatment are crucial. Retrospective data collection using electronic patient and billing database records of all patients <18 years of age with severe BKC between March 2010 and March 2022 was performed at the Eye Clinic at the Hospital for Sick Children in Toronto, Canada. Severe BKC was defined as including corneal inflammation, new vessel formation, scarring, thinning and lipid deposits. We excluded patients with mild or no corneal involvement, and those with other corneal pathologies. Over the study period, 257 patients were diagnosed with severe BKC (161 females), with an average age of 8 years. There was a statistically significant threefold increase in the diagnosis of severe BKC since the beginning of the COVID-19 pandemic in 2020 compared to the previous years. We speculate that the increased use of facial masks during the pandemic contributed to this significant increase.

Heated humidified high flow nasal cannula therapy in children with obstructive sleep apnea: A randomized cross-over trial.

OBJECTIVE/BACKGROUND: Moderate-to-severe obstructive sleep apnea (OSA) is highly prevalent in children with obesity and/or underlying medical complexity. The first line of therapy, adenotonsillectomy (AT), does not cure OSA in more than 50% of these children. Consequently, continuous positive airway pressure (CPAP) is the main therapeutic option but adherence is often poor. A potential alternative which may be associated with greater adherence is heated high-flow nasal cannula (HFNC) therapy; however, its efficacy in children with OSA has not been systematically investigated. The study aimed to compare the efficacy of HFNC with CPAP to treat moderate-to-severe OSA with the primary outcome measuring the change from baseline in the mean obstructive apnea/hypopnea index (OAHI). PARTICIPANTS/METHODS: This was a single-blinded randomized, two period crossover trial conducted from March 2019 to December 2021 at a Canadian pediatric quaternary care hospital. Children aged 2-18 years with obesity and medical complexity diagnosed with moderate-to-severe OSA via overnight polysomnography and recommended CPAP therapy were included in the study. Following diagnostic polysomnography, each participant completed two further sleep studies; a HFNC titration study and a CPAP titration study (9 received HFNC first, and 9 received CPAP first) in a random 1:1 allocation order. RESULTS: Eighteen participants with a mean ± SD age of 11.9 ± 3.8 years and OAHI 23.1 ± 21.7 events/hour completed the study. The mean [95% CI] reductions in OAHI (-19.8[-29.2, -10.5] vs. -18.8 [-28.2, -9.4] events/hour, p = 0.9), nadir oxygen saturation (7.1[2.2, 11.9] vs. 8.4[3.5, 13.2], p = 0.8), oxygen desaturation index (-11.6[-21.0, -2.3] vs. -16.0[-25.3, -6.6], p = 0.5) and sleep efficiency (3.5[-4.8, 11.8] vs. 9.2[0.9, 15.5], p = 0.2) with HFNC and CPAP therapy were comparable between conditions. CONCLUSION: HFNC and CPAP therapy yield similar reductions in polysomnography quantified measures of OSA severity among children with obesity and medical complexities. TRIAL REGISTRATION: NCT05354401 ClinicalTrials.gov.

Lipid emulsion therapy during management of the critically-ill poisoned patient: a prospective cohort study.

BACKGROUND: Despite conflicting data, intravenous lipid emulsion has emerged as a potential antidote. The "lipid sink" theory suggests that following intravenous administration of lipid, lipophilic drugs are sequestered in the vascular compartment, thereby reducing their tissue concentrations. This study sought to determine if survival is associated with the intoxicant's degree of lipophilicity. METHODS: We reviewed all cases in the Toxicology Investigators Consortium's lipid sub-registry between May 2012 through December 2018. Information collected included demographics, exposure circumstances, clinical course, management, disposition, and outcome. The primary outcome was survival after lipid emulsion therapy. Survival was stratified by the log of the intoxicant's octanol-water partition coefficient. We also assessed the association between intoxicant lipophilicity and an increase in systolic blood pressure after lipid emulsion administration. RESULTS: We identified 134 patients, including 81 (60.4%) females. The median age was 40 years (interquartile range 21-75). One hundred and eight (80.6%) patients survived, including 45 (33.6%) with cardiac arrest during their intoxication. Eighty-two (61.2%) were hypotensive, and 98 (73.1%) received mechanical ventilation. There was no relationship between survival and the log of the partition coefficient of the intoxicant on linear analysis (P = 0.89) or polynomial model (P = 0.10). Systolic blood pressure increased in both groups. The median (interquartile range) systolic blood pressure before lipid administration was 68 (60-78) mmHg for those intoxicants with a log partition coefficient < 3.6 compared with 89 (76-104) mmHg after lipid administration. Among those drugs with a log partition coefficient > 3.6, the median (interquartile range) was 69 (60-84) mmHg before lipid and 89 (80-96) mmHg after lipid administration. CONCLUSION: Most patients in this cohort survived. Lipophilicity was not correlated with survival or the observed changes in blood pressure. The study did not address the efficacy of lipid emulsion.

Early transient dysautonomia predicts the risk of infantile epileptic spasm syndrome onset: A prospective cohort study.

Background: Infantile epileptic spasm syndrome (IESS) is an age-dependent epileptic encephalopathy with a significant risk of developmental regression. This study investigates the association between heart rate variability (HRV) in infants at risk of IESS and the clinical onset of IESS. Methods: Sixty neonates at risk of IESS were prospectively followed from birth to 12 months with simultaneous electroencephalogram (EEG) and electrocardiogram recordings for 60 min at every 2-month interval. HRV metrics were calculated from 5 min time-epoch during sleep including frequency domain measures, Poincare analysis including cardiac vagal index (CVI) and cardiac sympathetic index (CSI), and detrended fluctuation analysis (DFA α1, DFA α2). To assess the effect of each HRV metric at the 2-month baseline on the time until the first occurrence of either hypsarrhythmia on EEG and/or clinical spasm, univariate cox-proportional hazard models were fitted for each HRV metric. Results: Infantile epileptic spasm syndrome was diagnosed in 20/60 (33%) of the cohort in a 12-month follow-up and 3 (5%) were lost to follow-up. The median age of developing hypsarrhythmia was 25 (7-53) weeks and clinical spasms at 24 (8-40) weeks. Three (5%) patients had clinical spasms without hypsarrhythmia, and 5 (8%) patients had hypsarrhythmia before clinical spasms at the initial presentation. The infants with high CSI (hazard ratio 2.5, 95% CI 1.2-5.2, P = 0.01) and high DFA α1 (hazard ratio 16, 95% CI 1.1-240, P = 0.04) at 2 months were more likely to develop hypsarrhythmia by the first year of age. There was a trend toward decreasing CSI and DFA α1 and increasing CVI in the first 8 months of age. Conclusion: Our data suggest that relative sympathetic predominance at an early age of 2 months may be a potential predictor for developing IESS. Hence, early HRV patterns may provide valuable prognostic information in children at risk of IESS allowing early detection and optimization of cognitive outcomes. Whether early intervention to restore sympathovagal balance per se would provide clinical benefit must be addressed by future studies.

Housing Need Among Children With Medical Complexity: A Cross-Sectional Descriptive Study of Three Populations.

OBJECTIVE: Children with medical complexity (CMC) are hypothesized to have unique housing and accessibility needs due to their medical fragility and medical technology dependency; however, research on prevalence and types of housing need in CMC is limited. The objective was to describe housing need in families of CMC, and to compare housing need across CMC, children with one chronic condition (Type 1 diabetes; CT1D) and healthy children (HC). METHODS: This cross-sectional descriptive study assessed housing suitability, adequacy, affordability, stress, stability, and accessibility using survey methodology. Participants were caregivers of CMC, CT1D and HC at a tertiary-care pediatric hospital. The association of housing need outcomes across groups was analyzed using logistic and ordinal logistic regression models, adjusting for income, educational attainment, employment status, community type, immigration status, child age, and number of people in household. RESULTS: Four hundred ninety caregivers participated. Caregivers of CMC reported increased risk of housing-related safety concerns (aOR 3.1 [1.3-7.5]), using a common area as a sleeping area (5.6 [2.0-16.8]), reducing spending (4.6 [2.3-9.5]) or borrowing money to afford rent (2.9 [1.2-6.7]), experiencing housing stress (3.3 [1.8-6.0]), and moving or considering moving to access health/community services (15.0 [6.4-37.6]) compared to HC. CONCLUSIONS: CMC were more likely to experience multiple indicators of housing need compared to CT1D and HC even after adjusting for sociodemographic factors, suggesting an association between complexity of child health conditions and housing need. Further research and practise should consider screening for and supporting housing need in CMC.