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BACKGROUND: Paediatric inflammatory multisystem syndrome (PIMS) is a rare condition temporally associated with SARS-CoV-2 infection. Using national surveillance data, we compare presenting features and outcomes among children hospitalized with PIMS by SARS-CoV-2 linkage, and identify risk factors for intensive care (ICU). METHODS: Cases were reported to the Canadian Paediatric Surveillance Program by a network of >2800 pediatricians between March 2020 and May 2021. Patients with positive versus negative SARS-CoV-2 linkages were compared, with positive linkage defined as any positive molecular or serologic test or close contact with confirmed COVID-19. ICU risk factors were identified with multivariable modified Poisson regression. RESULTS: We identified 406 children hospitalized with PIMS, including 49.8% with positive SARS-CoV-2 linkages, 26.1% with negative linkages, and 24.1% with unknown linkages. The median age was 5.4 years (IQR 2.5-9.8), 60% were male, and 83% had no comorbidities. Compared to cases with negative linkages, children with positive linkages experienced more cardiac involvement (58.8% vs. 37.4%; p < 0.001), gastrointestinal symptoms (88.6% vs. 63.2%; p < 0.001), and shock (60.9% vs. 16.0%; p < 0.001). Children aged ≥6 years and those with positive linkages were more likely to require ICU. CONCLUSIONS: Although rare, 30% of PIMS hospitalizations required ICU or respiratory/hemodynamic support, particularly those with positive SARS-CoV-2 linkages. IMPACT: We describe 406 children hospitalized with paediatric inflammatory multisystem syndrome (PIMS) using nationwide surveillance data, the largest study of PIMS in Canada to date. Our surveillance case definition of PIMS did not require a history of SARS-CoV-2 exposure, and we therefore describe associations of SARS-CoV-2 linkages on clinical features and outcomes of children with PIMS. Children with positive SARS-CoV-2 linkages were older, had more gastrointestinal and cardiac involvement, and hyperinflammatory laboratory picture. Although PIMS is rare, one-third required admission to intensive care, with the greatest risk amongst those aged ≥6 years and those with a SARS-CoV-2 linkage.
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COVID-19 , SARS-CoV-2 , Humanos , Masculino , Niño , Preescolar , Femenino , COVID-19/epidemiología , COVID-19/terapia , Canadá/epidemiología , Síndrome de Respuesta Inflamatoria Sistémica/diagnóstico , Síndrome de Respuesta Inflamatoria Sistémica/epidemiologíaRESUMEN
Background: Children living with chronic comorbid conditions are at increased risk for severe COVID-19, though there is limited evidence regarding the risks associated with specific conditions and which children may benefit from targeted COVID-19 therapies. The objective of this study was to identify factors associated with severe disease among hospitalized children with COVID-19 in Canada. Methods: We conducted a national prospective study on hospitalized children with microbiologically confirmed SARS-CoV-2 infection via the Canadian Paediatric Surveillance Program (CPSP) from April 2020-May 2021. Cases were reported voluntarily by a network of >2800 paediatricians. Hospitalizations were classified as COVID-19-related, incidental infection, or infection control/social admissions. Severe disease (among COVID-19-related hospitalizations only) was defined as disease requiring intensive care, ventilatory or hemodynamic support, select organ system complications, or death. Risk factors for severe disease were identified using multivariable Poisson regression, adjusting for age, sex, concomitant infections, and timing of hospitalization. Findings: We identified 544 children hospitalized with SARS-CoV-2 infection, including 60·7% with COVID-19-related disease and 39·3% with incidental infection or infection control/social admissions. Among COVID-19-related hospitalizations (n=330), the median age was 1·9 years (IQR 0·1-13·3) and 43·0% had chronic comorbid conditions. Severe disease occurred in 29·7% of COVID-19-related hospitalizations (n=98/330 including 60 admitted to intensive care), most frequently among children aged 2-4 years (48·7%) and 12-17 years (41·3%). Comorbid conditions associated with severe disease included pre-existing technology dependence requirements (adjusted risk ratio [aRR] 2·01, 95% confidence interval [CI] 1·37-2·95), body mass index Z-scores ≥3 (aRR 1·90, 95% CI 1·10-3·28), neurologic conditions (e.g. epilepsy and select chromosomal/genetic conditions) (aRR 1·84, 95% CI 1·32-2·57), and pulmonary conditions (e.g. bronchopulmonary dysplasia and uncontrolled asthma) (aRR 1·63, 95% CI 1·12-2·39). Interpretation: While severe outcomes were detected at all ages and among patients with and without comorbidities, neurologic and pulmonary conditions as well as technology dependence were associated with increased risk of severe COVID-19. These findings may help guide vaccination programs and prioritize targeted COVID-19 therapies for children. Funding: Financial support for the CPSP was received from the Public Health Agency of Canada.
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BACKGROUND/OBJECTIVES: Heavy menstrual bleeding (HMB) affects 34% to 37% of adolescent girls. The Menstrual Bleeding Questionnaire (MBQ) is a validated measure of menstrual bleeding-specific health-related quality of life (HRQoL) for women aged ≥18 years. No similar measure existed for adolescents with HMB. PATIENTS/METHODS: HMB was defined by the Pictorial Bleeding Assessment Chart (PBAC) score ≥100. In Phase 1, a focus group of adolescents with HMB adapted the MBQ, to generate the Adolescent MBQ (aMBQ). In phase 2, participants with and without HMB were recruited from clinics and self-referral. Each participant completed 3 questionnaires (aMBQ, Pediatric Quality of Life module [PedsQL]©, PBAC) at two time points. Validity of the aMBQ was assessed by Pearson's correlation with the PedsQL©. Reliability was calculated using intra-class correlation (ICC) in those without HMB. The receiver operating characteristic curve assessed the aMBQ's ability to identify those with HMB. RESULTS: Phase 1 included five girls with a mean age of 17.1 (13-18) years. The aMBQ was adapted from the MBQ by substituting four words/phrases that altered 8 of the 20 questions and by adding 1 new question. The 21-item aMBQ has a score range of 0 to 77 (77 = worst HRQoL). Phase 2 included 52 participants: 20 with and 32 without HMB, with a mean age of 14.8 (11-17) years. The validity of the aMBQ was confirmed by a moderate correlation with PedsQL© (r = -0.63; P < .001). Test-retest reliability was substantial (ICC = 0.73; P = .04). An aMBQ score of >30 identified those with HMB with excellent discrimination (area under the curve = 0.82; sensitivity, 70.0%; specificity, 84.4%). CONCLUSIONS: The aMBQ is a valid and reliable tool to assess HRQoL in adolescents with HMB.
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CONTEXTE: Les facteurs de risque de complications graves de l'infection par le SRAS-CoV-2 n'ont pas été bien établis chez les enfants. Nous avons voulu décrire les hospitalisations pédiatriques associées au SRAS-CoV-2 au Canada et identifier les facteurs de risque de maladie grave. MÉTHODES: Nous avons procédé à une étude prospective nationale en utilisant l'infrastructure du Programme canadien de surveillance pédiatrique (PCSP). Les hospitalisations d'enfants ayant contracté une infection par le SRAS-CoV-2 confirmée en laboratoire de microbiologie ont été rapportées du 8 avril au 31 décembre 2020 au moyen de questionnaires hebdomadaires en ligne distribués au réseau du PCSP, qui compte plus de 2800 pédiatres. Nous avons catégorisé les hospitalisations comme suit : liées à la COVID-19, infections découvertes fortuitement, ou hospitalisations pour des raisons sociales ou de contrôle des infections, et dégagé les facteurs de risque associés à la gravité de la maladie chez les patients hospitalisés. RÉSULTATS: Sur les 264 hospitalisations d'enfants ayant contracté le SRAS-CoV-2 au cours de la période de l'étude de 9 mois, 150 (56,8 %) ont été associées à la COVID-19 et 100 (37,9 %) étaient des cas découverts fortuitement (admission pour d'autres raisons et découverte fortuite du SRAS-CoV-2 par dépistage positif). Les nourrissons (37,3 %) et les adolescents (29,6 %) représentaient la majorité des cas. Parmi les hospitalisations liées à la COVID-19, 52 patients (34,7 %) étaient atteints d'une forme grave de la maladie, dont 42 (28,0 % des cas liés à la COVID-19) ont eu besoin d'une forme d'assistance respiratoire ou hémodynamique, et 59 (39,3 %) présentaient au moins 1 comorbidité sous-jacente. Les enfants atteints d'obésité, de maladies neurologiques chroniques ou de maladies pulmonaires chroniques, à l'exclusion de l'asthme, étaient plus susceptibles de présenter une forme grave ou critique de la COVID-19. INTERPRÉTATION: Parmi les enfants hospitalisés au Canada chez lesquels on a diagnostiqué une infection par le SRAS-CoV-2 au début de la pandémie de COVID-19, la découverte fortuite du SRAS-CoV-2 a été fréquente. Chez les enfants hospitalisés pour une COVID-19 aiguë, l'obésité et les comorbidités neurologiques et respiratoires ont été associées à une gravité accrue.
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COVID-19 , SARS-CoV-2 , Anticuerpos Antivirales , Canadá , Niño , Hospitalización , HumanosRESUMEN
BACKGROUND: This study examined the structural outcomes for joints of boys with severe hemophilia A receiving frequency/dose-escalated primary prophylaxis using magnetic resonance imaging (MRI), and the importance of interval MRI changes. METHODS: Forty-six subjects (27 with interval studies) were evaluated by radiographs (X-rays) and mid- and end-of-study MRIs (using the International Prophylaxis Study Group scale), as part of the Canadian Hemophilia Prophylaxis Study. The primary outcome was the presence of MRI osteochondral findings. RESULTS: The median (range) time on study at the end-of-study MRI examination was 9.6 (4.8-16.0) years, during which 18 of 46 subjects (39%) had osteochondral changes in at least one joint. An interval change in MRI score of at least 1 point was observed in 44% of joints (43 ankles, 21 elbows, 4 knees); at least one joint showed this change in all 27 subjects. Self-reported interval hemarthrosis was associated with a higher likelihood of interval osteochondral change (odds ratio [OR], 1.49; 95% confidence interval [CI] = 1.08-2.06). Presence of synovial hypertrophy or hemosiderin on interval MRIs was associated with an OR of 4.71 (95% CI, 1.92-11.57) and 5.25 (95% CI, 2.05-13.40) of later osteochondral changes on MRI. DISCUSSION: MRI changes were seen in 39% of subjects. Interval index joint bleeding was associated with an increased risk of later MRI changes, and earlier soft-tissue changes were associated with subsequent osteochondral changes.
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BACKGROUND: Risk factors for severe outcomes of SARS-CoV-2 infection are not well established in children. We sought to describe pediatric hospital admissions associated with SARS-CoV-2 infection in Canada and identify risk factors for more severe disease. METHODS: We conducted a national prospective study using the infrastructure of the Canadian Paediatric Surveillance Program (CPSP). Cases involving children who were admitted to hospital with microbiologically confirmed SARS-CoV-2 infection were reported from Apr. 8 to Dec. 31 2020, through weekly online questionnaires distributed to the CPSP network of more than 2800 pediatricians. We categorized hospital admissions as related to COVID-19, incidental, or for social or infection control reasons and determined risk factors for disease severity in hospital. RESULTS: Among 264 hospital admissions involving children with SARS-CoV-2 infection during the 9-month study period, 150 (56.8%) admissions were related to COVID-19 and 100 (37.9%) were incidental infections (admissions for other reasons and found to be positive for SARS-CoV-2 on screening). Infants (37.3%) and adolescents (29.6%) represented most cases. Among hospital admissions related to COVID-19, 52 (34.7%) had critical disease, 42 (28.0%) of whom required any form of respiratory or hemodynamic support, and 59 (39.3%) had at least 1 underlying comorbidity. Children with obesity, chronic neurologic conditions or chronic lung disease other than asthma were more likely to have severe or critical COVID-19. INTERPRETATION: Among children who were admitted to hospital with SARS-CoV-2 infection in Canada during the early COVID-19 pandemic period, incidental SARS-CoV-2 infection was common. In children admitted with acute COVID-19, obesity and neurologic and respiratory comorbidities were associated with more severe disease.
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COVID-19/epidemiología , Hospitalización , Índice de Severidad de la Enfermedad , Enfermedad Aguda , Adolescente , COVID-19/diagnóstico , COVID-19/etiología , COVID-19/terapia , Prueba de COVID-19 , Canadá/epidemiología , Niño , Preescolar , Comorbilidad , Femenino , Humanos , Hallazgos Incidentales , Lactante , Recién Nacido , Masculino , Estudios Prospectivos , Vigilancia en Salud Pública , Factores de RiesgoRESUMEN
INTRODUCTION: This study aimed to assess the impact of hemophilia on families, in the context of current and emerging hemostatic therapies, and explore the need for a hemophilia-specific tool targeted at parents of boys aged <4 years. A secondary aim was to develop and validate the new tool. METHODS: Focus groups were conducted with parents of boys with hemophilia and hemophilia health care providers at Canadian hemophilia treatment centers (HTCs) to review the relevance of the Pediatric Quality of Life Family Impact Module (PedsQL-FIM); a novel questionnaire was developed by identifying core themes expressed. This questionnaire, the Hemophilia Family Impact Tool (H-FIT) was validated in a sample of parents of boys with hemophilia relative to the PedsQL-FIM. RESULTS: Seven focus groups were conducted at four HTCs, generating themes specific to hemophilia not covered by the PedsQL-FIM, suggesting that a new tool be developed (the H-FIT). In the validation phase, 54 parents completed the H-FIT and PedsQL-FIM. The H-FIT had a strong correlation with the PedsQL-FIM across all ages (r = 0.79; P < .0001) and a moderate correlation for parents of boys aged <7 years (r = 0.64; P = .0007). There was a significant difference between the mean H-FIT scores for parents of boys using extended half-life factor (68.1; standard deviation [SD]=14.2) compared to standard half-life factor (54.7; SD=18.4; P = .04). CONCLUSION: A novel, disease-specific tool, the H-FIT, has been developed to measure the impact of hemophilia on families. The H-FIT has good preliminary measurement properties and may be responsive to changes in therapy associated with a decreased burden of administration.
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OBJECTIVE: The primary objective of this study was to assess whether there are different patterns (classes) of joint health in young boys with severe haemophilia A (SHA) prescribed primary tailored prophylaxis. We also assessed whether age at first index joint bleed, blood group, FVIII gene abnormality variant, factor VIII trough level, first-year bleeding rate and adherence to the prescribed prophylaxis regimen significantly predicted joint damage trajectory, and thus class membership. METHODS: Using data collected prospectively as part of the Canadian Hemophilia Primary Prophylaxis Study (CHPS), we implemented a latent class growth mixture model technique to determine how many joint damage classes existed within the cohort. We used a multinomial logistic regression to predict the odds of class membership based on the above predictors. We fitted a survival model to assess whether there were differences in the rate of dose escalation across the groups. RESULTS: We identified three distinct classes of trajectory: persistently low, moderately increasing and rapidly increasing joint scores. By multinomial regression, we found that only age at first index joint bleed predicted rapidly increasing joint scores. The rapidly increasing joint score class group moved through dose escalation significantly faster than the other two groups. CONCLUSIONS: Using tailored prophylaxis, boys with SHA follow one of three joint health trajectories. By using knowledge of disease trajectories, clinicians may be able to adjust treatment according to a subject's predicted long-term joint health and institute cost-effective programmes of prophylaxis targeted at the individual subject level.
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Hemofilia A , Canadá , Factor VIII/uso terapéutico , Hemartrosis/etiología , Hemartrosis/prevención & control , Hemofilia A/tratamiento farmacológico , Hemorragia , Humanos , MasculinoRESUMEN
INTRODUCTION: The purpose of this study was to review and update the content of the Canadian Hemophilia Outcomes-Kids' Life Assessment Tool version 2.0 (CHO-KLAT), in the context of extended half-life (EHL) factor concentrates (FCs) and to establish the validity and reliability of the updated CHO-KLAT. METHODS: Focus groups were conducted with boys with hemophilia, their parents, and health care providers across Canada to review the CHO-KLAT v2.0 and determine if any modifications were required. The validity of the revised CHO-KLAT (version 3.0) was then determined in a sample of boys with hemophilia and their parents by calculating its correlation with the Pediatric Quality of Life Core Module (PedsQL-Core). Test-retest reliability was assessed using an intraclass correlation coefficient (ICC). RESULTS: Thirteen focus groups at 5 pediatric hemophilia treatment centers (HTCs) (n = 71) resulted in 19 changes to the CHO-KLAT v2.0, generating a revised 40-item CHO-KLAT, the CHO-KLAT v3.0. Thirty-five boys with hemophilia (median age, 14; range, 7-17 years) and 47 parents participated in the validation of the CHO-KLAT v3.0. There was a moderate correlation between the CHO-KLAT v3.0 child self-report and PedsQL-Core (r = 0.56, P = .01), and a strong correlation between the CHO-KLAT v3.0 parent-proxy and PedsQL-Core (r = .79, P = .0007). The test-retest reliability ICC was 0.90 for the child self-report CHO-KLAT v3.0 and 0.68 for the parent-proxy CHO-KLAT v3.0. CONCLUSION: The CHO-KLAT v3.0 is a reliable and valid child-centric tool that effectively measures health-related quality of life in boys with hemophilia who are receiving standard half-life or EHL FCs.
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BACKGROUND: Fever in the setting of neutropenia is a potentially life-threatening complication of cancer treatment. A time of less than 60 minutes from presentation to antibiotic administration is therefore recommended. OBJECTIVE: To use Lean Six Sigma methodology, a quality improvement initiative, to improve time to antibiotics (TTA) for children with chemotherapy-induced febrile neutropenia presenting to the emergency department. METHODS: Lean Six Sigma is a quality improvement method that engages all impacted stakeholders and focuses on streamlining the process by removing process wastes. Stakeholders identified multiple process wastes in an in-depth study of 49 fever episodes in patients attending a tertiary care pediatric hospital, including patients waiting to be registered, waiting for laboratory technicians, delay in accessing central venous access device, waiting for absolute neutrophil count, and delayed antibiotics orders. We implemented multiple solutions: engaging patients in the process through predischarge tours of the emergency department, home application of topical anesthetic, nurse-initiated pathway, early access of central venous access device for all blood work, and planned antibiotic administration no later than 45 minutes after triage. We prospectively determined the impact of these interventions on TTA. RESULTS: The TTA significantly improved to a median of 59 minutes (interquartile range, 38.5-77.5 minutes) compared with the baseline of 99 minutes (interquartile range, 72.0-132.0 minutes; P < 0.0001). CONCLUSIONS: Lean methodology effectively identifies barriers and provides solutions to remove barriers and improve administration of antibiotics in febrile oncology patients. These can be widely applied, including in smaller institutions with minimal increased utilization of resources.
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Antibacterianos/uso terapéutico , Antineoplásicos/efectos adversos , Neutropenia Febril/tratamiento farmacológico , Tiempo de Tratamiento , Gestión de la Calidad Total , Niño , Preescolar , Neutropenia Febril/inducido químicamente , Estudio Históricamente Controlado , Humanos , Neoplasias/complicaciones , Neoplasias/tratamiento farmacológico , Estudios ProspectivosRESUMEN
BACKGROUND: There is no uniform guideline for postchemotherapy vaccination of children with acute lymphoblastic leukemia (ALL). We evaluated waning immunity to 14 pneumococcal serotypes, pertussis toxin (PT), tetanus toxoid (TT) and varicella, and immunogenicity of postchemotherapy diphtheria, tetanus, pertussis, hepatitis B, polio, and Haemophilus influenzae type b (DTaP-IPV-Hib) and pneumococcal vaccination among previously vaccinated children treated for ALL. METHODS: This was a multicenter trial of children with ALL enrolled 4-12 months postchemotherapy completion. Exclusion criteria included: infant ALL, relapsed ALL, and stem cell transplant recipients. Immunocompetent children were recruited as controls. Postchemotherapy participants received DTaP-IPV-Hib and 13-valent pneumococcal conjugate vaccine (PCV13) concurrently, followed by 23-valent pneumococcal polysaccharide vaccine (PPV23) 2 months later. Serology was measured at baseline, 2 and 12 months postvaccination. Adverse events were captured via surveys. RESULTS: At enrollment, postchemotherapy participants (nâ =â 74) were less likely than controls (nâ =â 78) to be age-appropriately immunized with DTaP (41% vs 89%, Pâ <â .001) and PCV (59% vs 79%, Pâ =â .008). Geometric mean concentrations (GMCs) to TT, PT, PCV serotypes, and varicella were lower in postchemotherapy participants than controls after adjusting for previous vaccine doses (Pâ <â .001). Two months postvaccination, GMCs to TT, PT, and PCV serotypes increased from baseline (Pâ <â .001 for all antigens) and remained elevated at 12 months postvaccination. Antibody levels to PPV23 serotypes also increased postvaccination (Pâ <â .001). No serious adverse events were reported. CONCLUSIONS: Children treated for ALL had lower antibody levels than controls against pneumococcal serotypes, tetanus, pertussis, and varicella despite previous vaccination. Postchemotherapy vaccination with DTaP-IPV-Hib, PCV13, and PPV23 was immunogenic and well tolerated. Children with ALL would benefit from systematic revaccination postchemotherapy. CLINICAL TRIALS REGISTRATION: NCT02447718.
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Vacunas contra Haemophilus , Leucemia-Linfoma Linfoblástico de Células Precursoras , Anticuerpos Antibacterianos , Canadá , Niño , Vacuna contra Difteria, Tétanos y Tos Ferina , Vacunas contra Hepatitis B , Humanos , Lactante , Vacuna Antipolio de Virus Inactivados , Vacunación , Vacunas Combinadas , Vacunas ConjugadasRESUMEN
INTRODUCTION: In many countries, there is a shift from standard half-life (SHL) to extended half-life (EHL) clotting factor concentrates (CFCs). AIM: To describe the experience of switching from SHL to an EHL FVIII CFC and the impact of this on frequency of infusions, factor consumption, bleeding rates and HRQoL using the Canadian Hemophilia Kids' Life Assessment Tool (CHO-KLAT). METHODS: A retrospective chart review was conducted at a single haemophilia treatment centre in 2018 that included boys (ages: 4-18 years) with moderate/severe haemophilia A, without inhibitors, who switched from a SHL to an EHL FVIII CFC in the previous 2 years and for whom HRQoL data were available. RESULTS: The study cohort comprised 38 boys [mean (SD) age: 11.0 (3.4) years] with moderate (n = 5)/severe (n = 33) haemophilia A. The switch was associated with a 33% reduction in the number of weekly infusions from a median of 3.5 to 2.3 (P < .0001) and a 17% reduction in median FVIII consumption from 103 IU/kg/wk to 85.5 IU/kg/wk (P = .004). There was no significant change in annualized joint bleed rates or in CHO-KLAT scores. CONCLUSIONS: Despite documenting several benefits of switching to EHL FVIII (less infusions, lower factor consumption with no increase in bleeding), our study did not demonstrate any improvement in HRQoL. We conclude that either the current CHO-KLAT tool is not optimized to measure burden of treatment administration in boys with low bleed rates switching from SHL to EHL FVIII CFCs or that a reduction of 1.2 infusions/week does not result in a meaningful change in HRQoL.
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Factor VIII/uso terapéutico , Semivida , Hemofilia A/tratamiento farmacológico , Calidad de Vida/psicología , Adolescente , Niño , Preescolar , Factor VIII/farmacología , Humanos , Masculino , Estudios RetrospectivosRESUMEN
BACKGROUND: Prophylaxis reduces the frequency of bleeds in boys with severe hemophilia and is the standard care for their management in resource-abundant countries. The effect of prophylaxis on Health-Related Quality of Life (HRQoL) has not been established, because the sample sizes of most studies are too small to explore the relationship of multiple factors that influence HRQoL. METHODS: The aim of this study was to assess the impact of hemophilia severity and treatment regimen on HRQoL and to establish the minimum important difference (MID) using the international level of score distributions. HRQoL data were pooled from 7 studies across 9 countries. HRQoL was measured using the Canadian Hemophilia Outcomes-Kids' Life Assessment Tool (CHO-KLAT). A mixed-effect linear regression analysis was employed to assess the impact of prophylaxis on the CHO-KLAT score. RESULTS: Data from 401 boys with hemophilia were analyzed (57.6% severe hemophilia and 57.6% receiving prophylaxis). The model revealed that receiving prophylaxis was significantly associated with higher HRQoL (regression coefficient 8.5, 95% confidence interval [CI] 3.9-13.1). Boys with severe hemophilia had a significantly lower HRQoL as compared to boys with moderate and mild hemophilia whose CHO-KLAT scores were 7.0 and 6.6 points higher, respectively. There was a significant interaction between treatment and disease severity (P = 0.023), indicating prophylaxis has the most significant impact in boys with severe hemophilia. Based on these pooled data, the MID of the CHO-KLAT was established at 6.5. CONCLUSIONS: This study confirms the positive effect of prophylaxis on HRQoL in boys with hemophilia in a real-world setting and provides initial benchmarks for interpreting HRQoL scores based on use of the CHO-KLAT instrument.
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Newborns with hemophilia are at risk of intracranial hemorrhage, extracranial hemorrhage, and other bleeding complications. The safe delivery of a healthy newborn with hemophilia is a complex process that can begin even before conception, and continues throughout pregnancy, birth, and the newborn period. This process involves the expectant parents and a wide variety of health-care professionals: genetic counselors, obstetricians, neonatologists, pediatricians, radiologists, adult and pediatric hematologists, and nurses with expertise in hemophilia. Because of this multidisciplinary complexity, the relative rarity of births of newborns with hemophilia, and the lack of high-quality evidence to inform decisions, there is considerable variation in practice in this area. We present a comprehensive multidisciplinary approach, from preconception counseling to discharge planning after birth, and describe available options for management decisions. We highlight a number of areas of important uncertainty and controversy, including the preferred mode of delivery, the appropriate use and timing of neuroimaging tests, and the appropriate use of clotting factor concentrates in the newborn period. While the approach presented here will aid clinicians in planning and providing care, further research is required to optimize the care of newborns with hemophilia.
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Enfermedades Fetales , Feto , Asesoramiento Genético , Hemofilia A , Enfermedades del Recién Nacido , Femenino , Enfermedades Fetales/diagnóstico , Enfermedades Fetales/genética , Enfermedades Fetales/terapia , Hemofilia A/diagnóstico , Hemofilia A/genética , Hemofilia A/terapia , Humanos , Recién Nacido , Enfermedades del Recién Nacido/diagnóstico , Enfermedades del Recién Nacido/genética , Enfermedades del Recién Nacido/terapia , Guías de Práctica Clínica como Asunto , EmbarazoRESUMEN
BACKGROUND: Severe haemophilia A has high morbidity, and treatment, while effective, is very expensive. We report the 16-year follow-up of the Canadian Hemophilia Prophylaxis Study, which examined the effectiveness of tailored frequency-escalated primary prophylaxis with a focus on health outcomes within the domains of body structures and functions, and activities and participation (according to the WHO International Classification of Functioning, Disability and Health [WHO-ICF] framework) and a view to reducing consumption of costly clotting factor, which accounts for more than 90% of the cost of care of severe haemophilia. METHODS: In this longitudinal study, boys with severe haemophilia A from 12 Canadian centres were enrolled at age 1·0-2·5 years. They were treated with standard half-life recombinant factor VIII (SHL-rFVIII), beginning as once-weekly prophylaxis with 50 IU/kg and escalating in frequency (with accompanying dose adjustments) in response to breakthrough bleeding as determined by the protocol. The primary endpoint for this analysis was joint health, as measured by the modified Colorado Child Physical Examination Scores (CCPES) at study end. All analyses were done by intention to treat. The trial is complete, and is registered with ClinicalTrials.gov, number NCT01085344. FINDINGS: Between June 26, 1997, and Jan 30, 2007, 56 boys were enrolled. They were followed for a median of 10·2 years (to a maximum of 16·1 years). Median rFVIII usage was about 3600 IU/kg per year. The median end-of-study CCPES physical examination score was 1 (IQR 1-3; range 0-12) for the left ankle and 1 (1-2; 0-12) for the right ankle, with all other joints having a median score of 0. No treatment-related safety events occurred over the duration of the study, including central venous catheter infections. The median annualised index joint bleeding rate was 0·95 per year (IQR 0·44-1·35; range 0·00-13·43), but 17 (30%) patients had protocol-defined unacceptable breakthrough bleeding at some point during the study. INTERPRETATION: Tailored frequency-escalated prophylaxis leads to very little arthropathy and very good health outcomes within the WHO-ICF domains, and only uses a moderate amount of expensive clotting factor as compared with standard prophylaxis protocols. Some sequelae of bleeding were observed in our cohort, and future studies should consider a more stringent protocol of escalation. FUNDING: This study was initially funded by grants from the Medical Research Council of Canada/Pharmaceutical Manufacturers Association of Canada Partnership Fund and the Bayer/Canadian Blood Services/Hema-Quebec Partnership Fund. Subsequent renewals were funded by Bayer.
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Factor VIII/uso terapéutico , Hemartrosis/prevención & control , Hemofilia A/tratamiento farmacológico , Adolescente , Canadá , Niño , Preescolar , Progresión de la Enfermedad , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Factor VIII/administración & dosificación , Hemartrosis/etiología , Hemofilia A/complicaciones , Hemofilia A/patología , Humanos , Lactante , Articulaciones/diagnóstico por imagen , Estudios Longitudinales , Masculino , Cooperación del PacienteRESUMEN
Congenital sideroblastic anemia (CSA) is a hematological disorder characterized by the presence of ringed sideroblasts in bone marrow erythroid precursors. Mutations in the erythroid-specific glycine mitochondrial transporter gene SLC25A38 have been found in a subset of patients with transfusion-dependent congenital CSA. Further studies in a zebrafish model identified a promising ameliorative strategy with combined supplementation with glycine and folate. We tested this combination in three individuals with SLC25A38 CSA, with a primary objective to decrease red blood cell transfusion requirements. No significant impact was observed on transfusion requirements or any hematologic parameters.
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Anemia Sideroblástica , Transfusión de Eritrocitos , Ácido Fólico/administración & dosificación , Glicina/administración & dosificación , Proteínas de Transporte de Membrana Mitocondrial/genética , Mutación , Adolescente , Adulto , Anemia Sideroblástica/genética , Anemia Sideroblástica/terapia , Femenino , Humanos , MasculinoRESUMEN
Children with asplenia or hyposplenia are at risk of developing overwhelming sepsis. Health care providers caring for children with asplenia should ensure the best outcomes by using preventive strategies that focus on parent and patient education, immunization, antibiotic prophylaxis and aggressive management of suspected infection. The present position statement offers current guidance on each of these issues and replaces a previous CPS statement, 'Prevention and therapy of bacterial infections for children with asplenia or hyposplenia', published in 1999.
Les enfants présentant une asplénie ou une hyposplénie sont vulnérables à un sepsis fulgurant. Les dispensateurs de soins qui s'occupent d'enfants présentant une asplénie devraient s'assurer des meilleurs résultats cliniques possible grâce à des stratégies préventives axées sur l'éducation des parents et des patients, la vaccination, la prophylaxie antibiotique et la prise en charge vigoureuse de l'infection présumée. Le présent document de principes, qui propose des conseils à jour sur chacun de ces sujets, remplace le document de la SCP intitulé « La prévention et le traitement des infections bactériennes chez les enfants aspléniques ou hypospléniques ¼, publié en 1999.
RESUMEN
Asparaginase (ASP) therapy is associated with depletion of antithrombin (AT) and fibrinogen (FG). Potential toxicities include central nervous system thrombosis (CNST) and hemorrhage. Historical practice at the Izaak Walton Killam Health Centre (IWK) involves measuring AT and FG levels after ASP administration and transfusing fresh-frozen plasma (FFP) or cryoprecipitate (CRY) to prevent thrombotic and hemorrhagic complications. To determine whether this reduced these complications in children with acute lymphoblastic leukemia (ALL), incidence, outcome, and clinical characteristics of ASP-related CNST in ALL patients at IWK were compared with a similar cohort from BC Children's Hospital (BCCH), where prophylaxis was not performed. Costs associated with preventative versus expectant management were estimated. From 1990 to 2005, 240 patients were treated at IWK and 479 at BCCH. Seven BCCH patients developed venous CNST (1.5%), compared with none at IWK. CNST occurred exclusively during induction. Six patients received anticoagulation and continued ASP. All 7 patients remain in remission. National Cancer Institute high-risk ALL predicted CNST risk (P = .02), whereas sex, age, race, and body mass index did not. Neither FFP nor CRY protected against CNST, suggesting prophylaxis is unwarranted for unselected ALL patients. However, prophylactic replacement for HR patients in induction may be cost-effective.
Asunto(s)
Asparaginasa/uso terapéutico , Factor VIII/uso terapéutico , Fibrinógeno/uso terapéutico , Hemorragia/prevención & control , Plasma , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Trombosis/prevención & control , Adolescente , Asparaginasa/efectos adversos , Colombia Británica , Sistema Nervioso Central/irrigación sanguínea , Niño , Preescolar , Costos y Análisis de Costo , Femenino , Hemorragia/inducido químicamente , Humanos , Lactante , Masculino , Nueva Escocia , Evaluación de Resultado en la Atención de Salud/economía , Leucemia-Linfoma Linfoblástico de Células Precursoras/economía , Inducción de Remisión , Factores Sexuales , Trombosis/inducido químicamenteRESUMEN
BACKGROUND: Disease-specific quality of life (QoL) measures have enhanced the capacity of outcome measures to evaluate subtle changes and differences between groups. However, when the specific disease is rare, the cohort of patients is small and international collaboration is often necessary to accomplish meaningful research. As many of the QoL measures have been developed in North American English, they require translation to ensure their usefulness in a multi-cultural and/or international society. Published guidelines provide formal methods to achieve cross-culturally comparable versions of a QoL tool. However, these guidelines describe a rigorous process that is not always feasible, particularly in rare disease groups. The objective of this manuscript is to describe the process that was developed to achieve accurate cross-cultural translations of a disease-specific QoL measure, to overcome the challenges of a small sample size, i.e. children with a rare disorder. PROCEDURE: A measurement study was conducted in the United Kingdom (UK), France, Germany and Uruguay, during which the validated measure was translated into the languages of the respective countries. RESULTS: This is a report of a modified, child-centric, cross-cultural translation and adaptation process in which culturally appropriate and methodologically valid translations of a disease-specific QoL measure, the Kids' ITP Tools (KIT), were performed in children with immune thrombocytopenic purpura (ITP). The KIT was translated from North American English into UK English, French, German, and Spanish. CONCLUSION: This study was a successful international collaboration. The modified process through which culturally appropriate and methodologically valid translations of QoL measures may be achieved in a pediatric population with a relatively rare disorder is reported.
Asunto(s)
Púrpura Trombocitopénica Idiopática , Calidad de Vida , Enfermedades Raras , Encuestas y Cuestionarios , Traducción , Adolescente , Adulto , Niño , Cultura , Francia , Alemania , Humanos , Cooperación Internacional , Traducciones , Reino Unido , UruguayRESUMEN
Bone marrow examination (BME) in paediatric Hodgkin lymphoma (HL) was evaluated, as evidence from adult HL suggests it may be unnecessary. An internet-based survey was used to examine the practice of Canadian paediatric oncologists regarding BME in children and the impact of routine BME was evaluated in patients with HL treated at our institution. Sixteen of 17 paediatric oncology centres were represented. Forty-three percent of eligible doctors completed the survey. Routine BME for stages III and IV disease was consistent nationally. By contrast, 54% and 70% of respondents reported performing routine BME for stages I and II HL respectively. Respondents were more likely to report performing routine BME in low-stage HL if trained outside Canada (P = 0.04, stage I; P = 0.07, stage II) or practicing at smaller centres (P = 0.05, stage I; P = 0.03, stage II). At our institution, 62 patients were eligible for analysis. Only four patients (6.5%) had a positive BME. Anaemia was the only significant risk factor (P = 0.006). No patient with otherwise low stage was found to have marrow involvement. Comparison of staging with and without BME demonstrated no significant difference to final risk classification. BME in paediatric patients with low-stage HL has extremely low yield and may be unnecessary.