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AIM: To assess the association between socioeconomic factors and mortality in Danish children diagnosed with different types of severe chronic disease, including cancer. METHODS: National cohort study 1994-2020 including Danish children with chronic disease. Inclusion was based on diagnoses in The National Patient Register, socioeconomic information was obtained from Statistics Denmark and mortality was ascertained from the Cause of Death Register. Hazard ratios (HR) with 95% confidence intervals (CIs) were based on Cox regression. The factors were combined in one common risk score and the association with disease-specific mortality was analysed overall and by ethnicity status. RESULTS: Overall, non-Danish ethnicity (HR = 1.96 (95% CI 1.69-2.28)) was associated with all-cause mortality in 128 129 children (69 435 male and 58 694 female) with chronic disease. Median age at first diagnosis was 1.42 years (range 0-18 years). Low family income was associated with mortality regardless of ethnicity status, and young maternal age was also a notable risk factor across ethnicities. The socioeconomic association was more pronounced in children with cancer. CONCLUSION: In the high-income setting of Denmark, ethnicity and differences in socioeconomic background were associated with child mortality even among children with severe chronic disease. The pattern was more pronounced in paediatric cancer patients.
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Estudos de Coortes , Criança , Humanos , Masculino , Feminino , Recém-Nascido , Lactente , Pré-Escolar , Adolescente , Sistema de Registros , Fatores Socioeconômicos , Fatores de Risco , Doença Crônica , Dinamarca/epidemiologiaAssuntos
Vacinas contra COVID-19 , COVID-19 , Humanos , Criança , Estudos Prospectivos , Vacinação , Anticorpos AntiviraisRESUMO
BACKGROUND: Recurrent wheeze (RW) is frequent in childhood. Studies have suggested that BCG vaccination can have nonspecific effects, reducing general nontuberculosis morbidity, including respiratory tract infections and atopic diseases. The mechanisms behind these nonspecific effects of BCG are not fully understood, but a shift from a TH2 to a TH1 response has been suggested as a possible explanation. OBJECTIVE: We hypothesized that BCG at birth would reduce the cumulative incidence of RW during the first year of life. METHODS: The Danish Calmette Study is a multicenter randomized trial conducted from 2012-2015 at 3 Danish hospitals. The 4262 newborns of 4184 included mothers were randomized 1:1 to BCG (SSI strain 1331) or to a no-intervention control group within 7 days of birth; siblings were randomized together as one randomization unit. Exclusion criteria were gestational age of less than 32 weeks, birth weight of less than 1000 g, known immunodeficiency, or no Danish-speaking parent. Information was collected through telephone interviews and clinical examinations at 3 and 13 months of age; data collectors were blind to randomization group. RW was defined in several ways, with the main definition being physician-diagnosed and medically treated RW up to 13 months of age. RESULTS: By 13 months, 211 (10.0%) of 2100 children in the BCG group and 195 (9.4%) of 2071 children in the control group had received a diagnosis of RW from a medical doctor and received antiasthma treatment (relative risk, 1.07; 95% CI, 0.89-1.28). Supplementary analyses were made, including an analysis of baseline risk factors for development of RW. CONCLUSION: Neonatal BCG had no effect on the development of RW before 13 months of age.
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Asma/imunologia , Vacina BCG/imunologia , Sons Respiratórios/imunologia , Antiasmáticos/uso terapêutico , Asma/prevenção & controle , Dinamarca , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Recidiva , Equilíbrio Th1-Th2 , Resultado do Tratamento , VacinaçãoRESUMO
OBJECTIVE: To explore the informational needs of mothers with different levels of education in order to improve counselling about vaccination. METHODS: In the setting of a large vaccination trial, mothers' assessments and yield of written information in combination with telephone consultations were evaluated in a survey. Furthermore, searching strategies for additional information were investigated. Mothers' perspectives on informational needs were explored in focus group discussions. RESULTS: Out of 2025 mothers, 95% felt well-informed. Of the 4% not feeling well-informed, there were significantly more mothers with basic schooling and nontheoretical education. There was no correlation between searching for additional information and feeling well-informed. The telephone consultation was found to be very supportive for the decision. CONCLUSION: The written information was digestible over time. The telephone consultation ensured the mothers' understanding by tailoring and deriving meaning from the information to her special needs. Moreover, it helped the mothers gain an overview of risks and benefits and inspired confidence. These findings indicate that the telephone consultation improved health literacy. PRACTICE IMPLICATIONS: Individual counselling about vaccines is required in addition to information about side effects and accurate instructions on how to react upon them.
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Adjuvantes Imunológicos/uso terapêutico , Vacina BCG/uso terapêutico , Tomada de Decisões , Conhecimentos, Atitudes e Prática em Saúde , Mães/psicologia , Vacinação/psicologia , Adulto , Atitude Frente a Saúde , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Inquéritos e QuestionáriosRESUMO
BACKGROUND: The Bacillus Calmette-Guérin vaccine (BCG) has been associated with beneficial nonspecific effects on infant health. We aimed to examine the effect of BCG at birth on thymic size and the associations between thymic output, circulating lymphocytes, risk of infection, and thymic size. METHODS: In infants randomized to BCG or no BCG, thymic index (TI), and thymic/weight index (TWI) were measured by ultrasound at birth and at the age of 3 mo. T cell subpopulations including CD4+ T cells, CD8+ T cells, and recent thymic emigrants (RTEs) were assessed by flow cytometry. Infections up to age 3 mo were parent-reported. RESULTS: BCG vaccination did not affect thymic size at age 3 mo, measured as TI. At birth, the number of lymphocytes, CD4+ T cells, CD8+ T cells, and RTEs were positively associated with TI and TWI. Furthermore, a reduced risk of infections up to age 3 mo was associated with a large thymic size at birth. CONCLUSION: We found no effect of BCG vaccination on thymic size. The positive association between thymic output, lymphocytes, reduced risk of infections, and TI/TWI suggests that assessment of TI/TWI by ultrasound may be a predictor of the immunological capacity in the newborn.
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Vacina BCG/administração & dosagem , Timo/anatomia & histologia , Subpopulações de Linfócitos B , Feminino , Citometria de Fluxo , Humanos , Recém-Nascido , Masculino , Subpopulações de Linfócitos T , Timo/diagnóstico por imagem , Timo/fisiologiaRESUMO
BACKGROUND: The incidence of atopic dermatitis, wheezing, asthma and allergic rhinoconjunctivitis has been increasing. Register-based studies are essential for research in subpopulations with specific diseases and facilitate epidemiological studies to identify causes and evaluate interventions. Algorithms have been developed to identify children with atopic dermatitis, asthma or allergic rhinoconjunctivitis using register information on disease-specific dispensed prescribed medication and hospital contacts, but the validity of the algorithms has not been evaluated. This study validated the algorithms vs gold standard deep telephone interviews with the caretaker about physician-diagnosed atopic dermatitis, wheezing, asthma or allergic rhinoconjunctivitis in the child. METHODS: The algorithms defined each of the three atopic diseases using register-based information on disease-specific hospital contacts and/or filled prescriptions of disease-specific medication. Confirmative answers to questions about physician-diagnosed atopic disease were used as the gold standard for the comparison with the algorithms, resulting in sensitivities and specificities and 95% confidence intervals. The interviews with the caretaker of the included 454 Danish children born 1997-2003 were carried out May-September 2015; the mean age of the children at the time of the interview being 15.2 years (standard deviation 1.3 years). RESULTS: For the algorithm capturing children with atopic dermatitis, the sensitivity was 74.1% (95% confidence interval: 66.9%-80.2%) and the specificity 73.0% (67.3%-78.0%). For the algorithm capturing children with asthma, both the sensitivity of 84.1% (78.0%-88.8%) and the specificity of 81.6% (76.5%-85.8%) were high compared with physician-diagnosed asthmatic bronchitis (recurrent wheezing). The sensitivity remained high when capturing physician-diagnosed asthma: 83.3% (74.3%-89.6%); however, the specificity declined to 66.0% (60.9%-70.8%). For allergic rhinoconjunctivitis, the sensitivity was 84.4% (78.0-89.2) and the specificity 81.6% (75.0-84.4). CONCLUSION: The algorithms are valid and valuable tools to identify children with atopic dermatitis, wheezing, asthma or allergic rhinoconjunctivitis on a population level using register data.
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Algoritmos , Asma/diagnóstico , Conjuntivite Alérgica/diagnóstico , Dermatite Atópica/diagnóstico , Sistema de Registros , Sons Respiratórios/diagnóstico , Rinite Alérgica/diagnóstico , Adolescente , Criança , Dinamarca , Feminino , Humanos , Masculino , Sensibilidade e EspecificidadeRESUMO
BACKGROUND: Vaccination with Bacillus Calmette-Guérin (BCG) is used in many countries as protection against tuberculosis. Studies have suggested that BCG may also have non-specific effects, reducing non-tuberculosis mortality, morbidity, and atopic manifestations. In this study, we evaluated the effect of neonatal BCG vaccination on allergic sensitization and suspected food allergy at 13 months of age. METHODS: The Danish Calmette Study was conducted from 2012 to 2015 at three Danish hospitals. Within 7 days of birth, the 4262 newborns of 4184 included mothers were randomized 1:1 to BCG or to a no-intervention control group. Exclusion criteria were gestational age <32 weeks, birth weight <1000 g, known immunodeficiency, or no Danish-speaking parent. Follow-up information was collected through telephone interviews at 3 and 13 months of age. Subgroups of participants were offered blood sampling at 13 months of age. RESULTS: By 13 months of age, the parents and/or general practitioners of 5.6% (117/2089) of the children in the BCG group and 6.1% (126/2061) of the control group suspected food allergy, resulting in a risk ratio comparing BCG-vaccinated children with control children of 0.91 (95% CI 0.71-1.16). Among 1370 blood samples, sensitization (Phadiatop Infant >0.35 kUA/L) was found in 55 of 743 (7.4%) children in the BCG group and 50 of 627 (8.0%) of the control group (risk ratio 0.94 [0.65-1.36]). CONCLUSION: In this randomized clinical trial, neonatal BCG had no significant effect on suspected food allergy or on sensitization at 13 months of age.
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Vacina BCG/uso terapêutico , Hipersensibilidade Alimentar/prevenção & controle , Vacina BCG/imunologia , Dinamarca/epidemiologia , Feminino , Seguimentos , Hipersensibilidade Alimentar/diagnóstico , Hipersensibilidade Alimentar/epidemiologia , Hipersensibilidade Alimentar/imunologia , Humanos , Hipersensibilidade Imediata/diagnóstico , Hipersensibilidade Imediata/epidemiologia , Hipersensibilidade Imediata/imunologia , Hipersensibilidade Imediata/prevenção & controle , Incidência , Lactente , Recém-Nascido , Masculino , Método Simples-Cego , Resultado do TratamentoRESUMO
BACKGROUND: The Bacillus Calmette-Guérin vaccine (BCG) against tuberculosis is administered intradermally, and vaccination is often followed by a scar at the injection site. Among BCG-vaccinated individuals, having a scar has been associated with lower mortality. We aimed to examine the impact of vaccination technique for scarring in a high income setting, by assessing the associations between the post injection reaction, the wheal size, and the probability of developing a scar, and scar size. METHODS: This study was nested within a clinical multicenter study randomizing 4262 infants to either BCG vaccination (BCG 1331 SSI) or no intervention. In this substudy, including 492 vaccinated infants, the immediate post BCG vaccination reaction was registered as either wheal (a raised, blanched papule at the injection site), bulge (a palpable element at the injection site), or no reaction. The presence or absence of a BCG scar and the size the scar was measured at 13 months of age. RESULTS: Of 492 infants included, 87% had a wheal after vaccination, 11% had a bulge, and 2% had no reaction. The mean wheal size was 3.8 mm (95% confidence interval 3.7-3.9). Overall, 95% (442/466, 26 lost to follow-up) of BCG-vaccinated infants had a scar at 13 months of age. In infants with a wheal, the probability of developing a scar was 96%, declining to 87% in the case of a bulge, and to 56% in the case of no reaction (p for same probability = 0.03). Wheal size was positively correlated with the probability of getting a scar and scar size. CONCLUSION: Scarring after BCG vaccination has been associated with lower infant mortality. In a high-income setting, we found that correct injection technique is highly important for the development of a BCG scar and that registration of the category of BCG skin reaction (as wheal, bulge, or no reaction) may be used to identify infants at risk of scar failure. Finally, the wheal size was positively associated with both the probability of getting a scar and scar size. TRIAL REGISTRATION: The study was registered at www.ClinicalTrials.gov with trial registration number NCT01694108 .
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Vacina BCG/efeitos adversos , Cicatriz/etiologia , Vacina BCG/administração & dosagem , Bacillus , Dinamarca/epidemiologia , Feminino , Humanos , Lactente , Mortalidade Infantil , Perda de Seguimento , Masculino , Teste Tuberculínico , Vacinação/efeitos adversos , Vacinação/métodosRESUMO
BACKGROUND: Several studies have shown that the prevalence of the frequent chronic conditions of atopic dermatitis, asthma, and allergy has increased substantially for reasons not fully understood. Atopic diseases affect quality of life in both children and their family members. OBJECTIVE: Using national registers, we sought to establish up-to-date incidence rates of atopic dermatitis, asthma, and allergic rhinoconjunctivitis in the Danish and Swedish child populations. METHODS: Children born in Denmark from 1997 to 2011 or born in Sweden from 2006 to 2010 participated in this cross-national, population-based cohort study. Incidence rates of atopic dermatitis, asthma, and allergic rhinoconjunctivitis in the Danish and Swedish child cohorts were ascertained through disease-specific dispensed prescribed medication, specific hospital contacts, or both. RESULTS: In both countries the incidence rate of atopic dermatitis was stable during the study periods. The incidence rate of asthma increased until 2006 and stabilized for the rest of the study period in Denmark and increased in Sweden. The incidence rate of allergic rhinoconjunctivitis decreased in both countries. CONCLUSION: The study revealed similar trends, with stable incidence rates of atopic dermatitis in both Danish and Swedish children, an increase and then stabilization in asthma incidence rates in Denmark and an increase in Sweden, and a decrease in allergic rhinoconjunctivitis incidence rates. At age 5 years, one third of all children were affected with at least one of the conditions of atopic dermatitis, asthma, or allergic rhinoconjunctivitis.
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Asma/epidemiologia , Conjuntivite Alérgica/epidemiologia , Dermatite Atópica/epidemiologia , Rinite Alérgica Sazonal/epidemiologia , Adolescente , Asma/imunologia , Asma/patologia , Criança , Pré-Escolar , Doença Crônica , Conjuntivite Alérgica/imunologia , Conjuntivite Alérgica/patologia , Estudos Transversais , Dinamarca , Dermatite Atópica/imunologia , Dermatite Atópica/patologia , Feminino , Humanos , Incidência , Masculino , Sistema de Registros , Rinite Alérgica Sazonal/imunologia , Rinite Alérgica Sazonal/patologia , SuéciaRESUMO
Pediatric health service differs between and within countries. To prioritize limited resources, data-driven studies on pediatric tertiary hospital contacts are warranted. This population-based register study identified all contacts with four Danish tertiary hospitals 2000-2018 by 0-17-year-old patients. During 2000-2018, 2,496,001 individuals resided in Denmark while 0-17 years old, and the study described 829,562 inpatient and 3,932,744 outpatient contacts at tertiary hospitals by hospital, sex, age, diagnosis, department, and residence. Male patients accounted for more contacts overall (inpatient 55.51%, outpatient 52.40%) and more contacts with severe chronic disease (inpatient 56.24%, outpatient 54.41%). Median (interquartile range) patient age was 3.09 (0.26-9.96) and 8.48 (2.78-13.70) years for in- and outpatient contacts. Overall, 28.23% and 21.02% of in- and outpatient contacts included a diagnosis of a severe chronic disease, but the proportions differed across hospitals. A pattern of pediatric healthcare directed towards less severe diseases was observed: While the total number of outpatient visits at tertiary hospitals increased from 2000 to 2018, the proportion of these contacts which had a diagnosis of a severe chronic disease decreased. Future comparisons between hospitals regarding pediatric outcomes should consider potential differences in terms of uptake and diagnosis severity. Such findings may have implications for future pediatric organization, nationally and internationally.
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Centros de Atenção Terciária , Humanos , Dinamarca/epidemiologia , Criança , Pré-Escolar , Centros de Atenção Terciária/estatística & dados numéricos , Masculino , Lactente , Feminino , Adolescente , Recém-Nascido , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Doença Crônica/epidemiologia , Serviços de Saúde da Criança/estatística & dados numéricos , Sistema de Registros , Pacientes Ambulatoriais/estatística & dados numéricosRESUMO
Background: Measles is a highly contagious viral disease. Vaccinated mothers transfer fewer antibodies during pregnancy, resulting in shortened infant immunity. Earlier primary vaccination might avert the gap in protection. Methods: Healthy 5-7-month-old Danish infants were assigned in a 1:1 ratio to M-M-RVaxPro or placebo (solvent) in a double-blind, randomized trial between April 15, 2019 and November 1, 2021 (ClinicalTrials.govNCT03780179, EudraCT 2016-001901-18). Eligibility criteria were birth weight >1000 g and gestational age ≥32 weeks.Immunogenicity was measured by plaque reduction neutralization test (PRNT) and IgG ELISA before intervention, four weeks after intervention and routine MMR. Reactogenicity data were collected for six weeks and measured by hazard ratios (HR). Findings: 647 and 6540 infants participated in the immunogenicity and reactogenicity study, respectively; 87% and 99% completed follow-up. After early MMR, seroprotection rates (SPRs) were 47% (13%) in measles PRNT; 28% (2%), 57% (8%) in mumps and rubella IgG (placebo). For measles PRNT, geometric mean ratio was 4.3 (95% CI: 3.4-5.3) between randomization groups after intervention and 1.5 (95% CI: 1.3-1.9) after routine MMR.Reactogenicity was independent of randomization (HR, 1.0; 95% CI: 0.9-1.1). Severe adverse events occurred in 25 infants (HR, 1.8; 95% CI: 0.8-4.0); none deemed vaccine related. Interpretation: Early MMR elicited low SPRs but did not negatively impact short-term responses to a subsequent MMR. MMR at 5-7 months was safe and not associated with higher rates of reactogenicity than placebo. Funding: Innovation Fund Denmark.
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OBJECTIVES: To investigate the hypothesis that mother's use of antibiotics in pregnancy could influence asthma and eczema in early life. STUDY DESIGN: Subjects were included from the Copenhagen Prospective Study on Asthma in Childhood cohort of children born of mothers with asthma (N = 411). Severe asthma exacerbations and eczema were diagnosed by research unit physicians. Replication was sought in children from the Danish National Birth Cohort (N = 30â675). Asthma outcomes were hospitalization and use of inhaled corticosteroids. Eczema was defined by an algorithm developed from cases of clinically verified eczema. All children were followed to age 5 years in a cohort study design. RESULTS: The Copenhagen Prospective Study on Asthma in Childhood data showed increased risk of asthma exacerbation (hazard ratio 1.98 [95% CI 1.08-3.63]) if mothers had used antibiotics during third trimester. The Danish National Birth Cohort confirmed increased risk of asthma hospitalization (hazard ratio 1.17 [1.00-1.36]), and inhaled corticosteroids (1.18 [1.10-1.27]) in the children if mothers used antibiotics any time during pregnancy. In the subgroup of mothers using antibiotics for nonrespiratory infection, the children also had increased risk of asthma. CONCLUSION: We found increased risk of asthma associated with maternal antibiotic use in a clinical study of a birth cohort with increased risk of asthma and replicated this finding in an unselected national birth cohort, and in a subgroup using antibiotics for nonrespiratory infections. This supports a role for bacterial ecology in pre- or perinatal life for the development of asthma.
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Antibacterianos/efeitos adversos , Asma/etiologia , Corticosteroides/uso terapêutico , Algoritmos , Pré-Escolar , Estudos de Coortes , Dinamarca , Eczema/etiologia , Feminino , Hospitalização , Humanos , Masculino , Gravidez , Complicações Infecciosas na Gravidez/tratamento farmacológico , Efeitos Tardios da Exposição Pré-Natal , Risco , Resultado do TratamentoRESUMO
INTRODUCTION: Anthropometric data are key to evaluating infant health. This study assessed the validity of parent-reported infant weight and length, and their reliability to categorise children by BMI z-score, as compared to clinical measurements. METHODS: From a cohort of 4,262 infants, parent-reported and clinically measured anthropometric data were obtained and compared at three months and one year of age. RESULTS: Parent-reported and clinically measured data generally correlated well. Mean differences at three months and at one year, respectively, were 0.08 kg (95% confidence interval (CI): 0.07-0.09 kg) and 0.10 kg (95% CI: 0.08-0.12 kg) for weight, 0.8 cm (95% CI: 0.8-0.9 cm) and 1.0 cm (95% CI: 0.9-1.1 cm) for length and -0.16 kg/m2 (95% CI: -0.20--0.12 kg/m2) and -0.22 kg/m2 (95% CI: -0.27--0.18 kg/m2) for BMI. Effect sizes were negligible to small. Bland-Altman plots showed clinically insignificant bias, but 95% limits of agreement were wide enough to be significant. Comparing categorisation of BMI z-score showed only fair agreement. CONCLUSION: Parents' reports of measured infant weight and length are reliable at a population level in a setting with routine preventive care. Parent-reported data should not be used for assessment of individual infants, particularly not if a health condition is suspected. BMI calculated from parent-reported anthropometrics is not reliable. FUNDING: None. TRIAL REGISTRATION: This study was registered with www. CLINICALTRIALS: gov, registration number NCT01694108.
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Pais , Projetos de Pesquisa , Criança , Humanos , Lactente , Reprodutibilidade dos Testes , AntropometriaRESUMO
BACKGROUND: Scant evidence exists on the real-world effectiveness of quadrivalent live attenuated influenza vaccines (LAIV-4) in younger children. We aimed to assess the real-world effectiveness of LAIV-4 against influenza-related hospital contacts and admission and morbidity. METHODS: Using nationwide Danish health-care registries, we designed a cohort study that emulates a target trial, comparing LAIV-4 to no vaccination in children aged 2-6 years. Eligible children vaccinated from Oct 1, 2021, to Jan 15, 2022, were matched to unvaccinated controls in a 1:1 ratio according to demographic characteristics and risk groups for influenza, and followed-up until May 31, 2022. Primary study outcomes any hospital contact for influenza and influenza-related hospital admissions more than 12 h in duration, while hospital admission for respiratory tract infections, or for wheezing or asthma, and antibiotic prescriptions were evaluated as secondary outcomes. We estimated incidence rate ratios (IRRs) and 95% CIs using Poisson regression for each outcome. Vaccine effectiveness was calculated as 1â-âIRR. FINDINGS: Among 308â520 Danish children aged 2-6 years, 95â434 vaccinated children were matched with 95â434 unvaccinated children who acted as controls. Receipt of LAIV-4 compared with no vaccination was associated with a reduced IRR of 0·36 (95% CI 0·27 to 0·46) and estimated vaccine effectiveness of 64·3% (53·6 to 72·6) against influenza-related hospital contacts (76 vs 210 events). The corresponding IRR and vaccine effectiveness against influenza-related hospital admissions were 0·63 (0·38 to 1·05) and 36·9% (-5·2 to 62·1; 24 vs 38 events), respectively. LAIV-4 was not associated with reductions in admission rates for respiratory tract infections (IRR 1·14, 95% CI 0·94 to 1·38), wheezing or asthma (1·04, 0·83 to 1·31), or antibiotic prescriptions for respiratory tract infections (0·97, 0·93 to 1·00). Vaccine effectiveness assessed across risk groups for influenza showed similar effectiveness in children with and without coexisting risk factors for severe influenza. INTERPRETATION: LAIV-4 offered moderate protection in younger children against influenza-related hospital contacts during a season dominated by influenza A(H3N2); however vaccination was not associated with reductions in secondary outcomes. This real-world study thereby supports trial evidence of moderate vaccine effectiveness of LAIV-4 against influenza-related outcomes when implementing broad vaccination schedules in younger children. FUNDING: Beckett-Fonden.
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Asma , Vacinas contra Influenza , Influenza Humana , Criança , Humanos , Vacinas contra Influenza/uso terapêutico , Influenza Humana/epidemiologia , Influenza Humana/prevenção & controle , Estudos de Coortes , Vírus da Influenza A Subtipo H3N2 , Sons Respiratórios , Hospitalização , Vacinas Atenuadas/uso terapêutico , Morbidade , Antibacterianos , Dinamarca/epidemiologiaRESUMO
Infectious mononucleosis (IM) often results from late primary infection with Epstein-Barr virus (EBV). Exposure to EBV at ages 0-2 years from, e.g., siblings therefore protects against IM. Using Danish registers, we therefore followed children born in 1997 through 2015 from age 3 years for a hospital contact with an IM diagnosis as outcome with the number of antimicrobial prescriptions filled before age 3 years as a proxy of infection pressure and the main exposure in stratified Cox regressions. The main analyses used sibships as strata primarily to adjust for health-seeking behaviour with further possible adjustments for age, sex, calendar period and sibship constellation. In these analyses we followed 7087 children, exposed on average to 3.76 antimicrobials prescriptions. We observed a crude hazard ratio for IM per unit increase in cumulative antimicrobial use of 1.00 (95% confidence interval 0.99, 1.02), with similar results in adjusted analyses. The hypothesis that children with the largest use of antimicrobials at ages 0-2 years would subsequently have the lowest risk of IM within a sibship was not corroborated by the data. Furthermore, sibship-matched analyses provided no support for some common early-life immune system characteristics being predictive of IM.
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Anti-Infecciosos , Infecções por Vírus Epstein-Barr , Mononucleose Infecciosa , Criança , Feminino , Humanos , Adulto , Pré-Escolar , Herpesvirus Humano 4 , Hospitais , Anti-Infecciosos/uso terapêuticoRESUMO
BACKGROUND: It has been suggested that the transiently increased infection risk following childcare enrolment is compensated by decreased infection risk later in childhood and adolescence. We investigated how childcare enrolment affected rates of antimicrobial-treated infections during childhood and adolescence. METHODS: In a register-based cohort study of all children born in Denmark 1997-2014 with available exposure information (n = 1â007â448), we assessed the association between childcare enrolment before age 6 years and infection risks up to age 20 years, using antimicrobial exposure as proxy for infections. Nationwide childcare and prescription data were used. We estimated infection rates and the cumulative number of infections using adjusted Poisson regression models. RESULTS: We observed 4â599â993 independent episodes of infection (antimicrobial exposure) during follow-up. Childcare enrolment transiently increased infection rates; the younger the child, the greater the increase. The resulting increased cumulative number of infections associated with earlier age at childcare enrolment was not compensated by lower infection risk later in childhood or adolescence. Accordingly, children enrolled in childcare before age 12 months had experienced 0.5-0.7 more infections at age 6 years (in total 4.5-5.1 infections) than peers enrolled at age 3 years, differences that persisted throughout adolescence. The type of childcare had little impact on infection risks. CONCLUSIONS: Early age at childcare enrolment is associated with a modest increase in the cumulative number of antimicrobial-treated infections at all ages through adolescence. Emphasis should be given to disrupting infectious disease transmission in childcare facilities through prevention strategies with particular focus on the youngest children.
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Cuidado da Criança , Infecções , Criança , Humanos , Adolescente , Pré-Escolar , Adulto Jovem , Adulto , Lactente , Estudos de Coortes , Creches , Saúde da Criança , Infecções/epidemiologiaRESUMO
OBJECTIVE: To test for potential non-specific effects of an additional, early measles, mumps, and rubella (MMR) vaccine at age 5-7 months on risk of infection related hospitalisation before age 12 months. DESIGN: Randomised, double blinded, placebo controlled trial. SETTING: Denmark, a high income setting with low exposure to MMR. PARTICIPANTS: 6540 Danish infants aged 5 to 7 months. INTERVENTIONS: Infants were randomly allocated 1:1 to intramuscular injection with standard titre MMR vaccine (M-M-R VaxPro) or placebo (solvent only). MAIN OUTCOME MEASURES: Hospitalisations for infection, defined as all hospital contacts of infants referred from primary care for hospital evaluation and with an infection diagnosed, analysed as recurrent events, from randomisation to 12 months of age. In secondary analyses implications of censoring for date of subsequent diphtheria, tetanus, pertussis, polio, Haemophilus influenzae type B, and immunisation with pneumococci conjugate vaccine (DTaP-IPV-Hib+PCV), potential effect modification by sex, prematurity (<37 weeks' gestation), season, and age at randomisation were tested, and the secondary outcomes of hospitalisations ≥12 hours and antibiotic use were evaluated. RESULTS: 6536 infants were included in the intention-to-treat analysis. 3264 infants randomised to MMR vaccine experienced 786 hospitalisations for infection before age 12 months compared with 762 for the 3272 infants randomised to placebo. In the intention-to-treat analysis the rate of hospitalisations for infection did not differ between the MMR vaccine and placebo groups (hazard ratio 1.03, 95% confidence interval 0.91 to 1.18). For infants randomised to MMR vaccine compared with those randomised to placebo, the hazard ratio of hospitalisations for infection with a duration of at least 12 hours was 1.25 (0.88 to 1.77), and for prescriptions of antibiotics was 1.04 (0.88 to 1.23). No significant effect modifications were found by sex, prematurity, age at randomisation, or season. The estimate did not change when censoring at the date infants received DTaP-IPV-Hib+PCV after randomisation (1.02, 0.90 to 1.16). CONCLUSION: Findings of this trial conducted in Denmark, a high income setting, do not support the hypothesis that live attenuated MMR vaccine administered early to infants aged 5-7 months decreases the rate of hospitalisations for non-targeted infection before age 12 months. TRIAL REGISTRATION: EU Clinical Trials Registry EudraCT 2016-001901-18 and ClinicalTrials.gov NCT03780179.
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Vacinas Anti-Haemophilus , Sarampo , Caxumba , Lactente , Humanos , Vacina contra Sarampo-Caxumba-Rubéola , Caxumba/prevenção & controle , Vacina contra Difteria, Tétano e Coqueluche , Vacina Antipólio de Vírus Inativado , Sarampo/prevenção & controle , Imunização , HospitalizaçãoRESUMO
Play is a non-invasive, safe, and inexpensive intervention that can help children and adolescents better manage difficult aspects of hospitalisation. Play has existed in hospitals for decades but is emerging as an interdisciplinary scientific field. The field concerns all medical specialties and healthcare professionals working with children. In this review, we describe play within different clinical contexts and recommend that directed and non-directed play activities should be prioritised in future paediatric departments. We also emphasise the need for professionalisation and research in the area.
Assuntos
Hospitais , Medicina , Criança , Adolescente , Humanos , Pessoal de Saúde , Departamentos HospitalaresRESUMO
INTRODUCTION: Children with bone and joint infections are traditionally treated with intravenous antibiotics for 3-10 days, followed by oral antibiotics. Oral-only treatment has not been tested in randomised trials. METHODS AND ANALYSIS: Children (3 months to 18 years) will be randomised 1:1 with the experimental group receiving high-dose oral antibiotics and the control group receiving intravenous antibiotics with a shift in both groups to standard oral antibiotics after clinical and paraclinical improvement. Children in need of acute surgery or systemic features requiring intravenous therapy, including septic shock, are excluded. The primary outcome is defined as a normal blinded standardised clinical assessment 6 months after end of treatment. Secondary outcomes are non-acute treatment failure and recurrent infection. Outcomes will be compared by a non-inferiority assumption with an inferiority margin of 5%. ETHICS AND DISSEMINATION: The trial has the potential to reduce unnecessary hospitalisation and use of intravenous antibiotics in children with bone or joint infections. Due to the close follow-up, exclusion of severely ill children and predefined criteria for discontinuation of the allocated therapy, we expect the risk of treatment failure to be minimal. TRIAL REGISTRATION NUMBER: NCT04563325.