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1.
Clin Infect Dis ; 68(7): 1213-1222, 2019 03 19.
Artigo em Inglês | MEDLINE | ID: mdl-30759183

RESUMO

BACKGROUND: Protection induced by acellular pertussis (aP) vaccines is partial and short-lived, especially in teenagers, calling for novel immunization strategies. METHODS: We conducted an investigator-driven proof-of-concept randomized controlled trial in aP-primed adolescents in Geneva to assess the immunogenicity and reactogenicity of a novel recombinant aP (r-aP) vaccine including recombinant pertussis toxin (PT) and filamentous hemagglutinin (FHA) coadministered with tetanus-diphtheria toxoids (Td), compared to a licensed tetanus-diphtheria-aP vaccine containing chemically detoxified PT (cd/Tdap). The primary immunological endpoints were day 28/365 geometric mean concentrations (GMCs) of total and neutralizing anti-PT antibodies. Memory B cells were assessed. RESULTS: Sixty-two aP-primed adolescents were randomized and vaccinated with r-aP + Td or cd/Tdap. Reactogenicity, adverse events, and baseline GMCs were similar between the groups. Day 28 PT-neutralizing GMCs were low after cd/Tdap (73.91 [95% confidence interval {CI}, 49.88-109.52] IU/mL) and approximately 2-fold higher after r-aP + Td (127.68 [95% CI, 96.73-168.53] IU/mL; P = .0162). Anti-PT GMCs were also low after cd/Tdap (52.43 [95% CI, 36.41-75.50] IU/mL) and 2-fold higher after r-aP + Td (113.74 [95% CI, 88.31-146.50] IU/mL; P = .0006). Day 28 anti-FHA GMCs were similar in both groups. Day 365 anti-PT (but not PT-neutralizing) GMCs remained higher in r-aP + Td vaccinees. PT-specific memory B cells increased significantly after r-aP + Td but not cd/Tdap boosting. CONCLUSIONS: Boosting aP-primed adolescents with r-aP induced higher anti-PT and PT-neutralizing responses than cd/Tdap and increased PT-specific memory B cells. Despite this superior immunogenicity, r-aP may have to be given repeatedly, earlier, and/or with novel adjuvants to exert an optimal influence in aP-primed subjects. CLINICAL TRIALS REGISTRATION: NCT02946190.


Assuntos
Anticorpos Neutralizantes/sangue , Imunização Secundária/métodos , Toxina Pertussis/imunologia , Vacina contra Coqueluche/imunologia , Coqueluche/prevenção & controle , Adesinas Bacterianas/genética , Adesinas Bacterianas/imunologia , Adolescente , Anticorpos Antibacterianos/sangue , Antitoxinas/sangue , Subpopulações de Linfócitos B/imunologia , Criança , Feminino , Humanos , Memória Imunológica , Masculino , Toxina Pertussis/genética , Vacina contra Coqueluche/administração & dosagem , Suíça , Vacinas Acelulares/administração & dosagem , Vacinas Acelulares/imunologia , Vacinas Sintéticas/administração & dosagem , Vacinas Sintéticas/imunologia , Fatores de Virulência de Bordetella/genética , Fatores de Virulência de Bordetella/imunologia
2.
Pulm Med ; 2023: 1532443, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36760693

RESUMO

Aim: It is known that children and adolescents with obesity are more prone to obstructive sleep apnea syndrome (OSAS) and that their lung function may show some disturbance. Literature is scarce about potential associations; therefore, we aimed to study the relationship between OSAS, lung function, and adiposity in a population of children suspected of OSAS. Material and Methods. We performed home respiratory polygraphy and spirometry in all subjects. The relationships between body mass index z-score (zBMI), polygraphy, and spirometry data were analyzed. Results: We recruited 81 subjects aged between 5 and 16 years, 63% being obese. 43.2% of subjects were diagnosed with OSAS (32.1% mild, 4.9% moderate, and 6.2% severe). We found no correlation between respiratory polygraphy and the zBMI. The mean spirometric value FEV1, FVC, and FEV1/FVC ratio z's were normal in all subjects, whereas FVC z's and FEV1/FVC ratio z's were significantly positively related for obesity and negatively for normal weight (p < 0.05). FEV1 z's was inversely correlated to the percentage of analyzed time passed below 90% of SpO2 (r = -0.224, p = 0.044). All subjects with FEV1 (n = 8) and/or FVC (n = 9) z's below the lower limit for normal (LLN) had an AHI ≥ 1 (FEV1: p = 0.001; FVC: p < 0.001), especially subjects with normal weight (FEV1: p = 0.003; FVC: p = 0.010). Conclusion: When comparing normal-weight children and adolescents with obesity, the prevalence of OSAS but not spirometric values was strongly related to BMI z-score, probably because obesity engenders advanced puberty and an accelerated growth spurt. FEV1 was more frequently

Assuntos
Obesidade Infantil , Apneia Obstrutiva do Sono , Adolescente , Humanos , Criança , Pré-Escolar , Volume Expiratório Forçado , Espirometria , Índice de Massa Corporal , Apneia Obstrutiva do Sono/diagnóstico , Capacidade Vital
3.
Int J Pediatr Otorhinolaryngol ; 143: 110635, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33535090

RESUMO

OBJECTIVES: The prevalence of obstructive sleep apnea syndrome (OSAS) in children referred for sleep-disordered breathing reaches up to 59%. We aimed to test the adequacy of a questionnaire compared to home respiratory polygraphy (HRP), in 45 subjects (5-16 years-old), without maxillofacial malformations nor other comorbidities, presenting with symptoms compatible with OSAS. METHODS: All children passed a 12-items questionnaire (Obstructive Airway Child test: OACT) and the HRP. OSAS was classified in severity according to the apnea-hypopnea index (AHI). RESULTS: With HRP, 60% and 15% children were detected to have at least mild (AHI ≥1) and moderate (AHI >5) OSAS, respectively. The sensitivity of the questionnaire to detect mild and moderate OSAS was good (93% and 71%, respectively) but the specificity was very low (11% and 34%). However, an OACT score under 61 showed a very good negative predictive value for moderate and severe OSAS (87%). With the questionnaire, we could have avoided a complementary PSG or HRP in 25/45 (56%) of our subjects as in children with mild OSAS and without comorbidities only clinical observation is usually advised. CONCLUSIONS: The OACT questionnaire has shown to be a good and quick instrument to exclude moderate and severe OSAS in our population of children without maxillofacial malformations. Indeed children scoring under 61 could avoid a constraining and expensive sleep exam. However, if the score is above this cut-off, the performance to recognize OSAS is low and the child's evaluation must be completed by a HRP or PSG.


Assuntos
Apneia Obstrutiva do Sono , Adolescente , Criança , Pré-Escolar , Humanos , Polissonografia , Sono , Apneia Obstrutiva do Sono/diagnóstico , Apneia Obstrutiva do Sono/epidemiologia , Inquéritos e Questionários
4.
Artigo em Inglês | MEDLINE | ID: mdl-33482352

RESUMO

OBJECTIVES: To evaluate longitudinally the persistence of humoral immunity for up to 6 months in a cohort of hospital employees with mild coronavirus disease 2019 (COVID-19). METHODS: We measured anti-RBD (receptor binding domain of viral spike protein), anti-N (viral nucleoprotein) and neutralizing antibodies at 1, 3 and 6 months after mostly mild COVID-19 in 200 hospital workers using commercial ELISAs and a surrogate virus neutralization assay. RESULTS: Antibodies specific for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) persisted in all participants for up to 6 months. Anti-RBD geometric mean concentrations (GMCs) progressively increased between months 1 (74.2 U/mL, 95%CI: 62.7-87.8), 3 (103.2 U/mL, 95%CI: 87.9-121.2; p < 0.001), and 6 (123.3 U/mL, 95%CI: 103.4-147.0; p < 0.001) in the whole cohort. Anti-N antibodies were detectable in >97% at all times. Neutralizing antibodies were detectable in 99.5% of participants (195/196) at 6 months post infection. Their GMC progressively decreased between months 1 (20.1 AU/mL, 95%CI: 16.9-24.0), 3 (15.2 AU/mL, 95%CI: 13.2-17.6; p < 0.001) and 6 (9.4 AU/mL, 95%CI: 7.7-11.4; p < 0.001). RBD-ACE2-inhibiting antibody titres and anti-RBD antibody concentrations strongly correlated at each timepoint (all r > 0.86, p < 0.001). Disease severity was associated with higher initial anti-RBD and RBD-ACE2-inhibiting antibody titres, but not with their kinetics. CONCLUSIONS: Neutralizing antibodies persisted at 6 months in almost all participants, indicating more durability than initially feared. Anti-RBD antibodies persisted better and even increased over time, possibly related to the preferential detection of progressively higher-affinity antibodies.

5.
Diabetes Technol Ther ; 20(12): 797-805, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30403495

RESUMO

BACKGROUND: Prevention of type 1 diabetes mellitus (T1DM)-related complications is dependent on metabolic control. The recommended glycated hemoglobin (HbA1c) values <7.5% (58.5 mmol/mol) are met only by a minority of diabetic children and especially adolescents. The aim of this study was to evaluate the impact of an intervention comprising the use of Webdia, a patient-designed app for smartphones, on metabolic control of T1DM in children. METHODS: Fifty-five patients with T1DM, 10-18 years of age, were included in this single-center, randomized double-crossover study. We tested an intervention consisting of using Webdia for 3 months with monthly feedback and adaptation of the treatment. Main outcome was modification of HbA1c. Secondary outcomes were the prevalence of hypoglycemia and quality of life (QoL). RESULTS: Of the 55 included patients, 33 completed the study, 9 dropped out, and 13 were excluded due to insufficient use of the app. The app was well accepted by the users who completed the study (46.4% rated the program as good and 39.3% as excellent). The intervention led to a reduction of HbA1c by 0.33%, compared to the control group in which HbA1c rose by 0.21% (P = 0.048) in patients with HbA1c values >8.0% (63.9 mmol/mol) at inclusion, without increasing the prevalence of hypoglycemia (8.52 ± 9.45 hypoglycemic events during last 2 weeks of intervention vs. 7.62 ± 6.37 observation, P = 0.680). QoL scores were not modified. CONCLUSIONS: The intervention resulted in a significant decrease in HbA1c, without increasing the prevalence of hypoglycemia in patients with initial HbA1c >8.0% (63.9 mmol/mol).


Assuntos
Automonitorização da Glicemia/instrumentação , Glicemia/análise , Diabetes Mellitus Tipo 1/sangue , Hemoglobinas Glicadas/análise , Aplicativos Móveis , Adolescente , Automonitorização da Glicemia/métodos , Criança , Estudos Cross-Over , Diabetes Mellitus Tipo 1/complicações , Feminino , Humanos , Hipoglicemia/epidemiologia , Hipoglicemia/etiologia , Masculino , Prevalência , Qualidade de Vida , Smartphone
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