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Research Interests: Clinical Trial, Global Health, Public Health, Medicine, Literature Review, and 15 moreBiological Sciences, Humans, Developing Country, Immunization, Data Collection, Definition, Evaluation Studies, Patient Care, Comparability, International Collaboration, Case definition, Immunization Programs, Adverse Events Following Immunization, Clinical Trials as Topic, and Medical and Health Sciences
Research Interests: Vaccines, Medicine, Biological Sciences, Humans, Child, and 14 moreInfant, Vaccine, Newborn Infant, Randomized Controlled Trial, Age Factors, Reproducibility of Results, Sensitivity and Specificity, Respiratory Sounds, Severity of Illness Index, Randomized Controlled Trials as Topic, Child preschool, Adverse effect, Wheeze, and Medical and Health Sciences
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Department of Neurology, King’s College Hospital, London, UK Department of Neurology, Medical College of Wisconsin, USA Department of Neurology, University of Pittsburgh Medical Center, USA Department of Neurology, National Taiwan... more
Department of Neurology, King’s College Hospital, London, UK Department of Neurology, Medical College of Wisconsin, USA Department of Neurology, University of Pittsburgh Medical Center, USA Department of Neurology, National Taiwan University Hospital, Taiwan Italian Medicines Agency (AIFA), Italy Brighton Collaboration Foundation, Basel, Switzerland University of Basel Children’s Hospital, Basel, Switzerland
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OBJECTIVE: Neonatal sepsis causes high mortality and morbidity in preterm infants, but less is known regarding the long-term outcome after sepsis. This study aimed to determine the impact of sepsis on neurodevelopment at 2 years'... more
OBJECTIVE: Neonatal sepsis causes high mortality and morbidity in preterm infants, but less is known regarding the long-term outcome after sepsis. This study aimed to determine the impact of sepsis on neurodevelopment at 2 years' corrected age in extremely preterm infants. PATIENTS AND METHODS: This was a multicenter Swiss cohort study on infants born between 2000 and 2007 at 2407 to 2767 weeks' gestational age. Neurodevelopmental outcome was assessed with the Bayley Scales of Infant Development–II. Neurodevelopmental impairment (NDI) was defined as a Mental or Psychomotor Developmental Index lower than 70, cerebral palsy (CP), or visual or auditory impairment. RESULTS: Of 541 infants, 136 (25%) had proven sepsis, 169 (31%) had suspected sepsis, and 236 (44%) had no signs of infection. CP occurred in 14 of 136 (10%) infants with proven sepsis compared with 10 of 236 (4%) uninfected infants (odds ratio [OR]: 2.90 [95% confidence interval (CI): 1.22–6.89]; P = .016). NDI occurred in 46 of 134 (34%) infants with proven sepsis compared with 55 of 235 (23%) uninfected infants (OR: 1.85 [95% CI: 1.12–3.05]; P = .016). Multivariable analysis confirmed that proven sepsis independently increased the risk of CP (OR: 3.23 [95% CI: 1.23–8.48]; P = .017) and NDI (OR: 1.69 [95% CI: 0.96–2.98]; P = .067). In contrast, suspected sepsis was not associated with neurodevelopmental outcome (P > .05). The presence of bronchopulmonary dysplasia, pathologic brain ultrasonography, retinopathy, and sepsis predicted the risk of NDI (P < .0001). CONCLUSIONS: Proven sepsis significantly contributes to NDI in extremely preterm infants, independent of other risk factors. Better strategies aimed at reducing the incidence of sepsis in this highly vulnerable population are needed.
Research Interests: Pediatrics, Cerebral Palsy, Medicine, Prospective studies, Humans, and 15 moreFemale, Male, Infant, Developmental disabilities, Cohort, Odds ratio, Neonatal Sepsis, Retinopathy of prematurity, Bronchopulmonary Dysplasia, Gestational Age, Cohort Studies, Child preschool, Psychology and Cognitive Sciences, Medical and Health Sciences, and Infant Premature
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Vaccine co-administration can facilitate the introduction of new vaccines in immunisation schedules and improve coverage. We analysed real life data to quantify the extent of routine paediatric vaccine co-administrations as recommended... more
Vaccine co-administration can facilitate the introduction of new vaccines in immunisation schedules and improve coverage. We analysed real life data to quantify the extent of routine paediatric vaccine co-administrations as recommended and as never recommended in the immunisation schedule in England, and assessed factors for recommended and never recommended vaccine co-administrations. Immunisation data for all scheduled routine paediatric vaccines between 2008 and 2018 was obtained from the Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC). We included 6′257′828 doses administered to 1′005′827 children. Twenty-one percent of vaccines were given separately, 79% were co-administered. Sixty-four percent of vaccines scheduled for co-administration were co-administered as recommended while 15% were administered separately. Among all vaccine co-administrations, 75% happened as recommended in the schedule, 4% were never recommended, while 21% deviated from the schedule. Vaccine co-administration according to the schedule varied greatly between vaccines. Forty-eight percent of English children received at least one of their vaccine co-administrations not as recommended in the immunisation schedule, with 19% of children receiving none of their co-administered vaccines as recommended. Late administration of one or more vaccines increased the odds for deviated co-administrations (OR 1.60) and strongly increased the odds for never recommended co-administrations (OR 5.34). Differences between genders, NHS regions, and IMD quintiles were statistically significant but small. Suboptimal co-administration rates for routine paediatric vaccines are a missed opportunity and should be optimised by concerted public health action.
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Research Interests: Pediatrics, Medicine, Review, Humans, Child, and 15 moreFemale, Male, Infant, Immunization, Vaccination, Clinical Sciences, Newborn Infant, Public health systems and services research, Gestational Age, immunoglobulin G, Child preschool, Immunization Schedule, Premature infant, Paediatrics and reproductive medicine, and Infant Premature
Background: The neutrophil-to-lymphocyte-ratio (NLR), neutrophil-to-monocyte-plus-lymphocyte-ratio (NMLR) and monocyte-to-lymphocyte-ratio (MLR) may have diagnostic potential for tuberculosis (TB). Methods: Data of two prospective... more
Background: The neutrophil-to-lymphocyte-ratio (NLR), neutrophil-to-monocyte-plus-lymphocyte-ratio (NMLR) and monocyte-to-lymphocyte-ratio (MLR) may have diagnostic potential for tuberculosis (TB). Methods: Data of two prospective multicenter studies in Switzerland were used, which included children <18 years with TB exposure, infection or disease or with febrile non-TB lower-respiratory-tract infection (nTB-LRTI). Results: Of the 389 children included 25 (6.4%) had TB disease, 12 (3.1%) TB infection, 28 (7.2%) were healthy TB exposed and 324 (83.3%) nTB-LRTI. Median (IQR) NLR was highest with 2.0 (1.2, 2.2) in children with TB disease compared to TB exposed [0.8 (0.6, 1.3); P = 0.002] and nTB-LRTI [0.3 (0.1, 1.0); P < 0.001]. Median (IQR) NMLR was highest with 1.4 (1.2, 1.7) in children with TB disease compared to healthy exposed [0.7 (0.6, 1.1); P = 0.003] and children with nTB-LRTI [0.2 (0.1, 0.6); P < 0.001). Receiver operating characteristic curves to detect TB disease compared to nTB-LRTI for NLR and NMLR had an area under the curve of 0.82 and 0.86, the sensitivity of 88% and 88%, and specificity of 71% and 76%, respectively. Conclusion: NLR and NMLR are promising, easy-to-obtain diagnostic biomarkers to differentiate children with TB disease from other lower respiratory tract infections. These results require validation in a larger study and in settings with high and low TB endemicity.
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Research Interests: Terminology and Medicine
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Our goal was to determine the epidemiology of severe varicella-zoster virus (VZV) infections in hospitalised paediatric patients. Admissions associated with VZV infection of patients aged 0-16 years were reported by all 38 paediatric... more
Our goal was to determine the epidemiology of severe varicella-zoster virus (VZV) infections in hospitalised paediatric patients. Admissions associated with VZV infection of patients aged 0-16 years were reported by all 38 paediatric units in Switzerland to the Swiss Paediatric Surveillance Unit (SPSU) during 3 consecutive years (4/2000-3/2003). We verified completeness of reporting by capture-recapture analysis with patient records identified by ICD-10 codes. Outcome of illness was assessed 6 months after hospitalisation. A total of 335 cases (235 identified by SPSU reports, 100 by ICD-10 code) were included in this study. Mean age of patients was 4.1 years (median 3.5 years, range 0-16 years); 54% were male. Some 293 (87%) patients presented with chickenpox, 42 (13%) with herpes zoster and 291 (87%) patients were not immunocompromised. A total of 319 complications occurred in 237 (71%) patients: secondary bacterial infections (n =109); central nervous system involvement (n =76); VZV pneumonitis (n =7); others (n =127). Eleven (3%) patients required intensive care and three died. On follow-up, 303 (96%) of 315 patients had completely recovered; sequelae were present in 12 (4%) patients. The calculated hospitalisation rate was 13 per 10(4) cases. This study describes a sizeable hospitalisation and complication rate of varicella-zoster virus infections and provides a solid basis for future immunisation recommendations in Switzerland.
Research Interests: Adolescent, Medicine, Prospective studies, Humans, Child, and 15 moreHospitalization, Female, Male, Infant, Switzerland, Newborn Infant, Rotavirus, Immunocompromised host, Herpes Zoster, EMH, Chickenpox, Likelihood Functions, Child preschool, Prospective Cohort Study, and Paediatrics and reproductive medicine
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Both adequate coverage and adherence to paediatric immunisation schedules are required for optimal protection against vaccine preventable diseases. We studied the timeliness of routine paediatric vaccinations according to the NHS’s... more
Both adequate coverage and adherence to paediatric immunisation schedules are required for optimal protection against vaccine preventable diseases. We studied the timeliness of routine paediatric vaccinations according to the NHS’s immunisation schedule and potential factors of schedule adherence. Immunisation data was obtained from the Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC). We collected vaccine types, doses, and dates for all routine paediatric vaccines between 2008 and 2018: DTaP/IPV/Hib/HepB, DTaP/IPV/Hib, DTaP/IPV, dTaP/IPV, Td/IPV, MMR, PCV, MenB, MenC, MenACWY, Hib/MenC, RV, HPV. Adherence to the immunisation schedule was calculated for each vaccine and dose. Differences in adherence between genders, NHS regions, and IMD quintiles were analysed. Our study included 6′257′828 vaccinations in 1′005′827 children. Seventy-five percent of first doses were administered within one (for vaccines scheduled in the first year of life) or two months (for vaccines scheduled later in life) following the recommended age, 19% too late and 6% too early. About half of the subsequent doses were given timely. The time between first and second doses was too short for 36% of vaccinations while 13% of second doses were administered too long after the first dose. Third doses were administered timely for 45%, too short for 37%, and too long for 18% of vaccinations. Differences in immunisation schedule adherence between girls and boys were negligible, except for HPV, and differences between the four main NHS regions were small. Overall, immunisation schedule adherence improved slightly with decreasing deprivation according to the Index of Multiple Deprivation. Efforts are required to improve the timeliness of paediatric vaccinations and to assure adequate protection against vaccine preventable diseases. We propose developing a compound measure combining coverage and adherence to provide a better indication of the protection against vaccine preventable diseases in a community.
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Research Interests: Adolescent, Medicine, Biological Sciences, Children, Seasonality, and 15 moreCase Report, Humans, Child, influenza A, Infant, Vaccination, Children and Adolescents, Clinical Study, Influenza Vaccine, Pandemics, Pandemic, Adverse Events Following Immunization, Child preschool, Medical and Health Sciences, and Influenza vaccines
Objective: To review the diagnostic experience with acute haematogenous osteomyelitis (AHOM) and/or septic arthritis at our institution. Methods: Retrospective review of the medical records of those patients with a bacteriologically... more
Objective: To review the diagnostic experience with acute haematogenous osteomyelitis (AHOM) and/or septic arthritis at our institution. Methods: Retrospective review of the medical records of those patients with a bacteriologically and/or radiologically confirmed diagnosis, hospitalised in the University Children's Hospital Basel, Switzerland between January 1980 and July 2000. Results: 90 patients (61% males), 4 weeks to 14 years of age, met the inclusion criteria. Median duration of disease prior to hospitalisation was 3 days (range 0-14); 88% were admitted during the first week after onset of complaints. 81 patients received no antimicrobial therapy prior to hospitalisation and are the subject of this presentation. ESR (1st hour in mm; median 36; range 11-124), CRP (mg/l; median 64; range 0-221) and WBC (x 10(9)/l; median 13; range 5-34) were elevated in 100%, 82% and 58% of patients, respectively. Blood cultures (BC) and/or tissue cultures (TC) were performed in 79 (98%) pa...
Research Interests: Magnetic Resonance Imaging, Adolescent, Medicine, Humans, Child, and 15 moreFemale, Male, Staphylococcus aureus, Infant, Switzerland, Osteomyelitis, Clinical Sciences, Newborn Infant, Anti-Bacterial Agents, Time Factors, Retrospective Studies, Septic arthritis, Haemophilus influenzae, Acute Disease, and Child preschool
Research Interests: Informed Consent, Adolescent, Medicine, Humans, Child, and 15 moreFemale, Male, Clinical Sciences, Children and Adolescents, Gold Standard, Group, Chickenpox, Cross sectional Study, Cross Sectional Studies, Enzyme Linked Immunosorbent Assay, Immunoglobulin, Age Groups, immunoglobulin G, Child preschool, and Negative predictive value
Background Kinetics of copeptin and mid regional proadrenomedullin (MR-proADM) during febrile pediatric lower respiratory tract infections (LRTI) are unknown. We aimed to analyze kinetic profiles of copeptin and MR-proADM and the impact... more
Background Kinetics of copeptin and mid regional proadrenomedullin (MR-proADM) during febrile pediatric lower respiratory tract infections (LRTI) are unknown. We aimed to analyze kinetic profiles of copeptin and MR-proADM and the impact of clinical and laboratory factors on those biomarkers. Methods This is a retrospective post-hoc analysis of a randomized controlled trial, evaluating procalcitonin guidance for antibiotic treatment of LRTI (ProPAED-study). In 175 pediatric patients presenting to the emergency department plasma copeptin and MR-proADM concentrations were determined on day 1, 3, and 5. Their association with clinical characteristics and other inflammatory biomarkers were tested by non-linear mixed effect modelling. Results Median copeptin and MR-proADM values were elevated on day 1 and decreased during on day 3 and 5 (-26%; -34%, respectively). The initial concentrations of MR-proADM at inclusion were higher in patients receiving antibiotics intravenously compared to o...
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Osteomyelitis is a serious disease characterised by an infection of the bone marrow, compacta and periosteum. Various classifications have been pro-posed [1]. For clinical decision making differenti-ation of acute from chronic,... more
Osteomyelitis is a serious disease characterised by an infection of the bone marrow, compacta and periosteum. Various classifications have been pro-posed [1]. For clinical decision making differenti-ation of acute from chronic, haematogenous from contiguous and unifocal from multifocal osteo-myelitis is helpful. The spectrum of causative organisms varies by age group [2–6]. The most commonly identified pathogen in children above 5 years of age is Staphy-lococcus aureus. It is implicated in 50–90 percent of cases in otherwise healthy children [2, 7–9]. A broader spectrum of causative organisms is found particularly in infants, where Streptococci, gram-negative bacteria such as H. influenzae and E. coli are responsible for up to 60 percent of cases [3, 10–12]. In about one third of cases no causative organism can be isolated [11, 13–15]. It was proposed that fas-tidious organisms like Kingella kingae might be re-sponsible for a considerable proportion of osteo-myelitis cases with nega...
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Research Interests: Terminology and Medicine
Research Interests: Medicine and Vasculitis
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Research Interests: Medicine and Vasculitis
Both adequate coverage and adherence to paediatric immunisation schedules are required for optimal protection against vaccine preventable diseases. We studied the timeliness of routine paediatric vaccinations according to the NHS’s... more
Both adequate coverage and adherence to paediatric immunisation schedules are required for optimal protection against vaccine preventable diseases. We studied the timeliness of routine paediatric vaccinations according to the NHS’s immunisation schedule and potential factors of schedule adherence. Immunisation data was obtained from the Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC). We collected vaccine types, doses, and dates for all routine paediatric vaccines between 2008 and 2018: DTaP/IPV/Hib/HepB, DTaP/IPV/Hib, DTaP/IPV, dTaP/IPV, Td/IPV, MMR, PCV, MenB, MenC, MenACWY, Hib/MenC, RV, HPV. Adherence to the immunisation schedule was calculated for each vaccine and dose. Differences in adherence between genders, NHS regions, and IMD quintiles were analysed. Our study included 6′257′828 vaccinations in 1′005′827 children. Seventy-five percent of first doses were administered within one (for vaccines scheduled in the first year of life) or two months (for vaccines scheduled later in life) following the recommended age, 19% too late and 6% too early. About half of the subsequent doses were given timely. The time between first and second doses was too short for 36% of vaccinations while 13% of second doses were administered too long after the first dose. Third doses were administered timely for 45%, too short for 37%, and too long for 18% of vaccinations. Differences in immunisation schedule adherence between girls and boys were negligible, except for HPV, and differences between the four main NHS regions were small. Overall, immunisation schedule adherence improved slightly with decreasing deprivation according to the Index of Multiple Deprivation. Efforts are required to improve the timeliness of paediatric vaccinations and to assure adequate protection against vaccine preventable diseases. We propose developing a compound measure combining coverage and adherence to provide a better indication of the protection against vaccine preventable diseases in a community.
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Background India introduced rotavirus vaccines (RVV, monovalent, Rotavac™ and pentavalent, Rotasiil™) in April 2016 with 6, 10 and 14 weeks schedule and expanded countrywide in phases. We describe the epidemiology of intussusception among... more
Background India introduced rotavirus vaccines (RVV, monovalent, Rotavac™ and pentavalent, Rotasiil™) in April 2016 with 6, 10 and 14 weeks schedule and expanded countrywide in phases. We describe the epidemiology of intussusception among children aged 2–23 months in India. Methods The prospective surveillance at 19 nationally representative sentinel hospitals from four regions recruited children with intussusception from April 2016 to September 2017. Data on sociodemography, immunization, clinical, treatment and outcome were collected. Along with descriptive analysis, key parameters between four regions were compared using Chi-Square/Fisher’s exact/Mann–Whitney U/Kruskal-Wallis tests. The pre- and post-RVV periods were compared to estimate the risk ratios. Results Six hundred twenty-one children with intussusception from South (n = 262), East (n = 190), North (n = 136) and West (n = 33) regions were recruited. Majority (n = 465, 74.8%) were infants (40.0% aged 4–7 months) with medi...
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The growing number of available vaccines that can be potentially co-administered makes the assessment of the safety of vaccine co-administration increasingly relevant but complex. We aimed to synthesize the available scientific evidence... more
The growing number of available vaccines that can be potentially co-administered makes the assessment of the safety of vaccine co-administration increasingly relevant but complex. We aimed to synthesize the available scientific evidence on the safety of vaccine co-administrations in children by performing a systematic literature review of studies assessing the safety of vaccine co-administrations in children between 1999 and 2019, in line with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Fifty studies compared co-administered vaccines versus the same vaccines administered separately. The most frequently studied vaccines included quadrivalent meningococcal conjugate (MenACWY) vaccine, diphtheria and tetanus toxoids and acellular pertussis (DTaP) or tetanus toxoid, reduced diphtheria toxoid and acellular pertussis (Tdap) vaccines, diphtheria and tetanus toxoids and acellular pertussis adsorbed, hepatitis B, inactivated poliovirus and Haemophi...
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Research Interests: Medicine and Vaccination
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Vaccines are increasingly based on new constructs, new technologies, and new compounds. Novel immunization programs are rapidly implemented globally. In this article, we highlight selected hot topics of this highly dynamic and broad field... more
Vaccines are increasingly based on new constructs, new technologies, and new compounds. Novel immunization programs are rapidly implemented globally. In this article, we highlight selected hot topics of this highly dynamic and broad field of scientific and public health development. The first section focuses on novel vaccines including malaria, dengue, serogroup B meningococcal, and respiratory syncytial virus vaccines and antibodies. The second section is addressing emerging strategies and programmatic challenges including maternal immunization, integrated mother-child safety monitoring, and finally coping strategies with vaccine shortages.