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BACKGROUND AND OBJECTIVE: Trichuriasis caused by the human whipworm Trichuris trichiura poses a significant public health concern. Albendazole-ivermectin co-medication is currently the most effective treatment. Studies conducted in Tanzania and Côte d'Ivoire unveiled differences in efficacy for albendazole-ivermectin combination therapy in both countries. A pharmacometrics approach was used to assess co-medication and study population effects on the pharmacokinetics of the two main metabolites of albendazole. An exploratory exposure-efficacy analysis was also carried out to investigate relationships between exposure measures and the egg reduction rate. METHODS: Pharmacokinetic data from studies in Tanzania and Côte d'Ivoire in adolescents (aged 12-19 years) were included in the pharmacometric analysis. Participants received a single dose of either albendazole 400 mg alone or in combination with ivermectin 200 µg/kg. A pharmacometric analysis was performed to investigate the potential effects of the study population and co-administered ivermectin on the apparent clearance of the metabolites of albendazole. Non-linear mixed-effects modeling was conducted with MonolixSuite 2023R1. The pharmacokinetic exposure measures derived from simulations with individual model parameters were used in the exploratory-exposure response analysis. RESULTS: Pharmacokinetic profiles were best described by a two-compartment model for albendazole sulfoxide and a one-compartment model for albendazole sulfone, with a transit compartment and linear elimination. While no co-medication effect was found, apparent clearance of albendazole sulfoxide (albendazole sulfone) in the Tanzanian study population was 75% (46%) higher than that in the Côte d'Ivoire study population. Exposure-efficacy response analyses indicated that peak concentration and the time-above-exposure threshold were associated with the egg reduction rate. CONCLUSIONS: Study population but not co-administered ivermectin showed an effect on apparent clearance of albendazole sulfoxide and albendazole sulfone. Polymorphisms in drug-metabolizing enzymes and host-parasite interaction may explain this result. Difference in drug exposure did not explain the disparate efficacy responses in Tanzania and Côte d'Ivoire. Peak concentration and time-above-threshold were exposure measures associated with the egg reduction rate. Further studies evaluating genetic and resistance patterns in various regions in Africa are warranted.
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Albendazol , Quimioterapia Combinada , Ivermectina , Tricuriasis , Trichuris , Albendazol/farmacocinética , Albendazol/análogos & derivados , Albendazol/administración & dosificación , Albendazol/farmacología , Albendazol/uso terapéutico , Humanos , Côte d'Ivoire , Adolescente , Tanzanía , Niño , Adulto Joven , Trichuris/efectos de los fármacos , Masculino , Tricuriasis/tratamiento farmacológico , Femenino , Animales , Ivermectina/farmacocinética , Ivermectina/uso terapéutico , Ivermectina/farmacología , Ivermectina/análogos & derivados , Antihelmínticos/farmacocinética , Antihelmínticos/uso terapéutico , Antihelmínticos/administración & dosificaciónRESUMEN
BACKGROUND: Pyomyositis, a bacterial muscle infection, is an important differential diagnosis in children and adolescents with musculoskeletal pain. In contrast to tropical regions, it is rarely recognized in temperate countries, but incidence is increasing and major studies are missing. METHODS: This retrospective multicenter study included patients <18 years of age hospitalized with pyomyositis in 11 Swiss children's hospitals between January 2010 and December 2022. Cases were identified by ICD-10 code (Myositis; M60-M60.9), and data was extracted from electronic hospital records. RESULTS: Of 331 patients identified, 102 fulfilled the case definition. Patient age at presentation ranged from 2 weeks to 17 years (median 8 years). The majority had no underlying illness and all presented with fever and localized pain. At the respective site of pyomyositis, 100 (98%) had impaired movement and 39 (38%) presented with local swelling. Pelvic (57%) and leg (28%) muscles were mostly affected. Blood or tissue cultures were obtained in 94 (92%) and 59 (57%) patients, respectively. Of those, 55 (58%) blood and 52 (88%) tissue cultures were positive, mainly for Staphylococcus aureus (35 and 19, respectively) and Streptococcus pyogene s (12 and 15, respectively). All patients received antibiotic treatment during hospitalization for a median of 10 days (interquartile range: 7-17), followed by outpatient treatment for a further median of 16 days (interquartile range: 11-22) in 95 (93%) patients. Fifty-nine (57%) patients required surgery. CONCLUSIONS: Pyomyositis is a challenging diagnosis that requires a high level of awareness. Blood and/or tissue cultures revealed S. aureus and S. pyogenes as the predominant causative agents.
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Antibacterianos , Hospitalización , Piomiositis , Humanos , Piomiositis/tratamiento farmacológico , Piomiositis/diagnóstico , Piomiositis/microbiología , Piomiositis/terapia , Niño , Adolescente , Estudios Retrospectivos , Masculino , Femenino , Preescolar , Lactante , Antibacterianos/uso terapéutico , Hospitalización/estadística & datos numéricos , Suiza , Recién Nacido , Staphylococcus aureus/aislamiento & purificación , Infecciones Estafilocócicas/tratamiento farmacológico , Infecciones Estafilocócicas/diagnóstico , Infecciones Estafilocócicas/microbiología , Streptococcus pyogenes/aislamiento & purificaciónRESUMEN
Ivermectin has been used since the 1980s as an anthelmintic and antiectoparasite agent worldwide. Currently, the only available oral formulation is tablets designed for adult patients. A patient-friendly orodispersible tablet formulation designed for pediatric use (CHILD-IVITAB) has been developed and is entering early phase clinical trials. To inform the pediatric program of CHILD-IVITAB, 16 healthy adults were enrolled in a phase I, single-center, open-label, randomized, 2-period, crossover, single-dose trial which aimed to compare palatability, tolerability, and bioavailability and pharmacokinetics of CHILD-IVITAB and their variability against the marketed ivermectin tablets (STROMECTOL) at a single dose of 12 mg in a fasting state. Palatability with CHILD-IVITAB was considerably enhanced as compared to STROMECTOL. Both ivermectin formulations were well tolerated and safe. Relative bioavailability of CHILD-IVITAB compared to STROMECTOL was estimated as the ratios of geometric means for Cmax, AUC 0-∞, and AUC0-last, which were 1.52 [90% CI: 1.13-2.04], 1.27 [0.99-1.62], and 1.29 [1.00-1.66], respectively. Maximum drug concentrations occurred earlier with the CHILD-IVITAB formulation, with a median Tmax at 3.0 h [range 2.0-4.0 h] versus 4.0 h [range 2.0-5.0 h] with STROMECTOL (P = .004). With CHILD-IVITAB, variability in exposure was cut in half (coefficient of variation: 37% vs 70%) compared to STROMECTOL. Consistent with a more controlled absorption process, CHILD-IVITAB was associated with reduced variability in drug exposure as compared to STROMECTOL. Together with a favorable palatability and tolerability profile, these findings motivate for further clinical studies to evaluate benefits of such a patient-friendly ODT formulation in pediatric patients with a parasitic disease, including infants and young children <15 kg.
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BACKGROUND AND AIMS: Pharmacometric in silico approaches are frequently applied to guide decisions concerning dosage regimes during the development of new medicines. We aimed to demonstrate how such pharmacometric modelling and simulation can provide a scientific rationale for optimising drug doses in the context of the Swiss national dose standardisation project in paediatrics using amikacin as a case study. METHODS: Amikacin neonatal dosage is stratified by post-menstrual age (PMA) and post-natal age (PNA) in Switzerland and many other countries. Clinical concerns have been raised for the subpopulation of neonates with a post-menstrual age of 30-35 weeks and a post-natal age of 0-14 days ("subpopulation of clinical concern"), as potentially oto-/nephrotoxic trough concentrations (Ctrough >5 mg/l) were observed with a once-daily dose of 15 mg/kg. We applied a two-compartmental population pharmacokinetic model (amikacin clearance depending on birth weight and post-natal age) to real-world demographic data from 1563 neonates receiving anti-infectives (median birth weight 2.3 kg, median post-natal age six days) and performed pharmacometric dose-exposure simulations to identify extended dosing intervals that would ensure non-toxic Ctrough (Ctrough <5 mg/l) dosages in most neonates. RESULTS: In the subpopulation of clinical concern, Ctrough <5 mg/l was predicted in 59% versus 79-99% of cases in all other subpopulations following the current recommendations. Elevated Ctrough values were associated with a post-natal age of less than seven days. Simulations showed that extending the dosing interval to ≥36 h in the subpopulation of clinical concern increased the frequency of a desirable Ctrough below 5 mg/l to >80%. CONCLUSION: Pharmacometric in silico studies using high-quality real-world demographic data can provide a scientific rationale for national paediatric dose optimisation. This may increase clinical acceptance of fine-tuned standardised dosing recommendations and support their implementation, including in vulnerable subpopulations.
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Amicacina , Neonatología , Recién Nacido , Humanos , Niño , Lactante , Amicacina/farmacocinética , Peso al Nacer , Antibacterianos , Esquema de MedicaciónRESUMEN
BACKGROUND: PIMS-TS (pediatric inflammatory multisystem syndrome-temporally associated with SARS-CoV-2) is a rare but serious condition in children following SARS-CoV-2 infection, characterized by a range of clinical symptoms with varying severity. Understanding risk factors for severe PIMS-TS is crucial for appropriate and timely intervention. OBJECTIVE: To identify factors associated with increased PIMS-TS severity in children. METHODS: In this nationwide prospective observational study, epidemiological and clinical data was collected from children <18 years of age with suspected or confirmed PIMS-TS from all 29 pediatric hospitals in Switzerland. Children were categorized into 3 groups according to admission to intensive care unit (ICU): non-ICU, ICU-moderate and ICU-severe, defined as requirement of invasive ventilation and/or inotropic support. RESULTS: A total of 204 children were included; 99 (49%) were categorized as non-ICU, 50 (25%) as ICU-moderate and 55 (27%) as ICU-severe. In ICU-severe cases, respiratory and neurological symptoms were more frequent compared with non-ICU cases: 72% versus 47%, P < 0.001 and 66% versus 41%, P = 0.001, respectively. Compared with the non-ICU group, children in the ICU-severe group had lower lymphocyte counts, higher neutrophil-lymphocyte ratios, lower platelet counts, as well as higher C-reactive protein, N-terminal pro-B-type natriuretic peptide, troponin T and creatinine levels at admission. Lymphopenia and elevated troponin T levels at admission were associated with an increased risk of being in the ICU-severe group. CONCLUSION: The severity of PIMS-TS may be predicted using clinical symptoms and laboratory biomarkers, which help clinicians in decision-making and management of patients.
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Biomarcadores , COVID-19 , SARS-CoV-2 , Índice de Severidad de la Enfermedad , Síndrome de Respuesta Inflamatoria Sistémica , Humanos , COVID-19/sangre , COVID-19/epidemiología , COVID-19/diagnóstico , COVID-19/complicaciones , Suiza/epidemiología , Síndrome de Respuesta Inflamatoria Sistémica/diagnóstico , Síndrome de Respuesta Inflamatoria Sistémica/sangre , Síndrome de Respuesta Inflamatoria Sistémica/epidemiología , Niño , Estudios Prospectivos , Masculino , Femenino , Preescolar , Biomarcadores/sangre , Lactante , Adolescente , Factores de RiesgoRESUMEN
In the last 10 years, an increase in tularemia cases has been observed in both humans and animals in Switzerland. In these, infection with Francisella tularensis, the causative agent of the zoonotic disease tularemia, can occur through arthropod vectors or contact to infected animals or exposure to contaminated environmental sources. Currently, we are only able to postulate potential aetiologies: (i) behavioral changes of humans with more exposure to endemic habitats of infected arthropod vectors; (ii) an increased rate of tularemia infected ticks; (iii) increasing number and geographical regions of tick biotopes; (iv) increasing and/or more diverse reservoir populations; (v) increasing presence of bacteria in the environment; (vi) raised awareness and increased testing among physicians; (vii) improved laboratory techniques including molecular testing. To approach these questions, a one-health strategy is necessary. A functioning collaboration between public health, human medicine, and diagnostic and veterinary units for the control of tularemia must be established. Furthermore, the public should be included within citizen-supported-science-projects.
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Francisella tularensis , Salud Única , Tularemia , Tularemia/epidemiología , Tularemia/transmisión , Tularemia/diagnóstico , Suiza/epidemiología , Humanos , Animales , Zoonosis/transmisión , Zoonosis/epidemiología , Zoonosis/microbiología , Garrapatas/microbiología , Vectores Artrópodos/microbiologíaRESUMEN
AIM: To investigate the evolution of clinical symptoms of COVID-19 in children throughout the pandemic. METHODS: In this national prospective surveillance study, symptoms in children hospitalised with COVID-19 were collected from all paediatric hospitals in Switzerland between March 2020 and March 2023. Data was analysed across four time periods, according to the predominantly circulating SARS-CoV-2 variant: T1 (wild-type), T2 (Alpha), T3 (Delta) and T4 (Omicron), as well as by age group. RESULTS: The study included 1323 children. The proportion of children admitted to an intensive care unit remained stable throughout the pandemic. However, the pattern and frequency of clinical manifestations changed over time. Respiratory symptoms were less prevalent during T1 (wild-type), fever during T2 (Alpha) and rash during T4 (Omicron). In contrast, fever and neurological symptoms were more prevalent during T4 (Omicron). Newly described symptoms during T4 (Omicron) included conjunctivitis, laryngotracheitis and seizures. Fever was more prevalent among neonates and infants whereas respiratory symptoms were more common among infants. Gastrointestinal symptoms were more frequent among toddlers, while both toddlers and school-aged children presented with neurological symptoms more often than other age groups. CONCLUSION: Continuous surveillance is required to detect changes in manifestations and there by be prepared for the optimal management of complications in children with COVID-19.
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COVID-19 , Lactante , Recién Nacido , Niño , Humanos , COVID-19/epidemiología , SARS-CoV-2 , Pandemias , Estudios Prospectivos , Fiebre/etiologíaRESUMEN
Vaccinations play an important role in the prevention of potentially fatal diseases. Vaccine hesitancy has become an important problem both in the public discourse and for public health. We aimed to identify and characterize this potentially unvaccinated or incompletely vaccinated group of children presenting to the pediatric emergency department (PED) of the tertiary children's hospital in central Switzerland, a region that has anecdotally been claimed as a hotspot for vaccine hesitancy. All patients presenting to the PED (N = 20,247) between September 2018 and September 2019 were screened for their vaccination status and categorized as incomplete, unvaccinated, or fully vaccinated in a retrospective cohort study. Some 2.6% (n = 526) visits to the PED were not or incompletely vaccinated according to age, or their vaccination status was unknown. Most of the children in the cohort were not critically ill, and the minority had to be hospitalized. Undervaccinated patients were overrepresented in rural areas. Of all cohort visits, 18 (3.4%) patients received opportunistic vaccination in the PED. No cases of vaccine-preventable diseases were observed. In summary, incompletely vaccinated and unvaccinated status was less frequent than initially expected. The PED may play a role in increasing vaccination coverage by providing opportunistic vaccinations.
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BACKGROUND: Paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS) may occur 4 to 8 weeks after SARS-CoV-2 infection. The acute presentation of PIMS-TS has been well described, but data on longer-term outcomes, particularly cardiac, is scarce. METHODS: This prospective nationwide surveillance study included children and adolescents less than 18 years of age who were hospitalised with PIMS-TS in Switzerland between March 2020 and March 2022. Data was collected from all 29 paediatric hospitals through the Swiss Paediatric Surveillance Unit (SPSU) during hospitalisation and approximately six weeks after discharge. The data was analysed after categorising the participants into three groups based on their admission status to the intensive care unit (ICU) (non-ICU, ICU-moderate) and the requirement for invasive ventilatory and/or inotropic support (ICU-severe). RESULTS: Overall, 204 children were included of whom 194 (95.1%) had follow-up data recorded. Median age was 9.0 years (interquartile range [IQR] 6.0-11.5) and 142 (69.6%) were male. In total, 105/204 (51.5%) required ICU admission, of whom 55/105 (52.4%) received inotropic support and 14/105 (13.3%) mechanical ventilation (ICU-severe group). Echocardiography was performed in 201/204 (98.5%) children; 132 (64.7%) had a cardiac abnormality including left ventricular systolic dysfunction (73 [36.3%]), a coronary artery abnormality (45 [22.4%]), pericardial effusion (50 [24.9%]) and mitral valve regurgitation (60 [29.9%]). Left ventricular systolic dysfunction was present at admission in 62/201 (30.8%) children and appeared during hospitalisation in 11 (5.5%) children. A coronary artery abnormality was detected at admission in 29/201 (14.2%) children and developed during hospitalisation or at follow-up in 13 (6.5%) and 3 (1.5%) children, respectively. None of the children had left ventricular systolic dysfunction at follow-up, but a coronary abnormality and pericardial effusion were found in 12 (6.6%) and 3 (1.7%) children, respectively. School absenteeism at the time of follow-up was more frequent in children who had been admitted to the ICU (2.5% in the non-ICU group compared to 10.4% and 17.6% in the ICU-moderate and ICU-severe group, respectively) (p = 0.011). CONCLUSION: Cardiac complications in children presenting with PIMS-TS are common and may worsen during the hospitalisation. Irrespective of initial severity, resolution of left ventricular systolic dysfunction is observed, often occurring rapidly during the hospitalisation. Most of the coronary artery abnormalities regress; however, some are still present at follow-up, emphasising the need for prolonged cardiac evaluation after PIMS-TS.
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COVID-19 , Enfermedad de la Arteria Coronaria , Derrame Pericárdico , Disfunción Ventricular Izquierda , Adolescente , Masculino , Niño , Humanos , Femenino , COVID-19/complicaciones , COVID-19/epidemiología , SARS-CoV-2 , Estudios ProspectivosRESUMEN
A majority of therapeutics are not available as suitable dosage forms for administration to pediatric patients. The first part of this review provides an overview of clinical and technological challenges and opportunities in the development of child-friendly dosage forms such as taste masking, tablet size, flexibility of dose administration, excipient safety and acceptability. In this context, developmental pharmacology, rapid onset of action in pediatric emergency situations, regulatory and socioeconomic aspects are also reviewed and illustrated with clinical case studies. The second part of this work discusses the example of Orally Dispersible Tablets (ODTs) as a child-friendly drug delivery strategy. Inorganic particulate drug carriers can thereby be used as multifunctional excipients offering a potential solution to address unique medical needs in infants and children while maintaining a favorable excipient safety and acceptability profile in these vulnerable patient populations.
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Tularemia, an endemic disease that mainly affects wild animals and humans, is caused by Francisella tularensis subsp. holarctica (Fth) in Switzerland. The Swiss Fth population consist of multiple different subclades which are distributed throughout the country. The aim of this study is to characterize the genetic diversity of Fth in Switzerland and to describe the phylogeographic relationship of isolates by single nucleotide polymorphism (SNP) analysis. This analysis is combined with human surveillance data from reported cases over the last 10 years and in vitro and in silico antibiotic resistance tests to provide insight into the epidemiology of tularemia in Switzerland. We sequenced the whole genomes of 52 Fth strains of human or tick origin collected in Switzerland between 2009 and 2022 and analyzed together with all publicly available sequencing data of Swiss and European Fth. Next, we performed a preliminary classification with the established canonical single nucleotide polymorphism nomenclature. Furthermore, we tested 20 isolates from all main Swiss clades for antimicrobial susceptibility against a panel of antimicrobial agents. All 52 sequenced isolates from Switzerland belong to major clade B.6, specifically subclades B.45 and B.46, previously described in Western Europe. We were able to accurately reconstruct the population structure according to the global phylogenetic framework. No resistance to clinically recommended antibiotics could be identified in vitro or in silico in the western B.6 strains.
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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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Infecciones del Sistema Respiratorio , Tuberculosis , Humanos , Niño , Monocitos , Neutrófilos , Estudios Prospectivos , Linfocitos , Tuberculosis/diagnóstico , Biomarcadores , Estudios RetrospectivosRESUMEN
BACKGROUND: The emergence of paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS) led to the widespread use of anti-inflammatory treatments in the absence of evidence from randomised controlled trials (RCTs). We aimed to assess the effectiveness of intravenous methylprednisolone compared with intravenous immunoglobulins. METHODS: This is an open-label, multicentre, two-arm RCT done at ten hospitals in Switzerland in children younger than 18 years hospitalised with PIMS-TS (defined as age <18 years; fever and biochemical evidence of inflammation, and single or multiorgan dysfunction; microbiologically proven or putative contact with SARS-CoV-2; and exclusion of any other probable disease). Patients were randomly assigned 1:1 to intravenous methylprednisolone (10 mg/kg per day for 3 days) or intravenous immunoglobulins (2 g/kg as a single dose). The primary outcome was length of hospital stay censored at day 28, death, or discharge. Secondary outcomes included proportion and duration of organ support. Analyses were done by intention-to-treat. The study was registered with Swiss National Clinical Trials Portal (SNCTP000004720) and ClinicalTrials.gov (NCT04826588). FINDINGS: Between May 21, 2021, and April 15, 2022, 75 patients with a median age of 9·1 years (IQR 6·2-12·2) were included in the intention-to-treat population (37 in the methylprednisolone group and 38 in the intravenous immunoglobulins group). The median length of hospital stay was 6·0 days (IQR 4·0-8·0) in the methylprednisolone group and 6·0 days (IQR 5·0-8·8) in the intravenous immunoglobulins group (estimated effect size -0·037 of the log10 transformed times, 95% CI -0·13 to 0·065, p=0·42). Fewer patients in the methylprednisolone group (ten [27%] of 37) required respiratory support compared with the intravenous immunoglobulin group (21 [55%] of 38, p=0·025). Need and duration of inotropes, admission to intensive care units, cardiac events after baseline, and major bleeding and thrombotic events were not significantly different between the study groups. INTERPRETATION: In this RCT, treatment with methylprednisolone in children with PIMS-TS did not significantly affect the length of hospital stay compared with intravenous immunoglobulins. Intravenous methylprednisolone could be an acceptable first-line treatment in children with PIMS-TS. FUNDING: NOMIS Foundation, Vontobel Foundation, and Gaydoul Foundation.
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COVID-19 , Humanos , Niño , Adolescente , SARS-CoV-2 , Inmunoglobulinas Intravenosas/uso terapéutico , Metilprednisolona/uso terapéutico , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
AIM OF THE STUDY: The global prevalence of scabies is estimated to be up to 200 million cases annually, with young children particularly affected. In Europe, most cases are thought to originate in migrant populations. Scabies management is challenging in children. To identify knowledge gaps and research needs, we aimed to descriptively evaluate the management of children with scabies by different Swiss healthcare providers. METHODS: An invitation for an anonymous online survey (36 questions) was sent to members of Swiss societies of dermatologists, general practitioners, paediatricians, paediatric dermatologists, paediatric infectious diseases specialists, and tropical medicine specialists, inviting clinicians to participate from 25th May to 8th August 2020. One reminder invitation was sent. Hospital pharmacies and the distributor of permethrin were contacted to report consumption trends of scabicides in 2018 and 2019. RESULTS: The survey was completed by 248 clinicians: 146 (59%) paediatricians, 47 (19%) dermatologists, 28 (11%) general practitioners, 6 (2%) paediatric dermatologists, 13 (5%) paediatric infectious diseases specialists, and 8 (3%) tropical medicine specialists. Most consulted up to 10 scabies cases within a 16-month period, with similar numbers in migrant and Swiss children. Dermoscopy was used by 24% of non-dermatologists. Non-dermatologists did not consider co-treatment of close contacts in up to 59% of cases. While permethrin was the first-line treatment, treatment failures were frequently reported in children aged <5 years. Up to 67% of paediatric dermatologists regularly used oral ivermectin off-label in children weighing <15 kg. None of the paediatric dermatologists, 15% of the dermatologists, and 9% of the non-dermatologists used only one treatment cycle.Scabicide consumption increased. Treatment studies on ivermectin use in children weighing <15 kg had the highest research priority. CONCLUSION: In Switzerland, scabies is a frequent dermatosis in migrant and Swiss children. While accessible, optimal diagnostics are underutilised, and treatment is suboptimal. Permethrin resistance appears to be an increasing problem. Dermatologists regularly use ivermectin off-label in children weighing <15 kg. Treatment studies on ivermectin use in children weighing <15 kg, user-friendly diagnostic tools, new treatment protocols, and child-friendly dosage forms are needed to improve the diagnosis and treatment of children with scabies.
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Enfermedades Transmisibles , Insecticidas , Escabiosis , Humanos , Niño , Preescolar , Escabiosis/diagnóstico , Escabiosis/tratamiento farmacológico , Escabiosis/epidemiología , Permetrina/uso terapéutico , Ivermectina/uso terapéutico , SuizaRESUMEN
Background: Psoriasis is a chronic immune-mediated inflammatory skin disease affecting both adults and children. To better understand the efficacy-safety profile of biologics in children with moderate-to-severe psoriasis, this study aimed to analyze efficacy and safety data of randomized controlled trials (RCTs) performed in pediatric psoriasis and to compare efficacy outcomes in children with those in adults. Methods: RCTs investigating biologics in children with moderate-to-severe psoriasis were identified in a systematic literature review. PASI75/90 treatment responses at weeks 11/12 were analyzed comparing biologics with control arms. Serious adverse events (SAEs) were analyzed at the end of each study. Efficacy data from RCTs in adults with psoriasis were selected for the same biologics. Risk ratios (RR) of selected RCTs were pooled together in a statistical random effects model using the inverse variance method. Results: For children, there were 1 etanercept, 2 secukinumab, 1 ixekizumab and 1 ustekinumab placebo-controlled RCTs and 1 adalimumab RCT using methotrexate as reference arm at weeks 11/12. For adults, out of 263 RCTs, 7 adalimumab and 15 etanercept (TNF inhibitors) and 4 ixekizumab and 12 ustekinumab (IL-17 and IL-12/23 inhibitors) RCTs reported PASI75/90 efficacy responses at weeks 11/12. Regarding efficacy, all biologics showed improved PASI responses over control arms. RRs ranges were 2.02-7.45 in PASI75 and 4.10-14.50 in PASI90. The highest PASI75 responses were seen for ustekinumab 0.375 mg/kg (RR = 7.25, 95% CI 2.83-18.58) and ustekinumab 0.75 mg/kg (RR = 7.45, 95% CI 2.91-19.06) in the CADMUS study. The highest PASI90 response was seen for ixekizumab (RR = 14.50, 95% CI 4.82-43.58) in the IXORA-PEDS study. SAE incidences in pediatric and adult arms with biologics were 0 to 3% except for a pediatric arm with adalimumab 0.40 mg/kg (8%). For adults, pooled RR also showed improved PASI responses over placebo for all biologics, with highest PASI75 response observed for ixekizumab (pooled RR = 16.18, 95% CI 11.83-22.14). Conclusion: Both adults and children with psoriasis show superior efficacy with biologics compared to control arms after 3 months of treatment with SAE incidences in the low percentages. Additional longer-term clinical studies are warranted to fully understand the overall efficacy-safety profile of biologics in children with moderate-to-severe psoriasis.
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Infection following surgical procedures leads to significant morbidity and mortality in all age groups. Sterile techniques, antibiotic prophylaxis and improved postoperative wound care have contributed to the decline of surgical site infections since the early days of surgery. Recommendations on the use of perioperative antimicrobial prophylaxis exist for adults, but are rare for the paediatric population. Here, we provide a standardised approach to the effective use of antimicrobial agents for the prevention of surgical site infections in children contributing to a targeted and rational perioperative use of antibiotics in Switzerland.
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Antiinfecciosos , Infección de la Herida Quirúrgica , Antibacterianos/uso terapéutico , Antiinfecciosos/uso terapéutico , Profilaxis Antibiótica/métodos , Niño , Humanos , Infección de la Herida Quirúrgica/epidemiología , Infección de la Herida Quirúrgica/prevención & control , SuizaRESUMEN
Introduction: In 2020, a new disease entitled Pediatric Inflammatory Multisystem Syndrome temporally associated with COVID-19 (PIMS-TS), or Multisystem Inflammatory Syndrome in Children (MIS-C), emerged, with thousands of children affected globally. There is no available evidence based on randomized controlled trials (RCT) to date on the two most commonly used immunomodulatory treatments, intravenous immunoglobulins (IVIG) and corticosteroids. Therefore, the Swissped RECOVERY trial was conducted to assess whether intravenous (IV) methylprednisolone shortens hospital length of stay compared with IVIG. Methods and Analysis: Swissped RECOVERY is an ongoing investigator-initiated, open-label, multicenter two-arm RCT in children and adolescents <18 years hospitalized with a diagnosis of PIMS-TS. The trial is recruiting at 10 sites across Switzerland. Patients diagnosed with PIMS-TS are randomized 1:1 to methylprednisolone IV (10 mg/kg/day for 3 days) or IVIG (2 g/kg as a single dose). The primary outcome is hospital length of stay censored at day 28, death, or discharge (whichever is first). The target total sample size is ~80 patients 1:1 randomized to each study arm. Ancillary and exploratory studies on inflammation, vaccination acceptance and coverage, long-term outcomes, and healthcare costs are pre-planned. Significance: Currently, robust trial evidence for the treatment of PIMS-TS is lacking, with a controversy surrounding the use of corticosteroids vs. IVIG. This trial will provide evidence for the effectiveness and safety of these two treatments. Ethics and Dissemination: The study protocol, which was designed based on the U.K. RECOVERY trial, the patient information and consent forms, and other study-specific study documents were approved by the local ethics committees (Project ID: 2021-00362). Registration Details: The study is registered on the Swiss National Clinical Trials Portal (SNCTP000004720) and Clinicaltrials.gov (NCT04826588).
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BACKGROUND: Coronavirus disease 2019 (COVID-19) can be more severe in infants than in older children. To date, only a few case series have reported data on neonates with COVID-19, including mostly asymptomatic neonates who were tested because of exposure to maternal SARS-CoV-2 infection. This study summarises nationwide epidemiological data, clinical characteristics, treatment and outcomes of neonates presenting with symptomatic SARS-CoV-2 infection. METHODS: Data were prospectively collected through the Swiss Paediatric Surveillance Unit from hospitalised neonates with laboratory-confirmed SARS-CoV-2 infection (positive polymerase chain reaction on a respiratory sample) from 1 March 2020 to 31 September 2021. All 29 paediatric hospitals in Switzerland reported cases. RESULTS: In total, 73 neonates were included; 7 (10%) were preterm. The median age at presentation was 17 days (interquartile range [IQR] 11-23); 40 (55%) were female. The majority of neonates (64, 88%) were admitted from home. Nine (12%) had a pre-existing medical condition. Overall, the most common symptom recorded was fever in 52 (71%), followed by rhinorrhoea or nasal congestion in 32 (44%) and respiratory distress in 19 (26%). Twenty (27%) neonates presented with fever without a source. Seven (10%) neonates were admitted to an intensive care unit (5 for respiratory failure and 2 for monitoring). One (1%) neonate required inotropic support. The median length of hospital stay in term neonates was 4 days (IQR 3-5). Two (3%) were treated with corticosteroids and 1 (1%) with remdesivir. In total, 60 (82%) neonates had contact with a known or suspected SARS-CoV-2 index case. All of the 71 neonates for whom data were available were discharged to their homes without symptoms. CONCLUSION: In neonates, COVID-19 mainly presents with fever, and symptoms of upper and lower respiratory tract infection. The clinical course is mostly mild, requiring a short period of hospitalisation. COVID-19 needs to be added as a differential diagnosis in neonates who present with fever without a source. However, the presence of SARS-CoV-2 should not deter from the search for a serious bacterial infection. Further data from surveillance studies are needed to better understand COVID-19 in neonates, guide therapy and to evaluate whether the clinical spectrum is changing with new SARS-CoV-2 variants.
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COVID-19 , SARS-CoV-2 , COVID-19/epidemiología , Niño , Femenino , Fiebre/epidemiología , Fiebre/etiología , Humanos , Lactante , Recién Nacido , Unidades de Cuidados Intensivos , Masculino , Estudios ProspectivosRESUMEN
BACKGROUND: With the invasion of Ukraine by the Russian Army in February 2022, refugees, the majority of whom are women and children, started fleeing the war to neighbouring countries. Even before the current escalation, the conflict in the eastern part of Ukraine has led to the internal displacement of more than 200,000 children, and many others have experienced attacks, e.g. on schools. This inevitably leads to limitations in health care delivery. During transit, overcrowding, poor shelter and vulnerability may further put refugees at increased risk for infectious diseases. This consensus document aims to provide information and guidance regarding health issues that paediatricians and general practitioners may face when caring for Ukrainian children. METHODS: Members of the Migrant Health Reference Group of Paediatrics Switzerland and the Paediatric Infectious Disease Group in Switzerland developed this recommendation between March and April 2022 in a modified Delphi process. RESULTS: A total of 50 recommendations were agreed on with a ≥80% consensus. These include the following topics: i) general aspects, including interpreter services, urgent health needs, personal history and general check-ups; ii) mental health, including how to search for signs of psychological distress without going into traumatic details; iii) vaccinations, including recommendations for evaluation and catch-up; iv) screening for tuberculosis, human immunodeficiency virus, and hepatitis B and C; and v) providing age-appropriate preventive and health service information. CONCLUSION: This document provides current evidence and guidance when caring for paediatric refugees from Ukraine. The recommendations focus on Switzerland but may well be used in other countries. These are based on current evidence and may need to be adapted to individual situations and once further evidence becomes available.
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Enfermedades Transmisibles , Pediatría , Refugiados , Niño , Femenino , Personal de Salud , Servicios de Salud , Humanos , Masculino , UcraniaRESUMEN
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 oral administration (difference 0.62 pmol/L, 95%CI 0.44;1.42, p<0.001). Intensive care unit (ICU) admission was associated with a daily increase of MR-proADM (increase/day 1.03 pmol/L, 95%CI 0.43;1.50, p<0.001). Positive blood culture in patients with antibiotic treatment and negative results on nasopharyngeal aspirates, or negative blood culture were associated with a decreasing MR-proADM (decrease/day -0.85 pmol/L, 95%CI -0.45;-1.44), p<0.001). CONCLUSION: Elevated MR-proADM and increases thereof were associated with ICU admission suggesting the potential as a prognostic factor for severe pediatric LRTI. MR-proADM might only bear limited value for decision making on stopping antibiotics due to its slow decrease. Copeptin had no added value in our setting.