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1.
Infection ; 52(3): 1165-1169, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38480644

RESUMO

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.


Assuntos
Francisella tularensis , Saúde Única , Tularemia , Tularemia/epidemiologia , Tularemia/transmissão , Tularemia/diagnóstico , Suíça/epidemiologia , Humanos , Animais , Zoonoses/transmissão , Zoonoses/epidemiologia , Zoonoses/microbiologia , Carrapatos/microbiologia , Vetores Artrópodes/microbiologia
2.
Acta Paediatr ; 113(4): 771-777, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-38102898

RESUMO

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.


Assuntos
COVID-19 , Lactente , Recém-Nascido , Criança , Humanos , COVID-19/epidemiologia , SARS-CoV-2 , Pandemias , Estudos Prospectivos , Febre/etiologia
3.
Eur J Pediatr ; 181(3): 1245-1255, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34845526

RESUMO

Coronavirus disease 2019 (COVID-19) is usually less severe in children compared to adults. This study describes detailed clinical characteristics, treatment and outcomes of children with COVID-19 in a non-hospitalised and hospitalised setting and quantifies factors associated with admission to hospital and intensive care unit in children with SARS-CoV-2 infection on a nationwide level. Data were collected through the Swiss Paediatric Surveillance Unit from children < 18 years with confirmed SARS-CoV-2 infection. All 33 paediatric hospitals in Switzerland reported non-hospitalised and hospitalised cases from March 1 to October 31, 2020 during both pandemic peaks. In total, 678 children were included. The median age was 12.2 years (IQR 5.0-14.6), 316 (46.6%) were female and 106 (15.6%) had comorbidities. Overall, 126 (18.6%) children were hospitalised of whom 16 (12.7%) required ICU admission. Comorbidities were the only factor associated with hospital admission in a multivariable regression analysis (odds ratio 3.23, 95%CI 1.89 to 5.50; p-value < 0.01). Children with preexisting comorbidities did not require ICU admission more often. Hospitalised children more often presented with fever (96 [76.2%] vs 209 [38.1%], p-value < 0.01) and rash (16 [12.8%] vs 6 [1.1%], p-value < 0.01). Anosmia/dysgeusia was more prevalent in non-hospitalised children (73 [13.3%] vs 3 [2.4%], p-value < 0.01). In hospitalised children, oxygen treatment was required in 34 (27.0%), inotropes in nine (7.3%) and mechanical ventilation in eight (6.3%) cases. Complications were reported in 28 (4.1%) children with cardiovascular complications being most frequent (12 [1.8%]). Three deaths were recorded.Conclusion: This study confirms that COVID-19 is mostly a mild disease in children. Fever, rash and comorbidities are associated with higher admission rates. Continuous observation is necessary to further understand paediatric COVID-19, guide therapy and evaluate the necessity for vaccination in children. What is Known: • Clinical manifestations of SARS-CoV-2 infection in children vary from asymptomatic to critical disease requiring intensive care unit admission. • Most studies are based on hospitalised children only; currently, there is limited data on non-hospitalised children. What is New: • The clinical spectrum and severity of COVID-19 is influenced by age: in children less than 2 years, fever, cough and rhinorrhoea are the most common symptoms and in adolescents, fever, cough and headache are more common. • Hospitalised children more often presented with fever and rash, while anosmia/dysgeusia is more prevalent in non-hospitalised children. • Children with pre-existing comorbidities are more frequently hospitalised but do not require ICU admission more often.


Assuntos
COVID-19 , Adolescente , Adulto , COVID-19/epidemiologia , COVID-19/terapia , Criança , Pré-Escolar , Cuidados Críticos , Feminino , Hospitalização , Hospitais Pediátricos , Humanos , Unidades de Terapia Intensiva , Estudos Prospectivos , SARS-CoV-2
4.
Euro Surveill ; 27(1)2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34991775

RESUMO

BackgroundSince the onset of the COVID-19 pandemic, the disease has frequently been compared with seasonal influenza, but this comparison is based on little empirical data.AimThis study compares in-hospital outcomes for patients with community-acquired COVID-19 and patients with community-acquired influenza in Switzerland.MethodsThis retrospective multi-centre cohort study includes patients > 18 years admitted for COVID-19 or influenza A/B infection determined by RT-PCR. Primary and secondary outcomes were in-hospital mortality and intensive care unit (ICU) admission for patients with COVID-19 or influenza. We used Cox regression (cause-specific and Fine-Gray subdistribution hazard models) to account for time-dependency and competing events with inverse probability weighting to adjust for confounders.ResultsIn 2020, 2,843 patients with COVID-19 from 14 centres were included. Between 2018 and 2020, 1,381 patients with influenza from seven centres were included; 1,722 (61%) of the patients with COVID-19 and 666 (48%) of the patients with influenza were male (p < 0.001). The patients with COVID-19 were younger (median 67 years; interquartile range (IQR): 54-78) than the patients with influenza (median 74 years; IQR: 61-84) (p < 0.001). A larger percentage of patients with COVID-19 (12.8%) than patients with influenza (4.4%) died in hospital (p < 0.001). The final adjusted subdistribution hazard ratio for mortality was 3.01 (95% CI: 2.22-4.09; p < 0.001) for COVID-19 compared with influenza and 2.44 (95% CI: 2.00-3.00, p < 0.001) for ICU admission.ConclusionCommunity-acquired COVID-19 was associated with worse outcomes compared with community-acquired influenza, as the hazards of ICU admission and in-hospital death were about two-fold to three-fold higher.


Assuntos
COVID-19 , Influenza Humana , Estudos de Coortes , Mortalidade Hospitalar , Hospitalização , Hospitais , Humanos , Influenza Humana/diagnóstico , Influenza Humana/epidemiologia , Unidades de Terapia Intensiva , Masculino , Pandemias , Estudos Retrospectivos , SARS-CoV-2 , Suíça/epidemiologia
5.
Eur J Pediatr ; 180(3): 663-674, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32621135

RESUMO

The kidneys and the urinary tract are a common source of infection in children of all ages, especially infants and young children. The main risk factors for sequelae after urinary tract infections (UTI) are congenital anomalies of the kidney and urinary tract (CAKUT) and bladder-bowel dysfunction. UTI should be considered in every child with fever without a source. The differentiation between upper and lower UTI is crucial for appropriate management. Method of urine collection should be based on age and risk factors. The diagnosis of UTI requires urine analysis and significant growth of a pathogen in culture. Treatment of UTI should be based on practical considerations regarding age and presentation with adjustment of the initial antimicrobial treatment according to antimicrobial sensitivity testing. All children, regardless of age, should have an ultrasound of the urinary tract performed after pyelonephritis. In general, antibiotic prophylaxis is not recommended.Conclusion: Based on recent data and in line with international guidelines, multidisciplinary Swiss consensus recommendations were developed by members of Swiss pediatric infectious diseases, nephrology, and urology societies giving the clinician clear recommendations in regard to diagnosis, type and duration of therapy, antimicrobial treatment options, indication for imaging, and antibiotic prophylaxis. What is Known: • Urinary tract infections (UTI) are a common and important clinical problem in childhood. Although children with pyelonephritis tend to present with fever, it can be difficult on clinical grounds to distinguish cystitis from pyelonephritis, particularly in young children less than 2 years of age. • Method of urine collection is based on age and risk factors. The diagnosis of UTI requires urine analysis and significant growth of a pathogen in culture. What is New: • Vesicoureteric reflux (VUR) remains a risk factor for UTI but per se is neither necessary nor sufficient for the development of renal scars. Congenital anomalies of the kidney and urinary tract (CAKUT) and bladder-bowel dysfunction play a more important role as causes of long-term sequelae. In general, antibiotic prophylaxis is not recommended. • A switch to oral antibiotics should be considered already in young infants. Indications for invasive imaging are more restrictive and reserved for patients with abnormal renal ultrasound, complicated UTI, and infections with pathogens other than E. coli.


Assuntos
Infecções Urinárias , Refluxo Vesicoureteral , Criança , Pré-Escolar , Consenso , Escherichia coli , Humanos , Lactente , Suíça , Infecções Urinárias/diagnóstico , Infecções Urinárias/tratamento farmacológico
6.
Clin Infect Dis ; 71(10): 2561-2569, 2020 12 17.
Artigo em Inglês | MEDLINE | ID: mdl-31796965

RESUMO

BACKGROUND: In adults, anti-tumor necrosis factor-α (TNF-α) therapy is associated with progression of latent tuberculosis (TB) infection (LTBI) to TB disease, but pediatric data are limited. METHODS: Retrospective multicenter study within the Paediatric Tuberculosis Network European Trials Group, capturing patients <18 years who developed TB disease during anti-TNF-α therapy. RESULTS: Sixty-six tertiary healthcare institutions providing care for children with TB participated. Nineteen cases were identified: Crohn's disease (n = 8; 42%) and juvenile idiopathic arthritis (n = 6; 32%) were the commonest underlying conditions. Immune-based TB screening (tuberculin skin test and/or interferon-γ release assay) was performed in 15 patients before commencing anti-TNF-α therapy but only identified 1 LTBI case; 13 patients were already receiving immunosuppressants at the time of screening. The median interval between starting anti-TNF-α therapy and TB diagnosis was 13.1 (IQR, 7.1-20.3) months. All cases presented with severe disease, predominantly miliary TB (n = 14; 78%). One case was diagnosed postmortem. TB was microbiologically confirmed in 15 cases (79%). The median duration of anti-TB treatment was 50 (IQR, 46-66) weeks. Five of 15 (33%) cases who had completed TB treatment had long-term sequelae. CONCLUSIONS: LTBI screening is frequently false-negative in this patient population, likely due to immunosuppressants impairing test performance. Therefore, patients with immune-mediated diseases should be screened for LTBI at the point of diagnosis, before commencing immunosuppressive medication. Children on anti-TNF-α therapy are prone to severe TB disease and significant long-term morbidity. Those observations underscore the need for robust LTBI screening programs in this high-risk patient population, even in low-TB-prevalence settings.


Assuntos
Tuberculose Latente , Tuberculose , Adolescente , Adulto , Criança , Humanos , Testes de Liberação de Interferon-gama , Tuberculose Latente/diagnóstico , Tuberculose Latente/epidemiologia , Necrose , Estudos Retrospectivos , Teste Tuberculínico , Tuberculose/epidemiologia , Fator de Necrose Tumoral alfa
11.
Pharmaceutics ; 16(9)2024 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-39339222

RESUMO

The antiparasitic drug ivermectin is approved for persons > 15 kg in the US and EU. A pharmacometric (PMX) population model with clinical PK data was developed (i) to characterize the effect of the patient-friendly ivermectin formulation CHILD-IVITAB on the absorption process and (ii) to evaluate dosing for studies in children < 15 kg. Simulations were performed to identify dosing with CHILD-IVITAB associated with similar exposure coverage in children ≥ 15 kg and < 15 kg as observed in adults receiving the reference formulation STROMECTOL®. A total of 448 ivermectin concentrations were available from 16 healthy adults. The absorption rate constant was 2.41 h-1 (CV 19%) for CHILD-IVITAB vs. 1.56 h-1 (CV 43%) for STROMECTOL®. Simulations indicated that 250 µg/kg of CHILD-IVITAB is associated with exposure coverage in children < 15 kg consistent with that observed in children ≥ 15 kg and adults receiving 200 µg/kg of STROMECTOL®. Performed analysis confirmed that CHILD-IVITAB is associated with faster and more controlled absorption than STROMECTOL®. Simulations indicate that 250 µg/kg of CHILD-IVITAB achieves equivalent ivermectin exposure coverage in children < 15 kg as seen in children ≥ 15 kg and adults.

12.
Pediatr Infect Dis J ; 43(7): 675-681, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38506504

RESUMO

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.


Assuntos
Biomarcadores , COVID-19 , SARS-CoV-2 , Índice de Gravidade de Doença , Síndrome de Resposta Inflamatória Sistêmica , Humanos , COVID-19/sangue , COVID-19/epidemiologia , COVID-19/diagnóstico , COVID-19/complicações , Suíça/epidemiologia , Síndrome de Resposta Inflamatória Sistêmica/diagnóstico , Síndrome de Resposta Inflamatória Sistêmica/sangue , Síndrome de Resposta Inflamatória Sistêmica/epidemiologia , Criança , Estudos Prospectivos , Masculino , Feminino , Pré-Escolar , Biomarcadores/sangue , Lactente , Adolescente , Fatores de Risco
13.
Drugs R D ; 24(2): 331-340, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-39034337

RESUMO

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.


Assuntos
Albendazol , Quimioterapia Combinada , Ivermectina , Tricuríase , Trichuris , Albendazol/farmacocinética , Albendazol/análogos & derivados , Albendazol/administração & dosagem , Albendazol/farmacologia , Albendazol/uso terapêutico , Humanos , Côte d'Ivoire , Adolescente , Tanzânia , Criança , Adulto Jovem , Trichuris/efeitos dos fármacos , Masculino , Tricuríase/tratamento farmacológico , Feminino , Animais , Ivermectina/farmacocinética , Ivermectina/uso terapêutico , Ivermectina/farmacologia , Ivermectina/análogos & derivados , Anti-Helmínticos/farmacocinética , Anti-Helmínticos/uso terapêutico , Anti-Helmínticos/administração & dosagem
14.
Pediatr Infect Dis J ; 43(9): 831-840, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-38754004

RESUMO

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.


Assuntos
Antibacterianos , Hospitalização , Piomiosite , Humanos , Piomiosite/tratamento farmacológico , Piomiosite/diagnóstico , Piomiosite/microbiologia , Piomiosite/terapia , Criança , Adolescente , Estudos Retrospectivos , Masculino , Feminino , Pré-Escolar , Lactente , Antibacterianos/uso terapêutico , Hospitalização/estatística & dados numéricos , Suíça , Recém-Nascido , Staphylococcus aureus/isolamento & purificação , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/diagnóstico , Infecções Estafilocócicas/microbiologia , Streptococcus pyogenes/isolamento & purificação
15.
J Clin Pharmacol ; 64(10): 1295-1303, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38813747

RESUMO

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.


Assuntos
Antiparasitários , Disponibilidade Biológica , Estudos Cross-Over , Ivermectina , Comprimidos , Humanos , Ivermectina/farmacocinética , Ivermectina/administração & dosagem , Ivermectina/efeitos adversos , Masculino , Feminino , Administração Oral , Adulto , Antiparasitários/farmacocinética , Antiparasitários/administração & dosagem , Antiparasitários/efeitos adversos , Área Sob a Curva , Adulto Jovem , Pessoa de Meia-Idade
16.
Swiss Med Wkly ; 154: 3632, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38635904

RESUMO

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.


Assuntos
Amicacina , Neonatologia , Recém-Nascido , Humanos , Criança , Lactente , Amicacina/farmacocinética , Peso ao Nascer , Antibacterianos , Esquema de Medicação
17.
Swiss Med Wkly ; 154: 3773, 2024 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-39462475

RESUMO

BACKGROUND: The COVID-19 pandemic has placed unprecedented pressure on hospitals worldwide. In such a context of tension in healthcare systems, efficiently allocating hospital resources is a crucial aspect of crisis management. The aim of this study was to describe the clinical characteristics of readmitted patients and to determine risk factors for hospital readmission using data from the Swiss COVID-19 Hospital-Based Surveillance system (CH-SUR). METHODS: We investigated hospital readmissions within 60 days after discharge of patients from the CH-SUR surveillance system with a first hospitalisation between 1 December 2020 and 1 December 2021. Only community-acquired cases were considered. We compared the baseline characteristics of readmitted and non-readmitted patients. We performed univariable and multivariable logistic regression analyses to investigate the risk factors for hospital readmission. FINDINGS: Of the 8039 eligible patients, 239 (3.0%, 95% confidence interval [CI] 2.6-3.3%) were readmitted to hospital within 60 days of discharge, with no significant variations observed over the study period; 80% of all readmissions occurred within 10 days of discharge of the index hospital stay. Based on our multivariable logistic regression models, factors increasing the odds of hospital readmission were age ≥65 years (odds ratio [OR] 1.63, 95% CI 1.24-2.15), male sex (OR 1.47, 95% CI 1.12-1.93), being discharged to home after first hospitalisation (OR 1.77, 95% CI 1.19-2.62), having oncological pathology (OR 1.82, 95% CI 1.27-2.61) and being immunosuppressed (OR 2.34, 95% CI 1.67-3.29). INTERPRETATIONS: Age, sex, cardiovascular diseases, oncological pathologies and immunosuppression were the main risk factors identified for hospital readmission.


Assuntos
COVID-19 , Infecções Comunitárias Adquiridas , Readmissão do Paciente , SARS-CoV-2 , Humanos , Readmissão do Paciente/estatística & dados numéricos , COVID-19/epidemiologia , Suíça/epidemiologia , Masculino , Feminino , Idoso , Fatores de Risco , Pessoa de Meia-Idade , Infecções Comunitárias Adquiridas/epidemiologia , Adulto , Alta do Paciente/estatística & dados numéricos , Modelos Logísticos , Idoso de 80 Anos ou mais
18.
Pharmaceutics ; 15(4)2023 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-37111519

RESUMO

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.

19.
Pediatr Rep ; 15(4): 710-721, 2023 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-38133432

RESUMO

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.

20.
Swiss Med Wkly ; 153: 40129, 2023 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-38579328

RESUMO

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.


Assuntos
Doenças Transmissíveis , Inseticidas , Escabiose , Humanos , Criança , Pré-Escolar , Escabiose/diagnóstico , Escabiose/tratamento farmacológico , Escabiose/epidemiologia , Permetrina/uso terapêutico , Ivermectina/uso terapêutico , Suíça
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