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1.
BMC Res Notes ; 14(1): 355, 2021 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-34507611

RESUMO

OBJECTIVES: Induction of labour (IOL), or starting labour artificially, can be a lifesaving intervention for pregnant women and their babies, and rates are rising significantly globally. As rates increase, it becomes increasingly important to fully evaluate all available data, especially that from low income settings where the potential benefits and harms are greater. The goal of this paper is to describe the datasets collected as part of the Induction with Foley OR Misoprostol (INFORM) Study, a randomised trial comparing two of the recommended methods of cervical ripening for labour induction, oral misoprostol and Foley catheter, in women being induced for hypertension in pregnancy, at two sites in India during 2013-15. DATA DESCRIPTION: This dataset includes comprehensive data on 602 women who underwent IOL for hypertensive disorders in pregnancy. Women were randomly assigned to cervical ripening with oral misoprostol or a transcervical Foley catheter in two government hospitals in India. The main dataset has 367 variables including monitoring during the induction of labour, medications administered, timing and mode of delivery, measures of neonatal morbidity and mortality, maternal mortality and morbidity, maternal satisfaction and health economic data. The dataset is anonymised and available on ReShare.


Assuntos
Hipertensão , Misoprostol , Ocitócicos , Cateteres , Maturidade Cervical , Feminino , Humanos , Índia , Recém-Nascido , Trabalho de Parto Induzido , Gravidez
2.
Arch Dis Child ; 2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34479858

RESUMO

INTRODUCTION: The WHO Essential Medicine List for children (EMLc) is used for promoting access to medicines. The age-appropriateness of enteral (oral and rectal) formulations for children depend on their adaptability/flexibility to allow age-related or weight-related doses to be administered/prescribed and the child's ability to swallow, as appropriate. There is scant information on the age-appropriateness of essential enteral medicines for children. OBJECTIVE: To evaluate the age-appropriateness of enteral essential medicines. MATERIALS AND METHODS: Age-appropriateness of all enteral formulations indicated and recommended in the EMLc 3rd to 7th (2011-2019) editions were determined by assessing swallowability and/or dose adaptability for children under 12 years, stratified into five age groups. RESULTS: Enteral formulations in the EMLc were more age-appropriate for older children aged 6-11 years than for younger children. In the 3rd edition, for older children, 77%, n=342, of formulations were age-appropriate. For younger children, age-appropriateness decreased with age group: 34% in those aged 3-5 years, 30% in those aged 1-2 years, 22% among those aged 28 days to 11 months and 15% in those aged 0-27 days. Overall, similar proportions were found for the 7th edition. In contrast, the majority of medicines in the 7th list were age-appropriate in targeted diseases like HIV and tuberculosis. CONCLUSION: Most recommended enteral essential medicines in EMLc 2011 and 2019 were not age-appropriate for children <6 years. Medicines which are not age-appropriate must be manipulated before administration, leading to potential issues of safety and efficacy. Evaluation of the age-appropriateness of formulations for medicines to be included in EMLc could improve access to better medicines for children in the future.

3.
Br J Clin Pharmacol ; 2021 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-34180088

RESUMO

Developmental pharmacology describes the impact of maturation on drug disposition (pharmacokinetics, PK) and drug effects (pharmacodynamics, PD) throughout the paediatric age range. This paper, written by a multidisciplinary group of experts, summarizes current knowledge, and provides suggestions to pharmaceutical companies, regulatory agencies and academicians on how to incorporate the latest knowledge regarding developmental pharmacology and innovative techniques into neonatal and paediatric drug development. Biological aspects of drug absorption, distribution, metabolism and excretion throughout development are summarized. Although this area made enormous progress during the last two decades, remaining knowledge gaps were identified. Minimal risk and burden designs allow for optimally informative but minimally invasive PK sampling, while concomitant profiling of drug metabolites may provide additional insight in the unique PK behaviour in children. Furthermore, developmental PD needs to be considered during drug development, which is illustrated by disease- and/or target organ-specific examples. Identifying and testing PD targets and effects in special populations, and application of age- and/or population-specific assessment tools are discussed. Drug development plans also need to incorporate innovative techniques such as preclinical models to study therapeutic strategies, and shift from sequential enrolment of subgroups, to more rational designs. To stimulate appropriate research plans, illustrations of specific PK/PD-related as well as drug safety-related challenges during drug development are provided. The suggestions made in this joint paper of the Innovative Medicines Initiative conect4children Expert group on Developmental Pharmacology and the European Society for Developmental, Perinatal and Paediatric Pharmacology, should facilitate all those involved in drug development.

4.
BMJ Open ; 11(6): e044457, 2021 06 16.
Artigo em Inglês | MEDLINE | ID: mdl-34135034

RESUMO

INTRODUCTION: In conjunction with a beta-lactam, aminoglycosides are the first-choice antibiotic for empirical treatment of sepsis in the neonatal period. The m.1555A>G variant predisposes to ototoxicity after aminoglycoside administration and has a prevalence of 1 in 500. Current genetic testing can take over 24 hours, an unacceptable delay in the acute setting. This prospective-observational trial will implement a rapid point of care test (POCT), facilitating tailored antibiotic prescribing to avoid hearing loss. METHODS AND ANALYSIS: The genedrive POCT can detect the m.1555A>G variant in 26 min from buccal swab. This system will be integrated into the clinical pathways at two large UK neonatal centres over a minimum 6-month period. The primary outcome is the number of neonates successfully tested for the variant out of all babies prescribed antibiotics. As a secondary outcome, clinical timings will be compared with data collected prior to implementation, measuring the impact on routine practice. ETHICS AND DISSEMINATION: Approval for the trial was granted by the Research Ethics Committee (REC) and Human Research Authority in August 2019. Results will be published in full on completion of the study. TRIAL REGISTRATION NUMBER: ISRCTN13704894. PROTOCOL VERSION: V 1.3.


Assuntos
Surdez , Farmacogenética , Audição , Humanos , Recém-Nascido , Estudos Observacionais como Assunto , Testes Imediatos , Estudos Prospectivos
5.
Arch Dis Child ; 2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33858819

RESUMO

Conduct of clinical trials in babies, children and young people is often hindered by issues that could have been foreseen before the trial opened; that is, some clinical trials are often underprepared. In order to identify a good approach to trial preparedness, the European Network of Paediatric Research at the European Medicines Agency formed a working group. The Working Group included representation from regulators, industry, academics, paediatric clinical research networks and parents.The Working Group consulted widely about how to prepare for paediatric clinical trials. The Group's detailed recommendations have been published (https://www.ema.europa.eu/en/documents/other/preparedness-medicines-clinical-trials-paediatrics-recommendations-enpr-ema-working-group-trial_en.pdf).This paper is a summary of the key recommendations including the following: start early, preferably in parallel to designing the medicine's development plan and individual protocols; identify the rationale and clinical need; listen to the perspectives of children and families, and of patient advocacy groups; identify how many people will be eligible for the trial; identify the resources needed, such as clinical facilities (including play therapy) and out-of-pocket expenditure by participants and their families; use all available data to estimate what is possible; present information about preparedness in a structured way; deploy proportionate resources to support the preparation of trials.A well-prepared, well-designed trial is likely to require fewer changes during its course, be run in a shorter time frame and achieve expected objectives.

6.
JAMA Dermatol ; 157(4): 413-420, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33656512

RESUMO

Importance: The emerging paradigm of treat-to-target in psoriasis requires accurate monitoring of treatment response. The commonly used physician global assessment tool does not capture the patient's perception of their disease. Patient assessments facilitate shared decision-making and foster patient-centered care; however, recent research reports a discordance between patient- and physician-reported psoriasis severity. Understanding the factors underlying this discordance may improve treatment satisfaction and disease outcomes. Objectives: To evaluate the discordance between patient- and physician-reported measures of psoriasis severity and assess the association with patient mental health status. Design, Setting, and Participants: A cohort study using repeated cross-sectional analysis of real-world longitudinal data was conducted at a large specialist psoriasis service serving London and Southeast England. A total of 502 patients attending the psoriasis service between May 12, 2016, and November 1, 2018, were included. Data analysis was conducted July 22 to October 22, 2019. Main Outcomes and Measures: Psoriasis severity was assessed on each visit with identical 5-point physician and patient global assessment scales (clear/nearly clear, mild, moderate, severe, and very severe). Each patient completed validated self-report screens for depression and anxiety on each visit. Results: Longitudinal data from 502 individuals with psoriasis (1985 total observations) were available. A total of 339 patients (68%) were men, 396 (79%) were White, mean (SD) age was 47 (13) years, and 197 patients (39%) had concurrent psoriatic arthritis, 43 (9%) screened positive for depression, and 49 (10%) screened positive for anxiety. There was discordance between physician and patient measures of disease severity in 768 of 1985 office appointments (39%); on 511 visits (26%) patients rated their psoriasis as less severe and on 257 visits (13%) patients rated their psoriasis as more severe compared with their physician. Individuals who screened positive for depression or anxiety were more likely to overestimate their psoriasis severity compared with their physician (relative risk ratio: depression, 2.7; 95% CI, 1.6-4.5; anxiety, 2.1; 95% CI, 1.3-3.4). These findings remained statistically significant after adjustment for age, ethnicity, sex, body mass index, smoking, number of comorbidities, treatment modality, and presence of psoriatic arthritis. Conclusions and Relevance: The findings of this cohort study suggest that discordance between patient and physician assessments of psoriasis severity is associated with patients' mental health status. Recognition of anxiety and depression in individuals with psoriasis appears to be important when interpreting patient-reported outcome measures and informing appropriate treatment decisions.


Assuntos
Tomada de Decisão Compartilhada , Saúde Mental , Psoríase/patologia , Psoríase/psicologia , Índice de Gravidade de Doença , Adulto , Idoso , Ansiedade/epidemiologia , Ansiedade/psicologia , Consenso , Tomada de Decisões , Depressão/epidemiologia , Depressão/psicologia , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Medidas de Resultados Relatados pelo Paciente , Autoimagem , Autorrelato
7.
Pharmaceut Med ; 35(2): 71-79, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33539007

RESUMO

The need for information about new and existing drugs used in children was recognized in the European Union (EU) with the implementation of the Paediatric Regulation in 2007. In 2017, the 10-year review of the Paediatric Regulation identified barriers to the conduct of clinical trials, including delays in setting up and completing paediatric trials. Across Europe, the difficulties with clinical research are compounded by variation within countries and between countries. Ethics and regulatory review have national specificities. This paper describes the Collaborative Network for European Clinical Trials for Children (conect4children, c4c), which addresses selected difficulties in the design and conduct of paediatric clinical trials. c4c is a time-limited public-private consortium funded by the Innovative Medicines Initiative (IMI2). The elements of c4c are as follows: expert advice providing input on study design and/or paediatric development programmes (including patient involvement activities); a network of sites following harmonised procedures coordinated by National Hubs and a single point of contact for Europe; a facility for education and training for sites and trial teams; and support for managing data used by the network and a common paediatric data dictionary. c4c does not sponsor trials. c4c is taking a phased approach with careful piloting through industry and non-industry studies intended to demonstrate the viability of the network (proof-of-viability studies). c4c uses a co-design approach involving industry and academics within a clearly defined scope. A sustainable, successor organization open to all potential service users will be open for business before the end of IMI2 funding in 2024.

8.
Br J Clin Pharmacol ; 87(3): 1541-1546, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32696451

RESUMO

Neonates experience adverse drug reactions (ADRs), but under-reporting of suspected ADRs to national spontaneous reporting schemes in this population is particularly high. A prospective observational study collected suspected neonatal ADRs at a tertiary neonatal unit. Cases were analysed for causality by six assessors using three existing methods. Sixty-three suspected ADR cases were identified in 35/193 neonates (18.1%). The proportion of suspected ADRs where the drug was prescribed "off-label" was 30/68 (44.1%). When 34 cases were assessed for causality using three methods, global kappa scores of less than 0.3 for each tool suggested only "fair" inter-rater reliability. Neonatal ADRs can be captured and occur from a variety of drugs affecting many organ systems. The current tools for assessing causality need to be adapted before they can reliably assess neonatal ADRs.

10.
BMJ Open ; 10(10): e041528, 2020 10 06.
Artigo em Inglês | MEDLINE | ID: mdl-33028566

RESUMO

INTRODUCTION: Chronic lung disease of prematurity (CLD), also known as bronchopulmonary dysplasia (BPD), is a cause of significant respiratory morbidity in childhood and beyond. Coupled with lung immaturity, infections (especially by Ureaplasma spp) are implicated in the pathogenesis of CLD through promotion of pulmonary inflammation. Azithromycin, which is a highly effective against Ureaplasma spp also has potent anti-inflammatory properties. Thus, azithromycin therapy may improve respiratory outcomes by targeting infective and inflammatory pathways. Previous trials using macrolides have not been sufficiently powered to definitively assess CLD rates. To address this, the azithromycin therapy for chronic lung disease of prematurity (AZTEC) trial aims to determine if a 10-day early course of intravenous azithromycin improves rates of survival without CLD when compared with placebo with an appropriately powered study. METHODS AND ANALYSIS: 796 infants born at less than 30 weeks' gestational age who require at least 2 hours of continuous respiratory support within the first 72 hours following birth are being enrolled by neonatal units in the UK. They are being randomised to receive a double-blind, once daily dose of intravenous azithromycin (20 mg/kg for 3 days, followed by 10 mg/kg for a further 7 days), or placebo. CLD is being assessed at 36 weeks' PMA. Whether colonisation with Ureaplasma spp prior to randomisation modifies the treatment effect of azithromycin compared with placebo will also be investigated. Secondary outcomes include necrotising enterocolitis, intraventricular/cerebral haemorrhage, retinopathy of prematurity and nosocomial infections, development of antibiotic resistance and adverse reactions will be monitored. ETHICS AND DISSEMINATION: Ethics permission has been granted by Wales Research Ethics Committee 2 (Ref 18/WA/0199), and regulatory permission by the Medicines and Healthcare Products Regulatory Agency (Clinical Trials Authorisation reference 21323/0050/001-0001). The study is registered on ISRCTN (ISRCTN11650227). The study is overseen by an independent Data Monitoring Committee and an independent Trial Steering Committee. We shall disseminate our findings via national and international peer-reviewed journals, and conferences. A summary of the findings will also be posted on the trial website.


Assuntos
Doenças do Prematuro , Pneumopatias , Azitromicina/uso terapêutico , Criança , Doença Crônica , Dexametasona , Glucocorticoides , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Doenças do Prematuro/tratamento farmacológico , Doenças do Prematuro/prevenção & controle , Pneumopatias/tratamento farmacológico , Pneumopatias/prevenção & controle , Ensaios Clínicos Controlados Aleatórios como Assunto , País de Gales
12.
Br J Clin Pharmacol ; 2020 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-32893382

RESUMO

Paediatric drug development faces several barriers. These include fragmentation of stakeholders and inconsistent processes during the conduct of research. This review summarises recent efforts to overcome these barriers in Europe. Two exemplar initiatives are described. The European Paediatric Translational Research Infrastructure facilitates preclinical research and other work that underpins clinical trials. conect4children facilitates the design and implementation of clinical trials. Both these initiatives listen to the voices of children and their advocates. Coordination of research needs specific effort that supplements work on science, resources and the policy context.

13.
Trials ; 21(1): 329, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32293527

RESUMO

BACKGROUND: Vancomycin has been used in clinical practice for over 50 years; however, validated, pharmacokinetic (PK) data relating clinical outcomes to different dosing regimens in neonates are lacking. Coagulase negative staphylococci (CoNS) are the most commonly isolated organisms in neonatal, late-onset sepsis (LOS). Optimised use to maximise efficacy while minimising toxicity and resistance selection is imperative to ensure vancomycin's continued efficacy. METHODS: NeoVanc is a European, open-label, Phase IIb, randomised, controlled, non-inferiority trial comparing an optimised vancomycin regimen to a standard vancomycin regimen when treating LOS known/suspected to be caused by Gram-positive organisms (excluding Staphylococcus aureus) in infants aged ≤ 90 days. Three hundred infants will be recruited and randomised in a 1:1 ratio. Infants can be recruited if they have culture confirmed (a positive culture from a normally sterile site and at least one clinical/laboratory criterion) or clinical sepsis (presence of any ≥ 3 clinical/laboratory criteria) in the 24 h before randomisation. The optimised regimen consists of a vancomycin loading dose (25 mg/kg) followed by 5 ± 1 days of 15 mg/kg q12h or q8h, dependent on postmenstrual age (PMA). The standard regimen is a 10 ± 2 day vancomycin course at 15 mg/kg q24h, q12h or q8h, dependent on PMA. The primary endpoint is a successful outcome at the test of cure visit (10 ± 1 days after the end of vancomycin therapy). A successful outcome consists of the patient being alive, having successfully completed study vancomycin therapy and having not had a clinical/microbiological relapse/new infection requiring treatment with vancomycin or other anti-staphylococcal antibiotic for > 24 h. Secondary endpoints include clinical/microbiological relapse/new infection at the short-term follow-up visit (30 ± 5 days after the initiation of vancomycin), evaluation of safety (renal/hearing), vancomycin PK and assessment of a host biomarker panel over the course of vancomycin therapy. DISCUSSION: Based on previous pre-clinical data and a large meta-analysis of neonatal, PK/pharmacodynamic data, NeoVanc was set up to provide evidence on whether a loading dose followed by a short vancomycin course is non-inferior, regarding efficacy, when compared to a standard, longer course. If non-inferiority is demonstrated, this would support adoption of the optimised regimen as a way of safely reducing vancomycin exposure when treating neonatal, Gram-positive LOS. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02790996. Registered on 7 April 2016. EudraCT, 2015-000203-89. Entered on 18 July 2016.


Assuntos
Antibacterianos/uso terapêutico , Protocolos Clínicos/classificação , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Sepse Neonatal/tratamento farmacológico , Vancomicina/uso terapêutico , Antibacterianos/administração & dosagem , Antibacterianos/farmacocinética , Protocolos Clínicos/normas , Relação Dose-Resposta a Droga , Estudos de Equivalência como Asunto , Humanos , Lactente , Recém-Nascido , Sepse Neonatal/diagnóstico , Sepse Neonatal/microbiologia , Segurança , Infecções Estafilocócicas/prevenção & controle , Vancomicina/administração & dosagem , Vancomicina/farmacocinética
15.
J Matern Fetal Neonatal Med ; : 1-10, 2020 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-32138571

RESUMO

Background: Comprehensive measures to evaluate the effectiveness of medical interventions in extremely preterm infants are lacking. Although length of stay is used as an indicator of overall health among preterm infants in clinical studies, it is confounded by nonmedical factors (e.g. parental readiness and availability of home nursing support).Objectives: To develop the PREMature Infant Index (PREMII™), an electronic content-valid clinician-reported outcome measure for assessing functional status of extremely preterm infants (<28 weeks gestational age) serially over time in the neonatal intensive care unit. We report the development stages of the PREMII, including suggestions for scoring.Methods: We developed the PREMII according to US Food and Drug Administration regulatory standards. Development included five stages: (1) literature review, (2) clinical expert interviews, (3) Delphi panel survey, (4) development of items/levels, and (5) cognitive interviews/usability testing. Scoring approaches were explored via an online clinician survey.Results: Key factors reflective of functional status were identified by physicians and nurses during development of the PREMII, as were levels within each factor to assess functional status. The resulting PREMII evaluates eight infant health factors: respiratory support, oxygen administration, apnea, bradycardia, desaturation, thermoregulation, feeding, and weight gain, each scored with three to six gradations. Factor levels are standardized on a 0-100 scale; resultant scores are 0-100. No usability issues were identified. The online clinician survey identified optimal scoring methods to capture functional status at a given time point.Conclusions: Our findings support the content validity and usability of the PREMII as a multifunction outcome measure to assess functional status over time in extremely preterm infants. Psychometric validation is ongoing.

16.
Pediatr Res ; 88(1): 14-26, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32126571

RESUMO

Sepsis remains a leading cause of morbidity and mortality in the neonatal population, and at present, there is no unified definition of neonatal sepsis. Existing consensus sepsis definitions within paediatrics are not suited for use in the NICU and do not address sepsis in the premature population. Many neonatal research and surveillance networks have criteria for the definition of sepsis within their publications though these vary greatly and there is typically a heavy emphasis on microbiological culture. The concept of organ dysfunction as a diagnostic criterion for sepsis is rarely considered in neonatal literature, and it remains unclear how to most accurately screen neonates for organ dysfunction. Accurately defining and screening for sepsis is important for clinical management, health service design and future research. The progress made by the Sepsis-3 group provides a roadmap of how definitions and screening criteria may be developed. Similar initiatives in neonatology are likely to be more challenging and would need to account for the unique presentation of sepsis in term and premature neonates. The outputs of similar consensus work within neonatology should be twofold: a validated definition of neonatal sepsis and screening criteria to identify at-risk patients earlier in their clinical course. IMPACT: There is currently no consensus definition of neonatal sepsis and the definitions that are currently in use are varied.A consensus definition of neonatal sepsis would benefit clinicians, patients and researchers.Recent progress in adults with publication of Sepsis-3 provides guidance on how a consensus definition and screening criteria for sepsis could be produced in neonatology.We discuss common themes and potential shortcomings in sepsis definitions within neonatology.We highlight the need for a consensus definition of neonatal sepsis and the challenges that this task poses.

17.
Thyroid ; 30(7): 948-954, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32070246

RESUMO

Background: Infants below 28 weeks' gestation have low thyroid hormone plasma levels compared with more mature infants and this may contribute to their risk of developmental disability. We aimed at determining the effect of supplementation with levothyroxine (LT4) for extremely premature infants born below 28 weeks' gestations on neurodevelopmental outcomes at 42 months. Methods: An explanatory double-blind, randomized, placebo-controlled trial consecutively recruited 153 infants below 28 weeks' gestation from 5 neonatal units in the United Kingdom. Infants were either supplemented with LT4 started intravenously during the first 5 days after birth and then changed to oral LT4 when enteral feeds were fully established (8 µg/kg birthweight/day as a single daily dose) or given placebo until 32 weeks' corrected gestational age. Neurodevelopmental outcomes at 42 months (range 40-43) were evaluated in 59 of these infants (30 LT4-supplemented, 29 placebo) by using Bayley III Mental and Psychomotor Developmental Indices. Cognition outcomes was correlated with plasma free thyroxine (fT4) level at 36 weeks and diffusion tensor imaging (DTI) markers. Results: The LT4 supplemented group performed significantly better in motor, language, and cognitive function domains. The mean of the difference between each group (95% confidence intervals [CI], p-value) was motor domain 6.96 ([0.55-13.38], p = 0.034); language domain 8.93 ([0.16-17.70], p = 0.041); and cognition domain 6.35 ([0.14-12.55], p = 0.045). Neurodevelopmental outcome at 42 months had some associations with the trial's primary outcome (subarachnoid space width and motor outcome, p = 0.03), plasma fT4 level at 36 weeks (fT4 and cognition outcome, p = 0.01), and DTI at 36 weeks with cognition outcomes (p > 0.05). Conclusion: Our data suggest that early supplementation with LT4 may improve long-term neurodevelopment in infants born below 28 weeks' gestation, but larger trials are warranted as the current reported improvements shown are not strong enough to warrant a change in practice.


Assuntos
Encéfalo/efeitos dos fármacos , Desenvolvimento Infantil/efeitos dos fármacos , Terapia de Reposição Hormonal/métodos , Tiroxina/administração & dosagem , Pré-Escolar , Cognição/efeitos dos fármacos , Método Duplo-Cego , Feminino , Seguimentos , Idade Gestacional , Humanos , Lactente Extremamente Prematuro , Recém-Nascido , Idioma , Masculino , Destreza Motora/efeitos dos fármacos , Tiroxina/sangue , Resultado do Tratamento
18.
Eur J Pediatr ; 179(5): 839-847, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31897842

RESUMO

Health-care professionals who prescribe medicines have the professional duty to choose medicines that are in the best interest of their individual patient, irrespective if that patient is an adult or a child. However, the availability of medicines with an appropriate label for pediatric use is lagging behind those for adults, and even available pediatric drugs are sometimes not suitable to administer to children. Consequently, health-care professionals often have no other option than to prescribe off-label medicines to children. An important reason for use of off-label medicines is to improve access to (innovative) treatments or to address medical needs and preferences of patients, especially when no other options are available. However, off-label use of medicines is in general not supported by the same level of evidence as medicines licensed for pediatric use. This may result in increased uncertainty on efficacy as well as the risk for toxicity and other side effects. In addition, liability may also be of concern, counterbalanced by professional guidelines.Conclusion: The purpose of this joint EAP/ESDPPP policy statement is to offer guidance for HCPs on when and how to prescribe off-label medicines to children and to provide recommendations for future European policy.


Assuntos
Uso Off-Label/normas , Pediatria/normas , Adolescente , Criança , Pré-Escolar , Europa (Continente) , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pediatria/métodos , Padrões de Prática Médica/normas , Sociedades Médicas
19.
Pediatrics ; 145(2)2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31937606

RESUMO

Big data (BD) in pediatric medication safety research provides many opportunities to improve the safety and health of children. The number of pediatric medication and device trials has increased in part because of the past 20 years of US legislation requiring and incentivizing study of the effects of medical products in children (Food and Drug Administration Modernization Act of 1997, Pediatric Rule in 1998, Best Pharmaceuticals for Children Act of 2002, and Pediatric Research Equity Act of 2003). There are some limitations of traditional approaches to studying medication safety in children. Randomized clinical trials within the regulatory context may not enroll patients who are representative of the general pediatric population, provide the power to detect rare safety signals, or provide long-term safety data. BD sources may have these capabilities. In recent years, medical records have become digitized, and cell phones and personal devices have proliferated. In this process, the field of biomedical science has progressively used BD from those records coupled with other data sources, both digital and traditional. Additionally, large distributed databases that include pediatric-specific outcome variables are available. A workshop entitled "Advancing the Development of Pediatric Therapeutics: Application of 'Big Data' to Pediatric Safety Studies" held September 18 to 19, 2017, in Silver Spring, Maryland, formed the basis of many of the ideas outlined in this article, which are intended to identify key examples, critical issues, and future directions in this early phase of an anticipated dramatic change in the availability and use of BD.


Assuntos
Big Data , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Preparações Farmacêuticas , Canadá , Criança , Redes de Comunicação de Computadores/organização & administração , Congressos como Assunto , Coleta de Dados/métodos , Bases de Dados Factuais , Registros Eletrônicos de Saúde , Europa (Continente) , Humanos , Estados Unidos
20.
Pediatr Infect Dis J ; 39(3): 221-228, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31876614

RESUMO

BACKGROUND: Clostridium difficile is capable of causing severe enterocolitis in adults. The significance of toxin-producing C. difficile in children with diarrhea is unclear and practice differs on whether to institute treatment. We aimed to characterize the microbiome in relation to the presence of C. difficile and co-infection with other pathogens and to describe host response to infection. METHODS: Participants were children with acute diarrhea, 0-16 years of age, from whom stool samples had been submitted to the hospital laboratory for routine microbiology/virology. Convenience sampling was used for 50 prospective and 150 retrospective samples. No participants were treated for C. difficile. Rates of culture positivity for C. difficile, presence of toxin and PCR-ribotype were compared between age groups. Presence of other potential pathogens, comorbidities and complications were recorded. Microbiotal diversity was measured by 16S profiling. RESULTS: Nineteen of 77 (25%) children <2 years of age and 13 of 119 (11%) children >2 years of age were C. difficile positive, of whom 10 (53%) and 9 (69%), respectively, carried toxigenic strains. Increased Shannon diversity was seen in children carrying C. difficile, with altered milieu. Presence of C. difficile was not associated with adverse clinical outcomes. In stools containing both Norovirus and C. difficile, there was increased relative abundance of verrucomicrobia. CONCLUSIONS: Children with diarrhea regularly carried toxigenic and non-toxigenic strains of C. difficile, demonstrating enhanced microbiotal diversity, and change in milieu, without apparent morbidity. This unexpected finding is contrary to that seen in adults with C. difficile disease.


Assuntos
Bacteriemia , Diarreia/epidemiologia , Diarreia/etiologia , Enterocolite Pseudomembranosa/epidemiologia , Enterocolite Pseudomembranosa/microbiologia , Microbioma Gastrointestinal , Interações Hospedeiro-Patógeno , Adolescente , Toxinas Bacterianas/genética , Biomarcadores , Criança , Pré-Escolar , Clostridioides difficile/classificação , Citocinas/metabolismo , Fezes/química , Fezes/microbiologia , Feminino , Hospitalização , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Metagenômica/métodos , Tipagem Molecular , RNA Ribossômico 16S
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