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BACKGROUND: Wet wraps can be an effective means of improving atopic dermatitis (AD). Little research has been done regarding the comparative efficacy of topical steroid vehicles and patient preference. OBJECTIVE: This study aimed to compare the efficacy of 0.1% triamcinolone acetonide ointment vs cream used with wet wraps in pediatric patients with AD and to explore patient preference/opinion. METHODS: We performed a small, randomized, investigator-blind prospective study of 39 pediatric patients experiencing symmetric, bilateral AD flares. Patients were instructed to apply a topical steroid cream to one extremity and apply the same topical steroid in an ointment vehicle to the other extremity using the wet-wrap technique once or twice daily for 3 to 5 consecutive days. Patients were evaluated at a follow-up visit. RESULTS: Comparison of the change in Investigator's Global Assessment scores disclosed no significant difference between efficacy ratings of cream (mean difference = 0.72) and ointment (mean difference = 0.59) when used with wet wraps (P = 0.22). Although patients found the ointment more difficult to apply, they were more likely to prefer ointments for future prescriptions (P < 0.01). CONCLUSION: Patient preference of corticosteroid vehicle is what should ultimately drive treatment. In this small study, we found no difference in efficacy between triamcinolone acetonide wet wraps with cream vs ointment. Dermatologists should select the vehicle of the patient's choice as it may increase satisfaction with treatment.
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Dermatite Atópica/terapia , Pomadas/administração & dosagem , Creme para a Pele/administração & dosagem , Triancinolona Acetonida/uso terapêutico , Administração Tópica , Adolescente , Bandagens , Criança , Pré-Escolar , Dermatite Atópica/diagnóstico , Feminino , Seguimentos , Humanos , Masculino , Estudos Prospectivos , Método Simples-Cego , Absorção Cutânea/efeitos dos fármacos , Resultado do TratamentoRESUMO
OBJECTIVES: Antiepileptic drug (AED) monotherapy is usually effective in 60% of the patients with epilepsy while the remaining patients have refractory epilepsy. This study compared treatment patterns (adherence, persistence, addition, and switching) associated with refractory and nonrefractory epilepsy. METHODS: Texas Medicaid claims from 09/01/07-12/31/13 were analyzed, and patients eligible for the study 1) were between 18 and 62â¯years of age, 2) had a prescription claim for an AED during the identification period (03/01/08-12/31/11) with no prior baseline AED use (6-month), and 3) had evidence of epilepsy diagnosis within 6â¯months of AED use. Based on AED use in the identification period, patients were categorized into "refractory" (≥3AEDs) and "nonrefractory" (<3AEDs) cohorts. The index date was the date of the first AED claim. Patients in both cohorts were matched 1:1 using propensity scoring and compared for adherence (proportion of days covered (PDC) ≥80% vs. <80%), persistence, addition (yes/no), and switching (yes/no) using multivariate conditional regression models. Conditional logistic regression and Cox proportional hazard models were used to address the study objectives. RESULTS: Of the 10,599 eligible patients, 2798 (26.5%) patients in the refractory cohort were matched to patients in the nonrefractory cohort. Patients in the refractory cohort had significantly higher (pâ¯<â¯0.005) mean (±Standard deviation (SD)) adherence (88.6% (±19.1%) vs. 77.0%⯱â¯(25.8%)) and persistence (328.0 (±87.3) days vs. 294.9⯱â¯(113.4) days) as compared with patients in the nonrefractory cohort. Compared with patients with nonrefractory epilepsy, patients with refractory epilepsy were 3.6 times (odds ratio (OR)â¯=â¯3.553; 95% confidence interval (CI)â¯=â¯3.060-4.125; pâ¯<â¯0.0001) more likely to adhere to AEDs and had a 34.7% (hazard ratio (HR)â¯=â¯0.653; 95% CIâ¯=â¯0.608-0.702; pâ¯<â¯0.0001) lower hazard rate of discontinuation of AEDs. Also, patients with refractory epilepsy were 3.7 times (ORâ¯=â¯3.723; 95% CIâ¯=â¯2.902-4.776; pâ¯<â¯0.0001) more likely to add an alternative AED and 3.6 times (ORâ¯=â¯3.591; 95% CIâ¯=â¯3.010-4.284; pâ¯<â¯0.0001) more likely to switch to an alternative AED. CONCLUSION: Patients with refractory epilepsy were significantly more likely to adhere and persist to AED regimen and were significantly more likely to add and switch to an alternative AED than patients with nonrefractory epilepsy.
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Anticonvulsivantes/uso terapêutico , Epilepsia Resistente a Medicamentos/tratamento farmacológico , Epilepsia Resistente a Medicamentos/epidemiologia , Medicaid , Adesão à Medicação , Adolescente , Adulto , Idoso , Estudos de Coortes , Feminino , Humanos , Masculino , Medicaid/tendências , Pessoa de Meia-Idade , Estudos Retrospectivos , Texas/epidemiologia , Estados Unidos/epidemiologia , Adulto JovemRESUMO
OBJECTIVE: The objective of this study was to determine if a rapid albuterol delivery pathway with a breath-enhanced nebulizer can reduce emergency department (ED) length of stay (LOS), while maintaining admission rates and side effects, when compared to a traditional asthma pathway with a standard jet nebulizer. METHODS: Children aged 3-18 presenting to a large urban pediatric ED for asthma were enrolled if they were determined by pediatric asthma score to have a moderate to severe exacerbation. Subjects were randomized to either a standard treatment arm where they received up to 2 continuous albuterol nebulizations, or a rapid albuterol arm where they received up to 4 rapid albuterol treatments with a breath-enhanced nebulizer, depending on severity scoring. The primary endpoint was ED LOS from enrollment until disposition decision. Asthma scores, albuterol dose, side effects, and return visits were also recorded. RESULTS: A total of 50 subjects were enrolled (25 in each arm). The study LOS was shorter in the rapid albuterol group (118 vs. 163 minutes, p = 0.0002). When total ED LOS was analyzed, the difference was no longer statistically significant (192 vs. 203 minutes, p = 0.65). There were no statistically significant differences with respect to admission rates, asthma score changes, side effects, or return visits. CONCLUSION: A rapid albuterol treatment pathway that utilizes a breath-enhanced nebulizer is an effective alternative to traditional pathways that utilize continuous nebulizations for children with moderate to severe asthma exacerbations in the ED.
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Albuterol/administração & dosagem , Asma/tratamento farmacológico , Broncodilatadores/administração & dosagem , Serviço Hospitalar de Emergência/estatística & dados numéricos , Tempo de Internação/estatística & dados numéricos , Nebulizadores e Vaporizadores , Doença Aguda , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , MasculinoRESUMO
BACKGROUND AND PURPOSE: In adult stroke, the advent of thrombolytic therapy led to the development of primary stroke centers capable to diagnose and treat patients with acute stroke rapidly. We describe the development of primary pediatric stroke centers through preparation of participating centers in the Thrombolysis in Pediatric Stroke (TIPS) trial. METHODS: We collected data from the 17 enrolling TIPS centers regarding the process of becoming an acute pediatric stroke center with capability to diagnose, evaluate, and treat pediatric stroke rapidly, including use of thrombolytic therapy. RESULTS: Before 2004, <25% of TIPS sites had continuous 24-hour availability of acute stroke teams, MRI capability, or stroke order sets, despite significant pediatric stroke expertise. After TIPS preparation, >80% of sites now have these systems in place, and all sites reported increased readiness to treat a child with acute stroke. Use of a 1- to 10-Likert scale on which 10 represented complete readiness, median center readiness increased from 6.2 before site preparation to 8.7 at the time of site activation (P≤0.001). CONCLUSIONS: Before preparing for TIPS, centers interested in pediatric stroke had not developed systematic strategies to diagnose and treat acute pediatric stroke. TIPS trial preparation has resulted in establishment of pediatric acute stroke centers with clinical and system preparedness for evaluation and care of children with acute stroke, including use of a standardized protocol for evaluation and treatment of acute arterial stroke in children that includes use of intravenous tissue-type plasminogen activator. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT01591096.
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Ensaios Clínicos como Assunto/normas , Fibrinolíticos/administração & dosagem , Hospitais Pediátricos/normas , Qualidade da Assistência à Saúde/normas , Acidente Vascular Cerebral/terapia , Centros de Atenção Terciária/normas , Terapia Trombolítica/normas , Ativador de Plasminogênio Tecidual/administração & dosagem , Adolescente , Criança , Pré-Escolar , Feminino , Fibrinolíticos/efeitos adversos , Hospitais Pediátricos/organização & administração , Hospitais Pediátricos/estatística & dados numéricos , Humanos , Masculino , Estudos Multicêntricos como Assunto , Qualidade da Assistência à Saúde/estatística & dados numéricos , Acidente Vascular Cerebral/tratamento farmacológico , Centros de Atenção Terciária/organização & administração , Centros de Atenção Terciária/estatística & dados numéricos , Terapia Trombolítica/efeitos adversos , Terapia Trombolítica/métodos , Ativador de Plasminogênio Tecidual/efeitos adversosRESUMO
Multiple studies show that molecular genetic changes and epigenetic modifications affect the risk of cognitive disability or impairment. However, the role of epigenetic variation in cognitive development of neurotypical young children remains largely unknown. Using data from a prospective, community-based study of mother-infant pairs, we investigated the association of DNA methylation patterns in neonatal umbilical cord blood with cognitive and language development at 1 year of age. No CpG loci achieved genome-wide significance, although a small number of weakly suggestive associations with Bayley-III Receptive Communication scales were noted. While umbilical cord blood is a convenient resource for genetic analyses of birth outcomes, our results do not provide conclusive evidence that its use for DNA methylation profiling yields epigenetic markers that are directly related to postnatal neurocognitive outcomes at 1 year of age.
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Cognição/fisiologia , Metilação de DNA , Epigênese Genética/genética , Desenvolvimento da Linguagem , Feminino , Sangue Fetal , Estudo de Associação Genômica Ampla , Humanos , Lactente , GravidezRESUMO
BACKGROUND: Despite global efforts to improve paediatric clinical trials, significant delays continue in paediatric drug approvals. Collaboration between research networks is needed to address these delays. This paper is a first step to promote interoperability between paediatric networks from different jurisdictions by comparing drivers for, and content of, metrics about clinical trial conduct. METHODS: Three paediatric networks, Institute for Advanced Clinical Trials for Children, the Maternal Infant Child and Youth Research Network and conect4children, have each developed metrics to address delays and create efficiencies. We identified the methodology by which each network identified metrics, described the metrics of each network, and mapped consistency to come to consensus about core metrics that networks could share. RESULTS: Metric selection was driven by site quality improvement in one network (11 metrics), by network performance in one network (13 metrics), and by both in one network (five metrics). The domains of metrics were research capacity/capability, site identification/feasibility, trial start-up, and recruitment/enrolment. The network driven by site quality improvement did not have indicators for capacity/capability or identification/feasibility. Fifteen metrics for trial start up and conduct were identified. Metrics related to site approvals were found in all three networks. The themes for metrics can inform the development of 'shared' metrics. CONCLUSION: We found disparity in drivers, methodology and metrics. Tackling this disparity will result in a unified approach to addressing delays in paediatric drug approvals. Collaborative work to define inter-operable metrics globally is outlined.
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Ensaios Clínicos como Assunto , Pediatria , Melhoria de Qualidade , Humanos , Criança , Aprovação de DrogasRESUMO
Many antiepileptic drugs (AEDs) have short half-lives with large fluctuations in peak-to-trough plasma concentrations. Consequences of these pharmacokinetic (PK) properties may include adverse events (AEs) and breakthrough seizures, potentially leading to poor adherence. To address these challenges, newer formulations of these AEDs have been developed using unique extended-release (ER) technologies. These technologies extend the dosing interval such that dosing frequency can be minimized, which may improve patient adherence. Available ER formulations have the potential to minimize the spikes in maximum plasma concentrations (C(max) ) at steady-state that often contribute to AEs during treatment with immediate-release (IR) products. In so doing, tolerability advantages may lead to increased AED effectiveness by improving adherence and allowing higher doses if clinically indicated. Direct PK comparison studies of IR and ER formulations (e.g., carbamazepine, divalproate sodium, lamotrigine, oxcarbazepine, levetiracetam, and phenytoin) have found that dose-normalized ER formulations may or may not be bioequivalent to their IR counterparts, but most ER formulations have a lower fluctuation index ([C(max) -C(min) ]/C(avg) ) compared with the IR versions. This results in flatter concentration-time plots. Not all ER preparations improve the various PK parameters to the same extent, and PK nuances may impact the effectiveness, tolerability, and adherence rates of various ER formulations.
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Anticonvulsivantes/administração & dosagem , Anticonvulsivantes/farmacocinética , Anticonvulsivantes/uso terapêutico , Carbamazepina/administração & dosagem , Carbamazepina/farmacocinética , Carbamazepina/uso terapêutico , Preparações de Ação Retardada , Tolerância a Medicamentos , Epilepsia/tratamento farmacológico , Humanos , Ácido Valproico/administração & dosagem , Ácido Valproico/farmacocinética , Ácido Valproico/uso terapêuticoRESUMO
BACKGROUND: The objectives of this study were to use electronic health record data from a US national multicenter pediatric network to identify a large cohort of children with CKD, evaluate CKD progression, and examine clinical risk factors for kidney function decline. METHODS: This retrospective cohort study identified children seen between January 1, 2009, to February 28, 2022. Data were from six pediatric health systems in PEDSnet. We identified children aged 18 months to 18 years who met criteria for CKD: two eGFR values <90 and ≥15 ml/min per 1.73 m2 separated by ≥90 days without an intervening value ≥90. CKD progression was defined as a composite outcome: eGFR <15 ml/min per 1.73 m2, ≥50% eGFR decline, long-term dialysis, or kidney transplant. Subcohorts were defined based on CKD etiology: glomerular, nonglomerular, or malignancy. We assessed the association of hypertension (≥2 visits with hypertension diagnosis code) and proteinuria (≥1 urinalysis with ≥1+ protein) within 2 years of cohort entrance on the composite outcome. RESULTS: Among 7,148,875 children, we identified 11,240 (15.7 per 10,000) with CKD (median age 11 years, 50% female). The median follow-up was 5.1 (interquartile range 2.8-8.3) years, the median initial eGFR was 75.3 (interquartile range 61-83) ml/min per 1.73 m2, 37% had proteinuria, and 35% had hypertension. The following were associated with CKD progression: lower eGFR category (adjusted hazard ratio [aHR] 1.44 [95% confidence interval (95% CI), 1.23 to 1.69], aHR 2.38 [95% CI, 2.02 to 2.79], aHR 5.75 [95% CI, 5.05 to 6.55] for eGFR 45-59 ml/min per 1.73 m2, 30-44 ml/min per 1.73 m2, 15-29 ml/min per 1.73 m2 at cohort entrance, respectively, when compared with eGFR 60-89 ml/min per 1.73 m2), glomerular disease (aHR 2.01 [95% CI, 1.78 to 2.28]), malignancy (aHR 1.79 [95% CI, 1.52 to 2.11]), proteinuria (aHR 2.23 [95% CI, 1.89 to 2.62]), hypertension (aHR 1.49 [95% CI, 1.22 to 1.82]), proteinuria and hypertension together (aHR 3.98 [95% CI, 3.40 to 4.68]), count of complex chronic comorbidities (aHR 1.07 [95% CI, 1.05 to 1.10] per additional comorbid body system), male sex (aHR 1.16 [95% CI, 1.05 to 1.28]), and younger age at cohort entrance (aHR 0.95 [95% CI, 0.94 to 0.96] per year older). CONCLUSIONS: In large-scale real-world data for children with CKD, disease etiology, albuminuria, hypertension, age, male sex, lower eGFR, and greater medical complexity at start of follow-up were associated with more rapid decline in kidney function.
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Hipertensão , Insuficiência Renal Crônica , Humanos , Masculino , Criança , Feminino , Registros Eletrônicos de Saúde , Estudos Retrospectivos , Progressão da Doença , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/terapia , Hipertensão/epidemiologia , Hipertensão/complicações , Proteinúria/etiologia , Fatores de Risco , Taxa de Filtração Glomerular , RimRESUMO
BACKGROUND: Recent decades have seen many advances in policy and legislation that support the development of drugs used by neonates, infants, children, and young people. This review summarizes the characteristics and performance of networks capable of conducting studies needed to meet regulatory requirements and make advances in pediatric drug development. METHODS: Description of network goals and capabilities by network leaders. RESULTS: In the United States, Europe, Japan, and Canada, clinical research networks have been organized to meet the needs of biopharmaceutical and academic sponsors for timely access to high-quality sites, as well as to provide advice about drug development with regard to strategic and operational feasibility. Each network addresses the specificities of its context while working toward shared principles including standards and timelines; alignment of goals and processes, while not disturbing arrangements for conducting trials that work well; wide geographic coverage; all age groups and pediatric conditions; sources of funding; sites that compete on performance; performance monitoring for benchmarking, and opportunities to optimize the allocation of resources; and education and training for network members. Facilitation in interactions among these networks is based on a single point-of-contact for each; similar approaches to strategic and operational feasibility assessment, and site selection; and collaborative approaches to education and training. CONCLUSION: Within five years, clinical research networks will support the needs of biopharmaceutical and publicly funded pediatric drug development through locally appropriate and globally interoperable approaches.
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Produtos Biológicos , Adolescente , Canadá , Criança , Europa (Continente) , Humanos , Recém-Nascido , Japão , Estados UnidosRESUMO
Including adolescents in adult clinical trials can play an important role in making innovative new medicines available to children in a timelier fashion. Stakeholders involved in the processes leading to regulatory approval and labeling of new drugs recognize that challenges exist in involving adolescents and older children in clinical trials before the safety and efficacy of these drugs are established for adults. However, it has been possible to design and execute phase 3 trials that combine adults with adolescents which are medically and scientifically sound and ethically justified. Based on this experience and considerations of the medical and scientific, ethical, and operation-related matters, the 2019 Pediatric Innovation Research Forum advocated for the position that adolescents routinely be considered for enrollment in phase 3 clinical trials. The Forum also concluded that exclusion of adolescents in adult pivotal trials occur only when a thorough evaluation of the target disease and the potential benefit and risks of the study intervention supports a delay in their involvement until after completion of clinical trials in adults.
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Ensaios Clínicos como Assunto , Adolescente , Adulto , Criança , HumanosAssuntos
Fibrinolíticos/uso terapêutico , Acidente Vascular Cerebral/tratamento farmacológico , Terapia Trombolítica/métodos , Ativador de Plasminogênio Tecidual/uso terapêutico , Adolescente , Teorema de Bayes , Cardiologia/métodos , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Infusões Intravenosas , Masculino , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: The safety and efficacy of thrombolysis after acute stroke in children have not been established. Our aim was to describe current practices and results of the use of alteplase for acute arterial ischaemic stroke in children enrolled in an international pediatric stroke registry and to compare current practices with those published in case reports and with guidelines for the use of alteplase for adult stroke. METHODS: In this multicentre observational cohort study, we analysed the clinical features, the dosing and timing of treatment, and the short-term outcome in children treated with alteplase for acute arterial ischaemic stroke who were enrolled in the International Pediatric Stroke Study (IPSS) between January, 2003, and July, 2007. The findings from the IPSS were compared with published case reports for clinical features, adherence to adult guidelines for alteplase, and outcomes. FINDINGS: Of 687 children with acute arterial ischaemic stroke enrolled in the IPSS, 15 (2%) received alteplase: nine received intravenous alteplase and six received intra-arterial alteplase. The median time to treatment from stroke onset was 3.3 h (range 2.0-52.0 h) for intravenous alteplase and 4.5 h (3.8-24.0 h) for intra-arterial alteplase. Two patients died (one owing to massive infarction and brain herniation, and one owing to brainstem infarction). At discharge from hospital, one patient was healthy and 12 patients had neurological deficits. Intracranial haemorrhage after alteplase occurred in four of 15 patients, although none of the bleeding events was judged to be acutely symptomatic. When compared with ten patients reported in published articles who were given intravenous alteplase, the nine patients in the IPSS cohort were mostly younger, waited longer for treatment, and had worse outcomes, which suggests there is a publication bias towards short treatment intervals from symptom onset and favourable outcomes. INTERPRETATION: Children with acute stroke received alteplase infrequently and at time intervals that often deviated from adult guidelines. Although no alteplase-related deaths or symptomatic intracranial haemorrhage was reported, poor neurological outcome was common. Clinical trials to evaluate the dose and the safety and efficacy of alteplase are needed in childhood stroke.
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Fibrinolíticos/uso terapêutico , Pediatria , Acidente Vascular Cerebral/tratamento farmacológico , Ativador de Plasminogênio Tecidual/uso terapêutico , Adolescente , Isquemia Encefálica/complicações , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Fibrinolíticos/efeitos adversos , Humanos , Lactente , Cooperação Internacional , Hemorragias Intracranianas/induzido quimicamente , Masculino , Observação/métodos , Estudos Retrospectivos , Acidente Vascular Cerebral/etiologia , Fatores de Tempo , Ativador de Plasminogênio Tecidual/efeitos adversos , Resultado do TratamentoRESUMO
BACKGROUND: Although tissue plasminogen activator (tPA) has revolutionized the treatment of acute ischemic stroke in adults, no thrombolysis trials in childhood stroke have been conducted. Experience in adults cannot be applied to children due to fundamental age-related differences in coagulation systems, stroke pathophysiology and neuropharmacology. Obstacles to acute treatment trials in childhood stroke include delays in diagnosis and minimizing risk in a vulnerable population. STUDY DESIGN: Thrombolysis in Pediatric Stroke (TIPS) is an international multicenter study to assess the safety of intravenous tPA within 0-3 h and intra-arterial tPA within 3-6 h of onset of arterial ischemic stroke in childhood. Through the International Pediatric Stroke Study, 30 international centers will enroll a total of 48 patients: 24 will be treated with intravenous tPA (0.6, 0.75, 0.9, and 1.0 mg/kg) using the classical dose-finding method, and 24 will be treated with intra-arterial tPA (maximum 0.2, 0.3, 0.4, and 0.5 mg/kg) using a Bayesian dose-finding method. CONCLUSION: The TIPS trial will be the first clinical trial exploring the safety and feasibility of systemic and local thrombolytic therapy in childhood stroke and the obstacles in conducting such a trial.
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Isquemia Encefálica/tratamento farmacológico , Acidente Vascular Cerebral/tratamento farmacológico , Terapia Trombolítica/métodos , Ativador de Plasminogênio Tecidual/administração & dosagem , Adolescente , Teorema de Bayes , Criança , Pré-Escolar , Estudos de Coortes , Cálculos da Dosagem de Medicamento , Humanos , Injeções Intra-Arteriais , Injeções Intravenosas , Fatores de Tempo , Ativador de Plasminogênio Tecidual/uso terapêuticoRESUMO
A committee assembled by the American Academy of Neurology (AAN) reassessed the evidence related to the care of women with epilepsy (WWE) during pregnancy, including antiepileptic drug (AED) teratogenicity and adverse perinatal outcomes. It is highly probable that intrauterine first-trimester valproate (VPA) exposure has higher risk of major congenital malformations (MCMs) compared to carbamazepine (CBZ), and possibly compared to phenytoin (PHT) or lamotrigine (LTG). It is probable that VPA as part of polytherapy and possible that VPA as monotherapy contribute to the development of MCMs. AED polytherapy probably contributes to the development of MCMs and reduced cognitive outcomes compared to monotherapy. Intrauterine exposure to VPA monotherapy probably reduces cognitive outcomes and monotherapy exposure to PHT or phenobarbital (PB) possibly reduces cognitive outcomes. Neonates of WWE taking AEDs probably have an increased risk of being small for gestational age and possibly have an increased risk of a 1-minute Apgar score of <7. If possible, avoidance of VPA and AED polytherapy during the first trimester of pregnancy should be considered to decrease the risk of MCMs. If possible, avoidance of VPA and AED polytherapy throughout pregnancy should be considered and avoidance of PHT and PB throughout pregnancy may be considered to prevent reduced cognitive outcomes.
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Anormalidades Induzidas por Medicamentos/etiologia , Anticonvulsivantes/efeitos adversos , Transtornos Cognitivos/induzido quimicamente , Epilepsia/tratamento farmacológico , Complicações na Gravidez/tratamento farmacológico , Anticonvulsivantes/uso terapêutico , Peso ao Nascer/efeitos dos fármacos , Contraindicações , Quimioterapia Combinada , Feminino , Humanos , Recém-Nascido , Gravidez , Efeitos Tardios da Exposição Pré-Natal , Risco , Ácido Valproico/efeitos adversos , Ácido Valproico/uso terapêuticoRESUMO
A committee assembled by the American Academy of Neurology (AAN) reassessed the evidence related to the care of women with epilepsy (WWE) during pregnancy, including preconceptional folic acid and prenatal vitamin K use and the clinical implications of placental and breast-milk transfer of antiepileptic drugs (AEDs). The committee evaluated the available evidence based on a structured literature review and classification of relevant articles. Preconceptional folic acid supplementation is possibly effective in preventing major congenital malformations in the newborns of WWE taking AEDs. There is inadequate evidence to determine if the newborns of WWE taking AEDs have a substantially increased risk of hemorrhagic complications. Primidone and levetiracetam probably transfer into breast milk in clinically important amounts. Valproate, phenobarbital, phenytoin, and carbamazepine probably are not transferred into breast milk in clinically important amounts. Pregnancy probably causes an increase in the clearance and a decrease in the concentrations of lamotrigine, phenytoin, and, to a lesser extent carbamazepine, and possibly decreases the level of levetiracetam and the active oxcarbazepine metabolite, the monohydroxy derivative (MHD). Supplementing WWE with at least 0.4 mg of folic acid before pregnancy may be considered. Monitoring of lamotrigine, carbamazepine, and phenytoin levels during pregnancy should be considered, and monitoring of levetiracetam and oxcarbazepine (as MHD) levels may be considered. A paucity of evidence limited the strength of many recommendations.
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Anticonvulsivantes/uso terapêutico , Aleitamento Materno , Anormalidades Congênitas/prevenção & controle , Epilepsia/tratamento farmacológico , Ácido Fólico/administração & dosagem , Complicações na Gravidez/tratamento farmacológico , Vitamina K/administração & dosagem , Anticonvulsivantes/efeitos adversos , Anticonvulsivantes/farmacocinética , Anormalidades Congênitas/epidemiologia , Epilepsia/epidemiologia , Epilepsia/fisiopatologia , Feminino , Humanos , Recém-Nascido , Leite Humano/metabolismo , Placenta/metabolismo , Gravidez , Risco , Sangramento por Deficiência de Vitamina K/epidemiologia , Sangramento por Deficiência de Vitamina K/etiologia , Sangramento por Deficiência de Vitamina K/prevenção & controleRESUMO
A committee assembled by the American Academy of Neurology (AAN) reassessed the evidence related to the care of women with epilepsy (WWE) during pregnancy, including the risk of pregnancy complications or other medical problems during pregnancy, change in seizure frequency, the risk of status epilepticus, and the rate of remaining seizure-free during pregnancy. The committee evaluated the available evidence according to a structured literature review and classification of relevant articles. For WWE who are taking antiepileptic drugs (AEDs), there is probably no substantially increased risk (>2 times expected) of cesarean delivery or late pregnancy bleeding, and probably no moderately increased risk (>1.5 times expected) of premature contractions or premature labor and delivery. There is possibly a substantially increased risk of premature contractions and premature labor and delivery during pregnancy for WWE who smoke. WWE should be counseled that seizure freedom for at least 9 months prior to pregnancy is probably associated with a high likelihood (84-92%) of remaining seizure-free during pregnancy. WWE who smoke should be counseled that they possibly have a substantially increased risk of premature contractions and premature labor and delivery.
Assuntos
Epilepsia/epidemiologia , Complicações na Gravidez/epidemiologia , Aborto Espontâneo/epidemiologia , Anticonvulsivantes/uso terapêutico , Cesárea , Epilepsia/tratamento farmacológico , Feminino , Humanos , Hipertensão/epidemiologia , Trabalho de Parto Prematuro/epidemiologia , Razão de Chances , Pré-Eclâmpsia/epidemiologia , Gravidez , Complicações na Gravidez/tratamento farmacológico , Recidiva , Risco , Fumar/epidemiologia , Estado Epiléptico/tratamento farmacológico , Estado Epiléptico/epidemiologia , Hemorragia Uterina/epidemiologiaRESUMO
BACKGROUND AND PURPOSE: A safe and effective tissue plasminogen activator (tPA) dose for childhood stroke has not been established. This article describes a Bayesian outcome-adaptive method for determining the best dose of an experimental agent and explains how this method was used to design a dose-finding trial for tPA in childhood. METHODS: The method assigns doses to successive cohorts of patients on the basis of each dose's desirability, quantified in terms of the tradeoff between efficacy and toxicity. The tradeoff function is constructed from several pairs of equally desirable (efficacy, toxicity) probabilities specified by the physicians planning the trial. Each cohort's dose is chosen adaptively, based on dose-outcome data from the patients treated previously in the trial, to optimize the efficacy-toxicity tradeoff. Application of the method to design the tPA trial is described, including a computer simulation study to establish design properties. A hypothetical cohort-by-cohort example is given to illustrate how the method works during trial conduct. RESULTS: Because only a dose that is both safe and efficacious may be selected and the method combines phase I and phase II by integrating efficacy and toxicity to choose doses, it avoids the more time-consuming and expensive conventional approach of conducting a phase I trial based on toxicity alone followed by a phase II trial based on efficacy alone. This is especially useful in settings with low accrual rates, such as trials of tPA for pediatric acute ischemic stroke.
Assuntos
Isquemia Encefálica/tratamento farmacológico , Ensaios Clínicos como Assunto/métodos , Ensaios Clínicos como Assunto/normas , Fibrinolíticos/administração & dosagem , Acidente Vascular Cerebral/tratamento farmacológico , Ativador de Plasminogênio Tecidual/administração & dosagem , Adolescente , Fatores Etários , Teorema de Bayes , Isquemia Encefálica/fisiopatologia , Criança , Pré-Escolar , Protocolos Clínicos , Estudos de Coortes , Simulação por Computador , Relação Dose-Resposta a Droga , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Fibrinolíticos/efeitos adversos , Humanos , Lactente , Modelos Estatísticos , Projetos de Pesquisa , Acidente Vascular Cerebral/fisiopatologia , Ativador de Plasminogênio Tecidual/efeitos adversos , Resultado do TratamentoRESUMO
Non-adherence to epilepsy medications can interfere with treatment and may adversely affect clinical outcomes, although few studies have examined this relationship. This study assessed barriers and drivers to adherence, its impact on quality of life, and the importance of the patient-physician relationship to adherence. Two cross-sectional online surveys were conducted among 408 adult patients with epilepsy and 175 neurologists who treat epilepsy patients. Twenty-nine percent of patients self-reported being non-adherent to antiepileptic medications in the prior month. Non-adherence was found to be associated with reduced seizure control, lowered quality of life, decreased productivity, seizure-related job loss, and seizure-related motor vehicle accidents. Patient-oriented epilepsy treatment programs and clear communication strategies to promote self-management and patients' understanding of epilepsy are essential to maximizing treatment and quality of life outcomes while also minimizing economic costs.
Assuntos
Anticonvulsivantes/administração & dosagem , Epilepsia/tratamento farmacológico , Relações Médico-Paciente , Recusa do Paciente ao Tratamento , Acidentes de Trânsito/psicologia , Acidentes de Trânsito/tendências , Atividades Cotidianas/psicologia , Adolescente , Adulto , Anticonvulsivantes/efeitos adversos , Estudos Transversais , Epilepsia/epidemiologia , Epilepsia/psicologia , Feminino , Inquéritos Epidemiológicos , Humanos , Masculino , Pessoa de Meia-Idade , Motivação , Análise Multivariada , Educação de Pacientes como Assunto/estatística & dados numéricos , Qualidade de Vida/psicologia , Autocuidado/psicologia , Autocuidado/estatística & dados numéricos , Fatores Socioeconômicos , Recusa do Paciente ao Tratamento/psicologia , Recusa do Paciente ao Tratamento/estatística & dados numéricos , Desemprego/psicologia , Desemprego/estatística & dados numéricos , Estados UnidosRESUMO
Guidance for seizure emergency plans exists, although their impact and extent of use in patients with epilepsy are undetermined. This study's primary purpose was to measure the estimated use and content of seizure emergency plans. Secondary objectives included measuring: disease severity, quality of life, productivity, and adherence among patients with and without a plan. An online survey was conducted among 408 patients with epilepsy (ages 18-64) who took one or more antiepileptic drugs. Only 30% of patients reported having a plan, which included avoiding injury, notifying a physician, resting/relaxing, and seeking emergency assistance. Those with a plan were more likely to have experienced more seizures in the past year, to have missed school/work, to have incurred injury, to have visited the ER, to have been hospitalized, to fear additional seizures, and to have lost a job. Seizure emergency plans appear to be reserved for adults with more severe disease, but there may be clinical benefits to developing a plan for all adult patients with epilepsy.
Assuntos
Epilepsia/epidemiologia , Epilepsia/terapia , Pesquisas sobre Atenção à Saúde/métodos , Pesquisas sobre Atenção à Saúde/estatística & dados numéricos , Adolescente , Adulto , Estudos Transversais , Emergências , Epilepsia/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sistemas On-Line , Médicos/psicologia , Médicos/estatística & dados numéricos , Qualidade de Vida , Estudos Retrospectivos , Índice de Gravidade de Doença , Cônjuges/psicologia , Carga de Trabalho/estatística & dados numéricos , Adulto JovemRESUMO
OBJECTIVE: Patients diagnosed with delusions of infestation (DOI) at a psychodermatology clinic appeared to have a higher incidence of being prescribed narcotic or stimulant medications compared with the general dermatologic clinic population with chronic pruritic conditions. A retrospective study was conducted examining the correlation between patients with DOI and prescribed psychoactive medications. METHODS: Ninety-two patients with a diagnosis of DOI, seen at our University Psychodermatology Clinic, served as the study population. The comparison group (N=354) included dermatology patients seen at a dermatology clinic by the same dermatologist for itching, including adults seen for chronic pruritic conditions and contact dermatitis. For both groups, the reported use of any psychoactive prescription medications was noted. RESULTS: Patients with DOI were significantly more likely than other dermatology patients to receive prescriptions for narcotics [adjusted odds ratio (OR)=2.19; confidence interval (CI)=1.21-3.99) and stimulants (OR=5.44; CI=2.37-12.52). Patients with DOI were also more likely to be female (OR=2.49; CI=1.47-4.22) than patients who did not have such delusions. DISCUSSION: Few data are available concerning the etiology and management of DOI. Findings from this study indicated an association between the diagnosis of DOI and the prescribing of narcotics and stimulants, even when sex and age were taken into account. This information may be used to assist with the diagnosis of patients presenting with DOI and possible treatment options. It will be important to determine if these medications are a cause of the condition, or are merely correlated with other medical conditions.