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1.
Br J Clin Pharmacol ; 88(3): 1321-1333, 2022 03.
Artículo en Inglés | MEDLINE | ID: mdl-34528282

RESUMEN

AIMS: Little is known regarding the pharmacokinetics and pharmacodynamics of menthol, the active ingredient in peppermint oil (PMO). Our aim was to investigate the pharmacokinetics of menthol at 3 dose levels in children and determine their effects on gut motility and transit. METHODS: Thirty children ages 7-12 years with functional abdominal pain underwent wireless motility capsule (WMC) testing. Approximately 1 week later they were randomized to 180, 360 or 540 mg of enteric coated PMO (10 participants per dose). Menthol pharmacokinetics were determined via blood sampling over 24 hours. They then took their respective dose of PMO (180 mg once, 180 mg twice or 180 mg thrice daily) for 1 week during which time the WMC test was repeated. RESULTS: Evaluable area under the plasma concentration vs. time curve (AUClast ) data were available in 29 of 30 participants. A direct linear relationship (apparent dose-proportionality for systemic menthol exposure) was observed between PMO dose and menthol systemic exposure with mean elimination half-life 2.1, 3.5 and 4.6 hours for the 180, 360 and 540 mg doses, respectively. WMC technical issues precluded complete motility data in all participants. Colonic transit time was inversely related to AUClast (P = .003); transit time in other regions was not affected. In contrast, stomach, small bowel and whole gut (but not colonic) contractility positively correlated with menthol AUClast (P < .05). CONCLUSION: Pharmacokinetics and pharmacodynamics of menthol derived from PMO demonstrated apparent dose-proportionality. A higher dose of PMO may be needed to achieve maximal gut response. www.clinicaltrials.gov NCT03295747.


Asunto(s)
Mentol , Aceites de Plantas , Dolor Abdominal/tratamiento farmacológico , Niño , Humanos , Intestino Delgado , Mentha piperita , Mentol/farmacología , Aceites de Plantas/farmacocinética
2.
BMC Pediatr ; 20(1): 30, 2020 01 22.
Artículo en Inglés | MEDLINE | ID: mdl-31969129

RESUMEN

BACKGROUND: Weight is critical for the medical management of infants; however, scales can be unavailable or inaccessible in some practice settings. We recently developed and validated a robust infant weight estimation method based on chest circumference (CC) and head circumference (HC). This study was designed to determine the human factors (HF) experience with, and predictive performance of, an infant weight estimation device that implements this method. METHODS: Prospective, multi-center, observational, masked study of 486 preterm and term infants (0-90 days) assessed by 15 raters. Raters measured the infant using calibrated scales/measures and masked versions of the device. Raters also evaluated critical tasks associated with device use. Mean error (ME) and mean percentage error (MPE) were used to assess predictive performance. RESULT: Among 486 infants enrolled (36.8 ± 4.0 weeks gestational age, 31.5 ± 28.6 days postnatal age), predicted weight correlated highly with actual weight (r = 0.97, ME: - 69 ± 257 g, MPE: - 1.3 ± 6.9%). Predicted weight was within 10 and 15% of actual weight in 86 and 99%, of infants. HF errors were low, 0.1-0.8% depending on task. In all cases raters were confident or very confident in their measurements. CONCLUSION: The device was statistically equivalent to the method on which it was based and approximated weight with acceptable variance from the true weight. HF data suggest the device is easy to use. This device can be used to estimate weight in infants when calibrated scales are impractical or unavailable.


Asunto(s)
Estudios Prospectivos , Adolescente , Adulto , Peso Corporal , Cefalometría , Niño , Preescolar , Análisis Factorial , Edad Gestacional , Humanos , Lactante , Recién Nacido , Persona de Mediana Edad , Adulto Joven
3.
Pediatr Blood Cancer ; 64(8)2017 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-28295989

RESUMEN

BACKGROUND: A liquid formulation of 6-mercaptopurine (6-MP) was recently approved by the Food and Drug Administration (Purixan®) based on bioavailability (BA) data from healthy adults. We examined the pharmacokinetics (PK) and BA of 6-MP in children with acute lymphoblastic leukemia (ALL) comparing a marketed tablet, two extemporaneously prepared liquid formulations, and data from the approved liquid formulation. METHODS: Twenty-two children (6-17 years) participated in a randomized two-way, crossover study of two cohorts. Group 1 (n = 11; five males) received a 5 mg/ml liquid formulation and the marketed 50 mg 6-MP tablet on separate occasions, and Group 2 (n = 11; five males) received a 50 mg/ml liquid formulation and the marketed tablet. The usual prescribed 6-MP dose (25-115 mg/m2 ) was given after an 8-hr fast. Serial blood samples were collected over 8 hr postdose. Plasma 6-MP concentrations were determined using a good laboratory practice (GLP)-validated liquid chromatography-tandem mass spectrometry method. PK parameters were calculated using noncompartmental analysis and compared within and between cohorts, and thiopurine methyltransferase (TPMT) genotype was analyzed. RESULTS: No patient had a TPMT genotype reflective of a poor metabolizer phenotype. Comparison of PK parameters between 5 and 50 mg/ml treatments revealed significant differences (P <0.05) in AUCN (where AUC is area under the curve), CmaxN , and Tmax . Comparisons within each group revealed significant differences in AUC0-∞ and Tmax in the 5 mg/ml group. CONCLUSIONS: Pharmacokinetic profiles of 6-MP established in healthy adults with the approved liquid formulation may not reflect the PK profile in children with ALL. Formulation-specific differences in PK may significantly impact the dose-exposure profile in these children and must be considered.


Asunto(s)
Antimetabolitos Antineoplásicos/administración & dosificación , Antimetabolitos Antineoplásicos/farmacocinética , Mercaptopurina/administración & dosificación , Mercaptopurina/farmacocinética , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Adolescente , Área Bajo la Curva , Niño , Preescolar , Cromatografía Liquida , Estudios Cruzados , Formas de Dosificación , Femenino , Humanos , Masculino , Espectrometría de Masas en Tándem
4.
Ann Hum Biol ; 44(8): 678-686, 2017 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-29037091

RESUMEN

BACKGROUND: Anthropometric data prove valuable for screening and monitoring various medical conditions. In young infants, however, only weight, length and head circumference are represented in publicly accessible databases. AIM: To characterise length and circumferential measures in pre-term and full-term infants up to 90 days post-natal. SUBJECTS AND METHODS: In eight US medical centres, trained raters recorded humeral, ulnar, femoral, tibial and fibular lengths along with mid-upper arm, mid-thigh, chest, abdominal and neck circumference. Data were pooled by post-menstrual age into 1-week intervals and population curves created using the lambda, mu and sigma (LMS) method. Goodness-of-fit was assessed by examining de-trended quantile-quantile plots, Q statistics and fitted centiles overlaid on empirical centiles. RESULTS: In total, 2097 infants were enrolled in this study with a mean ± SD gestational age and post-natal age of 37.1 ± 3.3 weeks and 27.3 ± 25.3 days, respectively. A re-scale option was used to describe all curves. The resultant models reliably characterised anthropometric measures from 33-52 weeks PMA, with less certainty at the extremes (27-55 weeks). CONCLUSION: The population curves generated under this investigation expand existing reference data on a comprehensive set of anthropometric traits in infants through the first 90 days post-natal.


Asunto(s)
Antropometría , Recién Nacido/crecimiento & desarrollo , Lactante , Femenino , Edad Gestacional , Humanos , Recien Nacido Prematuro/crecimiento & desarrollo , Masculino , Estados Unidos
5.
Mycopathologia ; 182(1-2): 67-76, 2017 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-27502504

RESUMEN

Countless observational studies conducted over the last century reveal that dermatophytes infect humans of every age, race, gender, and socioeconomic status with strikingly high rates. The curious disparity in dermatophyte infection patterns observed within and between populations has led countless investigators to explore whether genetics underlie a susceptibility to, or confer protection against, dermatophyte infections. This paper examines the data that offer a link between genetics and dermatophytoses and discusses the underlying mechanisms that support these observations.


Asunto(s)
Predisposición Genética a la Enfermedad , Tiña/genética , Humanos
6.
Pediatr Emerg Care ; 33(8): 548-552, 2017 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-28777773

RESUMEN

OBJECTIVE: We compared performance characteristics of 7 weight estimation methods examining predictive performance and human factors errors. METHODS: This was a prospective study of 80 emergency care providers (raters) and 80 children aged 2 months to 16 years. Raters estimated weights in 5 children with the following 7 strategies: visual estimation, Advanced Pediatric Life Support, Luscombe and Owens, Broselow tape, devised weight estimation method, 2D Mercy TAPE (2DT), and 3D Mercy TAPE (3DT). Quantitative errors were determined by checking rater values against values returned with optimal method use. RESULTS: Four hundred rater-child pairings generated 2800 weight estimates. For all methods, rater-estimated weights were less accurate than weights derived by optimal application. Skill-based, perception, and judgment/decision error were observed. For visual estimation, weights were underestimated in most children. For Advanced Pediatric Life Support/Luscombe and Owens, order of operations markedly impacted errors with 23% of calculations requiring addition first performed incorrectly versus 9% of calculations requiring multiplication first. For Broselow tape, only 63% of cases were eligible for estimation with this device, yet raters assigned a weight in 96% of cases. For Devised Weight Estimation Method, 96% of overweight and 48% of obese children were classified as slim or average. For 2DT/3DT, the 2DT was prone to more errors most commonly use of the wrong side of the device (24%). The impact of rater characteristics on error was most pronounced for methods requiring calculation. CONCLUSIONS: Skill-based, perception, or judgment errors were observed in more than 1 of 20 cases. No singular strategy was used with 100% accuracy.


Asunto(s)
Peso Corporal , Precisión de la Medición Dimensional , Tratamiento de Urgencia/métodos , Adolescente , Adulto , Factores de Edad , Antropometría/métodos , Niño , Preescolar , Competencia Clínica , Femenino , Humanos , Lactante , Masculino , Persona de Mediana Edad , Estudios Prospectivos
7.
Clin Infect Dis ; 62(6): 761-769, 2016 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-26658057

RESUMEN

Tuberculosis is a major cause of morbidity and mortality in women of childbearing age (15-44 years). Despite increased tuberculosis risk during pregnancy, optimal clinical treatment remains unclear: safety, tolerability, and pharmacokinetic data for many tuberculosis drugs are lacking, and trials of promising new tuberculosis drugs exclude pregnant women. To advance inclusion of pregnant and postpartum women in tuberculosis drug trials, the US National Institutes of Health convened an international expert panel. Discussions generated consensus statements (>75% agreement among panelists) identifying high-priority research areas during pregnancy, including: (1) preventing progression of latent tuberculosis infection, especially in women coinfected with human immunodeficiency virus; (2) evaluating new agents/regimens for treatment of multidrug-resistant tuberculosis; and (3) evaluating safety, tolerability and pharmacokinetics of tuberculosis drugs already in use during pregnancy and postpartum. Incorporating pregnant women into clinical trials would extend evidence-based tuberculosis prevention and treatment standards to this special population.


Asunto(s)
Antituberculosos/uso terapéutico , Ensayos Clínicos como Asunto/métodos , Tuberculosis Latente/tratamiento farmacológico , Periodo Posparto , Tuberculosis Resistente a Múltiples Medicamentos/prevención & control , Tuberculosis/tratamiento farmacológico , Tuberculosis/prevención & control , Adulto , Antituberculosos/farmacocinética , Ensayos Clínicos como Asunto/ética , Ensayos Clínicos como Asunto/legislación & jurisprudencia , Femenino , Infecciones por VIH/tratamiento farmacológico , Humanos , Tuberculosis Latente/sangre , Tuberculosis Latente/microbiología , Embarazo , Tuberculosis/microbiología , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Tuberculosis Resistente a Múltiples Medicamentos/microbiología , Estados Unidos
8.
Pediatr Transplant ; 20(3): 443-8, 2016 May.
Artículo en Inglés | MEDLINE | ID: mdl-26854326

RESUMEN

TDM is intended to limit unintended consequences of drugs with narrow therapeutic indices. However, the application of different sampling strategies and pharmacokinetic approaches results in different dosing recommendations and ostensibly different outcomes. TDM approaches for intravenous busulfan dose individualization employ compartmental or non-compartmental modeling with anywhere from three to seven drug levels. This investigation was designed to examine the differences in dosing recommendations that arise in children (n = 30) when five different TDM approaches were employed. Significant differences in recommended doses between modeling strategies were observed. More importantly, the recommendations were discordant in 13 cases with at least one model recommending a dose adjustment in the opposite direction relative to the remaining models. The mathematical differences introduced by the application of different TDM approaches are not purely academic. Unification of busulfan TDM approaches should be considered to mitigate inconsistently applied dose adjustment, and facilitate comparisons of outcome, between clinical centers.


Asunto(s)
Busulfano/administración & dosificación , Busulfano/farmacocinética , Monitoreo de Drogas/métodos , Trasplante de Células Madre Hematopoyéticas/métodos , Acondicionamiento Pretrasplante/métodos , Área Bajo la Curva , Artefactos , Niño , Relación Dosis-Respuesta a Droga , Humanos , Infusiones Intravenosas , Modelos Teóricos , Farmacocinética , Estudios Retrospectivos , Factores de Tiempo , Resultado del Tratamiento
9.
Drug Metab Dispos ; 42(10): 1773-9, 2014 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-25097227

RESUMEN

Recent in vitro data obtained in our laboratory revealed similarities between baboons and humans in the biotransformation of bupropion (BUP) by both hepatic and placental microsomes. These data supported the use of baboons to study BUP biotransformation during pregnancy. The aim of this investigation was to determine the pharmacokinetics of BUP in baboons during pregnancy and postpartum, as well as fetal exposure to the drug after intravenous administration. Pregnant baboons (n = 5) received a single intravenous bolus dose of bupropion hydrochloride (1 mg/kg) at gestational ages 94-108 days (midpregnancy), 142-156 days (late pregnancy), and 6 weeks postpartum. Blood and urine samples were collected for 12 and 24 hours, respectively. The concentrations of BUP, hydroxybupropion (OH-BUP), threohydrobupropion, and erythrohydrobupropion in plasma were determined by liquid chromatography-tandem mass spectrometry. Relative to the postpartum period, the average midpregnancy clearance of BUP trended higher (3.6 ± 0.15 versus 2.7 ± 0.28 l/h per kg) and the average C(max) (294 ± 91 versus 361 ± 64 ng/ml) and the area under the curve (AUC) of BUP values (288 ± 22 versus 382 ± 42 h·ng/ml) trended lower. AUC(OH-BUP) also tended to be lower midpregnancy compared with postpartum (194 ± 76 versus 353 ± 165 h·ng/ml). Whereas the observed trend toward increased clearance of BUP during baboon pregnancy could be associated with a pregnancy-induced increase in its biotransformation, the trend toward increased renal elimination of OH-BUP may overshadow any corresponding change in the hydroxylation activity of CYP2B.


Asunto(s)
Bupropión/metabolismo , Bupropión/farmacocinética , Papio cynocephalus/metabolismo , Preñez/metabolismo , Animales , Biotransformación , Bupropión/sangre , Bupropión/orina , Femenino , Papio cynocephalus/sangre , Papio cynocephalus/orina , Periodo Posparto/sangre , Periodo Posparto/metabolismo , Periodo Posparto/orina , Embarazo , Preñez/sangre , Preñez/orina
10.
BMC Public Health ; 14: 270, 2014 Mar 21.
Artículo en Inglés | MEDLINE | ID: mdl-24650051

RESUMEN

BACKGROUND: This study evaluated the performance of a new weight estimation strategy (Mercy Method) with four existing weight-estimation methods (APLS, ARC, Broselow, and Nelson) in children from Ouelessebougou, Mali. METHODS: Otherwise healthy children, 2 mos to 16 yrs, were enrolled and weight, height, humeral length (HL) and mid-upper arm circumference (MUAC) obtained by trained raters. Weight estimation was performed as described for each method. Predicted weights were regressed against actual weights. Agreement between estimated and actual weight was determined using Bland-Altman plots with log-transformation. Predictive performance of each method was assessed using residual error (RE), percentage error (PE), root mean square error (RMSE), and percent predicted within 10, 20 and 30% of actual weight. RESULTS: 473 children (8.1±4.8 yr, 25.1±14.5 kg, 120.9±29.5 cm) participated in this study. The Mercy Method (MM) offered the best correlation between actual and estimated weight when compared with the other methods (r2=0.97 vs. 0.80-0.94). The MM also demonstrated the lowest ME (0.06 vs. 0.92-4.1 kg), MPE (1.6 vs. 7.8-19.8%) and RMSE (2.6 vs. 3.0-6.7). Finally, the MM estimated weight within 20% of actual for nearly all children (97%) as opposed to the other methods for which these values ranged from 50-69%. CONCLUSIONS: The MM performed extremely well in Malian children with performance characteristics comparable to those observed for U.S and India and could be used in sub-Saharan African children without modification extending the utility of this weight estimation strategy.


Asunto(s)
Antropometría/métodos , Peso Corporal , Pesos y Medidas Corporales/métodos , Pesos y Medidas Corporales/estadística & datos numéricos , Adolescente , Pesos y Medidas Corporales/normas , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Malí , Variaciones Dependientes del Observador , Estudios Prospectivos , Reproducibilidad de los Resultados
11.
Ann Emerg Med ; 62(4): 332-339.e6, 2013 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-23602655

RESUMEN

STUDY OBJECTIVE: We assessed the performance of 2 new devices (2D- and 3D-Mercy TAPE) to implement the Mercy Method for pediatric weight estimation and contrasted their accuracy with the Broselow method. METHODS: We enrolled children aged 2 months through 16 years in this prospective, multicenter, observational study. Height/length, weight, humeral length, and mid-upper arm circumference were obtained for each child, using calibrated scales and measures. We then made measurements with blinded versions of the 2D- and 3D-TAPEs. Using height/length data, we calculated the weight estimated by the Broselow method. We contrasted measures with mean error, mean percentage error, and percentage predicted within 10% and 20% of actual. RESULTS: Six hundred twenty-four participants (median 8.5 years, 27.6 kg, 17.3 kg/m(2)) completed the study. Mean error was 0.3 kg (mean percentage error 1.6%), 0.2 kg (mean percentage error 1.9%), and -1.3 kg (mean percentage error -4.1%) for 2D-, 3D-, and Broselow, respectively. Concordance between both TAPE devices and the Mercy Method was greater than 0.99. The proportion of children predicted within 10% and 20% of actual weight was 76% and 98% for the 2D-TAPE and 65% and 93% for the 3D-TAPE. Excluding the 209 (33%) children who were too tall for the device, Broselow predictions were within 10% and 20% of actual weight in 59% and 91%. CONCLUSION: The 2D- and 3D-Mercy TAPEs outperform the Broselow tape for pediatric weight estimation and can be used in a wider range of children.


Asunto(s)
Antropometría/instrumentación , Peso Corporal , Adolescente , Antropometría/métodos , Índice de Masa Corporal , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Estudios Prospectivos , Reproducibilidad de los Resultados
12.
Eur J Clin Pharmacol ; 69(4): 851-7, 2013 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-23052410

RESUMEN

PURPOSE: Acetaminophen (APAP) protein adducts are a biomarker of APAP metabolism, reflecting oxidation of APAP and generation of the reactive metabolite N-acetyl-p-benzoquinone imine. High levels of adducts correspond to liver toxicity in patients with APAP-related acute liver failure. Adduct formation following low-dose exposure to APAP has not been well studied. APAP protein adducts were measured in blood samples collected from fasted individuals who participated in a crossover study of APAP (80 mg/kg) comparing extended release (ER) and immediate release (IR) formulations. METHODS: Adducts were quantified in all postdose blood samples using a validated high-performance liquid chromatography electrochemical detection (HPLC-EC) assay. RESULTS: Comparison of pharmacokinetic parameters for adducts did not reveal significant differences between ER and IR formulations, with one exception. Formation rates for adducts were faster for IR than the ER formulation (0.420 ± 0.157 vs. 0.203 ± 0.080 1/h), respectively. Maximum plasma concentrations (Cmax) of adducts for IR and ER were 0.108 (±0.020) and 0.100 (±0.028) nmol/ml serum, respectively, and were two orders of magnitude lower than adduct levels previously reported in adults with acute liver failure secondary to APAP. CONCLUSIONS: APAP protein adducts are rapidly formed following nontoxic ingestion of APAP at levels significantly lower than those associated with acute liver failure.


Asunto(s)
Acetaminofén/análogos & derivados , Acetaminofén/sangre , Analgésicos no Narcóticos/sangre , Proteínas/metabolismo , Acetaminofén/administración & dosificación , Acetaminofén/química , Adolescente , Adulto , Analgésicos no Narcóticos/administración & dosificación , Analgésicos no Narcóticos/química , Cromatografía Líquida de Alta Presión , Estudios Cruzados , Cisteína/metabolismo , Preparaciones de Acción Retardada , Relación Dosis-Respuesta a Droga , Ayuno , Femenino , Humanos , Masculino , Unión Proteica , Adulto Joven
13.
Pediatr Rev ; 34(6): 258-69, 2013 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-23729775

RESUMEN

OBJECTIVES: After reading this article, the reader should be able to 1. Realize that volume of distribution, elimination clearance, and elimination half-life are crucial parameters of pharmacokinetics that must be understood to determine clinical pharmacologic decisions.2. Know that drug disposition is a complicated process of absorption, distribution,metabolism, and excretion. 3. Understand that any abnormality in absorption, distribution, metabolism, and/or excretion can potentially affect the efficacy or toxicity of a drug. 4. Understand that the anatomical and physiologic changes during development must be considered in predicting age-dependent changes in drug disposition.


Asunto(s)
Preparaciones Farmacéuticas , Farmacocinética , Absorción , Disponibilidad Biológica , Niño , Semivida , Humanos , Distribución Tisular
14.
Clin Transl Sci ; 15(5): 1155-1166, 2022 05.
Artículo en Inglés | MEDLINE | ID: mdl-35099109

RESUMEN

The 13 C-pantoprazole breath test (PAN-BT) is a safe, noninvasive, in vivo CYP2C19 phenotyping probe for adults. Our objective was to evaluate PAN-BT performance in children, with a focus on discriminating individuals who, according to guidelines from the Clinical Pharmacology Implementation Consortium (CPIC), would benefit from starting dose escalation versus reduction for proton pump inhibitors (PPIs). Children (n = 65, 6-17 years) genotyped for CYP2C19 variants *2, *3, *4, and *17 received a single oral dose of 13 C-pantoprazole. Plasma concentrations of pantoprazole and its metabolites, and changes in exhaled 13 CO2 (termed delta-over-baseline or DOB), were measured 10 times over 8 h using high performance liquid chromatography with ultraviolet detection and spectrophotometry, respectively. Pharmacokinetic parameters of interest were generated and DOB features derived using feature engineering for the first 180 min postadministration. DOB features, age, sex, and obesity status were used to run bootstrap analysis at each timepoint (Ti ) independently. For each iteration, stratified samples were drawn based on genotype prevalence in the original cohort. A random forest was trained, and predictive performance of PAN-BT was evaluated. Strong discriminating ability for CYP2C19 intermediate versus normal/rapid metabolizer phenotype was noted at DOBT30 min (mean sensitivity: 0.522, specificity: 0.784), with consistent model outperformance over a random or a stratified classifier approach at each timepoint (p < 0.001). With additional refinement and investigation, the test could become a useful and convenient dosing tool in clinic to help identify children who would benefit most from PPI dose escalation versus dose reduction, in accordance with CPIC guidelines.


Asunto(s)
Pruebas Respiratorias , Inhibidores de la Bomba de Protones , 2-Piridinilmetilsulfinilbencimidazoles/farmacocinética , Adulto , Pruebas Respiratorias/métodos , Niño , Citocromo P-450 CYP2C19/genética , Citocromo P-450 CYP2C19/metabolismo , Genotipo , Humanos , Pantoprazol , Inhibidores de la Bomba de Protones/farmacocinética
15.
Clin Transl Sci ; 15(4): 1036-1049, 2022 04.
Artículo en Inglés | MEDLINE | ID: mdl-35048535

RESUMEN

Peppermint oil (PMO) is effective in the treatment of functional abdominal pain disorders, but its mechanism of action is unclear. Evidence suggests PMO has microbicidal activity. We investigated the effect of three different doses of PMO on gut microbiome composition. Thirty children (7-12 years of age) with functional abdominal pain provided a baseline stool sample prior to randomization to 180, 360, or 540 mg of enteric coated PMO (10 participants per dose). They took their respective dose of PMO (180 mg once, 180 mg twice, or 180 mg thrice daily) for 1 week, after which the stool collection was repeated. Baseline and post-PMO stools were analyzed for microbiome composition. There was no difference in alpha diversity of the gut microbiome between the baseline and post-PMO treatment. Principal coordinate analysis revealed no significant difference in overall bacterial composition between baseline and post-PMO samples, as well as between the PMO dose groups. However, the very low abundant Collinsella genus and three operational taxonomic units (one belonging to Collinsella) were significantly different in samples before and after PMO treatment. The Firmicutes/Bacteroidetes ratio was lower in children who received 540 mg of PMO compared to the 180 mg and 360 mg dose groups (p = 0.04). Network analysis revealed separation between pre- and post-PMO fecal samples with the genus Collinsella driving the post-PMO clusters. PMO administration appeared to impact only low abundance bacteria. The 540 mg PMO dose differentially impacted the Firmicutes/Bacteroidetes ratio. A higher dose and/or longer duration of treatment might yield different results.


Asunto(s)
Microbioma Gastrointestinal , Dolor Abdominal/tratamiento farmacológico , Bacteroidetes , Niño , Heces/microbiología , Humanos , Mentha piperita , Aceites de Plantas
16.
Drug Des Devel Ther ; 15: 2815-2830, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34234413

RESUMEN

Tuberculosis (TB) is the most deadly infectious disease globally. Although most individuals achieve a cure, a substantial portion develop multi-drug resistant TB which is exceedingly difficult to treat, and the number of effective agents is dwindling. Development of new anti-tubercular medications is imperative to combat existing drug resistance and accelerate global eradication of TB. Pretomanid (PA-824) represents one of the newest drug classes (ie, nitroimidazooxazines) approved in 2019 by the United States Food and Drug Administration as part of a multi-drug regimen (with bedaquiline and linezolid, BPaL) and recommended by the World Health Organization (WHO) to treat extensively-resistant (XR-TB) and multi-drug resistant tuberculosis (MDR-TB). Approval was granted through the FDA's Limited Population Pathway for Antibacterial and Antifungal Drugs, which accelerates approval for antimicrobial drugs used to treat life-threatening or serious infections in a limited population with unmet need. This review details the pharmacology, efficacy, and safety of this new agent and describes evidence to date for its role in the treatment of drug resistant TB including published, ongoing, and planned studies.


Asunto(s)
Antituberculosos/administración & dosificación , Nitroimidazoles/administración & dosificación , Tuberculosis Resistente a Múltiples Medicamentos/tratamiento farmacológico , Animales , Antituberculosos/efectos adversos , Antituberculosos/farmacología , Quimioterapia Combinada , Tuberculosis Extensivamente Resistente a Drogas/tratamiento farmacológico , Tuberculosis Extensivamente Resistente a Drogas/microbiología , Humanos , Nitroimidazoles/efectos adversos , Nitroimidazoles/farmacología , Tuberculosis Resistente a Múltiples Medicamentos/microbiología
17.
Clin Transl Sci ; 14(6): 2095-2098, 2021 11.
Artículo en Inglés | MEDLINE | ID: mdl-34191409

RESUMEN

Individuals who identify as Black, indigenous, and people of color face well-documented health disparities. A root cause is the lack of empiric evidence for or against the use of various treatments in their medical management. This communication proposes a new benchmarking strategy for evaluating racial and ethnic representation in clinical research that can be compared across institutions with the intent of increasing accountability for diversity and inclusion among organizations that conduct clinical research.


Asunto(s)
Academias e Institutos , Diversidad Cultural , Empleo , Benchmarking , Ensayos Clínicos como Asunto
18.
Paediatr Drugs ; 23(1): 95-104, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33236188

RESUMEN

BACKGROUND: Medication refusal in children is largely driven by aversive taste profiles, which in turn influence adherence and therapeutic outcomes. However, there are no standardized methods for evaluating taste in young children. This study compares facial recognition technology with three hedonic visual scales in this population. METHODS: Children, 3-7 years of age, were enrolled with informed parental permission into an institutional review board-approved, double-blind, randomized investigation. Each child received three test articles: prednisone (bitter), simple syrup (sweet), and filtered water (neutral), with an appropriate washout. Facial recognition software (Noldus FaceReader 7) recorded facial expression and intensity for 30-60 s after administration. Participants subsequently rated taste using three hedonic scales (5-point Sjövall and 5- and 3-point TASTY) and responded to simple questions on their perception of the test article. Repeated measures analysis of variance and multiple regression analysis were used to explore associations between palatability measures. RESULTS: Twelve children (seven males: ten white and two black) completed the study without adverse effects. There were no significant differences in participant characteristics by randomization sequence. The three hedonic scales tracked similarly for each test substance, with correlations between the 5-point scales (r = 0.899) comparable to those between the 3- and 5-point scales (r = 0.860-0.903). Hedonic scales appeared more reliable in assessing taste response than facial recognition, which did not effectively discriminate positive and negative responses. CONCLUSIONS: Our experience suggests that the TASTY scales appear to offer the greatest promise for assessing palatability in future clinical use.


Asunto(s)
Evaluación de Necesidades/normas , Gusto/fisiología , Niño , Preescolar , Método Doble Ciego , Femenino , Humanos , Masculino , Proyectos Piloto
19.
Pediatrics ; 147(5)2021 05.
Artículo en Inglés | MEDLINE | ID: mdl-33846237

RESUMEN

BACKGROUND AND OBJECTIVES: The Best Pharmaceuticals for Children Act (BPCA) incentivizes the study of on-patent medicines in children and mandates that the National Institutes of Health sponsor research on off-patent drugs important to pediatric therapeutics. Failing to enroll cohorts that reflect the pediatric population at large restricts the generalizability of such studies. In this investigation, we evaluate racial and ethnic minority representation among participants enrolled in BPCA-sponsored studies. METHODS: Data were obtained for all participants enrolled in 33 federally funded studies of drugs and devices conducted from 2008 through June 2020. Observed racial and ethnic distributions were compared with expected distributions by sampling Census data at the same geographic frequency as in the studies. Racial and ethnic enrollment was examined by demography, geography, study type, study burden, and expected bias. Standard descriptive statistics, χ2, generalized linear models, and linear regression were applied. RESULTS: A total of 10 918 participants (51% male, 6.6 ± 8.2 years) were enrolled across 46 US states and 4 countries. Studies ranged from treatment outcome reviews to randomized, placebo-controlled trials. Minority enrollment was comparable to, or higher than, expected (+0.1% to +2.6%) for all groups except Asian Americans (-3.7%, P < .001). American Indian and Alaskan Native and multiracial enrollment significantly increased over the evaluation period (P < .01). There were no significant differences in racial distribution as a function of age or sex, although differences were observed on the basis of geography, study type, and study burden. CONCLUSIONS AND RELEVANCE: This study revealed no evidence of racial and ethnic bias in enrollment for pediatric studies conducted with funding from BPCA, fulfilling the legislation's expectation to ensure adequate representation of all children.


Asunto(s)
Ensayos Clínicos como Asunto/economía , Ensayos Clínicos como Asunto/legislación & jurisprudencia , Etnicidad/estadística & datos numéricos , Preparaciones Farmacéuticas/economía , Grupos Raciales/estadística & datos numéricos , Adolescente , Canadá , Niño , Preescolar , Inglaterra , Femenino , Humanos , Lactante , Israel , Legislación de Medicamentos , Masculino , Singapur , Estados Unidos , Adulto Joven
20.
Med Mycol ; 48(3): 480-5, 2010 May.
Artículo en Inglés | MEDLINE | ID: mdl-19824879

RESUMEN

Tinea capitis gladiatorum and tinea corporis gladiatorum caused by the anthropophilic dermatophyte Trichophyton tonsurans are well-known clinical entities in individuals involved in combat sports, e.g., wrestlers and judo practitioners. We present an outbreak of Trichophyton tonsurans tinea capitis gladiatorum among wrestlers at a boarding school in Adana, Turkey. Fourteen of the 29 wrestlers examined (48.3%) harbored the pathogen, including eight asymptomatic scalp carriers, five with tinea capitis superficialis, and one asymptomatic trunk carrier. Dermatophytes were isolated from samples of the neck (1), nape (1), trunk (3) and inguinal area (2) in four of the five tinea capitis cases. A total of five inanimate objects, i.e., two wrestling mats, two pillowcases, and one sheet were also found to be positive for T. tonsurans. Mixed-marker strain typing examining 24 sequence variations in 12 gene loci confirmed that the outbreak was caused by a single strain of T. tonsurans.


Asunto(s)
Atletas , Brotes de Enfermedades , Tiña del Cuero Cabelludo/epidemiología , Tiña del Cuero Cabelludo/microbiología , Trichophyton/clasificación , Trichophyton/aislamiento & purificación , Adolescente , Niño , Dermatoglifia del ADN , ADN de Hongos/química , ADN de Hongos/genética , Microbiología Ambiental , Proteínas Fúngicas/genética , Genotipo , Humanos , Instituciones Académicas , Piel/microbiología , Estudiantes , Trichophyton/genética , Turquía/epidemiología
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