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1.
Pediatr Res ; 2019 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-31578038

RESUMO

BACKGROUND: Privacy-protecting analytic approaches without centralized pooling of individual-level data, such as distributed regression, are particularly important for vulnerable populations, such as children, but these methods have not yet been tested in multi-center pediatric studies. METHODS: Using the electronic health data from 34 healthcare institutions in the National Patient-Centered Clinical Research Network (PCORnet), we fit 12 multivariable-adjusted linear regression models to assess the associations of antibiotic use <24 months of age with body mass index z-score at 48 to <72 months of age. We ran these models using pooled individual-level data and conventional multivariable-adjusted regression (reference method), as well as using the more privacy-protecting pooled summary-level intermediate statistics and distributed regression technique. We compared the results from these two methods. RESULTS: Pooled individual-level and distributed linear regression analyses produced virtually identical parameter estimates and standard errors. Across all 12 models, the maximum difference in any of the parameter estimates or standard errors was 4.4833 × 10-10. CONCLUSIONS: We demonstrated empirically the feasibility and validity of distributed linear regression analysis using only summary-level information within a large multi-center study of children. This approach could enable expanded opportunities for multi-center pediatric research, especially when sharing of granular individual-level data is challenging.

2.
EGEMS (Wash DC) ; 7(1): 11, 2019 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-30993145

RESUMO

Researchers often use prescribing data from electronic health records (EHR) or dispensing data from medication or medical claims to determine medication utilization. However, neither source has complete information on medication use. We compared antibiotic prescribing and dispensing records for 200,395 patients in the National Patient-Centered Clinical Research Network (PCORnet) Antibiotics and Childhood Growth Study. We stratified analyses by delivery system type [closed integrated (cIDS) and non-cIDS]; 90.5 percent and 39.4 percent of prescribing records had matching dispensing records, and 92.7 percent and 64.0 percent of dispensing records had matching prescribing records at cIDS and non-cIDS, respectively. Most of the dispensings without a matching prescription did not have same-day encounters in the EHR, suggesting they were medications given outside the institution providing data, such as those from urgent care or retail clinics. The sensitivity of prescriptions in the EHR, using dispensings as a gold standard, was 99.1 percent and 89.9 percent for cIDS and non-cIDS, respectively. Only 0.7 percent and 6.1 percent of patients at cIDS and non-cIDS, respectively, were classified as false-negative, i.e. entirely unexposed to antibiotics when they in fact had dispensings. These patients were more likely to have a complex chronic condition or asthma. Overall, prescription records worked well to identify exposure to antibiotics. EHR data, such as the data available in PCORnet, is a unique and vital resource for clinical research. Closing data gaps by understanding why prescriptions may not be captured can improve this type of data, making it more robust for observational research.

3.
Int J Obes (Lond) ; 43(6): 1202-1209, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30670848

RESUMO

OBJECTIVE: The benefits of antibiotic treatment during pregnancy are immediate, but there may be long-term risks to the developing child. Prior studies show an association between early life antibiotics and obesity, but few have examined this risk during pregnancy. SUBJECTS: To evaluate the association of maternal antibiotic exposure during pregnancy on childhood BMI-z at 5 years, we conducted a retrospective cohort analysis. Using electronic health record data from seven health systems in PCORnet, a national distributed clinical research network, we included children with same-day height and weight measures who could be linked to mothers with vital measurements during pregnancy. The primary independent variable was maternal outpatient antibiotic prescriptions during pregnancy (any versus none). We examined dose response (number of antibiotic episodes), spectrum and class of antibiotics, and antibiotic episodes by trimester. The primary outcome was child age- and sex-specific BMI-z at age 5 years. RESULTS: The final sample was 53,320 mother-child pairs. During pregnancy, 29.9% of mothers received antibiotics. In adjusted models, maternal outpatient antibiotic prescriptions during pregnancy were not associated with child BMI-z at age 5 years (ß = 0.00, 95% CI -0.03, 0.02). When evaluating timing during pregnancy, dose-response, spectrum and class of antibiotics, there were no associations of maternal antibiotics with child BMI-z at age 5 years. CONCLUSION: In this large observational cohort, provision of antibiotics during pregnancy was not associated with childhood BMI-z at 5 years.

4.
Pediatrics ; 142(6)2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30381474

RESUMO

: media-1vid110.1542/5839981580001PEDS-VA_2018-0290Video Abstract OBJECTIVES: To determine the association of antibiotic use with weight outcomes in a large cohort of children. METHODS: Health care data were available from 2009 to 2016 for 35 institutions participating in the National Patient-Centered Clinical Research Network. Participant inclusion required same-day height and weight measurements at 0 to <12, 12 to <30, and 48 to <72 months of age. We assessed the association between any antibiotic use at <24 months of age with BMI z score and overweight or obesity prevalence at 48 to <72 months (5 years) of age, with secondary assessments of antibiotic spectrum and age-period exposures. We included children with and without complex chronic conditions. RESULTS: Among 1 792 849 children with a same-day height and weight measurement at <12 months of age, 362 550 were eligible for the cohort. One-half of children (52%) were boys, 27% were African American, 18% were Hispanic, and 58% received ≥1 antibiotic prescription at <24 months of age. At 5 years, the mean BMI z score was 0.40 (SD 1.19), and 28% of children had overweight or obesity. In adjusted models for children without a complex chronic condition at 5 years, we estimated a higher mean BMI z score by 0.04 (95% confidence interval [CI] 0.03 to 0.05) and higher odds of overweight or obesity (odds ratio 1.05; 95% CI 1.03 to 1.07) associated with obtaining any (versus no) antibiotics at <24 months. CONCLUSIONS: Antibiotic use at <24 months of age was associated with a slightly higher body weight at 5 years of age.


Assuntos
Antibacterianos/administração & dosagem , Antibacterianos/efeitos adversos , Peso Corporal/efeitos dos fármacos , Peso Corporal/fisiologia , Obesidade Pediátrica/induzido quimicamente , Obesidade Pediátrica/epidemiologia , Índice de Massa Corporal , Pré-Escolar , Estudos de Coortes , Esquema de Medicação , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Obesidade Pediátrica/diagnóstico
5.
Acad Pediatr ; 18(5): 569-576, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29477481

RESUMO

OBJECTIVES: The National Patient-Centered Clinical Research Network (PCORnet) supports observational and clinical research using health care data. The PCORnet Antibiotics and Childhood Growth Study is one of PCORnet's inaugural observational studies. We sought to describe the processes used to integrate and analyze data from children across 35 participating institutions, the cohort characteristics, and prevalence of antibiotic use. METHODS: We included children in the cohort if they had at least one same-day height and weight measured in each of 3 age periods: 1) before 12 months, 2) 12 to 30 months, and 3) after 24 months. We distributed statistical queries that each institution ran on its local version of the PCORnet Common Data Model, with aggregate data returned for analysis. We defined overweight or obesity as age- and sex-specific body mass index ≥85th percentile, obesity ≥95th percentile, and severe obesity ≥120% of the 95th percentile. RESULTS: A total of 681,739 children met the cohort inclusion criteria, and participants were racially/ethnically diverse (24.9% black, 17.5% Hispanic). Before 24 months of age, 55.2% of children received at least one antibiotic prescription; 21.3% received a single antibiotic prescription; 14.3% received 4 or more; and 33.3% received a broad-spectrum antibiotic. Overweight and obesity prevalence was 27.6% at age 4 to <6 years (n = 362,044) and 36.2% at 9 to <11 years (n = 58,344). CONCLUSIONS: The PCORnet Antibiotics and Childhood Growth Study is a large national longitudinal observational study in a diverse population that will examine the relationship between early antibiotic use and subsequent growth patterns in children.


Assuntos
Antibacterianos/uso terapêutico , Uso de Medicamentos/estatística & dados numéricos , Sobrepeso/epidemiologia , Estatura , Índice de Massa Corporal , Peso Corporal , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Lactente , Estudos Longitudinais , Masculino , Assistência Centrada no Paciente , Estados Unidos/epidemiologia
6.
JMIR Res Protoc ; 6(12): e222, 2017 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-29208590

RESUMO

BACKGROUND: Although bariatric procedures are commonly performed in clinical practice, long-term data on the comparative effectiveness and safety of different procedures on sustained weight loss, comorbidities, and adverse effects are limited, especially in important patient subgroups (eg, individuals with diabetes, older patients, adolescents, and minority patients). OBJECTIVE: The objective of this study was to create a population-based cohort of patients who underwent 3 commonly performed bariatric procedures-adjustable gastric band (AGB), Roux-en-Y gastric bypass (RYGB), and sleeve gastrectomy (SG)-to examine the long-term comparative effectiveness and safety of these procedures in both adults and adolescents. METHODS: We identified adults (20 to 79 years old) and adolescents (12 to 19 years old) who underwent a primary (first observed) AGB, RYGB, or SG procedure between January 1, 2005 and September 30, 2015 from 42 health systems participating in the Clinical Data Research Networks within the National Patient-Centered Clinical Research Network (PCORnet). We extracted information on patient demographics, encounters with healthcare providers, diagnoses recorded and procedures performed during these encounters, vital signs, and laboratory test results from patients' electronic health records (EHRs). The outcomes of interest included weight change, incidence of major surgery-related adverse events, and diabetes remission and relapse, collected for up to 10 years after the initial bariatric procedure. RESULTS: A total of 65,093 adults and 777 adolescents met the eligibility criteria of the study. The adult subcohort had a mean age of 45 years and was predominantly female (79.30%, 51,619/65,093). Among adult patients with non-missing race or ethnicity information, 72.08% (41,248/57,227) were White, 21.13% (12,094/57,227) were Black, and 20.58% (13,094/63,637) were Hispanic. The average highest body mass index (BMI) recorded in the year prior to surgery was 49 kg/m2. RYGB was the most common bariatric procedure among adults (49.48%, 32,208/65,093), followed by SG (45.62%, 29,693/65,093) and AGB (4.90%, 3192/65,093). The mean age of the adolescent subcohort was 17 years and 77.5% (602/777) were female. Among adolescent patients with known race or ethnicity information, 67.3% (473/703) were White, 22.6% (159/703) were Black, and 18.0% (124/689) were Hispanic. The average highest recorded BMI in the year preceding surgery was 53 kg/m2. The majority of the adolescent patients received SG (60.4%, 469/777), followed by RYGB (30.8%, 239/777) and AGB (8.9%, 69/777). A BMI measurement (proxy for follow-up) was available in 84.31% (44,978/53,351), 68.09% (20,783/30,521), and 68.56% (7159/10,442) of the eligible adult patients at 1, 3, and 5 years of follow-up, respectively. The corresponding proportion was 82.0% (524/639), 49.9% (174/349), and 38.8% (47/121) in the adolescent subcohort. CONCLUSIONS: Our study cohort is one of the largest cohorts of patients with bariatric procedures in the United States. Patients are geographically and demographically diverse, which improves the generalizability of the research findings and allows examination of treatment effect heterogeneity. Ongoing and planned investigations will provide real-world evidence on the long-term benefits and risks of these most commonly used bariatric procedures in current clinical practice.

7.
Paediatr Perinat Epidemiol ; 29(4): 360-71, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26111445

RESUMO

BACKGROUND: We launched the Boston University Pregnancy Study Online (PRESTO) to assess the feasibility of carrying out an Internet-based preconception cohort study in the US and Canada. METHODS: We recruited female participants age 21-45 and their male partners through Internet advertisements, word of mouth, and flyers. Female participants were randomised with 50% probability to receive a subscription to FertilityFriend.com (FF), a web-based programme that collects real-time data on menstrual characteristics. We compared recruitment methods within PRESTO, assessed the cost-efficiency of PRESTO relative to its Danish counterpart (Snart-Gravid), and validated retrospectively reported date of last menstrual period (LMP) against the FF data. RESULTS: After 99 weeks of recruitment (2013-15), 2421 women enrolled; 1384 (57%) invited their male partners to participate, of whom 693 (50%) enrolled. Baseline characteristics were balanced across randomisation groups. Cohort retention was similar among those randomised vs. not randomised to FF (84% vs. 81%). At study enrollment, 56%, 22%, and 22% couples had been trying to conceive for < 3, 3-5, and ≥ 6 months, respectively. The cost per subject enrolled was $146 (2013 US$), which was similar to our companion Danish study and half that of a traditional cohort study. Among FF users who conceived, > 97% reported their LMP on the PRESTO questionnaire within 1 day of the LMP recorded via FF. CONCLUSIONS: Use of the Internet as a method of recruitment and follow-up in a North American preconception cohort study was feasible and cost-effective.


Assuntos
Fertilização , Cuidado Pré-Concepcional/estatística & dados numéricos , Adulto , Comportamento Contraceptivo , Análise Custo-Benefício , Dinamarca/epidemiologia , Estudos de Viabilidade , Feminino , Humanos , Internet , Masculino , América do Norte/epidemiologia , Educação de Pacientes como Assunto , Seleção de Pacientes , Cuidado Pré-Concepcional/métodos , Gravidez , Estudos Prospectivos , Projetos de Pesquisa , Inquéritos e Questionários
8.
Mol Reprod Dev ; 82(5): 387-96, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25914258

RESUMO

Preterm premature rupture of fetal membranes (PPROM) is associated with infection, and is one of the most common causes of preterm birth. Abnormal expression of biglycan and decorin, two extracellular matrix proteoglycans, leads to preterm birth and aberrant fetal membrane morphology and signaling in the mouse. In humans and mice, decorin dysregulation is associated with inflammation in PPROM. We therefore investigated the link between biglycan and decorin and inflammation in fetal membranes using mouse models of intraperitoneal Escherichia coli injections superimposed on genetic biglycan and decorin deficiencies. We assessed outcomes in vivo as well as in vitro using quantitative PCR, Western blotting, and enzyme-linked immunosorbent assays. Our results suggest that biglycan and decorin compensate for each other in the fetal membranes, but lose the ability to do so under inflammation, leading to decreased latency to preterm birth. Furthermore, our findings suggest that biglycan and decorin play discrete roles in fetal membrane signaling pathways during inflammation, leading to changes in the abundance of MMP8 and collagen α1VI, two components of the fetal membrane extracellular matrix that influence the pathophysiology of PPROM. In summary, these findings underline the importance of biglycan and decorin as targets for the manipulation of fetal membrane extracellular matrix stability in the context of inflammation.


Assuntos
Biglicano/genética , Decorina/genética , Membranas Extraembrionárias/metabolismo , Membranas Extraembrionárias/patologia , Inflamação/genética , Inflamação/patologia , Animais , Biglicano/metabolismo , Corioamnionite/genética , Corioamnionite/metabolismo , Corioamnionite/patologia , Decorina/metabolismo , Embrião de Mamíferos , Infecções por Escherichia coli/patologia , Feminino , Ruptura Prematura de Membranas Fetais/genética , Ruptura Prematura de Membranas Fetais/metabolismo , Ruptura Prematura de Membranas Fetais/patologia , Inflamação/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C3H , Camundongos Endogâmicos C57BL , Camundongos Knockout , Gravidez , Complicações Infecciosas na Gravidez/patologia
9.
Biol Reprod ; 91(5): 105, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25232019

RESUMO

Humans with Ehlers-Danlos syndrome, a subtype of which is caused by abnormal decorin expression, are at increased risk of preterm birth due to preterm premature rupture of fetal membranes (PPROM). In the mouse model, the absence of decorin leads to fetal membrane abnormalities, preterm birth, and dysregulation of decorin's downstream pathway components, including the transcription factor p-Smad-2. However, the role of decorin and p-Smad-2 in idiopathic human PPROM is unknown. Fetal membranes from 20-25 pregnancies per group were obtained as a cross-sectional sample of births at one institution between January 2010 and December 2012. The groups were term, preterm without PPROM, and preterm with PPROM. Immunohistochemical analysis of fetal membranes was performed for decorin and p-Smad-2 using localization and quantification assessment. Decorin expression is developmentally regulated in fetal membranes and is decreased in preterm birth with PPROM compared to preterm birth without PPROM. In preterm with PPROM samples, the presence of infection is associated with significant decorin downregulation compared to preterm with PPROM samples without infection. The preterm with PPROM group exhibited decreased p-Smad-2 staining compared to both the term controls and the preterm-without-PPROM group. Our findings suggest that dysregulation of decorin and its downstream pathway component p-Smad-2 occurs in fetal membranes during the second trimester in pathological pregnancies, thus supporting a role for decorin and p-Smad-2 in the pathophysiology of fetal membranes and adverse pregnancy outcomes. These findings may lead to the discovery of new targets for the diagnosis and treatment of PPROM.


Assuntos
Decorina/metabolismo , Membranas Extraembrionárias/metabolismo , Ruptura Prematura de Membranas Fetais/metabolismo , Proteína Smad2/metabolismo , Estudos de Casos e Controles , Estudos Transversais , Membranas Extraembrionárias/patologia , Feminino , Ruptura Prematura de Membranas Fetais/epidemiologia , Ruptura Prematura de Membranas Fetais/patologia , Idade Gestacional , Humanos , Masculino , Fosfoproteínas/metabolismo , Gravidez , Resultado da Gravidez/epidemiologia , Nascimento Prematuro/metabolismo , Nascimento Prematuro/patologia , Nascimento a Termo/metabolismo
10.
Matrix Biol ; 35: 266-75, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24373743

RESUMO

Preterm birth is the leading cause of newborn mortality in the United States and about one third of cases are caused by preterm premature rupture of fetal membranes, a complication that is frequently observed in patients with Ehlers-Danlos Syndrome. Notably, a subtype of Ehlers-Danlos Syndrome is caused by expression of abnormal biglycan and decorin proteoglycans. As compound deficiency of these two small leucine-rich proteoglycans is a model of preterm birth, we investigated the fetal membranes of Bgn(-/-); Dcn(-/-) double-null and single-null mice. Our results showed that biglycan signaling supported fetal membrane remodeling during early gestation in the absence of concomitant changes in TGFß levels. In late gestation, biglycan signaling acted in a TGFß-dependent manner to aid in membrane stabilization. In contrast, decorin signaling supported fetal membrane remodeling at early stages of gestation in a TGFß-dependent manner, and fetal membrane stabilization at later stages of gestation without changes in TGFß levels. Furthermore, exogenous soluble decorin was capable of rescuing the TGFß signaling pathway in fetal membrane mesenchymal cells. Collectively, these findings provide novel targets for manipulation of fetal membrane extracellular matrix stability and could represent novel targets for research on preventive strategies for preterm premature rupture of fetal membranes.


Assuntos
Biglicano/metabolismo , Decorina/metabolismo , Modelos Animais de Doenças , Membranas Extraembrionárias/fisiologia , Nascimento Prematuro/genética , Transdução de Sinais/fisiologia , Análise de Variância , Animais , Biglicano/genética , Western Blotting , Técnicas de Cultura de Células , Primers do DNA/genética , Decorina/genética , Síndrome de Ehlers-Danlos/genética , Ensaio de Imunoadsorção Enzimática , Membranas Extraembrionárias/metabolismo , Imuno-Histoquímica , Camundongos , Nascimento Prematuro/metabolismo , Fator de Crescimento Transformador beta/metabolismo
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