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3.
Gut ; 70(6): 1037-1043, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-32895335

RESUMO

OBJECTIVE: Our objective was to estimate the relative risk of IBD among first-generation and second-generation immigrants in Denmark compared with native Danes. DESIGN: Using national registries, we established a cohort of Danish residents between 1977 and 2018. Cohort members with known country of birth were followed for Crohn's disease (CD) and ulcerative colitis (UC) diagnoses. Incidence rate ratios (IRRs) served as measures of relative risk and were calculated by log-linear Poisson regression, using rates among native Danes as reference, stratified by IBD risk in parental country of birth, and among first-generation immigrants by age at immigration and duration of stay in Denmark. RESULTS: Among 8.7 million Danes, 4156 first-generation and 898 second-generation immigrants were diagnosed with CD or UC. Overall, comparing first-generation immigrants with native Danes, the IRR was 0.80 (95% CI 0.76 to 0.84) for CD and 0.74 (95% CI 0.71 to 0.77) for UC. The IRR of IBD increased with ≥20 years stay in Denmark. The IRR of CD increased with immigration at ≥40 years of age. Comparing second-generation immigrants with native Danes, the IRR of IBD was 0.97 (95% CI 0.91 to 1.04). There was significant interaction with sex, with higher IRR of IBD in male than in female immigrants. CONCLUSION: Relative to native Danish men and women, IBD risk among first-generation immigrants was lower, reflected the risk in their parental country of birth and increased with ≥20 years stay in Denmark. For second-generation immigrants, relative risk of IBD was lower only among women. These complex patterns suggest the role of environmental IBD risk factors.


Assuntos
Colite Ulcerativa/etnologia , Doença de Crohn/etnologia , Emigrantes e Imigrantes/estatística & dados numéricos , População Branca/estatística & dados numéricos , Adolescente , Adulto , Fatores Etários , Idoso , Criança , Pré-Escolar , Estudos de Coortes , Dinamarca/epidemiologia , Características da Família/etnologia , Feminino , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Medição de Risco , Fatores de Tempo , Adulto Jovem
4.
Inflamm Bowel Dis ; 27(3): 364-370, 2021 02 16.
Artigo em Inglês | MEDLINE | ID: mdl-32405642

RESUMO

BACKGROUND: Prior studies have identified racial disparities in the treatment and outcomes of inflammatory bowel disease (IBD). These disparities could be secondary to differences in biology, care delivery, or access to appropriate therapy. The primary aim of this study was to compare medication use among Medicaid-insured black and white patients with IBD, given uniform access to gastroenterologists and therapies. METHODS: We analyzed Medicaid Analytic eXtract data from 4 states (California, Georgia, North Carolina, and Texas) between 2006 and 2011. We compared the use of IBD-specific therapies, including analyses of postoperative therapy among patients with Crohn disease (CD). We performed bivariate analyses and multivariable logistic regression, adjusting for potential confounders. RESULTS: We identified 14,735 patients with IBD (4672 black [32%], 8277 with CD [58%]). In multivariable analysis, there was no significant difference in the odds of anti-tumor necrosis factor use by race for CD (adjusted odds ratio [aOR] = 1.13; 95% confidence interval [CI], 0.99-1.28] or ulcerative colitis (aOR = 1.12; 95% CI, 0.96-1.32). Black patients with CD were more likely than white patients to receive combination therapy (aOR = 1.50; 95% CI, 1.15-1.96), and black patients were more likely than white patients to receive immunomodulator monotherapy after surgery for CD (31% vs 18%; P = 0.004). CONCLUSIONS: In patients with Medicaid insurance, where access to IBD-specific therapy should be similar for all individuals, there was no significant disparity by race in the utilization of IBD-specific therapies. Disparities in IBD treatment discussed in prior literature seem to be driven by socioeconomic or other issues affecting access to care.


Assuntos
Produtos Biológicos , Colite Ulcerativa , Doença de Crohn , Negro ou Afro-Americano , Produtos Biológicos/uso terapêutico , Doença Crônica , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/etnologia , Doença de Crohn/tratamento farmacológico , Doença de Crohn/etnologia , Disparidades em Assistência à Saúde , Humanos , Seguro Saúde , Medicaid , Estados Unidos/epidemiologia , População Branca
5.
Gastroenterology ; 160(5): 1546-1557, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33359885

RESUMO

BACKGROUND AND AIMS: Polygenic risk scores (PRS) may soon be used to predict inflammatory bowel disease (IBD) risk in prevention efforts. We leveraged exome-sequence and single nucleotide polymorphism (SNP) array data from 29,358 individuals in the multiethnic, randomly ascertained health system-based BioMe biobank to define effects of common and rare IBD variants on disease prediction and pathophysiology. METHODS: PRS were calculated from European, African American, and Ashkenazi Jewish (AJ) reference case-control studies, and a meta-GWAS run using all three association datasets. PRS were then combined using regression to assess which combination of scores best predicted IBD status in European, AJ, Hispanic, and African American cohorts in BioMe. Additionally, rare variants were assessed in genes associated with very early-onset IBD (VEO-IBD), by estimating genetic penetrance in each BioMe population. RESULTS: Combining risk scores based on association data from distinct ancestral populations improved IBD prediction for every population in BioMe and significantly improved prediction among European ancestry UK Biobank individuals. Lower predictive power for non-Europeans was observed, reflecting in part substantially lower African IBD case-control reference sizes. We replicated associations for two VEO-IBD genes, ADAM17 and LRBA, with high dominant model penetrance in BioMe. Autosomal recessive LRBA risk alleles are associated with severe, early-onset autoimmunity; we show that heterozygous carriage of an African-predominant LRBA protein-altering allele is associated with significantly decreased LRBA and CTLA-4 expression with T-cell activation. CONCLUSIONS: Greater genetic diversity in African populations improves prediction across populations, and generalizes some VEO-IBD genes. Increasing African American IBD case-collections should be prioritized to reduce health disparities and enhance pathophysiological insight.


Assuntos
Negro ou Afro-Americano/genética , Colite Ulcerativa/genética , Doença de Crohn/genética , Hispânico ou Latino/genética , Judeus/genética , Herança Multifatorial , Penetrância , Polimorfismo de Nucleotídeo Único , População Branca/genética , Idade de Início , Estudos de Casos e Controles , Colite Ulcerativa/diagnóstico , Colite Ulcerativa/etnologia , Doença de Crohn/diagnóstico , Doença de Crohn/etnologia , Europa (Continente)/epidemiologia , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Humanos , Fenótipo , Prevalência , Fatores Raciais , Medição de Risco , Fatores de Risco , Estados Unidos/epidemiologia
6.
J Pediatr ; 225: 146-151, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32544479

RESUMO

OBJECTIVES: To compare patient-reported outcomes in black/African American patients with white patients participating in IBD Partners Kids & Teens, in order to identify possible racial healthcare disparities in pediatric inflammatory bowel disease (IBD) as future targets for improvement. STUDY DESIGN: This was a cross-sectional analysis comparing patient-reported outcomes in black/African American patients with white patients, aged 9-18 years, with IBD participating in the IBD Partners Kids & Teens cohort from August 2013 to April 2018. Secondary outcomes included number of IBD-related hospitalizations and surgeries, current medication use, and disease activity. RESULTS: We included 401 patients with Crohn's disease (white = 378 [94%]; black/African American = 23 [6%]). For children with Crohn's disease, black/African American patients compared with white patients reported less anxiety (40.7 vs 47.5, P = .001) and fatigue (44.3 vs 48.4, P = .047) despite more frequently reported treatment with biologics (91% vs 61%, P = .006) and antibiotics (17% vs 5%, P = .03) and history of hospitalizations (81% vs 52%, P = .02). CONCLUSIONS: Black/African American children with Crohn's disease were less likely to report anxiety or fatigue than white patients, despite an apparent more severe disease course reflected by greater reported frequency of treatment with biologics and antibiotics and history of hospitalizations.


Assuntos
Ansiedade/etnologia , Doença de Crohn/etnologia , Fadiga/etnologia , Adolescente , Negro ou Afro-Americano/psicologia , Negro ou Afro-Americano/estatística & dados numéricos , Criança , Estudos de Coortes , Doença de Crohn/psicologia , Doença de Crohn/terapia , Estudos Transversais , Progressão da Doença , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Masculino , Medidas de Resultados Relatados pelo Paciente , Índice de Gravidade de Doença , População Branca/psicologia , População Branca/estatística & dados numéricos
7.
BMC Gastroenterol ; 20(1): 170, 2020 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-32503428

RESUMO

BACKGROUND: Colitis is generally considered a risk factor for colon neoplasia. However, not all types of colitis seem to have equal neoplastic transformation potential. AIM: To determine the prevalence of colorectal polyps in a predominantly African American population with inflammatory bowel disease (IBD) and Non-IBD/Non-Infectious Colitis (NIC). METHODS: We retrospectively evaluated medical records of 1060 patients previously identified with colitis at Howard University Hospital, based on ICD-10 code. Among these, 485 patients were included in the study: 70 IBD and 415 NIC based on a thorough review of colonoscopy, pathology and clinical reports. Logistic regression analysis was applied to estimate the risk of polyps in patients with IBD compared to those with NIC after adjusting for age and sex. A subgroup analysis within the IBD group was performed. RESULTS: Of the 485 patients, 415 were NIC and 70 were IBD. Seventy-three percent of the NIC patients and 81% of the IBD patients were African Americans. Forty six percent of IBD and 41% of NIC cases were male. IBD patients were younger than NIC patients (median age of 38 years vs. 50, P < 0.001). The prevalence of all types of polyps was 15.7 and 8.2% in the IBD and NIC groups, respectively (P = 0.045). Among patients with polyps, the prevalence of inflammatory polyps was higher in the IBD group (55%) compared to the NIC group (12%). After adjusting for age, sex and race, odds ratio of inflammatory polyps in IBD patients was 6.0 (P = 0.016). Adenoma prevalence was 4.3% (3/70) in IBD patients and 3.9% (16/415) in the NIC patients (p = 0.75). The anatomic distribution of lesions and colitis shows that polyps occur predominantly in the colitis field regardless of colitis type. More polyps were present in the ulcerative colitis patients when compared to Crohn's disease patients (27% vs. 5%, P < 0.001) within the IBD group. CONCLUSION: Our study shows that inflammatory polyps are more common in IBD patients when compared to NIC patients. Most polyps were in the same location as the colitis.


Assuntos
Colite Ulcerativa/complicações , Colite/complicações , Pólipos do Colo/epidemiologia , Doença de Crohn/complicações , Doenças Inflamatórias Intestinais/complicações , Adulto , Negro ou Afro-Americano/estatística & dados numéricos , Colite/etnologia , Colite Ulcerativa/etnologia , Pólipos do Colo/etnologia , Pólipos do Colo/etiologia , Colonoscopia/estatística & dados numéricos , Doença de Crohn/etnologia , Feminino , Humanos , Doenças Inflamatórias Intestinais/etnologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Prevalência , Estudos Retrospectivos , Medição de Risco , Fatores de Risco
8.
Inflamm Bowel Dis ; 26(12): 1933-1942, 2020 11 19.
Artigo em Inglês | MEDLINE | ID: mdl-32115633

RESUMO

BACKGROUND: South Asians have recently been identified as having a rapidly rising incidence and prevalence of inflammatory bowel disease (IBD) throughout the world. However, longitudinal phenotypic studies of South Asians living in the United States remain scarce. METHODS: We retrospectively studied 171 South Asian patients with IBD treated at 2 US tertiary centers who presented between 2000 and 2016. South Asian IBD patients were randomly matched in a 1:2 ratio with sex and IBD subtype-matched (ulcerative colitis [UC] vs Crohn disease [CD]) white control patients (n = 342). Demographic and phenotypic characteristics were evaluated and compared between the 2 groups. Odds ratios (OR), logistic regression, and survival analysis were performed using R studio and STATA. RESULTS: 81 South Asian patients and 162 white patients had CD, and 90 South Asians and 180 white patients had UC. Among the CD group, South Asian patients were diagnosed at a median older age (age 28) than white patients (21 years; P < 0.003). Fistulizing disease (24.1% vs 8.6%; P < 0.002), perianal disease (20.3% vs 2.5%; P < 0.005), and presentation of rectal pain (16.2% vs 2.9%; P < 0.001) were more common among South Asian patients with CD than among white patients. After adjusting for covariates, South Asian patients with CD were less likely to be placed on thiopurines (OR = 0.36; P < 0.007) or to receive more than 1 biologic (OR = 0.42; P < 0.040). South Asian patients with UC were less likely to have proctitis (10% vs 22.2%; P < 0.022) and more likely to have primary sclerosing cholangitis (n = 7 vs n = 2; P < 0.007). South Asian patients born in the United States or those who had migrated before age 5 were younger at the age of IBD diagnosis (age 18.9 vs 32.4; P < 0.0005). CONCLUSION: We found unique demographic and phenotypic characteristics among South Asian patients, including more penetrating disease in those with CD and less proctitis among those with UC, along with altered medication use patterns. Distinct environmental exposures and a potentially unique genetic profile of South Asian patients may confer this variable phenotypic expression, influencing management of this increasingly at-risk population.


Assuntos
Doenças do Ânus/etnologia , Povo Asiático/estatística & dados numéricos , Colite Ulcerativa/etnologia , Doença de Crohn/etnologia , Fístula Intestinal/etnologia , Adulto , Doenças do Ânus/epidemiologia , Sudeste Asiático/etnologia , Povo Asiático/etnologia , Colite Ulcerativa/complicações , Colite Ulcerativa/patologia , Doença de Crohn/complicações , Doença de Crohn/patologia , Feminino , Humanos , Incidência , Fístula Intestinal/epidemiologia , Estudos Longitudinais , Masculino , Fenótipo , Estudos Retrospectivos , Estados Unidos/epidemiologia , População Branca/estatística & dados numéricos , Adulto Jovem
9.
Inflamm Bowel Dis ; 26(12): 1869-1877, 2020 11 19.
Artigo em Inglês | MEDLINE | ID: mdl-32144933

RESUMO

BACKGROUND: The prevalence and clinical features of inflammatory bowel disease (IBD) vary among different racial and ethnic groups. The aim of this study was to compare the clinical and phenotypic features of Crohn's disease (CD) and ulcerative colitis (UC) in South Asian patients living in the United States with those of a white cohort. METHODS: The demographic, clinical, and phenotypic characteristics of 73 South Asian patients (31 CD and 42 UC) who presented initially to our tertiary referral center from 2012 to 2016 and had subsequent follow-up were retrospectively compared with those of 408 consecutive white patients (245 CD and 163 UC). RESULTS: South Asian IBD patients were significantly more likely to have UC (58.0% vs 40.0%; P = 0.005) than white patients. South Asians with CD were less likely to have a family history of IBD (9.7% vs 26.9%; P = 0.037) and required fewer CD-related surgeries (22.5% vs 46.1; P = 0.012). South Asians were also less likely to be active or former smokers in both the CD (P = 0.004) and UC (P = 0.020) groups. South Asians with UC had a higher incidence of Clostridium difficile infection compared with white patients (19.0% vs 8.6%; P = 0.050). CONCLUSIONS: A cohort of South Asian patients with IBD were more likely to have UC and had differing family and tobacco risk factors, requirements for surgery, and Clostridium difficile infection rates as compared with white patients.


Assuntos
Povo Asiático/estatística & dados numéricos , Colite Ulcerativa/etnologia , Doença de Crohn/etnologia , Doenças Inflamatórias Intestinais/etnologia , População Branca/estatística & dados numéricos , Adolescente , Adulto , Clostridioides difficile , Colite Ulcerativa/microbiologia , Colite Ulcerativa/patologia , Doença de Crohn/microbiologia , Doença de Crohn/patologia , Enterocolite Pseudomembranosa/epidemiologia , Enterocolite Pseudomembranosa/etnologia , Feminino , Humanos , Incidência , Doenças Inflamatórias Intestinais/microbiologia , Doenças Inflamatórias Intestinais/patologia , Masculino , Pessoa de Meia-Idade , Fenótipo , Prevalência , Pontuação de Propensão , Estudos Retrospectivos , Fatores de Risco , Centros de Atenção Terciária , Adulto Jovem
10.
Pediatr Neonatol ; 61(3): 263-271, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32005607

RESUMO

Pediatric inflammatory bowel disease (PIBD) in Asia, once considered a rare entity, has seen a sharp increase in incidence over the preceding decade. However, there is a paucity of epidemiological data on PIBD in Asia, and the true disease burden is difficult to estimate due to the lack of national disease registries, prospective databases and the fact that much of existing published data are limited to single-center experiences. This sets the stage for examining recent published data on epidemiological trends and its natural history. Hence, we reviewed the relevant published literature on PIBD in order to summarize the epidemiological data in the Asian populations and compare it with the data available from the other population including Western population. Our review demonstrates that the rapid surge in PIBD incidence across Asian centers lies in contrast to the plateauing albeit high incidence rates in larger established Western cohorts. Important epidemiological trends observed across emerging Asian literature are the higher rates of perianal involvement at disease onset amongst pediatric Crohn's disease (CD) patients, a higher proportion of early-onset disease and the over-representation of the Indian ethnicity in multi-ethnic cohorts. A number of issues currently limit a robust comparison and hence the way forward would be to advocate the recognition of PIBD as an increasingly important public health problem with the need to establish robust disease registries.


Assuntos
Colite Ulcerativa/epidemiologia , Doença de Crohn/epidemiologia , Adolescente , Criança , Colite Ulcerativa/etnologia , Doença de Crohn/etnologia , Feminino , Humanos , Incidência , Masculino
11.
Inflamm Bowel Dis ; 26(7): 1068-1076, 2020 06 18.
Artigo em Inglês | MEDLINE | ID: mdl-31587061

RESUMO

BACKGROUND: The incidence of pediatric inflammatory bowel diseases (PIBDs: Crohn's disease [CD], ulcerative colitis [UC]) is on the rise around the world. Yet, the critical risk factors for this rising incidence are not well understood. Demographic characteristics of PIBD may improve our understanding of their developmental origins and aid in prevention. METHODS: Four hundred eighty-eight consecutive PIBD patients diagnosed at Texas Children's Hospital from 13 counties around Houston were studied. An annual incidence map was created by ZIP code of residence at diagnosis by using ArcGIS and the American Community Survey from the US Census Bureau. Correlation between demographic variables and PIBD incidence was examined. A model to explain incidence from different health factors was created in R. RESULTS: Hispanic children were more likely to be diagnosed with UC (P < 0.01) and unclassified IBD (IBD-U) (P < 0.03) compared with other races/ethnicities. A significant positive correlation (r = 0.35, P < 0.0001) between median household income and PIBD incidence was observed (UC: r = 0.23, P < 0.0001; CD: r = 0.22, P = 0.0004). ZIP codes with majority college-educated adults had a higher incidence of PIBD than ZIP codes with majority high school-educated adults (P < 0.0001). Pediatric cases with CD were more common in ZIP codes where the majority of adults were college educated (P < 0.0001). Pediatric cases with UC, however, were more common in ZIP codes where the majority of adults were high school educated (P = 0.0036). CONCLUSIONS: Hispanic children more commonly present with UC and IBD-U in southern USA. Household income and/or adult education-related environmental/dietary differences may be important in the developmental origins of PIBD in large metro areas, such as Houston.


Assuntos
Saúde da Criança/estatística & dados numéricos , Colite Ulcerativa/epidemiologia , Doença de Crohn/epidemiologia , Escolaridade , Pais/educação , Adolescente , Criança , Saúde da Criança/etnologia , Estudos de Coortes , Colite Ulcerativa/etnologia , Colite Ulcerativa/etiologia , Doença de Crohn/etnologia , Doença de Crohn/etiologia , Características da Família , Feminino , Hispânico ou Latino/educação , Hispânico ou Latino/estatística & dados numéricos , Humanos , Incidência , Renda , Masculino , Fenótipo , Sistema de Registros , Análise de Regressão , Fatores de Risco , Texas/epidemiologia
12.
World J Gastroenterol ; 25(40): 6145-6157, 2019 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-31686769

RESUMO

BACKGROUND: The current epidemiology of inflammatory bowel disease (IBD) in the multi-ethnic United Kingdom is unknown. The last incidence study in the United Kingdom was carried out over 20 years ago. AIM: To describe the incidence and phenotype of IBD and distribution within ethnic groups. METHODS: Adult patients (> 16 years) with newly diagnosed IBD (fulfilling Copenhagen diagnostic criteria) were prospectively recruited over one year in 5 urban catchment areas with high South Asian population. Patient demographics, ethnic codes, disease phenotype (Montreal classification), disease activity and treatment within 3 months of diagnosis were recorded onto the Epicom database. RESULTS: Across a population of 2271406 adults, 339 adult patients were diagnosed with IBD over one year: 218 with ulcerative colitis (UC, 64.3%), 115 with Crohn's disease (CD, 33.9%) and 6 with IBD unclassified (1.8%). The crude incidence of IBD, UC and CD was 17.0/100000, 11.3/100000 and 5.3/100000 respectively. The age adjusted incidence of IBD and UC were significantly higher in the Indian group (25.2/100000 and 20.5/100000) compared to White European (14.9/100000, P = 0.009 and 8.2/100000, P < 0.001) and Pakistani groups (14.9/100000, P = 0.001 and 11.2/100000, P = 0.007). The Indian group were significantly more likely to have extensive disease than White Europeans (52.7% vs 41.7%, P = 0.031). There was no significant difference in time to diagnosis, disease activity and treatment. CONCLUSION: This is the only prospective study to report the incidence of IBD in an ethnically diverse United Kingdom population. The Indian ethnic group showed the highest age-adjusted incidence of UC (20.5/100000). Further studies on dietary, microbial and metabolic factors that might explain these findings in UC are underway.


Assuntos
Colite Ulcerativa/etnologia , Doença de Crohn/etnologia , Adulto , Povo Asiático/estatística & dados numéricos , Área Programática de Saúde/estatística & dados numéricos , Bases de Dados Factuais/estatística & dados numéricos , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Reino Unido/epidemiologia , População Branca/estatística & dados numéricos
13.
Immunol Invest ; 48(8): 809-821, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31405308

RESUMO

Aims The aryl hydrocarbon receptor (AhR) plays a pivotal role in regulating the innate and the acquired immune systems. The present study aimed to investigate the association of Crohn's disease (CD) with AhR polymorphisms in a cohort of patients from Southeast China. Methods An improved multiple ligase detection reaction technique was applied to examine the polymorphisms of rs2158041, rs2066853, and rs10249788 in 310 patients with CD and 573 controls. Results Compared to the controls, the variant allele (T) and genotype (CT+TT) of rs2158041 were less frequent in patients with CD (both p < 0.05). Similar conclusions were drawn from patients with ileal CD and with stricture CD as compared to the controls (all p < 0.0083). However, no significant differences were observed in allele and genotype frequencies of rs2066853 and rs10249788 between patients with CD and the controls (all p > 0.05). Although rs2158041 and rs10249788 were in complete linkage disequilibrium with rs2066853, respectively, only the frequency of haplotype (TG) formed by rs2158041 and rs2066853 was significantly lower in patients with CD than that in the controls (p < 0.05). Conclusions AhR (rs2158041) might be a susceptible locus for CD, especially for the two subtypes: ileal CD and stricture CD.


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Doença de Crohn/genética , Predisposição Genética para Doença/genética , Polimorfismo de Nucleotídeo Único , Receptores de Hidrocarboneto Arílico/genética , Adulto , Alelos , Povo Asiático/genética , China , Doença de Crohn/etnologia , Feminino , Frequência do Gene , Predisposição Genética para Doença/etnologia , Genótipo , Haplótipos , Humanos , Desequilíbrio de Ligação , Masculino , Pessoa de Meia-Idade , Adulto Jovem
14.
Clin Pharmacokinet ; 58(3): 375-387, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30123942

RESUMO

BACKGROUND AND OBJECTIVES: Risankizumab is a humanized anti-interleukin-23 monoclonal antibody in development for the treatment of several inflammatory diseases. This work characterized the pharmacokinetics of risankizumab and evaluated covariates that may affect its exposures using phase I and II trial data in subjects with psoriasis and Crohn's disease. METHODS: Plasma concentration measurements from a phase I study and a phase II study in subjects with psoriasis (n = 157; single doses of 0.01-5 mg/kg intravenously, 0.25-1 mg/kg subcutaneously, and 18 mg subcutaneously, and multiple doses of 90 and 180 mg subcutaneously), and a phase II study in subjects with Crohn's disease (n = 115; doses of 200 or 600 mg intravenously every 4 weeks followed by 180 mg subcutaneously every 8 weeks) were analyzed using non-linear mixed-effects modeling. The model was qualified using bootstrap and simulation-based diagnostics. RESULTS: A two-compartment model with first-order absorption and elimination described the pharmacokinetics of risankizumab. Considering the body weight and baseline albumin central tendency differences between disease populations, risankizumab clearance, steady-state volume of distribution, and terminal-phase elimination half-life were estimated to be approximately 0.35 L/day, 11.7 L, and 27 days, respectively, for a typical 90-kg subject with psoriasis with an albumin level of 42 g/L, and 0.31 L/day, 8.45 L, and 22 days, respectively, for a typical 65-kg subject with Crohn's disease with an albumin level of 37 g/L. Risankizumab absolute subcutaneous bioavailability and absorption rate constant were 72% and 0.18 day-1, respectively. Inter-individual variability for clearance was 37%. CONCLUSIONS: Risankizumab displayed pharmacokinetic characteristics typical for an IgG1 monoclonal antibody with no apparent target-mediated disposition. Accounting for the effects of body weight and baseline albumin explained the small differences in the pharmacokinetics of risankizumab between psoriasis and Crohn's disease, with no further differences between the patient populations.


Assuntos
Anticorpos Monoclonais Humanizados/farmacocinética , Anticorpos Monoclonais/farmacocinética , Doença de Crohn/tratamento farmacológico , Interleucina-23/antagonistas & inibidores , Psoríase/tratamento farmacológico , Administração Intravenosa , Adulto , Idoso , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/uso terapêutico , Disponibilidade Biológica , Variação Biológica da População/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Doença de Crohn/sangue , Doença de Crohn/etnologia , Feminino , Humanos , Injeções Subcutâneas , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , Psoríase/sangue , Psoríase/etnologia , Albumina Sérica/efeitos dos fármacos
15.
Inflamm Bowel Dis ; 25(1): 194-203, 2019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-29850811

RESUMO

Background: Racial and socioeconomic disparities exist in the treatment and outcomes of children and adults with Crohn's disease (CD). This study investigated the impact of race and insurance status on emergency department (ED) evaluation and treatment among children with CD in the United States. Methods: Data from the Pediatric Health Information System included ED visits between January 2007 and December 2013 for patients aged ≤21 years with a primary diagnosis of CD, or a secondary diagnosis of CD plus a primary CD-related diagnosis. Analyses were performed using mixed-effects logistic regression. Results: Subjects included 2618 unique patients (black, 612 [23%]; white, 2006 [77%]) with 3779 visits from 38 hospitals, a median age of 14.0 ± 4.0 years, and 50% male. White children had a higher median neighborhood income and were more likely to have private insurance (57% vs 30%; P < 0.001). Emergency department visits for privately insured patients had higher odds of complete blood count (odds ratio [OR], 1.43; 95% CI, 1.08-1.90) and C-reactive protein/erythrocyte sedimentation rate (OR, 1.39; 95% CI, 1.06-1.82) vs Medicaid insured. Visits for white children had higher odds of receiving antiemetics (OR, 1.52; 95% CI, 1.06-2.17) vs black children. The proportion of patients with repeat visits was greater for black children (33%) than white children (22%; P < 0.001) and greater for Medicaid-insured (27%) than privately insured patients (21%; P < 0.01). Conclusions: This cross-sectional database study demonstrated that black children and those with Medicaid insurance made more ED visits and received somewhat fewer treatments, which may be explained by greater use of the ED for routine care. An opportunity exists for better outpatient management of children with IBD so that nonemergent problems are more effectively handled.


Assuntos
Doença de Crohn/economia , Doença de Crohn/etnologia , Serviço Hospitalar de Emergência/economia , Etnicidade/estatística & dados numéricos , Cobertura do Seguro , Seguro Saúde , Fatores Socioeconômicos , Adolescente , Adulto , Criança , Pré-Escolar , Doença de Crohn/tratamento farmacológico , Estudos Transversais , Feminino , Seguimentos , Pesquisas sobre Atenção à Saúde , Humanos , Lactente , Recém-Nascido , Masculino , Prognóstico , Estudos Retrospectivos , Estados Unidos , Adulto Jovem
16.
BMC Gastroenterol ; 18(1): 153, 2018 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-30342474

RESUMO

BACKGROUND: Serological markers used for diagnostic purposes and disease stratification in inflammatory bowel disease. We aimed to investigate the frequency of ASCA and ANCA among Arab Bedouin IBD patients and its relationship to disease phenotype and course. METHODS: From cohort of 68, 25 Crohn's disease (CD) and 25 Ulcerative colitis (UC) patients were recruited (72%). ASCA IgG was determined by ELISA assay. Immunofluorescence analysis of ANCA was performed. RESULTS: The IgG ASCA was detected in 13 (52%) of the CD patients and in three (12%) UC patients. The prevalence of ANCA among UC patients was positive with 76%, sub-grouped, atypical ANCA in 9 patients (36%), pANCA in six patients (24%) and cANCA in 4 patients (16%). The detection of ASCA among CD patients was found not to be a reliable predictor of young age at diagnosis, gender, ileal involvement, anti-TNF treatment or surgery. UC patients with positive ANCA were younger, mean age 40.2 ± 11.9 compared with 57.3 ± 21.2 (p = 0.03), and diagnosed at a younger age, 29.2 ± 11.8 compared with 43.5 ± 15.3 (p = 0.05). CONCLUSION: The frequency of ASCA among Bedouin CD patients and ANCA among UC patients was high, however ASCA was not found to have a predictive value for disease phenotype or course. Positive ANCA in UC patients was predictive for younger age and age at diagnosis.


Assuntos
Anticorpos Anticitoplasma de Neutrófilos/sangue , Árabes , Colite Ulcerativa/etnologia , Colite Ulcerativa/imunologia , Doença de Crohn/etnologia , Doença de Crohn/imunologia , Imunoglobulina G/sangue , Saccharomyces cerevisiae/imunologia , Adulto , Biomarcadores/sangue , Colite Ulcerativa/diagnóstico , Doença de Crohn/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo
17.
Aliment Pharmacol Ther ; 48(9): 933-940, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30126019

RESUMO

BACKGROUND: Many patients with Crohn's disease will develop complications that require surgery. Recurrence after surgery is common. AIM: To assess racial differences in postoperative recurrence between African-Americans and Caucasians. METHODS: Medical records of Crohn's disease patients who underwent surgery (ileal, colonic, or ileocolonic resection) between June 2014 and June 2016 were reviewed. The primary endpoints were clinical and endoscopic remission at 6-12 months after a Crohn's disease surgery. Secondary outcomes included biological and histologic remission. Risks of recurrence were assessed by univariate, multivariate, and propensity score-matched analysis. RESULTS: Thirty-six African-American and 167 Caucasian patients with Crohn's disease were included for analysis. There was no difference in disease location, disease behaviour, type of surgery performed, and pre- or postoperative medication use between the two groups. The rate of endoscopic remission did not differ between African-American and Caucasian patients (50% vs 42%, P = 0.76), and race did not influence the risk of endoscopic recurrence on univariate, multivariate, or propensity score-matched analysis. The rate of clinical remission was significantly lower in African-American patients compared to Caucasian patients (36% vs. 63%, P = 0.008). African-American race was significantly associated with clinical recurrence on univariate (odds ratio (OR) 6.76, 95% CI 1.50-30.40; P = 0.01), multivariate (OR 5.02, 95% CI 1.60-15.80; P = 0.006), and propensity-matched analysis (68% vs. 32% in Caucasians, P = 0.005). Rates of biologic and histologic remission were similar between the two groups on all analyses. CONCLUSIONS: We found that African-American patients with Crohn's disease have a similar degree of objective measures of mucosal inflammation after surgery including endoscopic recurrence as compared to Caucasian patients. However, African-American race was significantly associated with clinical recurrence, suggesting the presence of ethnic variation in postoperative presentation in Crohn's disease.


Assuntos
Negro ou Afro-Americano/etnologia , Doença de Crohn/diagnóstico , Doença de Crohn/etnologia , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/etnologia , População Branca/etnologia , Adulto , Colo/patologia , Colo/cirurgia , Doença de Crohn/cirurgia , Endoscopia/efeitos adversos , Endoscopia/tendências , Feminino , Humanos , Íleo/patologia , Íleo/cirurgia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Recidiva , Estudos Retrospectivos , Fatores de Risco
18.
JAMA Dermatol ; 154(7): 814-818, 2018 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-29800049

RESUMO

Importance: Limited evidence supports a link between hidradenitis suppurativa (HS) and Crohn disease (CD), and this relationship has not been established in the United States. Objective: To evaluate the prevalence of CD among patients with HS in the United States and to determine the strength of association between the 2 conditions. Design, Setting, and Participants: Cross-sectional analysis of data from 51 340 patients with HS identified using electronic health records data in the Explorys multiple health system data analytics and research platform, which includes data from more than 50 million unique patients across all US census regions. Main Outcomes and Measures: Primary outcome was diagnosis of CD. Results: Of the 18 455 660 total population considered, 51 340 had HS (35 000 women). Of these patients with HS, 29 010 (56.5%) were aged 18 to 44 years; 17 580 (34,2%), 45 to 64 years; and 4750 (9.3%), 65 years or older. Prevalence of CD among patients with HS was 2.0% (1025/51 340), compared with 0.6% (113 360/18 404 260) among those without HS (P < .001). Prevalence of CD was greatest among patients with HS who were white (2.3%), aged 45 to 64 years (2.4%), nonobese (2.8%), and tobacco smokers (2.3%). In univariable and multivariable analyses, patients with HS had 3.29 (95% CI, 3.09-3.50) and 3.05 (95% CI, 2.87-3.25) times the odds of having CD, respectively, compared with patients without HS. Crohn disease was associated with HS across all patient subgroups. The association was strongest for men (OR, 3.61; 95% CI, 3.24-4.03), patients aged 45 to 64 years (OR, 3.49; 95% CI, 3.16-3.85), nonobese patients (OR, 4.09; 95% CI, 3.69-4.54), and nonsmokers (OR, 3.44; 95% CI, 3.10-3.82). Conclusions and Relevance: These data suggest that patients with HS are at risk for CD. Gastrointestinal symptoms or signs suggestive of CD warrant additional evaluation by a gastroenterologist.


Assuntos
Doença de Crohn/epidemiologia , Hidradenite Supurativa/epidemiologia , Adolescente , Adulto , Negro ou Afro-Americano/estatística & dados numéricos , Fatores Etários , Doença de Crohn/diagnóstico , Doença de Crohn/etnologia , Estudos Transversais , Feminino , Humanos , Masculino , não Fumantes/estatística & dados numéricos , Prevalência , Fatores Sexuais , Fumar/epidemiologia , Estados Unidos/epidemiologia , População Branca/estatística & dados numéricos , Adulto Jovem
19.
Cell Mol Biol (Noisy-le-grand) ; 64(5): 46-51, 2018 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-29729713

RESUMO

This study explored whether the functional protein tyrosine phosphatase nonreceptor 22 (PTPN22) G788A (R263Q) polymorphism is associated with susceptibility to autoimmune diseases. A meta-analysis was conducted using 23 comparative studies with a total of 16,719 patients and 17,783 controls. The meta-analysis showed an association between the A allele of the PTPN22 G788A polymorphism and decreased risk of autoimmune diseases in all subjects (p < 0.001). Analysis after stratification by ethnicity indicated that the PTPN22 788A allele was significantly associated with autoimmune diseases in Europeans (p < 0.001) but not in Latin Americans. Meta-analysis by autoimmune disease type showed a significant negative association between the PTPN22 788A allele and systemic lupus erythematous (SLE) (p = 001), rheumatoid arthritis (RA) (p = 0.008), ulcerative colitis (UC) (p = 0.016), but not Crohn's disease (CD). A single study for each showed no association between the PTPN22 788A allele and systemic sclerosis, giant cell arteritis, Henoch-schonlein purpura, uveitis, and Grave's disease. This meta-analysis demonstrates that the PTPN22 G788A polymorphism confers protection against SLE, RA, and UC, supporting evidence of association of the PTPN22 gene with a subgroup of autoimmune diseases.


Assuntos
Artrite Reumatoide/genética , Colite Ulcerativa/genética , Resistência à Doença/genética , Lúpus Eritematoso Sistêmico/genética , Polimorfismo de Nucleotídeo Único , Proteína Tirosina Fosfatase não Receptora Tipo 22/genética , Artrite Reumatoide/etnologia , Artrite Reumatoide/imunologia , Artrite Reumatoide/patologia , Estudos de Casos e Controles , Colite Ulcerativa/etnologia , Colite Ulcerativa/imunologia , Colite Ulcerativa/patologia , Doença de Crohn/etnologia , Doença de Crohn/genética , Doença de Crohn/imunologia , Doença de Crohn/patologia , Expressão Gênica , Estudos de Associação Genética , Genótipo , Arterite de Células Gigantes/etnologia , Arterite de Células Gigantes/genética , Arterite de Células Gigantes/imunologia , Arterite de Células Gigantes/patologia , Doença de Graves/etnologia , Doença de Graves/genética , Doença de Graves/imunologia , Doença de Graves/patologia , Hispânico ou Latino , Humanos , Vasculite por IgA/etnologia , Vasculite por IgA/genética , Vasculite por IgA/imunologia , Vasculite por IgA/patologia , Lúpus Eritematoso Sistêmico/etnologia , Lúpus Eritematoso Sistêmico/imunologia , Lúpus Eritematoso Sistêmico/patologia , Escleroderma Sistêmico/etnologia , Escleroderma Sistêmico/genética , Escleroderma Sistêmico/imunologia , Escleroderma Sistêmico/patologia , Uveíte/etnologia , Uveíte/genética , Uveíte/imunologia , Uveíte/patologia , População Branca
20.
Dig Dis Sci ; 63(6): 1558-1571, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29594975

RESUMO

BACKGROUND: Inflammatory bowel disease (IBD) is a devastating immune-mediated disease on the rise in Hispanics living in the USA. Prior observational studies comparing IBD characteristics between Hispanics and non-Hispanic whites (NHW) have yielded mixed results. AIMS: We performed a meta-analysis of observational studies examining IBD phenotype in Hispanics compared to NHW. METHODS: We conducted a systematic search of US-based studies comparing IBD subtype (Ulcerative Colitis: UC or Crohn's disease: CD) and phenotype (disease location and behavior) between Hispanics and NHW. We evaluated differences in age at IBD diagnosis, the presence of family history and smoking history. A random effects model was chosen "a priori." Categorical and continuous variables were analyzed using odds ratio (OR) or standard mean difference (SMD), respectively. RESULTS: Seven studies were included with 687 Hispanics and 1586 NHW. UC was more common in Hispanics compared to NHW (OR 2.07, CI 1.13-3.79, p = 0.02). Location of disease was similar between Hispanics and NHW except for the presence of upper gastrointestinal CD, which was less common in Hispanics (OR 0.58, CI 0.32-1.06, p = 0.07). Hispanics were less likely to smoke (OR 0.48, CI 0.26-0.89, p = 0.02) or have a family history of IBD (OR 0.35, CI 0.22-0.55, p < 0.001). CD behavior classified by Montreal classification and age at IBD diagnosis were similar between Hispanics and NHW. CONCLUSION: UC was more common among US Hispanics compared to NHW. Age at IBD diagnosis is similar for both Hispanics and NHW. For CD, disease behavior is similar, but Hispanics show a trend for less upper gastrointestinal involvement. A family history of IBD and smoking history were less common in Hispanics.


Assuntos
Colite Ulcerativa/etnologia , Doença de Crohn/etnologia , Hispânico ou Latino , População Branca , Fatores Etários , Colite Ulcerativa/diagnóstico , Colite Ulcerativa/genética , Doença de Crohn/diagnóstico , Doença de Crohn/genética , Predisposição Genética para Doença , Humanos , Estudos Observacionais como Assunto , Razão de Chances , Linhagem , Fenótipo , Fatores de Risco , Fumar/efeitos adversos , Fumar/etnologia , Estados Unidos/epidemiologia
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