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1.
Inflamm Bowel Dis ; 2019 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-31504569

RESUMO

BACKGROUND: The effectiveness of the switch to another anti-tumor necrosis factor (anti-TNF) agent is not known. The aim of this study was to analyze the effectiveness and safety of treatment with a second and third anti-TNF drug after intolerance to or failure of a previous anti-TNF agent in inflammatory bowel disease (IBD) patients. METHODS: We included patients diagnosed with IBD from the ENEIDA registry who received another anti-TNF after intolerance to or failure of a prior anti-TNF agent. RESULTS: A total of 1122 patients were included. In the short term, remission was achieved in 55% of the patients with the second anti-TNF. The incidence of loss of response was 19% per patient-year with the second anti-TNF. Combination therapy (hazard ratio [HR], 2.4; 95% confidence interval [CI], 1.8-3; P < 0.0001) and ulcerative colitis vs Crohn's disease (HR, 1.6; 95% CI, 1.1-2.1; P = 0.005) were associated with a higher probability of loss of response. Fifteen percent of the patients had adverse events, and 10% had to discontinue the second anti-TNF. Of the 71 patients who received a third anti-TNF, 55% achieved remission. The incidence of loss of response was 22% per patient-year with a third anti-TNF. Adverse events occurred in 7 patients (11%), but only 1 stopped the drug. CONCLUSIONS: Approximately half of the patients who received a second anti-TNF achieved remission; nevertheless, a significant proportion of them subsequently lost response. Combination therapy and type of IBD were associated with loss of response. Remission was achieved in almost 50% of patients who received a third anti-TNF; nevertheless, a significant proportion of them subsequently lost response.

2.
Rev. esp. enferm. dig ; 111(8): 586-592, ago. 2019. tab, graf
Artigo em Inglês | IBECS-Express | ID: ibc-ET1-4853

RESUMO

Introduction: adequate knowledge of inflammatory bowel disease (IBD) is essential for a successful patient-centered management of IBD. Objective: due to the scarcity of up-to-date tools for measuring IBD literacy, this single-center, prospective study aimed to develop and validate a new questionnaire to assess IBD-related knowledge. Material and methods: the study included patients followed up at the Crohn-Colitis Care Unit (UACC) at the Hospital Vall d'Hebron (Barcelona, Spain). Patients admitted to the UACC for the first time were subsequently enrolled into a standard IBD educational program. A pilot questionnaire was developed and validated in 92 IBD patients by determining the internal consistency reliability (Cronbach's α test), feasibility, construct validity (correlation with the Crohn's and Colitis Knowledge [CCKNOW] questionnaire and a knowledge visual analog scale [VAS]) and sensitivity (score change before and after a standard IBD educational program). The questionnaire, named "Qüestionari Coneixements Malaltia Inflamatòria Intestinal Catalunya" (IBD-knowledge questionnaire Catalonia) (QUECOMIICAT) was written in Spanish and had 25 items addressing six dimensions: general concepts, clinic, treatment, surgery, habits and social context. Results: the median (interquartile range) completion time was 15 (10-20) minutes and the floor and ceiling effects were 1.1% and 2.1%, respectively. The Cronbach's α coefficient was α = 0.75. QUECOMIICAT significantly correlated with the VAS (rho = 0.34, p < 0.01) and CCKNOW questionnaires (rho = 0.74, p < 0.01). Patient knowledge significantly increased 24 hours after attending a standard IBD educational program and remained statistically significant one month later (Pearson's test-retest correlation coefficient r = 0.81, p < 0.001). Conclusion: in conclusion, the QUECOMIICAT questionnaire is a new up-to-date tool to assess IBD-related knowledge with good feasibility and validation results for use in the routine clinical practice


No disponible

3.
Rev Esp Enferm Dig ; 111(8): 586-592, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31317762

RESUMO

INTRODUCTION: adequate knowledge of inflammatory bowel disease (IBD) is essential for a successful patient-centered management of IBD. OBJECTIVE: due to the scarcity of up-to-date tools for measuring IBD literacy, this single-center, prospective study aimed to develop and validate a new questionnaire to assess IBD-related knowledge. MATERIAL AND METHODS: the study included patients followed up at the Crohn-Colitis Care Unit (UACC) at the Hospital Vall d'Hebron (Barcelona, Spain). Patients admitted to the UACC for the first time were subsequently enrolled into a standard IBD educational program. A pilot questionnaire was developed and validated in 92 IBD patients by determining the internal consistency reliability (Cronbach's α test), feasibility, construct validity (correlation with the Crohn's and Colitis Knowledge [CCKNOW] questionnaire and a knowledge visual analog scale [VAS]) and sensitivity (score change before and after a standard IBD educational program). The questionnaire, named "Qüestionari Coneixements Malaltia Inflamatòria Intestinal Catalunya" (IBD-knowledge questionnaire Catalonia) (QUECOMIICAT) was written in Spanish and had 25 items addressing six dimensions: general concepts, clinic, treatment, surgery, habits and social context. RESULTS: the median (interquartile range) completion time was 15 (10-20) minutes and the floor and ceiling effects were 1.1% and 2.1%, respectively. The Cronbach's α coefficient was α = 0.75. QUECOMIICAT significantly correlated with the VAS (rho = 0.34, p < 0.01) and CCKNOW questionnaires (rho = 0.74, p < 0.01). Patient knowledge significantly increased 24 hours after attending a standard IBD educational program and remained statistically significant one month later (Pearson's test-retest correlation coefficient r = 0.81, p < 0.001). CONCLUSION: in conclusion, the QUECOMIICAT questionnaire is a new up-to-date tool to assess IBD-related knowledge with good feasibility and validation results for use in the routine clinical practice.

4.
Aliment Pharmacol Ther ; 49(11): 1410-1420, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31025420

RESUMO

BACKGROUND: Colorectal cancer is the second commonest cause of cancer mortality. Some countries are implementing colorectal cancer screening to detect lesions at an early stage using non-invasive tools like the faecal immunochemical test. Despite affordability, this test shows a low sensitivity for precancerous lesions and a low positive predictive value for colorectal cancer, resulting in a high false-positive rate. AIM: To develop a new, non-invasive colorectal cancer screening tool based on bacterial faecal biomarkers, which in combination with the faecal immunochemical test, could allow a reduction in the false-positive rate. This tool is called risk assessment of intestinal disease for colorectal cancer (RAID-CRC). METHODS: We performed both the faecal immunochemical test and the bacterial markers analysis (RAID-CRC test) in stool samples from individuals with normal colonoscopy (167), non-advanced adenomas (88), advanced adenomas (30) and colorectal cancer (48). All the participants showed colorectal cancer-associated symptoms. RESULTS: Performance of the faecal immunochemical test for advanced neoplasia (ie advanced adenoma and colorectal cancer) was determined by using the cut-off value established in Catalonia (20 µg haemoglobin/g of faeces) for a population-based screening approach. Sensitivity and specificity values of 83% and 80%, respectively, and positive and negative predictive values of 56% and 94%, respectively, were obtained. When both the immunological and the biological analysis were combined, the corresponding values were 80% and 90% for sensitivity and specificity, respectively, and 70% and 94% for positive and negative predictive values, respectively, resulting in a 50% reduction of the false-positive rate. CONCLUSIONS: RAID-CRC test allows a substantial reduction in the faecal immunochemical test false-positive results (50%) in a symptomatic population. Further validation is indicated in a colorectal cancer-screening scenario.

5.
Medicine (Baltimore) ; 97(46): e13136, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30431582

RESUMO

BACKGROUND: The diagnostic accuracy of the Gaxilose test (GT) for hypolactasia diagnosis has already been proved. The objectives of this clinical trial were to demonstrate the noninferiority of the GT compared to the hydrogen breath test (HBT) on the impact on diagnostic thinking and patient management, to evaluate the GT reproducibility with urine accumulated from 0 to 4 hours and from 0 to 5 hours and to assess test safety. METHODS: We conducted a randomized, parallel, noninferiority clinical trial. Patients with clinical symptoms suggestive of lactose intolerance were screened for inclusion and randomly assigned to the GT arm or the HBT arm of the study. The impact on diagnostic thinking and patient management was analyzed with pretest and posttest questionnaires in which the investigators indicated their estimated probability of hypolactasia diagnosis and the intended management before and after the GT or the HBT (noninferiority margin: -10%). The primary outcome of the study was the impact on diagnostic thinking, expressed as the mean of the absolute values of the differences between the pretest and posttest probabilities of hypolactasia diagnosis. Patients randomized to the GT arm performed also the retest to evaluate the reproducibility of the GT. RESULTS: A total of 147 patients were included in the intend-to-treat (ITT) population. Among them, 74 performed the HBT and 73 performed the GT. The results proved the noninferiority of the GT compared to the HBT on the impact on diagnostic thinking (ImpactGT = 31.74 ±â€Š23.30%; ImpactHBT = 24.28 ±â€Š19.87%; ΔGT-HBT = 7.46%; 95% confidence interval of ΔGT-HBT: 1.55%, infinite) and on patient management. The test-retest reproducibility was better for the GT with urine accumulated from 0 to 5 h: the intraclass correlation coefficient (ICC) was 0.5761, and the Kappa coefficient was 0.7548, indicative of substantial agreement between both tests. No serious adverse events were reported during the study. CONCLUSIONS: The GT has an impact on diagnostic thinking and patient management noninferior to that of the HBT, is reproducible and well tolerated. These results prove the clinical benefit of its use in the clinical practice (ClinicalTrials.gov identifier: NCT02636413).


Assuntos
Testes Respiratórios/métodos , Dissacarídeos/metabolismo , Intolerância à Lactose/diagnóstico , Xilose/urina , Adulto , Idoso , Tomada de Decisões , Dissacarídeos/administração & dosagem , Dissacarídeos/efeitos adversos , Feminino , Humanos , Hidrogênio/metabolismo , Análise de Intenção de Tratamento , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes
6.
Aliment Pharmacol Ther ; 48(8): 839-851, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30281832

RESUMO

BACKGROUND: Effectiveness of vedolizumab in real world clinical practice is unknown. AIM: To evaluate the short and long-term effectiveness of vedolizumab in patients with inflammatory bowel disease (IBD). METHODS: Patients who received at least 1 induction dose of vedolizumab were included. Effectiveness was defined based on Harvey-Bradshaw index (HBI) in Crohn's disease (CD) and Partial Mayo Score (PMS) in ulcerative colitis (UC). Short-term response was assessed at week 14. Variables associated with short-term remission were identified by logistic regression analysis. The Kaplan-Meier method was used to evaluate the long-term durability of vedolizumab treatment. Cox model was used to identify factors associated with discontinuation of treatment and loss of response. RESULTS: 521 patients were included (median follow-up 10 months [interquartile range 5-18 months]). At week 14, 46.8% had remission and 15.7% clinical response. CD (vs UC), previous surgery, higher CRP concentration and disease severity at baseline were significantly associated with impaired response. The rate of vedolizumab discontinuation was 37% per patient-year of follow-up (27.6% in UC and 45.3% in CD, P < 0.01). CD (vs UC), anaemia at baseline, steroids during induction and CRP concentration were associated with lower durability of treatment. Seven per cent of patients developed adverse events, infections being the most frequent. CONCLUSIONS: Over 60% of IBD patients respond to vedolizumab. Many patients discontinue treatment over time. CD and disease burden impair both short- and long-term response. Vedolizumab seems to be safe in clinical practice.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Fármacos Gastrointestinais/uso terapêutico , Doenças Inflamatórias Intestinais/diagnóstico , Doenças Inflamatórias Intestinais/tratamento farmacológico , Sistema de Registros , Adulto , Anticorpos Monoclonais Humanizados/efeitos adversos , Colite Ulcerativa/diagnóstico , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/epidemiologia , Doenças Transmissíveis/induzido quimicamente , Doenças Transmissíveis/diagnóstico , Doenças Transmissíveis/epidemiologia , Doença de Crohn/diagnóstico , Doença de Crohn/tratamento farmacológico , Doença de Crohn/epidemiologia , Feminino , Seguimentos , Fármacos Gastrointestinais/efeitos adversos , Humanos , Doenças Inflamatórias Intestinais/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Indução de Remissão , Espanha/epidemiologia , Resultado do Tratamento
7.
Artigo em Inglês | MEDLINE | ID: mdl-30245977

RESUMO

Akkermansia muciniphila and Faecalibacterium prausnitzii, cohabitants in the intestinal mucosa, are considered members of a healthy microbiota and reduction of both species occurs in several intestinal disorders, including inflammatory bowel disease. Little is known however about a possible link between the reduction in quantity of these species, and in which circumstances this may occur. This study aims to determine the abundances and co-occurrence of the two species in order to elucidate conditions that may compromise their presence in the gut. Loads of A. muciniphila, total F. prausnitzii and its two phylogroup (16S rRNA gene copies) were determined by quantitative polymerase chain reaction in colonic biopsies from 17 healthy controls (H), 23 patients with ulcerative colitis (UC), 31 patients with Crohn's disease (CD), 3 with irritable bowel syndrome (IBS) and 3 with colorectal cancer (CRC). Data were normalized to total bacterial 16S rRNA gene copies in the same sample. Prevalence, relative abundances and correlation analyses were performed according to type of disease and considering relevant clinical characteristics of patients such as IBD location, age of disease onset, CD behavior, current medication and activity status. Co-occurrence of both species was found in 29% of H, 65% of UC and 29% of CD. Lower levels of total F. prausnitzii and phylogroups were found in subjects with CD, compared with H subjects (P ≤ 0.044). In contrast, no differences were found with the regard to A. muciniphila abundance across different disease states, but CD patients with disease onset below 16 years of age featured a marked depletion of this species. In CD patients, correlation between A. muciniphila and total F. prausnitzii (ρ = 0.362, P = 0.045) was observed, and particularly in those with non-stricturing, non-penetrating disease behavior and under moderate immunosuppressants therapy. Altogether, this study revealed that co-occurrence of both species differs between disease status. In addition, IBD patients featured a reduction of F. prausnitzii but similar loads of A. muciniphila when compared to H subjects, with the exception of those with early onset CD. Depletion of A. muciniphila in this subgroup of subjects suggests that it could be a potential biomarker to assist in pediatric CD diagnosis.


Assuntos
Colo/microbiologia , Faecalibacterium prausnitzii/isolamento & purificação , Doenças Inflamatórias Intestinais/microbiologia , Mucosa Intestinal/microbiologia , Verrucomicrobia/isolamento & purificação , Adulto , Idoso , Idoso de 80 Anos ou mais , Carga Bacteriana , Biópsia , Coinfecção/microbiologia , Feminino , Infecções por Bactérias Gram-Negativas/microbiologia , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , RNA Ribossômico 16S/genética , Reação em Cadeia da Polimerase em Tempo Real , Adulto Jovem
8.
Helicobacter ; 23(5): e12529, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30141228

RESUMO

OBJECTIVE: To evaluate the safety, tolerability and efficacy of a probiotic supplementation for Helicobacter pylori (H. pylori) eradication therapy. DESIGN: Consecutive adult naive patients with a diagnosis of H. pylori infection who were prescribed eradication therapy according to clinical practice (10-day triple or nonbismuth quadruple concomitant therapy) randomly received probiotics (1 × 109 colony-forming units each strain, Lactobacillus plantarum and Pediococcus acidilactici) or matching placebo. Side effects at the end of the treatment, measured through a modified De Boer Scale, were the primary outcome. Secondary outcomes were compliance with therapy and eradication rates. RESULTS: A total of 209 patients (33% triple therapy, 66% non-bismuth quadruple therapy) were included [placebo (n = 106) or probiotic (n = 103)]. No differences were observed regarding side effects at the end of the treatment between groups (ß -0.023, P 0.738). Female gender (P < 0.001) and quadruple therapy (P 0.007) were independent predictors of side effects. No differences in compliance were observed, regardless of the study group or eradication therapy. Eradication rates were similar between groups [placebo 95% (95% confidence interval (CI), 89% to 98%) vs probiotic 97% (95% CI, 92% to 99%), P 0.721]. There were no relevant differences in cure rates (>90% in all cases) between triple and quadruple concomitant therapy. CONCLUSION: Probiotic supplementation containing Lactobacillus Plantarum and Pediococcus acidilactici to H. pylori treatment neither decreased side effects nor improved compliance with therapy or eradication rates.


Assuntos
Antibacterianos/uso terapêutico , Infecções por Helicobacter/tratamento farmacológico , Lactobacillus plantarum/fisiologia , Pediococcus acidilactici/fisiologia , Probióticos/uso terapêutico , Adulto , Amoxicilina/uso terapêutico , Claritromicina/uso terapêutico , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Helicobacter pylori/efeitos dos fármacos , Helicobacter pylori/patogenicidade , Humanos , Masculino , Metronidazol/uso terapêutico , Pessoa de Meia-Idade
9.
Gastroenterol. hepatol. (Ed. impr.) ; 39(1): 9-19, ene. 2016. graf, tab
Artigo em Inglês | IBECS | ID: ibc-149315

RESUMO

Objectives: To estimate the management of UC associated costs from the societal perspective in Spain. Methods: Observational, longitudinal study with retrospective data collection based on reviews of outpatient health records. Socio-demographic, clinical and sick leave information was gathered. Patients diagnosed of UC between 2002 and 2012, older than 18 years, followed-up by a minimum of 12 months post diagnosis, with at least two clinical and use of resources data recorded, were included. Results: 285 UC patients [51.2% men; 44.5 (SD: 15.6) years old; 88.4% without family history of UC; 39.3% proctitis; 5.6 (2.5) years disease follow-up] participated. More than half (65.6%) were active workers, 75.9% were on sick leave for reasons different from UC [mean 0.66 (0.70) times per year] during (mean) 28.43 (34.45) days. Only 64 patients were on UC-related sick-leaves, lasting (mean) 26.17 (37.43) days. Absenteeism due to medical visits caused loss of 29.55 (21.38) working hours per year. Mean direct and indirect annual cost per UC patient were €1754.10 (95%CI: 1473.37–2034.83) and €399.32 (282.31–422.69), respectively. Absenteeism was estimated at €88.21(32.72–50.06) per patient per year, in which sick-leaves were the main component of indirect costs (88.2%). Age, UC family history, diarrhea at diagnosis, blood and blood-forming organs diseases and psychological disorders were the main predictors of indirect costs. Conclusions: UC is a costly disease for the society and the Spanish National Healthcare System. Indirect costs imply a major burden by affecting the most productive years of patients. Further research is needed considering all components of productivity loss, including presenteeism-associated costs (AU)


Objetivos: Evaluar la gestión de los gastos asociados a la CU desde la perspectiva social en España. Métodos: Estudio observacional, longitudinal con recopilación de datos retrospectiva basado en reseñas de registros sanitarios ambulatorios. Se compiló información sociodemográfica, clínica y de bajas por enfermedad. Se incluyó a aquellos pacientes diagnosticados con CU entre 2002 y 2012, mayores de 18 años, con un seguimiento después del diagnóstico como mínimo a los 12 meses y con al menos 2 de los datos clínicos y de uso de recursos registrados. Resultados: Participaron 285 pacientes con CU (51,2% hombres; 44,5 ± 15,6 años); 88,4% sin antecedentes familiares de CU; 39,3% proctitis; 5,6 ± 2,5 años de seguimiento de la enfermedad). Más de la mitad (65,6%) eran trabajadores en activo, un 75,9% estaban de baja por enfermedad por motivos ajenos a la CU (un promedio de 0,66 [0,70] veces al año) durante (media ± desviación estándar) 28,43 ± 34,45 días. Solo 64 pacientes estuvieron de baja por enfermedad relacionada con la CU, con una duración (media) de 26,17 ± 37,43 días. El absentismo ocasionado por las visitas al médico originó una pérdida de 29,55 ± 21,38 hs de trabajo al año. El promedio directo e indirecto del coste anual por cada paciente con CU fue de 1.754,10 € (IC95%, 1.473,37-2.034,83) y de 399,32€ (282,31-422,69), respectivamente. El absentismo se calculó en 88,21€ (32,72-50,06) por paciente al año, donde las bajas médicas son el mayor componente de los gastos indirectos (88,3%). La edad, los antecedentes familiares, la diarrea en el momento de diagnóstico, las enfermedades sanguíneas o de los órganos hematopoyéticos y los trastornos psicológicos fueron los principales factores predisponentes de los gastos indirectos. Conclusiones: La CU es una enfermedad costosa para la sociedad y el Sistema Nacional de Salud español. Los gastos indirectos suponen una gran carga, al afectar a los años más productivos de los pacientes. Se precisa una mayor investigación que tenga en cuenta todos los componentes de la pérdida de productividad, entre otros los gastos asociados al presentismo laboral (AU)


Assuntos
Humanos , Colite Ulcerativa/epidemiologia , Custos de Cuidados de Saúde/estatística & dados numéricos , Registros de Doenças/estatística & dados numéricos , Colite Ulcerativa/economia , Efeitos Psicossociais da Doença
10.
Gastroenterol Hepatol ; 39(1): 9-19, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26211705

RESUMO

OBJECTIVES: To estimate the management of UC associated costs from the societal perspective in Spain. METHODS: Observational, longitudinal study with retrospective data collection based on reviews of outpatient health records. Socio-demographic, clinical and sick leave information was gathered. Patients diagnosed of UC between 2002 and 2012, older than 18 years, followed-up by a minimum of 12 months post diagnosis, with at least two clinical and use of resources data recorded, were included. RESULTS: 285 UC patients [51.2% men; 44.5 (SD: 15.6) years old; 88.4% without family history of UC; 39.3% proctitis; 5.6 (2.5) years disease follow-up] participated. More than half (65.6%) were active workers, 75.9% were on sick leave for reasons different from UC [mean 0.66 (0.70) times per year] during (mean) 28.43 (34.45) days. Only 64 patients were on UC-related sick-leaves, lasting (mean) 26.17 (37.43) days. Absenteeism due to medical visits caused loss of 29.55 (21.38) working hours per year. Mean direct and indirect annual cost per UC patient were €1754.10 (95%CI: 1473.37-2034.83) and €399.32 (282.31-422.69), respectively. Absenteeism was estimated at €88.21(32.72-50.06) per patient per year, in which sick-leaves were the main component of indirect costs (88.2%). Age, UC family history, diarrhea at diagnosis, blood and blood-forming organs diseases and psychological disorders were the main predictors of indirect costs. CONCLUSIONS: UC is a costly disease for the society and the Spanish National Healthcare System. Indirect costs imply a major burden by affecting the most productive years of patients. Further research is needed considering all components of productivity loss, including presenteeism-associated costs.


Assuntos
Colite Ulcerativa/economia , Efeitos Psicossociais da Doença , Absenteísmo , Adulto , Feminino , Custos de Cuidados de Saúde , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Programas Nacionais de Saúde , Estudos Retrospectivos , Espanha
11.
Inflamm Bowel Dis ; 22(1): 28-41, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26595550

RESUMO

BACKGROUND: Faecalibacterium prausnitzii comprises 2 phylogroups, whose abundance in healthy and diseased gut and in conjunction with Escherichia coli has not yet been studied. This work aims to determine the contribution of F. prausnitzii phylogroups I and II in intestinal disease and to assess their potential diagnostic usefulness as biomarkers for gut diseases. METHODS: Total F. prausnitzii, its phylogroups, and E. coli loads were determined by quantitative polymerase chain reaction targeting the 16S rRNA gene on biopsies from 31 healthy controls (H), 45 patients with Crohn's disease (CD), 25 patients with ulcerative colitis, 10 patients with irritable bowel syndrome, and 20 patients with colorectal cancer. Data were normalized to total bacterial counts and analyzed according to patients' disease location and clinical characteristics. RESULTS: Lower levels of both total F. prausnitzii and phylogroup I were found in subjects with CD, ulcerative colitis, and colorectal cancer (P < 0.001) compared with H subjects. Phylogroup I load was a better biomarker than total F. prausnitzii to discriminate subjects with gut disorders from H. Phylogroup II depletion was observed only in patients with CD (P < 0.001) and can be potentially applied to differentiate ulcerative pancolitis from colonic CD. No statistically significant correlation between E. coli and any of the 2 F. prausnitzii phylogroups was found in any group of patients or by inflammatory bowel disease location. Phylogroup I was lower in active patients with CD, whereas those CD with intestinal resection showed a reduction in phylogroup II. Treatments with mesalazine and immunosuppressants did not result in the recovery of F. prausnitzii phylogroups abundance. CONCLUSIONS: F. prausnitzii phylogroup I was depleted in CD, ulcerative colitis, and colorectal cancer, whereas phylogroup II was specifically reduced in CD. Quantification of F. prausnitzii phylogroups and E. coli may help to identify gut disorders and to classify inflammatory bowel disease location.


Assuntos
Neoplasias Colorretais/microbiologia , Bactérias Gram-Positivas/classificação , Bactérias Gram-Positivas/isolamento & purificação , Infecções por Bactérias Gram-Positivas/microbiologia , Doenças Inflamatórias Intestinais/microbiologia , Mucosa Intestinal/microbiologia , Adulto , Estudos de Casos e Controles , Estudos de Coortes , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/genética , DNA Bacteriano/genética , Feminino , Seguimentos , Bactérias Gram-Positivas/genética , Infecções por Bactérias Gram-Positivas/diagnóstico , Infecções por Bactérias Gram-Positivas/epidemiologia , Infecções por Bactérias Gram-Positivas/genética , Humanos , Doenças Inflamatórias Intestinais/diagnóstico , Doenças Inflamatórias Intestinais/epidemiologia , Doenças Inflamatórias Intestinais/genética , Masculino , Pessoa de Meia-Idade , Filogenia , Prevalência , Prognóstico , RNA Ribossômico 16S/genética , Reação em Cadeia da Polimerase em Tempo Real
12.
Appl Environ Microbiol ; 81(21): 7582-92, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26296733

RESUMO

Faecalibacterium prausnitzii depletion in intestinal diseases has been extensively reported, but little is known about intraspecies variability. This work aims to determine if subjects with gastrointestinal disease host mucosa-associated F. prausnitzii populations different from those hosted by healthy individuals. A new species-specific PCR-denaturing gradient gel electrophoresis (PCR-DGGE) method targeting the 16S rRNA gene was developed to fingerprint F. prausnitzii populations in biopsy specimens from 31 healthy control (H) subjects and 36 Crohn's disease (CD), 23 ulcerative colitis (UC), 6 irritable bowel syndrome (IBS), and 22 colorectal cancer (CRC) patients. The richness of F. prausnitzii subtypes was lower in inflammatory bowel disease (IBD) patients than in H subjects. The most prevalent operational taxonomic units (OTUs) consisted of four phylotypes (OTUs with a 99% 16S rRNA gene sequence similarity [OTU99]), which were shared by all groups of patients. Their distribution and the presence of some disease-specific F. prausnitzii phylotypes allowed us to differentiate the populations in IBD and CRC patients from that in H subjects. At the level of a minimum similarity of 97% (OTU97), two phylogroups accounted for 98% of the sequences. Phylogroup I was found in 87% of H subjects but in under 50% of IBD patients (P = 0.003). In contrast, phylogroup II was detected in >75% of IBD patients and in only 52% of H subjects (P = 0.005). This study reveals that even though the main members of the F. prausnitzii population are present in both H subjects and individuals with gut diseases, richness is reduced in the latter and an altered phylotype distribution exists between diseases. This approach may serve as a basis for addressing the suitability of F. prausnitzii phylotypes to be quantified as a putative biomarker of disease and depicting the importance of the loss of these subtypes in disease pathogenesis.


Assuntos
Clostridiales/classificação , Clostridiales/isolamento & purificação , Variação Genética , Genótipo , Doenças Inflamatórias Intestinais/microbiologia , Mucosa Intestinal/microbiologia , Biópsia , Clostridiales/genética , Análise por Conglomerados , DNA Bacteriano/química , DNA Bacteriano/genética , DNA Ribossômico/química , DNA Ribossômico/genética , Eletroforese em Gel de Gradiente Desnaturante , Humanos , Dados de Sequência Molecular , Filogenia , Reação em Cadeia da Polimerase , RNA Ribossômico 16S/genética , Análise de Sequência de DNA
13.
J Crohns Colitis ; 9(10): 899-906, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26142465

RESUMO

BACKGROUND: The composition of the intestinal microbiota is altered in Crohn's disease [CD] patients. The objective of this study was to evaluate the qualitative and quantitative changes in the microbiota of CD patients in 3 months of treatment with adalimumab [ADA], and determine whether or not these changes are produced towards the recovery of the normal, healthy-like microbiota. METHODS: The microbiota composition, and the Faecalibacterium prausnitzii / Escherichia coli quantitative relationship as dysbiosis indicator, were studied at baseline [T0], one month [T1], and 3 months [T3] after starting treatment using a polymerase chain reaction-denaturing gradient gel electrophoresis [PCR-DGGE] of 16S rRNA gene fragments and quantitative PCR, respectively, in rectal mucosal biopsies from 15 CD patients and four healthy subjects. RESULTS: T0 and T3 fingerprints were different in all patients; whereas T1 and T3 presented similar patterns. Recovered phylogroups were Firmicutes [79.1%], Bacteroides [12.5%], and Actinobacteria [6.25%]. The prevalence of E. coli decreased during treatment. Relative E. coli loads in CD samples were significantly reduced at every analysed step [T1 and T3] [p < 0.005] whereas no significant changes were observed in relative F. prausnitzii counts. CONCLUSION: Treatment with ADA induces short-term changes in the microbiota composition which seem to parallel the partial recovery of the gut bacterial ecology, with recovery parameters tending to eubiosis recovery. The quantitative determination of dysbiosis-representative bacteria, such as E. coli, may provide a fast and reliable indicator of the healing state of the intestinal mucosa.


Assuntos
Adalimumab/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Doença de Crohn/tratamento farmacológico , Doença de Crohn/microbiologia , Microbioma Gastrointestinal/efeitos dos fármacos , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Mucosa Intestinal/microbiologia , Masculino , Pessoa de Meia-Idade , Adulto Jovem
14.
Int J Med Microbiol ; 304(3-4): 464-75, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24713205

RESUMO

BACKGROUND: Crohn's disease (CD) and ulcerative colitis (UC) diagnosis requires comprehensive examination of the patient. Faecalibacterium prausnitzii and Escherichia coli have been reported as representatives of Inflammatory Bowel Disease (IBD) dysbiosis. The aim was to determine whether or not quantification of these species can be used as a complementary tool either for diagnostic or prognostic purposes. METHODS: Mucosa-associated F. prausnitzii and E. coli abundance was determined in 28 controls (H), 45 CD, 28 UC patients and 10 irritable bowel syndrome (IBS) subjects by quantitative polymerase chain reaction (qPCR) and the F. prausnitzii-E. coli index (F-E index) was calculated. Species abundances were normalized to total bacteria and human cells. Data was analyzed taking into account patients' phenotype and most relevant clinical characteristics. RESULTS: IBD patients had lower F. prausnitzii abundance than H and IBS (P<0.001). CD patients showed higher E. coli counts than H and UC patients (P<0.001). The F-E index discriminated between H, CD and UC patients, and even between disease phenotypes that are usually difficult to distinguish as ileal-CD (I-CD) from ileocolonic-CD and colonic-CD from extensive colitis. E. coli increased in active CD patients, and remission in I-CD patients was compromised by high abundance of this species. Treatment with anti-tumor necrosis factor (TNF) α diminished E. coli abundance in I-CD whereas none of the treatments counterbalanced F. prausnitzii depletion. CONCLUSION: F. prausnitzii and E. coli are useful indicators to assist in IBD phenotype classification. The abundance of these species could also be used as a supporting prognostic tool in I-CD patients. Our data indicates that current medication does not restore the levels of these two species to those found in a healthy gut.


Assuntos
Carga Bacteriana , Escherichia coli/isolamento & purificação , Bactérias Gram-Positivas/isolamento & purificação , Doenças Inflamatórias Intestinais/microbiologia , Mucosa Intestinal/microbiologia , Síndrome do Intestino Irritável/microbiologia , Adolescente , Adulto , Estudos de Coortes , Feminino , Humanos , Doenças Inflamatórias Intestinais/diagnóstico , Síndrome do Intestino Irritável/diagnóstico , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase em Tempo Real , Adulto Jovem
15.
Inflamm Bowel Dis ; 19(7): 1404-10, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23665964

RESUMO

BACKGROUND: To evaluate the safety of thiopurines in patients with inflammatory bowel disease. To identify predictive factors associated with the development of thiopurine-induced adverse events. METHODS: Long-term incidence of adverse events was estimated in patients from a prospectively maintained Spanish nationwide database using Kaplan-Meier analysis. Cox regression analysis was performed to identify potential predictive factors of adverse events. RESULTS: Three thousand nine hundred and thirty-one patients were included. Ninety-five percent of patients were on azathioprine. The median follow-up with thiopurines was 44 months (range, 0-420). Adverse events occurred at a median of 1 month after starting treatment. The cumulative incidence of adverse events was 26%, with an annual risk of 7% per patient-year of treatment. Most frequent adverse events were nausea (8%), hepatotoxicity (4%), myelotoxicity (4%), and pancreatitis (4%). Four patients had lymphoma. Female and Crohn's disease increased the risk of having nausea. The risk of hepatotoxicity was lower in females and higher in Crohn's disease. The risk of myelotoxicity was significantly higher in patients treated with mercaptopurine and in females. The risk of pancreatitis was higher in Crohn's disease. Overall, 17% of patients discontinued thiopurine treatment due to adverse events. Thirty-seven percent of these patients started thiopurines again and 40% of them had adverse events again. CONCLUSIONS: As many as 1 of 4 patients on thiopurine therapy had adverse events during follow-up. A relatively high proportion of patients (17%) had to discontinue the treatment with thiopurines due to adverse events. However, more than half of patients that restarted thiopurine treatment after its discontinuation due to adverse events tolerated it. Several predictive factors for some adverse events have been identified.


Assuntos
Azatioprina/efeitos adversos , Colite Ulcerativa/complicações , Doença de Crohn/complicações , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Imunossupressores/efeitos adversos , Adulto , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/mortalidade , Doença de Crohn/tratamento farmacológico , Doença de Crohn/mortalidade , Feminino , Seguimentos , Humanos , Masculino , Prognóstico , Estudos Prospectivos , Fatores de Risco , Taxa de Sobrevida
18.
BMC Microbiol ; 9: 202, 2009 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-19772580

RESUMO

BACKGROUND: Crohn's disease (CD) is a high morbidity chronic inflammatory disorder of unknown aetiology. Adherent-invasive Escherichia coli (AIEC) has been recently implicated in the origin and perpetuation of CD. Because bacterial biofilms in the gut mucosa are suspected to play a role in CD and biofilm formation is a feature of certain pathogenic E. coli strains, we compared the biofilm formation capacity of 27 AIEC and 38 non-AIEC strains isolated from the intestinal mucosa. Biofilm formation capacity was then contrasted with the AIEC phenotype, the serotype, the phylotype, and the presence of virulence genes. RESULTS: Specific biofilm formation (SBF) indices were higher amongst AIEC than non-AIEC strains (P = 0.012). In addition, 65.4% of moderate to strong biofilms producers were AIEC, whereas 74.4% of weak biofilm producers were non-AIEC (P = 0.002). These data indicate that AIEC strains were more efficient biofilm producers than non-AIEC strains. Moreover, adhesion (P = 0.009) and invasion (P = 0.003) indices correlated positively with higher SBF indices. Additionally, motility (100%, P < 0.001), H1 type flagellin (53.8%, P < 0.001), serogroups O83 (19.2%, P = 0.008) and O22 (26.9%, P = 0.001), the presence of virulence genes such as sfa/focDE (38.5%, P = 0.003) and ibeA (26.9%, P = 0.017), and B2 phylotype (80.8%, P < 0.001) were frequent characteristics amongst biofilm producers. CONCLUSION: The principal contribution of the present work is the finding that biofilm formation capacity is a novel, complementary pathogenic feature of the recently described AIEC pathovar. Characterization of AIEC specific genetic determinants, and the regulatory pathways, involved in biofilm formation will likely bring new insights into AIEC pathogenesis.


Assuntos
Biofilmes , Infecções por Escherichia coli/microbiologia , Escherichia coli/genética , Mucosa Intestinal/microbiologia , Aderência Bacteriana , Linhagem Celular , Doença de Crohn/microbiologia , Escherichia coli/classificação , Escherichia coli/crescimento & desenvolvimento , Genótipo , Humanos , Fenótipo , Sorotipagem
19.
Inflamm Bowel Dis ; 15(6): 872-82, 2009 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19235912

RESUMO

BACKGROUND: Escherichia coli, particularly the adherent-invasive E. coli (AIEC) pathovar, has been increasingly implicated in the ethiopathogenesis of Crohn's disease (CD). We describe the richness, abundance, diversity, and pathogenic features of E. coli and AIEC strains that colonize the intestinal mucosa. METHODS: Approximately 100 E. coli colonies per biopsy from 20 CD patients (18 biopsies from colon and 23 from ileum) and 28 healthy controls (C) (25, colon; 27, ileum) were isolated. Repetitive extragenic palindrome-polymerase chain reaction (Rep-PCR) and pulsed field gel electrophoresis (PFGE) were used to analyze the clonality of isolates. For AIEC identification, adhesion and invasion assays were performed over Intestine-407 cells, and the capacity to survive and replicate intracellularly was determined over macrophages J774. The serotypes, phylotypes, and genotypes (19 virulence genes) of strains were also investigated. RESULTS: Mucosa-associated E. coli richness (E. coli subtypes/patient: C = 2.0 +/- 1.0; CD = 2.1 +/- 1.3) and diversity (Shannon Index: H'(C): 2.1 +/- 0.6; H'(CD): 2.5 +/- 0.8) were similar between CD and C, but higher E. coli counts were characteristic of CD patients (P = 0.010), particularly those with Crohn's ileitis (P = 0.001). Host-specific pulsotypes shared virulence features of ExPEC at similar frequencies between CD and C, except for iucD, which was more prevalent in E. coli from controls (C: 75%, CD: 40%, P = 0.027). In contrast, greater AIEC prevalence (% subjects with AIEC: CD = 51.9%; C = 16.7%; P = 0.003), abundance (% AIEC/E. coli: CD = 3.8 +/- 5.0%; C = 1.5 +/- 3.8%; P = 0.039), and richness (number of AIEC subtypes: CD = 0.8 +/- 1.4; C = 0.2 +/- 0.4; P = 0.015) of E. coli strains belonging to the AIEC pathovar was observed for CD patients. AIEC subtypes showed a high variability of seropathotypes and pulsotypes, although the B2 phylogroup was the most prevalent (AIEC: 64%, non-AIEC: 38%, P = 0.044). CONCLUSIONS: New data about ecological parameters of AIEC reinforces the implication of AIEC in CD.


Assuntos
Doença de Crohn/microbiologia , Infecções por Escherichia coli/microbiologia , Escherichia coli/classificação , Escherichia coli/genética , Mucosa Intestinal/microbiologia , Adulto , Aderência Bacteriana , Biópsia , Linhagem Celular , Doença de Crohn/epidemiologia , Doença de Crohn/patologia , Células Epiteliais/citologia , Células Epiteliais/microbiologia , Escherichia coli/patogenicidade , Infecções por Escherichia coli/epidemiologia , Infecções por Escherichia coli/patologia , Feminino , Variação Genética , Humanos , Ileíte/epidemiologia , Ileíte/microbiologia , Ileíte/patologia , Mucosa Intestinal/patologia , Macrófagos/citologia , Macrófagos/microbiologia , Masculino , Pessoa de Meia-Idade , Fenótipo , Prevalência , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Virulência , Adulto Jovem
20.
Inflamm Bowel Dis ; 12(12): 1136-45, 2006 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-17119388

RESUMO

BACKGROUND: Bacteria might play a role in the pathogenesis of Crohn's disease (CD), and patients harbor a different type and density of gut microbiota compared with normal healthy subjects. Thus, the aim of this study was to compare the microbiota adhered to the mucosa of CD patients with that of healthy subjects. METHODS: Polymerase chain reaction-denaturing gradient gel electrophoresis (PCR-DGGE) of 16S rRNA gene fragments was used to identify the dominant bacterial species present in fresh biopsy samples obtained from the mucosa of 15 healthy and 19 CD subjects. Two patients suffering from ulcerative colitis and 1 suffering from ischemic colitis also were included. RESULTS: Individuals were clustered in 2 groups according to their molecular fingerprint, which differentiated the majority of CD specimens (88.2%) from the majority of healthy/ulcerative colitis/ischemic colitis specimens (82.3%). In addition, the patient-to-patient variability in microbiota was greater within the CD cluster than in the healthy/ulcerative colitis cluster (P = 0.000). One hundred forty-one sequences were obtained from the PCR-DGGE bands that were grouped into 58 different phylotypes, 8 of which were novel. BLAST analysis revealed that 74.5% of the sequences were similar to those of bacteria that have never been cultivated. In CD samples, prevalence values for Clostridium spp Ruminococcus torques and Escherichia coli were significantly higher, whereas Faecalibacterium was more frequently found in healthy specimens. Opportunistic pathogenic gamma-proteobacteria were found occasionally, only in CD mucosal microbiota. CONCLUSIONS: Microbiota attached to the ileocolonic mucosa of CD patients is distinguishable from that of healthy subjects. We postulate that individuals who are predisposed to CD are less able to regulate the microbial makeup of their intestines, which leads to an unstable microbial population.


Assuntos
Doença de Crohn/microbiologia , Eletroforese em Gel de Poliacrilamida/métodos , Ileíte/microbiologia , Mucosa Intestinal/microbiologia , Reação em Cadeia da Polimerase/métodos , Adulto , Estudos de Casos e Controles , Análise por Conglomerados , Impressões Digitais de DNA , DNA Bacteriano/genética , DNA Bacteriano/isolamento & purificação , Feminino , Humanos , Masculino , Filogenia , RNA Ribossômico 16S/análise , RNA Ribossômico 16S/genética , Análise de Sequência de DNA
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