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BACKGROUND & AIMS: Patients with inflammatory bowel disease (IBD) frequently develop extraintestinal manifestations (EIMs) that contribute substantially to morbidity. We assembled the largest multicohort data set to date to investigate the clinical, serologic, and genetic factors associated with EIM complications in IBD. METHODS: Data were available in 12,083 unrelated European ancestry IBD cases with presence or absence of EIMs (eg, ankylosing spondylitis [ankylosing spondylitis and sacroiliitis], primary sclerosing cholangitis [PSC], peripheral arthritis, and skin and ocular manifestations) across 4 cohorts (Cedars-Sinai Medical Center, National Institute for Diabetes and Digestive and Kidney Diseases IBD Genetics Consortium, Sinai Helmsley Alliance for Research Excellence Consortium, and Risk Stratification and Identification of Immunogenetic and Microbial Markers of Rapid Disease Progression in Children with Crohn's Disease cohort). Clinical and serologic parameters were analyzed by means of univariable and multivariable regression analyses using a mixed-effects model. Within-case logistic regression was performed to assess genetic associations. RESULTS: Most EIMs occurred more commonly in female subjects (overall EIM: P = 9.0E-05, odds ratio [OR], 1.2; 95% CI, 1.1-1.4), with CD (especially colonic disease location; P = 9.8E-09, OR, 1.7; 95% CI, 1.4-2.0), and in subjects who required surgery (both CD and UC; P = 3.6E-19, OR, 1.7; 95% CI, 1.5-1.9). Smoking increased risk of EIMs except for PSC, where there was a "protective" effect. Multiple serologic associations were observed, including with PSC (anti-nuclear cytoplasmic antibody; IgG and IgA, anti-Saccharomyces cerevisiae antibodies; and anti-flagellin) and any EIM (anti-nuclear cytoplasmic antibody; IgG and IgA, anti-Saccharomyces cerevisiae antibodies; and anti-Pseudomonas fluorescens-associated sequence). We identified genome-wide significant associations within major histocompatibility complex (ankylosing spondylitis and sacroiliitis, P = 1.4E-15; OR, 2.5; 95% CI, 2.0-3.1; PSC, P = 2.7E-10; OR, 2.8; 95% CI, 2.0-3.8; ocular, P = 2E-08, OR, 3.6; 95% CI, 2.3-5.6; and overall EIM, P = 8.4E-09; OR, 2.2; 95% CI, 1.7-2.9) and CPEB4 (skin, P = 2.7E-08; OR, 1.5; 95% CI, 1.3-1.8). Genetic associations implicated tumor necrosis factor, JAK-STAT, and IL6 as potential targets for EIMs. Contrary to previous reports, only 2% of our subjects had multiple EIMs and most co-occurrences were negatively correlated. CONCLUSIONS: We have identified demographic, clinical, and genetic associations with EIMs that revealed underlying mechanisms and implicated novel and existing drug targets-important steps toward a more personalized approach to IBD management.
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Colangite Esclerosante , Colite Ulcerativa , Doença de Crohn , Humanos , Feminino , Masculino , Adulto , Colangite Esclerosante/imunologia , Colangite Esclerosante/genética , Colangite Esclerosante/diagnóstico , Colangite Esclerosante/complicações , Pessoa de Meia-Idade , Colite Ulcerativa/imunologia , Colite Ulcerativa/genética , Colite Ulcerativa/diagnóstico , Doença de Crohn/imunologia , Doença de Crohn/genética , Doença de Crohn/diagnóstico , Adolescente , Fatores de Risco , Criança , Espondilite Anquilosante/genética , Espondilite Anquilosante/imunologia , Espondilite Anquilosante/diagnóstico , Espondilite Anquilosante/complicações , Predisposição Genética para Doença , Adulto Jovem , Fatores Sexuais , Dermatopatias/etiologia , Dermatopatias/imunologia , Dermatopatias/genética , Oftalmopatias/etiologia , Oftalmopatias/imunologia , Oftalmopatias/diagnóstico , Oftalmopatias/genética , Oftalmopatias/epidemiologia , Fenótipo , Doenças Inflamatórias Intestinais/genética , Doenças Inflamatórias Intestinais/imunologia , Doenças Inflamatórias Intestinais/diagnóstico , Modelos Logísticos , IdosoRESUMO
OBJECTIVE: Perianal Crohn's disease (pCD) occurs in up to 40% of patients with CD and is associated with poor quality of life, limited treatment responses and poorly understood aetiology. We performed a genetic association study comparing CD subjects with and without perianal disease and subsequently performed functional follow-up studies for a pCD associated SNP in Complement Factor B (CFB). DESIGN: Immunochip-based meta-analysis on 4056 pCD and 11 088 patients with CD from three independent cohorts was performed. Serological and clinical variables were analysed by regression analyses. Risk allele of rs4151651 was introduced into human CFB plasmid by site-directed mutagenesis. Binding of recombinant G252 or S252 CFB to C3b and its cleavage was determined in cell-free assays. Macrophage phagocytosis in presence of recombinant CFB or serum from CFB risk, or protective CD or healthy subjects was assessed by flow cytometry. RESULTS: Perianal complications were associated with colonic involvement, OmpC and ASCA serology, and serology quartile sum score. We identified a genetic association for pCD (rs4151651), a non-synonymous SNP (G252S) in CFB, in all three cohorts. Recombinant S252 CFB had reduced binding to C3b, its cleavage was impaired, and complement-driven phagocytosis and cytokine secretion were reduced compared with G252 CFB. Serine 252 generates a de novo glycosylation site in CFB. Serum from homozygous risk patients displayed significantly decreased macrophage phagocytosis compared with non-risk serum. CONCLUSION: pCD-associated rs4151651 in CFB is a loss-of-function mutation that impairs its cleavage, activation of alternative complement pathway, and pathogen phagocytosis thus implicating the alternative complement pathway and CFB in pCD aetiology.
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Fator B do Complemento , Doença de Crohn , Humanos , Fator B do Complemento/genética , Doença de Crohn/complicações , Qualidade de Vida , Seguimentos , FagocitoseRESUMO
BACKGROUND: Multiple biologics are available to treat inflammatory bowel disease (IBD), which can either be administered subcutaneously or intravenously. The factors that determine patients' preferences for SC/IV administration in IBD are largely unknown. This study aims to elucidate how IBD patients trade off between medications' route of administration and other medication characteristics and to understand what drives patients' preferences. METHODS: We employed a mixed methods design using data from a prior quantitative conjoint analysis survey and a series of 22 qualitative interviews. We quantitatively assessed individual patients' preferences for subcutaneous (SC) or intravenous (IV) medications based on the part-worth utilities derived from the conjoint analysis and identified predictors for these preferences. We used a qualitative analysis to identify key themes surrounding patients' preferences in the interview data. RESULTS: Of 1,077 survey participants, 49% preferred an SC medication every 2 weeks, whereas 51% preferred an IV medication every 8 weeks. More people preferred SC at reduced administration frequencies, whereas less people preferred SC at the expense of lower efficacy or higher side-effects rates. Prior experience with SC/IV was the strongest predictor for patients' preferences. Qualitatively, we obtained in-depth insights in the perceived advantages and disadvantages of SC and IV medications and in patients' preconceived ideas. CONCLUSION: While prior SC/IV exposure was a strong predictor for SC/IV preferences, patients' preferences largely are determined by a variety of other personal factors. The themes we identified could help guide clinicians when discussing therapeutic options with their patients and support shared decision-making.
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Doenças Inflamatórias Intestinais , Preferência do Paciente , Humanos , Injeções Subcutâneas , Doenças Inflamatórias Intestinais/tratamento farmacológico , Administração Intravenosa , Inquéritos e QuestionáriosRESUMO
INTRODUCTION: To support shared decision-making (SDM) between patients and providers surrounding biologic treatments, we created IBD&me ( ibdandme.org )-a freely available, unbranded, interactive decision aid. We performed a multicenter comparative effectiveness trial comparing the impact of IBD&me on SDM vs a biologics fact sheet developed by the Crohn's & Colitis Foundation. METHODS: We enrolled patients with inflammatory bowel disease (IBD) being seen at a clinic within IBD Qorus-a multicenter adult IBD learning health system-between March 5, 2019, and May 14, 2021. Eligible patients included those with recent IBD-related symptoms who reported that they wanted to discuss biologics with their provider during their upcoming visit. Patients were randomized 1:1 using stratified block randomization and received an e-mail 1 week before their visit inviting them to review either IBD&me or a fact sheet. The primary outcome was patient perception of SDM as measured by the 9-Item SDM Questionnaire (0-100 scale; higher = better); the Student t test was used to compare outcomes between arms. RESULTS: Overall, 152 patients were randomized (biologics fact sheet 75, IBD&me 77); most patients had Crohn's disease (66.4%) and were biologic-experienced (82.9%). No differences were seen between groups regarding SDM (fact sheet 72.6 ± 25.6, IBD&me 75.0 ± 20.8; P = .57). Most patients stated they would be likely to recommend the fact sheet (79.6%) or IBD&me (84.9%; P = .48) to another patient with IBD. DISCUSSION: No differences in outcomes were seen between IBD&me and the biologics fact sheet in this comparative effectiveness study; patients reported high satisfaction with both resources. Further study, particularly among biologic naïve patients, is needed to determine the utility of interactive components to IBD decision aids.
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Produtos Biológicos , Doença de Crohn , Doenças Inflamatórias Intestinais , Adulto , Produtos Biológicos/uso terapêutico , Doença Crônica , Doença de Crohn/terapia , Técnicas de Apoio para a Decisão , Humanos , Doenças Inflamatórias Intestinais/tratamento farmacológicoRESUMO
INTRODUCTION: To broadly disseminate 5 user-centered educational videos for patients with inflammatory bowel disease and their family and friends on social media. METHODS: Relevant social media users were iteratively identified based on their online behavior. For each video, 2 different accompanying texts were tested. RESULTS: We reached 4.2 million social media users of whom 320,302 watched at least 50% of the video. A short description resulted in higher view rates than posing an open-ended question. DISCUSSION: We showed the feasibility of large-scale dissemination of health-related educational videos through social media. Our findings can inform future online dissemination approaches of educational content.
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Doenças Inflamatórias Intestinais , Mídias Sociais , Humanos , Disseminação de Informação/métodos , Gravação em Vídeo/métodosRESUMO
OBJECTIVE: We developed five educational videos through a user-centered approach for patients with inflammatory bowel diseases (IBD) and their families and friends. Here, we assessed if IBD patient activation and family and friends' abilities to understand IBD patients' thoughts, feelings, and behaviors (i.e., perspective taking) changed after watching the videos. METHODS: Through a pre-post survey, we assessed patient activation and perspective taking levels in people with a self-reported IBD diagnosis and their family and friends, respectively, before and after watching one of the videos. RESULTS: Among 767 participants with IBD, patient activation scores increased significantly after watching each video. In regression analyses, patient activation levels were less likely to increase in biologic-naïve participants after viewing the coping video. Among 232 people who knew someone with IBD, perspective taking scores increased significantly in 8/9 domains, which was more likely to occur among women. CONCLUSIONS: Educational videos developed through a user-centered approach were associated with higher self-reported IBD patient activation scores and perspective taking levels among family and friends. PRACTICE IMPLICATIONS: These videos, which are now widely disseminated on social media, serve as a model for how to create educational materials for improving patient activation and empathy in the social media era.
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Doenças Inflamatórias Intestinais , Mídias Sociais , Doença Crônica , Feminino , Amigos , Humanos , Doenças Inflamatórias Intestinais/terapia , Participação do PacienteRESUMO
BACKGROUND: Vedolizumab has been proposed to lead to fewer postoperative complications because of its gut specificity. Studies, however, suggest an increased risk of surgical site infections, yet the data are conflicting. OBJECTIVE: This study aimed to assess the effect of vedolizumab drug levels on postoperative outcomes in patients undergoing major abdominal surgery for IBD. DESIGN: This was a retrospective study of a prospectively maintained database. SETTING: Patients were operated on by a single surgeon at an academic medical center. PATIENTS: A total of 72 patients with IBD undergoing major abdominal surgery were included. INTERVENTIONS: Patients were exposed preoperatively to vedolizumab. MAIN OUTCOME MEASURES: The primary outcome measured was the postoperative morbidity in patients who had IBD with detectable vs undetectable vedolizumab levels. RESULTS: A total of 72 patients were included in the study. Thirty-eight patients had detectable vedolizumab levels (>1.6 µg/mL), and 34 had undetectable vedolizumab levels. The overall rate of complications was 39%, and ileus was the most common complication. There were no significant differences in clinical variables between the detectable and undetectable vedolizumab level patient groups except for the time between the last dose and surgery (p < 0.01). There were 42 patients in the ulcerative colitis cohort; 48% had an undetectable vedolizumab level and 52% had a detectable vedolizumab level. There were no differences in any postoperative morbidity between ulcerative colitis groups. The Crohn's cohort had 27 patients; 48% had an undetectable vedolizumab levels and 52% had a detectable vedolizumab level. There was a significantly lower incidence of postoperative ileus in patients who had Crohn's disease with detectable vedolizumab levels compared with patients with an undetectable vedolizumab level (p < 0.04). LIMITATIONS: Limitations include a low overall patient population and a high rate of stoma formation. CONCLUSIONS: Serum vedolizumab levels do not influence postoperative morbidity in IBD. Vedolizumab may reduce the incidence of postoperative ileus in patients with Crohn's disease. See Video Abstract at http://links.lww.com/DCR/B574. LOS NIVELES DE VEDOLIZUMAB EN SUERO PREOPERATORIO, NO AFECTAN LOS RESULTADOS POSTOPERATORIOS EN LA ENFERMEDAD INFLAMATORIA INTESTINAL: ANTECEDENTES:Se ha propuesto que el vedolizumab presenta menos complicaciones postoperatorias debido a su especificidad intestinal. Sin embargo, estudios sugieren un mayor riesgo de infecciones en el sitio quirúrgico, aunque los datos son contradictorios.OBJETIVO:Evaluar el efecto en los niveles del fármaco vedolizumab, en resultados postoperatorios de pacientes sometidos a cirugía mayor abdominal, por enfermedad inflamatoria intestinal.DISEÑO:Estudio retrospectivo de una base de datos mantenida prospectivamente.ENTORNO CLÍNICO:Pacientes intervenidos por un solo cirujano en un centro médico académico.PACIENTES:Un total de 72 pacientes con enfermedad inflamatoria intestinal sometidos a cirugía mayor abdominal.INTERVENCIONES:Exposición preoperatoria a vedolizumab.PRINCIPALES MEDIDAS DE VALORACIÓN:Morbilidad postoperatoria en pacientes con enfermedad inflamatoria intestinal, con niveles detectables versus no detectables de vedolizumab.RESULTADOS:Se incluyó en el estudio a un total de 72 pacientes. Treinta y ocho pacientes tuvieron niveles detectables de vedolizumab (> 1,6 mcg / ml) y 34 con niveles no detectables de vedolizumab. La tasa global de complicaciones fue del 39% y el íleo fue la complicación más común. No hubo diferencias significativas en las variables clínicas entre los grupos de pacientes con niveles detectables y no detectables de vedolizumab, excepto por el intervalo de tiempo entre la última dosis y la cirugía (p <.01). La cohorte de colitis ulcerosa tuvo 42 pacientes, el 48% con un nivel no detectable de vedolizumab y el 52% un nivel detectable de vedolizumab. No hubo diferencias en ninguna morbilidad postoperatoria entre los grupos de colitis ulcerosa. La cohorte de Crohn tuvo 27 pacientes, 48% con niveles no detectables de vedolizumab y el 52% con niveles detectables de vedolizumab. Hubo una incidencia significativamente menor de íleo postoperatorio en pacientes de Crohn con niveles detectables de vedolizumab, comparados con los pacientes con un nivel no detectable de vedolizumab (p <0,04).LIMITACIONES:Las limitaciones incluyen una baja población general de pacientes y una alta tasa de formación de estomas.CONCLUSIONES:Los niveles séricos de vedolizumab no influyen en la morbilidad postoperatoria de la enfermedad inflamatoria intestinal. Vedolizumab puede reducir la incidencia de íleo postoperatorio en pacientes de Crohn. Consulte Video Resumen en http://links.lww.com/DCR/B574.
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Anticorpos Monoclonais Humanizados/uso terapêutico , Fármacos Gastrointestinais/uso terapêutico , Doenças Inflamatórias Intestinais/sangue , Doenças Inflamatórias Intestinais/cirurgia , Adulto , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/metabolismo , Colite Ulcerativa/sangue , Colite Ulcerativa/epidemiologia , Colite Ulcerativa/cirurgia , Doença de Crohn/sangue , Doença de Crohn/epidemiologia , Doença de Crohn/cirurgia , Feminino , Fármacos Gastrointestinais/efeitos adversos , Fármacos Gastrointestinais/metabolismo , Humanos , Íleus/epidemiologia , Incidência , Masculino , Pessoa de Meia-Idade , Morbidade , Avaliação de Resultados em Cuidados de Saúde , Complicações Pós-Operatórias/epidemiologia , Período Pós-Operatório , Período Pré-Operatório , Estudos Retrospectivos , Estomas Cirúrgicos , Infecção da Ferida Cirúrgica/induzido quimicamente , Infecção da Ferida Cirúrgica/epidemiologiaRESUMO
BACKGROUND AND AIMS: Infliximab rescue therapy is effective in patients with corticosteroid refractory acute severe ulcerative colitis, but predictors of response remain poorly understood. We aimed to identify predictors of colectomy in this high-risk patient population. METHODS: Patients hospitalized with acute severe ulcerative colitis who received infliximab after failing intravenous corticosteroid therapy between July 2012 and June 2017 were retrospectively identified. Stepwise regression with backward elimination was used to identify predictors of colectomy at 90 days and 1 year. Ninety-day and 1-year colectomy rates were compared between the patients who received 5 mg/kg and 10 mg/kg IFX rescue dose. RESULTS: Sixty-three patients met the eligibility criteria. Twenty-nine patients received 5 mg/kg, and 34 received 10 mg/kg infliximab dose. Serum albumin on admission (OR 0.10; p = 0.04) and band neutrophil percentage at the time of infliximab administration (OR 1.21; p = 0.02) were independent predictors of 90-day colectomy. A combination of serum albumin ≤ 2.5 g/dl and band neutrophil count ≥ 13% had a 100% positive predictive value for 90-day colectomy. Unadjusted 90-day and 1-year colectomy rates were similar in the 5 mg/kg and 10 mg/kg infliximab groups. After adjusting for confounding factors, 10 mg/kg infliximab dose was potentially protective for 90-day (OR 0.07; p = 0.06) but not for 1-year colectomy (OR 0.19; p = 0.16). CONCLUSIONS: Bandemia and low serum albumin are independent predictors of failure of infliximab rescue therapy in acute severe ulcerative colitis. Serum albumin ≤ 2.5 g/dl and band neutrophil count ≥ 13% had a 100% positive predictive value for 90-day colectomy.
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Colectomia/tendências , Colite Ulcerativa/tratamento farmacológico , Fármacos Gastrointestinais/administração & dosagem , Hipoalbuminemia/tratamento farmacológico , Infliximab/administração & dosagem , Falha de Tratamento , Doença Aguda , Adulto , Colite Ulcerativa/diagnóstico , Colite Ulcerativa/cirurgia , Feminino , Hospitalização/tendências , Humanos , Hipoalbuminemia/diagnóstico , Hipoalbuminemia/cirurgia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Retrospectivos , Índice de Gravidade de DoençaRESUMO
BACKGROUND AND AIMS: It is unclear whether pre-pouch ileitis heralds an aggressive inflammatory pouch disease in patients with ileal pouch-anal anastomosis [IPAA]. We compared outcomes of patients with pouchitis and concomitant pre-pouch ileitis with those with pouchitis alone. METHODS: Patients undergoing IPAA surgery for inflammatory bowel disease, who subsequently developed pouchitis with concomitant pre-pouch ileitis [pre-pouch ileitis group], were matched by year of IPAA surgery and preoperative diagnosis [ulcerative colitis or inflammatory bowel disease-unclassified] with patients who developed pouchitis alone [pouchitis group]. Primary outcomes were development of Crohn's disease [CD]-like complications [non-anastomotic strictures or perianal disease >6 months after ileostomy closure] and pouch failure. Secondary outcomes were need for surgical/endoscopic interventions and immunosuppressive therapy. Log-rank testing was used to compare outcome-free survival, and Cox regression was performed to identify predictors of outcomes. RESULTS: There were 66 patients in each group. CD-like complications and pouch failure developed in 36.4% and 7.6% patients in the pre-pouch ileitis group and 10.6% and 1.5% in pouchitis group, respectively. CD-like complications-free survival [log-rank p = 0.0002] and pouch failure-free survival [log-rank p = 0.046] were significantly lower in the pre-pouch ileitis group. The pre-pouch ileitis group had a higher risk of requiring surgical/endoscopic interventions [log-rank p = 0.0005] and immunosuppressive therapy [log-rank p <0.0001]. Pre-pouch ileitis was independently associated with an increased risk of CD-like complications (hazard ratio [HR] 3.8; p = 0.0007), need for surgical/endoscopic interventions [HR 4.1; p = 0.002], and immunosuppressive therapy [HR 5.0; p = 0.0002]. CONCLUSIONS: Pre-pouch ileitis is associated with a higher risk of complicated disease and pouch failure than pouchitis. It should be considered a feature of CD.
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Colite Ulcerativa , Bolsas Cólicas/efeitos adversos , Doença de Crohn , Imunossupressores/uso terapêutico , Complicações Pós-Operatórias , Pouchite , Adulto , Colite Ulcerativa/diagnóstico , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/cirurgia , Constrição Patológica/diagnóstico , Constrição Patológica/etiologia , Constrição Patológica/cirurgia , Doença de Crohn/diagnóstico , Doença de Crohn/tratamento farmacológico , Doença de Crohn/cirurgia , Intervalo Livre de Doença , Feminino , Humanos , Ileíte/complicações , Ileíte/diagnóstico , Masculino , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/cirurgia , Pouchite/etiologia , Pouchite/terapia , Proctocolectomia Restauradora/efeitos adversos , Proctocolectomia Restauradora/métodos , Reoperação/métodos , Reoperação/estatística & dados numéricos , Medição de Risco , Fatores de RiscoRESUMO
BACKGROUND: Recent drug approvals have increased the number of therapies available for inflammatory bowel disease (IBD), making it difficult for patients to navigate available treatment options. We examined patient decision-making surrounding biologic and small-molecule therapies in an international cohort of patients from the United States, Canada, and the United Kingdom using conjoint analysis (CA), a form of tradeoff analysis examining how respondents make complex decisions. METHODS: We performed a CA survey that quantified the relative importance of therapy attributes (eg, efficacy, adverse effects) in decision-making. Patients with IBD were recruited from the general population and through specialty IBD clinics. We used a hierarchical Bayes analysis to model individual patients' preferences and compared the relative importance of medication attributes between countries and practice settings. Using a series of multivariable linear regression models, we assessed whether demographic and clinical characteristics (eg, IBD subtype, severity) predicted how patients made decisions. RESULTS: Overall, 1077 patients in 3 countries completed the survey. No differences in the relative importance of medication attributes were observed between the 3 countries' general IBD populations. However, efficacy was more important for patients in the US-based IBD specialty care cohort than for the general IBD population (29% and 23% importance, respectively; P < 0.0001). A few demographic and clinical characteristics were associated with small changes in individual preferences. CONCLUSIONS: In this large international CA study, patients prioritized efficacy as the most important therapeutic attribute. Decision-making seemed to be highly personalized in that therapeutic preferences were hard to predict based on patient characteristics.
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Produtos Biológicos , Doenças Inflamatórias Intestinais , Teorema de Bayes , Humanos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Preferência do Paciente , Reino Unido , Estados UnidosRESUMO
BACKGROUND: Important knowledge gaps have been identified related to the causes and symptoms of inflammatory bowel disease (IBD) and medical treatments and their side effects. Patients with IBD turn to social media to learn more about their disease. However, such information found on the web is misleading and often of low quality. OBJECTIVE: This study aims to gain an in-depth understanding of the unmet educational needs of patients with IBD and to use the resulting insights to develop a collection of freely available, evidence-based educational videos optimized for dissemination through social media. METHODS: We used design thinking, a human-centered approach, to guide our qualitative research methodology. We performed focus groups and interviews with a diverse sample of 29 patients with IBD. Data collection was performed in 3 phases (inspiration, ideation, and implementation) based on IDEO design thinking. Phase 1 offered insights into the needs of patients with IBD, whereas phases 2 and 3 involved ideation, prototyping, and video testing. A thematic analysis was performed to analyze the resulting data. RESULTS: Patients emphasized the need for educational videos that address their challenges, needs, and expectations. From the data analysis, 5 video topics and their content emerged: IBD treatments' risks and benefits; how to be a self-advocate; how to stay healthy with IBD; how to cope with IBD; and educating families, friends, and colleagues about experiences of patients with IBD. CONCLUSIONS: Design thinking offers a deep understanding and recognition of the unmet educational needs of patients with IBD; this approach informed the development of 5 evidence-based educational videos. Future research will formally test and disseminate these freely available videos through social media.
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Tumor-infiltrating lymphocytes (TILs) are an important histopathologic feature of colorectal cancer that confer prognostic information. Previous clinical and epidemiologic studies have found that the presence and quantification of tumor-infiltrating lymphocytes are significantly associated with disease-specific and overall survival in colorectal cancer. We performed a systematic review and meta-analysis, establishing pooled estimates for survival outcomes based on the presence of TILs in colon cancer. PubMed (Medline), Embase, Cochrane Library, Web of Science, and ClinicalTrials.gov were searched from inception to April 2017. Studies were included, in which the prognostic significance of intratumoral tumor infiltrating lymphocytes, as well as subsets of CD3, CD8, FOXP3, CD45R0 lymphocytes, were determined within the solid tumor center, the invasive margin, and tumor stroma. Random-effects models were calculated to estimated summary effects using hazard ratios. Forty-three relevant studies describing 21,015 patients were included in our meta-analysis. The results demonstrate that high levels of generalized TILS as compared to low levels had an improved overall survival (OS) with a HR of 0.65 (p = <0.01). In addition, histologically localized CD3+ T-cells at the tumor center were significantly associated with better disease-free survival (HR = 0.46, 95% CI 0.36-0.61, p = 0.05), and CD3 + cells at the invasive margin were associated with improved disease-free survival (HR = 0.57, 95% CI 0.38-0.86, p = 0.05). CD8+ T-cells at the tumor center had statistically significant prognostic value on cancer-specific survival and overall survival with HRs of 0.65 (p = 0.02) and 0.71 (p < 0.01), respectively. Lastly, FOXP3+ T-cells at the tumor center were associated with improved prognosis for cancer-specific survival (HR = 0.65, p < 0.01) and overall survival (HR = 0.70, p < 0.01). These findings suggest that TILs and specific TIL subsets serve as prognostic biomarkers for colorectal cancer.
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Neoplasias Colorretais/imunologia , Linfócitos do Interstício Tumoral/imunologia , Prognóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Linfócitos T CD8-Positivos/imunologia , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/patologia , Intervalo Livre de Doença , Feminino , Humanos , Linfócitos do Interstício Tumoral/patologia , Masculino , Pessoa de Meia-Idade , Modelos de Riscos ProporcionaisRESUMO
PURPOSE OF REVIEW: Inflammatory bowel disease affects approximately 800,000 women in the USA with the peak incidence between ages 15 to 40. Thus for many females, IBD can impact nearly every stage of their life from menarche to pregnancy, menopause, and beyond. This paper will review the most recent updates on the topics of sexual health, cervical cancer screening, menstruation, fertility, contraception, and menopause. RECENT FINDINGS: Menarche can be delayed in females especially those who are underweight, malnourished, or with active inflammatory bowel disease. Cyclical GI symptoms during a menstrual cycle are very common in women with IBD and should not be confused with flares. Overall fertility is similar to the general population unless females with IBD have had significant abdominal surgery but reassuringly this infertility appears to be restored with the use of in vitro fertilization. Discussion regarding family planning is imperative in women with IBD with a strong recommendation to consider long-acting highly effective contraceptives such as intrauterine devices or implants. Cervical cancer screening should be tailored in women on immunosuppressive medications and all women under 26 years of age should be advised to receive the human papilloma virus vaccination. As gastroenterologists will have longitudinal relationships with their female IBD patients, they must be knowledgeable about sex-specific issues during each stage of life from puberty to after menopause to optimize their patient's care.
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Women with angina pectoris and abnormal stress test findings commonly have no epicardial coronary artery disease (CAD) at catheterization. The aim of the present study was to develop a risk score to predict obstructive CAD in such patients. Data were analyzed from 337 consecutive women with angina pectoris and abnormal stress test findings who underwent cardiac catheterization at our center from 2003 to 2007. Forward selection multivariate logistic regression analysis was used to identify the independent predictors of CAD, defined by ≥50% diameter stenosis in ≥1 epicardial coronary artery. The independent predictors included age ≥55 years (odds ratio 2.3, 95% confidence interval 1.3 to 4.0), body mass index <30 kg/m(2) (odds ratio 1.9, 95% confidence interval 1.1 to 3.1), smoking (odds ratio 2.6, 95% confidence interval 1.4 to 4.8), low high-density lipoprotein cholesterol (odds ratio 2.9, 95% confidence interval 1.5 to 5.5), family history of premature CAD (odds ratio 2.4, 95% confidence interval 1.0 to 5.7), lateral abnormality on stress imaging (odds ratio 2.8, 95% confidence interval 1.5 to 5.5), and exercise capacity <5 metabolic equivalents (odds ratio 2.4, 95% confidence interval 1.1 to 5.6). Assigning each variable 1 point summed to constitute a risk score, a graded association between the score and prevalent CAD (ptrend <0.001). The risk score demonstrated good discrimination with a cross-validated c-statistic of 0.745 (95% confidence interval 0.70 to 0.79), and an optimized cutpoint of a score of ≤2 included 62% of the subjects and had a negative predictive value of 80%. In conclusion, a simple clinical risk score of 7 characteristics can help differentiate those more or less likely to have CAD among women with angina pectoris and abnormal stress test findings. This tool, if validated, could help to guide testing strategies in women with angina pectoris.