RESUMO
BACKGROUND & AIMS: It is currently unclear whether reported changes in the gut microbiome are cause or consequence of inflammatory bowel disease (IBD). Therefore, we studied the gut microbiome of IBD-discordant and -concordant twin pairs, which offers the unique opportunity to assess individuals at increased risk of developing IBD, namely healthy cotwins from IBD-discordant twin pairs. METHODS: Fecal samples were obtained from 99 twins (belonging to 51 twin pairs), 495 healthy age-, sex-, and body mass index-matched controls, and 99 unrelated patients with IBD. Whole-genome metagenomic shotgun sequencing was performed. Taxonomic and functional (pathways) composition was compared among healthy cotwins, IBD-twins, unrelated patients with IBD, and healthy controls with multivariable (ie, adjusted for potential confounding) generalized linear models. RESULTS: No significant differences were observed in the relative abundance of species and pathways between healthy cotwins and their IBD-twins (false discovery rate <0.10). Compared with healthy controls, 13, 19, and 18 species, and 78, 105, and 153 pathways were found to be differentially abundant in healthy cotwins, IBD-twins, and unrelated patients with IBD, respectively (false discovery rate <0.10). Of these, 8 (42.1%) of 19 and 1 (5.6%) of 18 species, and 37 (35.2%) of 105 and 30 (19.6%) of 153 pathways overlapped between healthy cotwins and IBD-twins, and healthy cotwins and unrelated patients with IBD, respectively. Many of the shared species and pathways have previously been associated with IBD. The shared pathways include potentially inflammation-related pathways, for example, an increase in propionate degradation and L-arginine degradation pathways. CONCLUSIONS: The gut microbiome of healthy cotwins from IBD-discordant twin pairs displays IBD-like signatures. These IBD-like microbiome signatures might precede the onset of IBD. However, longitudinal follow-up studies are needed to infer a causal relationship.
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Microbioma Gastrointestinal , Neoplasias Inflamatórias Mamárias/epidemiologia , Neoplasias Inflamatórias Mamárias/microbiologia , Adulto , Antígenos de Bactérias/biossíntese , Estudos de Casos e Controles , Estudos Transversais , Fezes/microbiologia , Feminino , Microbioma Gastrointestinal/fisiologia , Humanos , Masculino , Metagenômica , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Fenótipo , Fatores de Risco , Sideróforos/biossíntese , Gêmeos Dizigóticos , Gêmeos Monozigóticos , Adulto JovemRESUMO
BACKGROUND & AIMS: Lynch syndrome is caused by variants in DNA mismatch repair (MMR) genes and associated with an increased risk of colorectal cancer (CRC). In patients with Lynch syndrome, CRCs can develop via different pathways. We studied associations between Lynch syndrome-associated variants in MMR genes and risks of adenoma and CRC and somatic mutations in APC and CTNNB1 in tumors in an international cohort of patients. METHODS: We combined clinical and molecular data from 3 studies. We obtained clinical data from 2747 patients with Lynch syndrome associated with variants in MLH1, MSH2, or MSH6 from Germany, the Netherlands, and Finland who received at least 2 surveillance colonoscopies and were followed for a median time of 7.8 years for development of adenomas or CRC. We performed DNA sequence analyses of 48 colorectal tumors (from 16 patients with mutations in MLH1, 29 patients with mutations in MSH2, and 3 with mutations in MSH6) for somatic mutations in APC and CTNNB1. RESULTS: Risk of advanced adenoma in 10 years was 17.8% in patients with pathogenic variants in MSH2 vs 7.7% in MLH1 (P < .001). Higher proportions of patients with pathogenic variants in MLH1 or MSH2 developed CRC in 10 years (11.3% and 11.4%) than patients with pathogenic variants in MSH6 (4.7%) (P = .001 and P = .003 for MLH1 and MSH2 vs MSH6, respectively). Somatic mutations in APC were found in 75% of tumors from patients with pathogenic variants in MSH2 vs 11% in MLH1 (P = .015). Somatic mutations in CTNNB1 were found in 50% of tumors from patients with pathogenic variants in MLH1 vs 7% in MSH2 (P = .002). None of the 3 tumors with pathogenic variants in MSH6 had a mutation in CTNNB1, but all had mutations in APC. CONCLUSIONS: In an analysis of clinical and DNA sequence data from patients with Lynch syndrome from 3 countries, we associated pathogenic variants in MMR genes with risk of adenoma and CRC, and somatic mutations in APC and CTNNB1 in colorectal tumors. If these findings are confirmed, surveillance guidelines might be adjusted based on MMR gene variants.
Assuntos
Adenoma/epidemiologia , Neoplasias Colorretais Hereditárias sem Polipose/epidemiologia , Proteínas de Ligação a DNA/genética , Proteína 1 Homóloga a MutL/genética , Proteína 2 Homóloga a MutS/genética , Adenoma/diagnóstico , Adenoma/genética , Proteína da Polipose Adenomatosa do Colo/genética , Adulto , Colonoscopia , Neoplasias Colorretais Hereditárias sem Polipose/diagnóstico , Neoplasias Colorretais Hereditárias sem Polipose/genética , Reparo de Erro de Pareamento de DNA , Análise Mutacional de DNA , Feminino , Finlândia/epidemiologia , Alemanha/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Países Baixos/epidemiologia , Estudos Prospectivos , beta Catenina/genéticaRESUMO
BACKGROUND & AIMS: Patients with Lynch syndrome are at high risk for developing colorectal cancer (CRC). Regular colonoscopic surveillance is recommended, but there is no international consensus on the appropriate interval. We investigated whether shorter intervals are associated with lower CRC incidence and detection at earlier stages by comparing the surveillance policies in Germany, which evaluates patients by colonoscopy annually, in the Netherlands (patients evaluated at 1-2-year intervals), and Finland (patients evaluated at 2-3-year intervals). METHODS: We collected data from 16,327 colonoscopic examinations (conducted from 1984 through 2015) of 2747 patients with Lynch syndrome (pathogenic variants in the MLH1, MSH2, or MSH6 genes) from the German HNPCC Consortium, the Dutch Lynch Syndrome Registry, and the Finnish Lynch Syndrome Registry. Our analysis included 23,309 person-years of cumulative observation time. Time from the index colonoscopy to incident CRC or adenoma was analyzed using the Kaplan-Meier method; groups were compared using the log-rank test. We performed multivariable Cox regression analyses to identify factors associated with CRC risk (diagnosis of CRC before the index colonoscopy, sex, mutation, age, and presence of adenoma at the index colonoscopy). RESULTS: The 10-year cumulative CRC incidence ranged from 4.1% to 18.4% in patients with low- and high-risk profiles, respectively, and varied with age, sex, mutation, and prior detection of CRC or adenoma. Observed colonoscopy intervals were largely in accordance with the country-specific recommendations. We found no significant differences in cumulative CRC incidence or CRC stage at detection among countries. There was no significant association between CRC stage and time since last colonoscopy. CONCLUSIONS: We did not find a significant reduction in CRC incidence or stage of detection in Germany (annual colonoscopic surveillance) than in countries with longer surveillance intervals (the Netherlands, with 1-2-year intervals, and Finland, with 2-3-year intervals). Overall, we did not find a significant association of the interval with CRC risk, although age, sex, mutation, and prior neoplasia were used to individually modify colonoscopy intervals. Studies are needed to develop and validate risk-adapted surveillance strategies and to identify patients who benefit from shorter surveillance intervals.
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Colonoscopia , Neoplasias Colorretais Hereditárias sem Polipose/diagnóstico , Neoplasias Colorretais/diagnóstico , Adulto , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/patologia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Modelos de Riscos ProporcionaisRESUMO
PURPOSE: Previous studies have shown that > 50% of colorectal cancer (CRC) patients treated with adjuvant chemotherapy gain weight after diagnosis. This may affect long-term health. Therefore, prevention of weight gain has been incorporated in oncological guidelines for CRC with a focus on patients that undergo adjuvant chemotherapy treatment. It is, however, unknown how changes in weight after diagnosis relate to weight before diagnosis and whether weight changes from pre-to-post diagnosis are restricted to chemotherapy treatment. We therefore examined pre-to-post diagnosis weight trajectories and compared them between those treated with and without adjuvant chemotherapy. METHODS: We included 1184 patients diagnosed with stages I-III CRC between 2010 and 2015 from an ongoing observational prospective study. At diagnosis, patients reported current weight and usual weight 2 years before diagnosis. In the 2 years following diagnosis, weight was self-reported repeatedly. We used linear mixed models to analyse weight trajectories. RESULTS: Mean pre-to-post diagnosis weight change was -0.8 (95% CI -1.1, -0.4) kg. Post-diagnosis weight gain was + 3.5 (95% CI 2.7, 4.3) kg in patients who had lost ≥ 5% weight before diagnosis, while on average clinically relevant weight gain after diagnosis was absent in the groups without pre-diagnosis weight loss. Pre-to-post diagnosis weight change was similar in patients treated with (-0.1 kg (95%CI -0.8, 0.6)) and without adjuvant chemotherapy (-0.9 kg (95%CI -1.4, -0.5)). CONCLUSIONS: Overall, hardly any pre-to-post diagnosis weight change was observed among CRC patients, because post-diagnosis weight gain was mainly observed in patients who lost weight before diagnosis. This was observed independent of treatment with adjuvant chemotherapy.
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Trajetória do Peso do Corpo , Neoplasias Colorretais/diagnóstico , Idoso , Peso Corporal/efeitos dos fármacos , Peso Corporal/fisiologia , Quimioterapia Adjuvante/efeitos adversos , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/fisiopatologia , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Aumento de Peso/efeitos dos fármacos , Redução de Peso/efeitos dos fármacosRESUMO
BACKGROUND: Patients with Lynch syndrome (LS) are at an increased risk of developing gastric cancer. In 2010, a guideline that recommended to screen all patients for Helicobacter pylori was implemented in the Netherlands. H. pylori is an important risk factor in the development of gastric cancer in the general population, and eradication of the bacterium reduces this risk. We aimed to assess the proportion of LS patients being tested and the yield and also addressed the question whether H. pylori infection is more prevalent in LS families with known cases of gastric cancer. METHODS: Proven mutation carriers from five different Dutch hospitals were included. The implementation of H. pylori screening and its outcome was examined. The observation period was 2008-2013. The presence of first-degree family members with gastric cancer was noted, and it was observed if H. pylori infection was more prevalent in Lynch families with known cases of gastric cancer. Obtainable endoscopy reports were reviewed. RESULTS: Four hundred forty-three (male, 184) proven mutation carriers were included. The proportion of patients screened increased after 2010, from 37 to 68%. Twenty percent of the patients were infected. The 25 patients who had a first-degree family member with gastric cancer did not have a higher infection rate. In 30% of cases, an endoscopy was performed; in four patients, intestinal metaplasia and in eight patients, gastric cancer was found. CONCLUSION: The recommendation to screen for H. pylori is increasingly followed. The prevalence of infection in this patient group does not differ from the general population. Patients who had a first-degree family member with gastric cancer did not have a higher infection rate.
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Neoplasias Colorretais Hereditárias sem Polipose/genética , Neoplasias Colorretais Hereditárias sem Polipose/microbiologia , Família , Infecções por Helicobacter/microbiologia , Helicobacter pylori/fisiologia , Mutação/genética , Neoplasias Gástricas/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Endoscopia , Feminino , Heterozigoto , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
OBJECTIVE: The introduction of anti tumour necrosis factor-α (anti-TNFα) therapy might impact healthcare expenditures, but there are limited data regarding the costs of inflammatory bowel diseases (IBD) following the introduction of these drugs. We aimed to assess the healthcare costs and productivity losses in a large cohort of IBD patients. DESIGN: Crohn's disease (CD) and ulcerative colitis (UC) patients from seven university hospitals and seven general hospitals were invited to fill-out a web-based questionnaire. Cost items were derived from a 3 month follow-up questionnaire and categorised in outpatient clinic, diagnostics, medication, surgery and hospitalisation. Productivity losses included sick leave of paid and unpaid work. Costs were expressed as mean 3-month costs per patients with a 95% CI obtained using non-parametric bootstrapping. RESULTS: A total of 1315 CD patients and 937 UC patients were included. Healthcare costs were almost three times higher in CD as compared with UC, 1625 (95% CI 1476 to 1775) versus 595 (95% CI 505 to 685), respectively (p<0.01). Anti-TNFα use was the main costs driver, accounting for 64% and 31% of the total cost in CD and UC. Hospitalisation and surgery together accounted for 19% and <1% of the healthcare costs in CD and 23% and 1% in UC, respectively. Productivity losses accounted for 16% and 39% of the total costs in CD and UC. CONCLUSIONS: We showed that healthcare costs are mainly driven by medication costs, most importantly by anti-TNFα therapy. Hospitalisation and surgery accounted only for a minor part of the healthcare costs.
Assuntos
Colite Ulcerativa/economia , Efeitos Psicossociais da Doença , Doença de Crohn/economia , Custos de Cuidados de Saúde/estatística & dados numéricos , Gastos em Saúde/estatística & dados numéricos , Absenteísmo , Adalimumab , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anti-Inflamatórios/economia , Anti-Inflamatórios/uso terapêutico , Anticorpos Monoclonais/economia , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados/economia , Anticorpos Monoclonais Humanizados/uso terapêutico , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/cirurgia , Doença de Crohn/tratamento farmacológico , Doença de Crohn/cirurgia , Feminino , Seguimentos , Hospitalização/economia , Hospitalização/estatística & dados numéricos , Humanos , Infliximab , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Países Baixos , Licença Médica/economia , Licença Médica/estatística & dados numéricos , Inquéritos e Questionários , Adulto JovemRESUMO
BACKGROUND: Currently thioguanine is solely used as treatment for inflammatory bowel disease after azathioprine and/or mercaptopurine failure. This study aimed to determine the safety, effectiveness, and 12-month drug survival of thioguanine in thiopurine-naïve patients with inflammatory bowel disease. METHODS: A retrospective cohort study was performed in thiopurine-naïve patients with inflammatory bowel disease treated with thioguanine as first thiopurine derivate. Clinical effectiveness was defined as the continuation of thioguanine without the (re)initiation of concurrent biological therapy, systemic corticosteroids, or a surgical intervention. All adverse events were categorized by the Common Terminology Criteria for Adverse Events. RESULTS: A total of 114 patients (male 39%, Crohn's disease 53%) were included with a median treatment duration of 25 months and a median thioguanine dosage of 20 mg/d. Clinical effectiveness at 12 months was observed in 53% of patients, and 78% of these responding patients remained responsive until the end of follow-up. During the entire follow-up period, 26 patients were primary nonresponders, 8 had a secondary loss of response, and 11 patients were unable to cease therapy with systemic corticosteroids within 6 months and were therefore classified as nonresponders. After 12 months, thioguanine was still used by 86% of patients. Fifty (44%) patients developed adverse events (grade 1 or 2) and 9 (8%) patients ceased therapy due to the occurrence of adverse events. An infection was documented in 3 patients, none of them requiring hospitalization and pancytopenia occurred in 2 other patients. No signs of nodular regenerative hyperplasia or portal hypertension were observed. CONCLUSIONS: At 12 months, first-line thioguanine therapy was clinically effective in 53% of thiopurine-naïve inflammatory bowel disease patients with an acceptable safety profile.
After 12 months, first-line thioguanine therapy was still used by 86% of thiopurine-naïve patients with inflammatory bowel disease and clinically effective in 53%. The safety profile was acceptable and only 8% of patients ceased therapy due to adverse events.
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BACKGROUND: Lynch syndrome is a disorder caused by mismatch repair gene mutations. Mutation carriers have a high risk of developing colorectal cancer. In patients with Lynch syndrome in whom colon cancer has been diagnosed, in general, subtotal colectomy instead of partial colectomy is recommended because of the substantial risk of metachronous colorectal cancer. However, the effect of more extensive surgery on quality of life and functional outcome is unknown. OBJECTIVE: The aim of this study was to investigate quality of life and functional outcome in patients with Lynch syndrome after partial colectomy and subtotal colectomy. DESIGN: This is a nationwide cross-sectional study in the Netherlands. SETTINGS: Two quality-of-life questionnaires (Short Form-36 and The European Organization for Research and Treatment of Cancer Colorectal Cancer-specific Quality of Life Questionnaire Module) and a functional outcome questionnaire (Colorectal Functional Outcome) were used. PATIENTS: Patients with Lynch syndrome who underwent surgery for colon cancer were included. MAIN OUTCOME MEASURES: The primary outcomes measured were quality of life and functional outcome. RESULTS: Questionnaires were sent to 192 patients with Lynch syndrome who underwent surgery for colorectal cancer. A total of 136 patients returned the questionnaire (response rate, 71%). Eighteen patients with rectal cancer, 9 patients with a permanent ileostomy, and 5 patients with an IPAA were excluded. Fifty-one patients underwent partial colectomy, and 53 underwent subtotal colectomy. None of the scales of the Short Form-36 survey showed a significant difference. Analysis of the Colorectal Functional Outcome questionnaire revealed that, after subtotal colectomy, patients have a significantly higher stool frequency (p ≤ 0.01) and a significantly higher score on stool-related aspects (p = 0.06) and social impact (p = 0.03). The European Organization for Research and Treatment of Cancer Colorectal Cancer-specific Quality of Life Questionnaire Module presented more problems with defecation after subtotal colectomy (p ≤ 0.01). LIMITATIONS: Certain selection bias cannot be ruled out. CONCLUSIONS: Although functional outcome is worse after subtotal colectomy than after partial colectomy, generic quality of life does not differ after the 2 types of surgery in Lynch syndrome. When discussing the options for surgery with the patient, all advantages and disadvantages of both surgical procedures, including quality of life and functional outcome, should be discussed.
Assuntos
Colectomia/métodos , Neoplasias Colorretais Hereditárias sem Polipose/cirurgia , Qualidade de Vida , Distribuição de Qui-Quadrado , Neoplasias Colorretais Hereditárias sem Polipose/genética , Neoplasias Colorretais Hereditárias sem Polipose/fisiopatologia , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Países Baixos , Recuperação de Função Fisiológica , Sistema de Registros , Estatísticas não Paramétricas , Inquéritos e Questionários , Resultado do TratamentoRESUMO
BACKGROUND & AIMS: Two percent to 4% of all cases of colorectal cancer (CRC) are associated with Lynch syndrome. Dominant clustering of CRC (non-Lynch syndrome) accounts for 1%-3% of the cases. Because carcinogenesis is accelerated in Lynch syndrome, an intensive colonoscopic surveillance program has been recommended since 1995. The aim of the study was to evaluate the effectiveness of this program. METHODS: The study included 205 Lynch syndrome families with identified mutations in one of the mismatch repair genes (745 mutation carriers). We also analyzed data from non-Lynch syndrome families (46 families, 344 relatives). Patients were observed from January 1, 1995, until January 1, 2009. End points of the study were CRC or date of the last colonoscopy. RESULTS: After a mean follow-up of 7.2 years, 33 patients developed CRC under surveillance. The cumulative risk of CRC was 6% after the 10-year follow-up period. The risk of CRC was higher in carriers older than 40 years and in carriers of MLH1 and MSH2 mutations. After a mean follow-up of 7.0 years, 6 cases of CRC were detected among non-Lynch syndrome families. The risk of CRC was significantly higher among families with Lynch syndrome, compared with those without. CONCLUSIONS: With surveillance intervals of 1-2 years, members of families with Lynch syndrome have a lower risk of developing CRC than with surveillance intervals of 2-3 years. Because of the low risk of CRC in non-Lynch syndrome families, a less intensive surveillance protocol can be recommended.
Assuntos
Neoplasias Colorretais Hereditárias sem Polipose/genética , Neoplasias Colorretais/prevenção & controle , Proteínas Adaptadoras de Transdução de Sinal/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/etiologia , Neoplasias Colorretais/genética , Reparo de Erro de Pareamento de DNA/genética , Família , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Proteína 1 Homóloga a MutL , Proteína 2 Homóloga a MutS/genética , Mutação , Proteínas Nucleares/genética , Risco , Fatores de TempoRESUMO
Observational studies suggest that fish consumption is associated with a decreased colorectal cancer (CRC) risk. A possible mechanism by which fish could reduce CRC risk is by decreasing colonic genotoxicity. However, concerns have also been raised over the levels of toxic compounds found in mainly oil-rich fish, which could increase genotoxicity. Therefore, the objective was to investigate the effects of fish on genotoxicity markers in the colon in a randomized controlled parallel intervention study. For a period of 6 months, subjects were randomly allocated to receive two extra weekly portions of (i) oil-rich fish (salmon), (ii) lean fish (cod) or (iii) just dietary advice (DA). The Comet Assay was used to measure the DNA damage-inducing potential of fecal water (n = 89) and DNA damage in colonocytes (n = 70) collected pre- and post-intervention as markers of genotoxicity. Genotoxicity of fecal water was not markedly changed after fish consumption: 1.0% increase in tail intensity (TI) [95% confidence interval (CI) -5.1; 7.0] in the salmon group and 0.4% increase in TI (95% CI -5.3; 6.1) in the cod group compared with the DA group. DNA damage in colonocytes was also not significantly changed after fish consumption, in either the salmon group (-0.5% TI, 95% CI -6.9; 6.0) or cod group (-3.3% TI, 95% CI -10.8; 4.3) compared with the DA group. Measurements of genotoxicity of fecal water and DNA damage in colonocytes did not correlate (r = 0.06, n = 34). In conclusion, increasing consumption of either oil-rich or lean fish did not affect genotoxicity markers in the colon.
Assuntos
Biomarcadores/análise , Colo/química , Neoplasias Colorretais/prevenção & controle , Dieta , Peixes , Mutagênicos/análise , Alimentos Marinhos , Animais , Neoplasias Colorretais/induzido quimicamente , Ensaio Cometa , Dano ao DNARESUMO
Fish consumption is associated with a reduced colorectal cancer risk. A possible mechanism by which fish consumption could decrease colorectal cancer risk is by reducing inflammation. However, thus far, intervention studies investigating both systemic and local gut inflammation markers are lacking. Our objective in this study was to investigate the effects of fatty and lean fish consumption on inflammation markers in serum, feces, and gut. In an intervention study, participants were randomly allocated to receive dietary advice (DA) plus either 300 g of fatty fish (salmon) or 300 g of lean fish (cod) per week for 6 mo, or only DA. Serum C-reactive protein (CRP) concentrations were measured pre- and postintervention (n = 161). In a subgroup (n = 52), we explored the effects of the fish intervention on fecal calprotectin and a wide range of cytokines and chemokines in fecal water and in colonic biopsies. Serum CRP concentrations were lower in the salmon (-0.5 mg/L; 95% CI -0.9, -0.2) and cod (-0.4 mg/L; 95% CI -0.7, 0.0) groups compared with the DA group. None of the inflammation markers in fecal water and colonic biopsies differed between the DA group and the groups that consumed extra fish. In conclusion, increasing salmon or cod consumption for 6 mo resulted in lower concentrations of the systemic inflammation marker CRP. However, exploratory analysis of local markers of inflammation in the colon or feces did not reveal an effect of fish consumption.
Assuntos
Proteína C-Reativa/metabolismo , Colo/efeitos dos fármacos , Neoplasias Colorretais/prevenção & controle , Gorduras na Dieta/farmacologia , Inflamação/dietoterapia , Alimentos Marinhos , Adulto , Animais , Biomarcadores/sangue , Biópsia , Quimiocinas/metabolismo , Colo/metabolismo , Citocinas/metabolismo , Gorduras na Dieta/uso terapêutico , Ácidos Graxos Ômega-3/farmacologia , Ácidos Graxos Ômega-3/uso terapêutico , Fezes , Feminino , Humanos , Inflamação/metabolismo , Complexo Antígeno L1 Leucocitário/metabolismo , Masculino , Pessoa de Meia-Idade , SalmãoRESUMO
BACKGROUND: Nonadherence to medical therapy is frequently encountered in patients with inflammatory bowel disease (IBD). We aimed to identify predictors for future (non)adherence in IBD. METHODS: We conducted a multicenter prospective cohort study with adult patients with Crohn's disease (CD) and ulcerative colitis (UC). Data were collected by means of 3-monthly questionnaires on the course of disease and healthcare utilization. Medication adherence was assessed using a visual analogue scale, ranging from 0% to 100%. Levels <80% were considered to indicate nonadherence. The Brief Illness Perception Questionnaire was used to identify illness perceptions. We used a logistic regression analysis to identify patient- and disease-related factors predictive of nonadherence 3 months after the assessment of predictors. RESULTS: In total, 1558 patients with CD and 1054 patients with UC were included and followed for 2.5 years. On average, 12.1% of patients with CD and 13.3% of patients with UC using IBD-specific medication were nonadherent. Nonadherence was most frequently observed in patients using mesalazine (CD), budesonide (UC) and rectally administrated therapy (both CD and UC). A higher perceived treatment control and understanding of the disease were associated with adherence to medical therapy. Independent predictors of future nonadherence were age at diagnosis (odds ratio [OR]: 0.99 per year), nonadherence (OR: 26.91), a current flare (OR: 1.30) and feelings of anxiety/depression (OR: 1.17), together with an area under the receiver-operating-characteristics curve of 0.74. CONCLUSIONS: Lower age at diagnosis, flares, feelings of anxiety or depression, and nonadherence are associated with future nonadherence in patients with IBD. Altering illness perceptions could be an approach to improve adherence behavior.
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Colite Ulcerativa/psicologia , Doença de Crohn/psicologia , Fármacos Gastrointestinais/uso terapêutico , Adesão à Medicação/estatística & dados numéricos , Adulto , Idade de Início , Ansiedade/psicologia , Área Sob a Curva , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/patologia , Doença de Crohn/tratamento farmacológico , Doença de Crohn/patologia , Depressão/psicologia , Feminino , Inquéritos Epidemiológicos , Humanos , Masculino , Adesão à Medicação/psicologia , Pessoa de Meia-Idade , Razão de Chances , Estudos Prospectivos , Curva ROC , Fatores de Risco , Índice de Gravidade de Doença , Exacerbação dos SintomasRESUMO
INTRODUCTION: Laparoscopic sleeve gastrectomy (LSG) is considered to be an effective procedure for patients with morbid obesity. Belching is frequently reported after this procedure, but it has not been well studied in the bariatric population. This study aims to assess the changes in belching before and after sleeve gastrectomy, as measured with impedance monitoring. METHODS: In a prospective study, patients underwent 24-h pH-impedance monitoring before and 3 months after LSG. Using this technique, belches can be identified. Preoperative and postoperative upper gastrointestinal symptoms were assessed using the Reflux Disease Questionnaire (RDQ). RESULTS: Fifteen patients (1 M/14 F, mean age 42.2 ± 11.0 years, mean weight 134.5 ± 21.1 kg, mean BMI 46.4 ± 6.0 kg/m(2)) participated in this study. Belching occurred significantly more often after LSG, with an increase in symptom score from 2.9 ± 2.6 before to 5.3 ± 3.5 3 months after LSG (p = 0.04). The total number of gastric belches increased from 29.7 ± 11.7 before to 59.5 ± 38.3/24 h 3 months after LSG (p = 0.03). The total number of supragastric belches did not change after LSG. The number of swallows decreased from 746.9 ± 302.4 before to 555.7 ± 172.5 3 months after the procedure (p = 0.03). The number of air swallows tended to decrease (p = 0.08). Esophageal acid exposure increased significantly, from 3.7 ± 2.9 % before to 12.6 ± 10.5 % after LSG (p = 0.01). CONCLUSION: Subjectively (as reported by patients) and objectively (as measured by impedance monitoring), an increase in gastric belches is seen after LSG, while the number of (air) swallows tends to decrease after the procedure and the incidence of supragastric belches remains constant. The altered anatomy as well as increased gastroesophageal reflux after LSG may play a role in the increase of belching.
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Eructação/etiologia , Gastrectomia/efeitos adversos , Adulto , Deglutição , Monitoramento do pH Esofágico , Feminino , Humanos , Masculino , Estudos ProspectivosRESUMO
BACKGROUND AND STUDY AIMS: Conventional reporting of polyps is often incomplete. We tested the Polyp Manager (PM), a new software application permitting the endoscopist to document polyps in real time during colonoscopy. We studied completeness of polyp descriptions, user-friendliness and the potential time benefit. PATIENTS AND METHODS: In two Dutch hospitals colonoscopies were performed with PM (as a touchscreen endoscopist-operated device or nurse-operated desktop application). Completeness of polyp descriptions was compared to a historical group with conventional reporting (CRH). Prospectively, we compared user-friendliness (VAS-scores) and time benefit of the endoscopist-operated PM to conventional reporting (CR) in one hospital. Duration of colonoscopy and time needed to report polyps and provide a pathology request were measured. Provided that using PM does not prolong colonoscopy, the sum of the latter two was considered as a potential time-benefit if the PM were fully integrated into a digital reporting system. RESULTS: A total of 144 regular colonoscopies were included in the study. Both groups were comparable with regard to patient characteristics, duration of colonoscopy and number of polyps. Using the PM did reduce incomplete documentation of the following items in CRH-reports: location (96â% vs 82â%, Pâ=â0.01), size (95â% vs 89â%, Pâ=â0.03), aspect (71â% vs 36â%, Pâ<â0.001) and completeness of removal (61â% vs 37â%, Pâ<â0.001). In the prospective study 23 PM-colonoscopies where compared to 28 CR-colonoscopies. VAS-scores were significantly higher in the endoscopist-operated PM group.âTime to report was 01:27 ± 01:43 minutes (medianâ+âinterquartile range) in the entire group (PM as CR), reflecting potential time benefit per colonoscopy. CONCLUSIONS: The PM is a user-friendly tool that seems to improve completeness of polyp reporting. Once integrated with digital reporting systems, it is probably time saving as well.
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BACKGROUND: With the increasing use of anti-TNF therapy in inflammatory bowel disease (IBD), a shift of costs has been observed with medication costs replacing hospitalization and surgery as major cost driver. We aimed to explore the evolution of IBD-related costs over two years of follow-up. METHODS AND FINDINGS: In total 1,307 Crohn's disease (CD) patients and 915 ulcerative colitis (UC) patients were prospectively followed for two years by three-monthly web-based questionnaires. Changes of healthcare costs, productivity costs and out-of-pocket costs over time were assessed using mixed model analysis. Multivariable logistic regression analysis was used to identify costs drivers. In total 737 CD patients and 566 UC were included. Total costs were stable over two years of follow-up, with annual total costs of 7,835 in CD and 3,600 in UC. However, within healthcare costs, the proportion of anti-TNF therapy-related costs increased from 64% to 72% in CD (p<0.01) and from 31% to 39% in UC (p < 0.01). In contrast, the proportion of hospitalization costs decreased from 19% to 13% in CD (p<0.01), and 22% to 15% in UC (p < 0.01). Penetrating disease course predicted an increase of healthcare costs (adjusted odds ratio (adj. OR) 1.95 (95% CI 1.02-3.37) in CD and age <40 years in UC (adj. OR 4.72 (95% CI 1.61-13.86)). CONCLUSIONS: BD-related costs remained stable over two years. However, the proportion of anti-TNF-related healthcare costs increased, while hospitalization costs decreased. Factors associated with increased costs were penetrating disease course in CD and age <40 in UC.
Assuntos
Atenção à Saúde/economia , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/economia , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Fator de Necrose Tumoral alfa/economia , Feminino , Seguimentos , Custos de Cuidados de Saúde , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) is an effective bariatric procedure. However, postprandial symptoms can compromise its beneficial effect. It is not known if a changed gastric emptying and these symptoms are related. This study aimed to assess the association between postprandial symptoms and the gastric emptying pattern after LSG. METHODS: A gastric emptying study with a solid and liquid meal component was performed in the second year after LSG. Before the test, symptoms were assessed using a standardized questionnaire, and during the test, symptoms were scored on a visual analog scale (VAS). Gastric emptying results were expressed as lag phase, half time of gastric emptying (T½), and caloric emptying rate/minute. RESULTS: Twenty patients (14 F/6 M; age 45.6 ± 7.7 years, weight 93.4 ± 28.2 kg, BMI 31.6 ± 8.1 kg/m(2)) participated in this study; 13 had a low symptom score (≤9, group I), 7 a high symptom score (≥18, group II). VAS scores for epigastric pain, nausea, and belching were significantly higher in group II. Lag phase (solid) was 6.4 ± 4.5 min in group I, 7.3 ± 6.3 in group II (p = 0.94); T½ (solid) was 40.6 ± 10.0 min in group I, 34.4 ± 9.3 in group II (p = 0.27); caloric emptying rate was 3.9 ± 0.6 kcal/min in group I, 3.9 ± 1.0 kcal/min in group II (p = 0.32). CONCLUSIONS: Patients with postprandial symptoms after LSG reported more symptoms during the gastric emptying study than patients without symptoms. However, there was no difference between gastric emptying characteristics between both groups, suggesting that abnormal gastric emptying is not a major determinant of postprandial symptoms after LSG.
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Cirurgia Bariátrica/efeitos adversos , Gastrectomia/efeitos adversos , Esvaziamento Gástrico , Obesidade Mórbida/cirurgia , Dor Abdominal/etiologia , Adulto , Eructação/etiologia , Feminino , Humanos , Laparoscopia , Masculino , Pessoa de Meia-Idade , Náusea/etiologia , Obesidade Mórbida/fisiopatologia , Período Pós-PrandialRESUMO
BACKGROUND: The inflammatory bowel disease (IBD) disability index has recently been introduced to measure patients' physical, psychological, familial, and social limitations associated with IBD. We assessed factors related to self-reported disability and the relationship between disability and direct health care costs. METHODS: A large cohort of patients with Crohn's disease (CD) and ulcerative colitis (UC) was prospectively followed for 2 years by 3 monthly web-based questionnaires. At 2 years, patients completed the IBD disability index, with lower score indicating more disability. Linear regression analysis was used to examine the impact of demographics, clinical characteristics, and illness perceptions on self-reported disability. Trends in direct health care costs across the disability severity groups minimal, mild, moderate, and severe, were tested. RESULTS: A total of 554 patients with CD and 424 patients with UC completed the IBD disability index (response rate, 45%). Both clinical characteristics and illness perceptions significantly contributed to self-reported disability (45%-47%, P = 0.000 and 8%-12%, P = 0.000, respectively). Patients with CD scored lower on the self-reported IBD disability index than patients with UC (0.255 versus 3.890, P < 0.000), indicating more disability in patients with CD. Factors independently associated with higher self-reported disability rates were increased disease activity, illness identity (higher number of symptoms attributed to IBD), and stronger emotional response. Disease duration and disease phenotype were not associated with self-reported disability. Direct health care costs increased with the worsening of self-reported disability (P = 0.000). CONCLUSIONS: More disability was reported by patients with CD than by UC. Self-reported disability in IBD was mainly determined by clinical disease activity and illness perceptions but not by disease duration or disease phenotype.
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Colite Ulcerativa/fisiopatologia , Colite Ulcerativa/psicologia , Doença de Crohn/fisiopatologia , Doença de Crohn/psicologia , Pessoas com Deficiência/estatística & dados numéricos , Percepção , Autorrelato , Índice de Gravidade de Doença , Adulto , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Qualidade de Vida , Inquéritos e QuestionáriosRESUMO
BACKGROUND AND AIMS: More data are warranted on the economic impact of different treatment strategies in ulcerative colitis (UC) patients. We compared the costs and quality of life of UC patients with a pouch reconstruction, an ileostomy or anti-tumour necrosis factor α (TNFα) therapy. METHODS: UC patients filled out 3-monthly questionnaires for 2 years. Differences in 3-monthly healthcare costs, productivity costs and patient costs were tested using mixed model analysis. Quality of life was assessed employing the ) and the inflammatory bowel disease questionnaire (IBDQ). RESULTS: Out of 915 UC patients, 81 (9%) had a pouch and 48 (5%) an ileostomy, and 34 (4%) were on anti-TNFα therapy. Anti-TNFα-treated patients reported high UC related-healthcare costs per 3 months (5350). Medication use accounted for 92% of healthcare costs. UC-attributable healthcare costs were 3-fold higher in ileostomy patients compared with pouch patients (1581 versus 407; p < 0.01). Main cost drivers in ileostomy patients were healthcare costs and ileostomy supplies (2 and 23% of healthcare costs, respectively). In pouch patients, the main cost driver was hospitalization, accounting for 50% of healthcare costs. Productivity loss did not differ between pouch and ileostomy patients (483 versus 377; p < 0.23), but was significantly higher in anti-TNFα-treated patients (1085). No difference was found in IBDQ scores, but pouch patients were found to have higher quality-adjusted life years than ileostomy patients and anti-TNFα-treated patients (0.90 [interquartile range 0.78-1.00] versus 0.84 [0.78-1.00] and 0.84 [0.69-1.00], respectively; p < 0.01). CONCLUSION: Patients receiving anti-TNFα therapy reported the highest healthcare cost, in which medication use was the major cost driver. Ileostomy patients were three times more expensive than pouch patients due to frequent hospitalization and ileostomy supplies.
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Anticorpos Monoclonais/economia , Colite Ulcerativa/economia , Fármacos Gastrointestinais/economia , Custos de Cuidados de Saúde/estatística & dados numéricos , Ileostomia/economia , Proctocolectomia Restauradora/economia , Qualidade de Vida , Adalimumab/economia , Adalimumab/uso terapêutico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais/uso terapêutico , Colite Ulcerativa/terapia , Bolsas Cólicas/economia , Estudos Transversais , Feminino , Fármacos Gastrointestinais/uso terapêutico , Humanos , Infliximab/economia , Infliximab/uso terapêutico , Masculino , Pessoa de Meia-Idade , Modelos Estatísticos , Países Baixos , Estudos Prospectivos , Anos de Vida Ajustados por Qualidade de Vida , Inquéritos e Questionários , Resultado do Tratamento , Adulto JovemRESUMO
OBJECTIVES: This study aimed to investigate the association between BMI and esophageal acid exposure in a cohort of patients referred for esophageal pH monitoring. The contributing roles of hiatal hernia, lower esophageal sphincter (LES) pressure, and intragastric pressure (IGP) were investigated, with an emphasis on reflux in the supine position. METHODS: Esophageal manometry and 24-h pH-metry results were extracted from a prospectively collected database, and supplemental data (body mass, endoscopy results) from patient files. RESULTS: In total, 245 patients (mean age 52.2±14 years, 54% men) were included in this study. In the normal-weight subgroup (n=87), the median acid exposure time was 1.1% [0-8.1] in the supine position (with interquartile range 25-75%) and 7.7% [2.5-14.8] in the upright position; the total acid exposure time was 7.4% [2.7-11.7]/24 h. In the overweight subgroup (n=104), the median acid exposure time was 4.9% [0.3-13.3] in the supine position and 11.1% [5.4-16.9] in the upright position; the total acid exposure time was 8.9% [4.7-15.8]/24 h. In the obesity subgroup (n=54), the median acid exposure time was 4.1% [0.7-14.3] in the supine position and 10.5% [5-17.5] in the upright position; the total acid exposure time was 8.3% [5.3-14.7]/24 h. Supine acid exposure was significantly higher in overweight and obese patients than in normal-weight patients (both P=0.02). In overweight patients, a hiatal hernia was predictive of supine and total acid exposure, as was a decreasing LES pressure in both the supine and the upright position. In obese patients, increased IGP contributed toward an increased total acid exposure. Although an association between increasing BMI and acid exposure was observed, BMI was not independently predictive. CONCLUSION: Overweight and obesity is associated with increased reflux, especially in the supine position. The most important factors that contribute toward reflux are the presence of a hiatal hernia and a lower LES pressure in overweight patients and an increased IGP in obese patients.
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Ritmo Circadiano , Refluxo Gastroesofágico/etiologia , Peso Corporal Ideal , Obesidade/complicações , Sobrepeso/complicações , Adulto , Idoso , Índice de Massa Corporal , Esfíncter Esofágico Inferior/fisiopatologia , Monitoramento do pH Esofágico , Feminino , Refluxo Gastroesofágico/diagnóstico , Refluxo Gastroesofágico/fisiopatologia , Hérnia Hiatal/complicações , Humanos , Modelos Lineares , Masculino , Manometria , Pessoa de Meia-Idade , Análise Multivariada , Obesidade/diagnóstico , Sobrepeso/diagnóstico , Valor Preditivo dos Testes , Pressão , Estudos Retrospectivos , Fatores de Risco , Decúbito Dorsal , Fatores de TempoRESUMO
Laparoscopic sleeve gastrectomy (LSG) is effective as a stand-alone bariatric procedure. Despite its positive effect with regard to weight loss and improvement of obesity-related co-morbidities, some patients develop gastroesophageal reflux symptoms postoperatively. The pathogenesis of these symptoms is not completely understood. Hence, this study aimed to assess the effect of sleeve gastrectomy on acid and non-acid gastroesophageal reflux, reflux symptoms and esophageal function. In a prospective study, patients underwent esophageal function tests (high-resolution manometry (HRM) and 24-h pH/impedance metry) before and 3 months after LSG. Preoperative and postoperative symptoms were assessed using the Reflux Disease Questionnaire (RDQ). In total, 20 patients (4 male/16 female, mean age 43 ± 12 years, mean weight 137.3 ± 25 kg, and mean BMI 47.6 ± 6.1 kg/m(2)) participated in this study. GERD symptoms did not significantly change after sleeve gastrectomy, but other upper gastrointestinal symptoms, particularly belching, epigastric pain and vomiting increased. Esophageal acid exposure significantly increased after sleeve gastrectomy: upright from 5.1 ± 4.4 to 12.6 ± 9.8% (p = 0.003), supine from 1.4 ± 2.4 to 11 ± 15% (p = 0.003) and total acid exposure from 4.1 ± 3.5 to 12 ± 10.4% (p = 0.004). The percentage of normal peristaltic contractions remained unchanged, but the distal contractile integral decreased after LSG from 2,006.0 ± 1,806.3 to 1,537.4 ± 1,671.8 mmHg · cm · s (p = 0.01). The lower esophageal sphincter (LES) pressure decreased from 18.3 ± 9.2 to 11.0 ± 7.0 mmHg (p = 0.02). After LSG, patients have significantly higher esophageal acid exposure, which may well be due to a decrease in LES resting pressure following the procedure.