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BACKGROUND AND AIMS: Colonoscopy-based surveillance to prevent colorectal cancer (CRC) causes substantial burden for patients and healthcare. Stool tests may help to reduce surveillance colonoscopies, by limiting colonoscopies to individuals at increased risk of AN. METHODS: This cross-sectional observational study included individuals aged 50-75 with surveillance indication. Before bowel preparation, participants collected samples for a multitarget stool DNA (mt-sDNA) test and two fecal immunochemical tests (FITs). Test accuracies were calculated for all surveillance indications. Only for the post-polypectomy indication, most common and associated with a relatively low CRC risk, long-term impact of stool-based surveillance was evaluated with the ASCCA model. Stool-based strategies were simulated to tune each tests' positivity threshold to obtain strategies at least as effective as colonoscopy surveillance. RESULTS: 3453 individuals had results for all stool tests and colonoscopy. 2226 had previous polypectomy, 1003 previous CRC and 224 familial risk. Areas under the receiver operating characteristic curve for AN were 0.72 (95% CI; 0.69-0.75) for the mt-sDNA test, 0.61 (95% CI; 0.58-0.64) for the FIT OC-Sensor and 0.59 (95% CI; 0.56-0.61) for the FIT FOB-Gold. Stool-based post-polypectomy surveillance strategies at least as effective as colonoscopy surveillance, reduced the number of colonoscopies by 15-41% and required 5.6-9.5 stool tests over the lifetime of a person. Mt-sDNA-based surveillance was more costly than colonoscopy surveillance, whereas FIT-based surveillance saved costs. CONCLUSIONS: This study shows that stool-based post-polypectomy surveillance strategies can be safe and cost-effective, with potential to reduce the number of colonoscopies by up to 41%.
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OBJECTIVE: Endoscopic mucosal resection (EMR) is the preferred treatment for non-invasive large (≥20 mm) non-pedunculated colorectal polyps (LNPCPs) but is associated with an early recurrence rate of up to 30%. We evaluated whether standardised EMR training could reduce recurrence rates in Dutch community hospitals. DESIGN: In this multicentre cluster randomised trial, 59 endoscopists from 30 hospitals were randomly assigned to the intervention group (e-learning and 2-day training including hands-on session) or control group. From April 2019 to August 2021, all consecutive EMR-treated LNPCPs were included. Primary endpoint was recurrence rate after 6 months. RESULTS: A total of 1412 LNPCPs were included; 699 in the intervention group and 713 in the control group (median size 30 mm vs 30 mm, 45% vs 52% size, morphology, site and access (SMSA) score IV, 64% vs 64% proximal location). Recurrence rates were lower in the intervention group compared with controls (13% vs 25%, OR 0.43; 95% CI 0.23 to 0.78; p=0.005) with similar complication rates (8% vs 9%, OR 0.93; 95% CI 0.64 to 1.36; p=0.720). Recurrences were more often unifocal in the intervention group (92% vs 76%; p=0.006). In sensitivity analysis, the benefit of the intervention on recurrence rate was only observed in the 20-40 mm LNPCPs (5% vs 20% in 20-29 mm, p=0.001; 10% vs 21% in 30-39 mm, p=0.013) but less evident in ≥40 mm LNPCPs (24% vs 31%; p=0.151). In a post hoc analysis, the training effect was maintained in the study group, while in the control group the recurrence rate remained high. CONCLUSION: A compact standardised EMR training for LNPCPs significantly reduced recurrences in community hospitals. This strongly argues for a national dedicated training programme for endoscopists performing EMR of ≥20 mm LNPCPs. Interestingly, in sensitivity analysis, this benefit was limited for LNPCPs ≥40 mm. TRIAL REGISTRATION NUMBER: NTR7477.
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Pólipos do Colo , Neoplasias Colorretais , Ressecção Endoscópica de Mucosa , Humanos , Pólipos do Colo/cirurgia , Colonoscopia , Neoplasias Colorretais/cirurgiaRESUMO
OBJECTIVE: Assess the effectiveness of sacral neuromodulation (SNM) versus personalized conservative treatment (PCT) in patients with refractory idiopathic slow-transit constipation (STC). BACKGROUND: Evidence on SNM for idiopathic STC is conflicting and of suboptimal methodological quality. METHODS: The No.2-Trial was a multicenter, open-label, pragmatic, randomized trial performed in 2 Dutch hospitals. Sixty-seven patients with idiopathic STC, a defecation frequency <3 per week and refractory (ie, unresponsive) to maximal conservative (nonoperative) treatment were included. Exclusion criteria included outlet obstruction, rectal prolapse, and previous colon surgery. Patients were randomized (3:2) to SNM (n=41) or PCT (n=26) with randomization minimization between February 21, 2017 and March 12, 2020. In SNM patients, an implantable pulse generator was implanted after a successful 4-week test stimulation. PCT patients received conservative treatment such as laxatives or retrograde colonic irrigation. The primary outcome was treatment success (defined as average defecation frequency ≥3 per week) after 6 months. Secondary outcomes included constipation severity, fatigue, quality of life, and adverse events. Analysis was according to intention-to-treat. RESULTS: After 6 months, 22 (53.7%) patients were successfully treated with SNM versus 1 (3.8%) patient with PCT (odds ratio 36.4, 95% CI 3.4-387.5, P =0.003). At 6 months, SNM patients reported lower constipation severity and fatigue scores ( P <0.001) and improved quality of life compared with PCT ( P <0.001). Eight serious adverse events (6 SNM, 2 PCT) and 78 adverse events (68 SNM, 10 PCT) were reported. CONCLUSIONS: SNM is a promising surgical treatment option in a homogeneous group of adults and adolescents with refractory idiopathic STC. No.2-Trial registered at ClinicalTrials.gov NCT02961582.
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Tratamento Conservador , Terapia por Estimulação Elétrica , Adulto , Adolescente , Humanos , Qualidade de Vida , Constipação Intestinal/terapia , Terapia por Estimulação Elétrica/efeitos adversos , Resultado do TratamentoRESUMO
BACKGROUND AND AIMS: Computer-aided diagnosis (CADx) for the optical diagnosis of colorectal polyps is thoroughly investigated. However, studies on human-artificial intelligence interaction are lacking. Our aim was to investigate endoscopists' trust in CADx by evaluating whether communicating a calibrated algorithm confidence score improved trust. METHODS: Endoscopists optically diagnosed 60 colorectal polyps. Initially, endoscopists diagnosed the polyps without CADx assistance (initial diagnosis). Immediately afterward, the same polyp was again shown with a CADx prediction: either only a prediction (benign or premalignant) or a prediction accompanied by a calibrated confidence score (0-100). A confidence score of 0 indicated a benign prediction, 100 a (pre)malignant prediction. In half of the polyps, CADx was mandatory, and for the other half, CADx was optional. After reviewing the CADx prediction, endoscopists made a final diagnosis. Histopathology was used as the gold standard. Endoscopists' trust in CADx was measured as CADx prediction utilization: the willingness to follow CADx predictions when the endoscopists initially disagreed with the CADx prediction. RESULTS: Twenty-three endoscopists participated. Presenting CADx predictions increased the endoscopists' diagnostic accuracy (69.3% initial vs 76.6% final diagnosis, P < .001). The CADx prediction was used in 36.5% (n = 183 of 501) disagreements. Adding a confidence score led to lower CADx prediction utilization, except when the confidence score surpassed 60. Mandatory CADx decreased CADx prediction utilization compared to optional CADx. Appropriate trust-using correct or disregarding incorrect CADx predictions-was 48.7% (n = 244 of 501). CONCLUSIONS: Appropriate trust was common, and CADx prediction utilization was highest for the optional CADx without confidence scores. These results express the importance of a better understanding of human-artificial intelligence interaction.
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BACKGROUND: Recognition of submucosal invasive colorectal cancer (T1 CRC) is difficult, with sensitivities of 35â%-60â% in Western countries. We evaluated the real-life effects of training in the OPTICAL model, a recently developed structured and validated prediction model, in Dutch community hospitals. METHODS: In this prospective multicenter study (OPTICAL II), 383 endoscopists from 40 hospitals were invited to follow an e-learning program on the OPTICAL model, to increase sensitivity in detecting T1 CRC in nonpedunculated polyps. Real-life recognition of T1 CRC was then evaluated in 25 hospitals. Endoscopic and pathologic reports of T1 CRCs detected during the next year were collected retrospectively, with endoscopists unaware of this evaluation. Sensitivity for T1 CRC recognition, R0 resection rate, and treatment modality were compared for trained vs. untrained endoscopists. RESULTS: 1 year after e-learning, 528 nonpedunculated T1 CRCs were recorded for endoscopies performed by 251 endoscopists (118 [47â%] trained). Median T1 CRC size was 20âmm. Lesions were mainly located in the distal colorectum (66â%). Trained endoscopists recognized T1 CRCs more frequently than untrained endoscopists (sensitivity 74â% vs. 62â%; mixed model analysis odds ratio [OR] 2.90, 95â%CI 1.54-5.45). R0 resection rate was higher for T1 CRCs detected by trained endoscopists (69â% vs. 56â%; OR 1.73, 95â%CI 1.03-2.91). CONCLUSION: Training in optical recognition of T1 CRCs in community hospitals was associated with increased recognition of T1 CRCs, leading to higher en bloc and R0 resection rates. This may be an important step toward more organ-preserving strategies.
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The potential role of the transient receptor potential Vanilloid 1 (TRPV1) non-selective cation channel in gastric carcinogenesis remains unclear. The main objective of this study was to evaluate TRPV1 expression in gastric cancer (GC) and precursor lesions compared with controls. Patient inclusion was based on a retrospective review of pathology records. Patients were subdivided into five groups: Helicobacter pylori (H. pylori)-associated gastritis with gastric intestinal metaplasia (GIM) (n = 12), chronic atrophic gastritis (CAG) with GIM (n = 13), H. pylori-associated gastritis without GIM (n = 19), GC (n = 6) and controls (n = 5). TRPV1 expression was determined with immunohistochemistry and was significantly higher in patients with H. pylori-associated gastritis compared with controls (p = 0.002). TRPV1 expression was even higher in the presence of GIM compared with patients without GIM and controls (p < 0.001). There was a complete loss of TRPV1 expression in patients with GC. TRPV1 expression seems to contribute to gastric-mucosal inflammation and precursors of GC, which significantly increases in cancer precursor lesions but is completely lost in GC. These findings suggest TRPV1 expression to be a potential marker for precancerous conditions and a target for individualized treatment. Longitudinal studies are necessary to further address the role of TRPV1 in gastric carcinogenesis.
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Infecções por Helicobacter , Neoplasias Gástricas , Canais de Cátion TRPV , Humanos , Canais de Cátion TRPV/metabolismo , Canais de Cátion TRPV/genética , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Infecções por Helicobacter/metabolismo , Infecções por Helicobacter/complicações , Infecções por Helicobacter/patologia , Carcinogênese/metabolismo , Carcinogênese/patologia , Estudos Retrospectivos , Lesões Pré-Cancerosas/metabolismo , Lesões Pré-Cancerosas/patologia , Helicobacter pylori/patogenicidade , Metaplasia/metabolismo , Metaplasia/patologia , Gastrite/metabolismo , Gastrite/patologia , Gastrite/microbiologia , Adulto , Imuno-Histoquímica , Mucosa Gástrica/metabolismo , Mucosa Gástrica/patologia , Gastrite Atrófica/metabolismo , Gastrite Atrófica/patologiaRESUMO
BACKGROUND: Combining the faecal immunochemical test (FIT) result with risk factors for advanced neoplasia (AN) may increase the yield of colorectal cancer (CRC) screening without increasing the number of colonoscopies. We conducted a randomised controlled trial in the Dutch CRC screening programme to evaluate a previously developed risk model including FIT, age, sex, smoking status, and CRC family history. METHODS: A total of 22,748 individuals aged 56-75 years were pre-randomised to the risk-model group or the FIT-only group. Both groups received the FIT; those allocated to the risk-model group also received a single-page questionnaire. Study participants with a positive result (FIT ≥ 15 µg Hb/g faeces and/or risk ≥0.10) were referred for colonoscopy. The primary outcome measure was the proportion of invitees in whom AN was detected. RESULTS: In the risk-model group, 3113/11,364 invitees (27%) returned the FIT and questionnaire versus 3061/11,384 invitees (27%) in the FIT-only group (p = 0.40). The yield of AN was 3.70/1000 invitees in the risk-model group versus 3.43/1000 in the FIT-only group (absolute difference: 0.27/1000, 95%CI: -1.30 to 1.82, p = 0.82). CONCLUSIONS: Combining FIT with risk factors for CRC did not increase the yield of AN compared to FIT-only in an existing CRC screening programme. There was no difference in participation between groups. CLINICAL TRIAL REGISTRATION: NCT04490551 (ClinicalTrials.gov).
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Neoplasias Colorretais , Detecção Precoce de Câncer , Humanos , Colonoscopia , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/epidemiologia , Fatores de Risco , Sangue Oculto , Fezes/química , Hemoglobinas/análise , Programas de RastreamentoRESUMO
BACKGROUND & AIMS: Irritable bowel syndrome (IBS) is associated with substantial costs to society. Extensive data on direct costs (health care consumption) and indirect costs (health-related productivity loss) are lacking. Hence, we examined the socioeconomic costs of IBS and assessed which patient characteristics are associated with higher costs. METHODS: Cross-sectional data from 3 Rome-defined Dutch IBS patient cohorts (n = 419) were collected. Bootstrapped mean direct and indirect costs were evaluated per patient with IBS using validated questionnaires (ie, medical cost questionnaire and productivity cost questionnaire, respectively). Multivariable regression analyses were performed to identify variables associated with higher costs. RESULTS: Quarterly mean total costs per patient were 2.156 (95% confidence interval (CI), 1793-2541 [$2444]), consisting of 802 (95% CI, 625-1010 [$909]) direct costs and 1.354 (95% CI, 1072-1670 [$1535]) indirect costs. Direct costs consisted primarily of health care professional consultations, with costs related to gastrointestinal clinic visits accounting for 6% and costs related to mental health care visits for 20%. Higher direct costs were significantly associated with older age (P = .007), unemployment (P = .001), IBS subtypes other than constipation (P = .033), lower disease-specific quality of life (P = .027), and more severe depressive symptoms (P = .001). Indirect costs consisted of absenteeism (45%), presenteeism (42%), and productivity loss related to unpaid labor (13%) and were significantly associated with the male sex (P = .014) and more severe depressive symptoms (P = .047). CONCLUSIONS: Productivity loss is the main contributor to the socioeconomic burden of IBS. Direct costs were not predominantly related to gastrointestinal care, but rather to mental health care. Awareness of the nature of costs and contributing patient factors should lead to significant socioeconomic benefits for society.
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Síndrome do Intestino Irritável , Masculino , Humanos , Síndrome do Intestino Irritável/complicações , Qualidade de Vida , Estudos Transversais , Custos de Cuidados de Saúde , Atenção à Saúde , Fatores SocioeconômicosRESUMO
INTRODUCTION: Irritable bowel syndrome (IBS) has a major impact on emotional, social, and professional life. This study aimed to evaluate general life satisfaction, a subjective measure of well-being, in IBS patients, and to determine which factors are associated with higher life satisfaction. METHODS: IBS patients (n = 195, mean age 51.4 ± 16.5 years, 73.8% female) recruited from primary and secondary/tertiary care completed questionnaires regarding gastrointestinal symptoms, quality of life, psychological factors, and life satisfaction (Satisfaction With Life Scale, 5 items, range 5-35). A finite mixture model analysis was performed to identify latent classes. Multivariable linear regression was used to identify variables associated with life satisfaction. RESULTS: Overall, 71.3% of the patients were satisfied about their life (Satisfaction With Life Scale-score ≥21). Three latent subgroups could be identified with significantly higher life satisfaction in the subgroup with higher mental quality of life, fewer anxiety and depressive symptoms, lower gastrointestinal specific anxiety, and lower gastrointestinal symptom severity, compared with the other 2 groups. Multivariable linear regression showed that higher physical quality of life (B0.168, P < 0.001) and higher mental quality of life (B0.199, P < 0.001) were associated with higher life satisfaction. Using multivariable regression, no significant association was found between gastrointestinal symptom severity and life satisfaction. DISCUSSION: Higher physical and mental quality of life, but not gastrointestinal symptom severity, were independently associated with higher general life satisfaction in IBS. These findings reinforce the clinical need in IBS treatment to focus on the full extent of the disorder and not merely on gastrointestinal symptom improvement. ClinicalTrials.gov Identifier: NCT00775060.
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BACKGROUND: Post-colonoscopy colorectal cancers (PCCRCs) pose challenges in clinical practice. PCCRCs occur due to a combination of procedural and biological causes. In a nested case-control study, we compared clinical and molecular features of PCCRCs and detected CRCs (DCRCs). METHODS: Whole-genome chromosomal copy number changes and mutation status of genes commonly affected in CRC were examined by low-coverage WGS and targeted sequencing, respectively. MSI and CIMP status was also determined. RESULTS: In total, 122 PCCRCs and 98 DCRCs with high-quality DNA were examined. PCCRCs were more often located proximally (P < 0.001), non-polypoid appearing (P = 0.004), early stage (P = 0.009) and poorly differentiated (P = 0.006). PCCRCs showed significantly less 18q loss (FDR < 0.2), compared to DCRCs. No significant differences in mutations were observed. PCCRCs were more commonly CIMP high (P = 0.014) and MSI (P = 0.029). After correction for tumour location, only less 18q loss remained significant (P = 0.005). CONCLUSION: Molecular features associated with the sessile serrated lesions (SSLs) and non-polypoid colorectal neoplasms (CRNs) are more commonly seen in PCCRCs than in DCRCs. These together with the clinical features observed support the hypothesis that SSLs and non-polypoid CRNs are contributors to the development of PCCRCs. The future focus should be directed at improving the detection and endoscopic removal of these non-polypoid CRN and SSLs. CLINICAL TRIAL REGISTRATION: NTR3093 in the Dutch trial register ( www.trialregister.nl ).
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Colonoscopia , Neoplasias Colorretais , Estudos de Casos e Controles , Neoplasias Colorretais/patologia , HumanosRESUMO
BACKGROUND & AIMS: Irritable bowel syndrome (IBS) is a highly prevalent, chronic disorder of the gut-brain interaction that significantly affects quality of life. Several treatments, with comparable clinical efficacy, are available. Patient preferences can therefore be an important determinant of an effective management strategy. Treatment preferences of patients regarding decision making remain unclear. We aimed to examine these preferences and estimate trade-offs between different attributes. METHODS: A total of 427 patients from the Maastricht IBS cohort were invited to participate. A labeled discrete choice experiment survey, containing 9 scenarios with each 3 alternatives (medication, diet, psychotherapy), was developed in order to estimate preferences. The treatment scenarios were based on 6 attributes: effectiveness, time to response, time until recurrence, side effects, time required, and frequency of appointments. The preference weights and relative importance were analyzed using a mixed logit model. RESULTS: A total of 185 (43.3%) of 427 potential respondents completed the questionnaire (mean age 49.51 years, 69.2% female). The most preferred treatment was dietary intervention (48.1%), followed by pharmacotherapy (29.2%) and psychotherapy (22.7%). IBS patients preferred a higher effectiveness, shorter time interval to response, longer time interval until recurrence, no severe side effects, and frequent appointments when attending psychotherapy. Younger patients (≤50 years of age) preferred dietary interventions and a long period until recurrence, whereas older patients (>50 years of age) were more inclined to choose pharmacotherapy and the period until recurrence was not important. CONCLUSIONS: Dietary interventions were the most preferred IBS therapy. Identifying patients' treatment preferences during shared decision making will provide more optimal management strategies and could be the best approach to diminish disease burden.
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Síndrome do Intestino Irritável , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Síndrome do Intestino Irritável/terapia , Comportamento de Escolha , Qualidade de Vida , Preferência do Paciente , DietaRESUMO
OBJECTIVE: Fullness is a cardinal symptom in functional dyspepsia (FD). The use of real-time symptom assessment might provide more insight into factors, such as daily stress, that can influence fullness. Therefore, this study aimed to use the experience sampling method (a real-time, repeated-measurement method making use of repeated questionnaires available at random moments for a limited amount of time) to assess the association between stress and fullness in patients with FD and healthy controls (HCs). METHODS: Thirty-five patients with FD (25 female, mean age = 44.7 years) and 34 HCs (24 female, mean age = 44.1 years) completed the experience sampling method (a maximum of 10 random moments per day) for 7 consecutive days. Stress and fullness were rated on an 11-point Numeric Rating Scale. Data between patients with FD and HCs were statistically compared using a Student samples t test and linear mixed-effects models with repeated measures (level 1) nested within participants (level 2). RESULTS: Average fullness scores were 2.23 (standard error = 0.37) points higher in patients with FD compared with HCs (p < .001). Average stress scores were 1.37 (standard error = 0.30) points higher in patients with FD compared with HCs (p = .002).In FD, fullness scores increased with 0.14 for every 1-point increase in concurrent stress scores (p = .010). Fullness scores at t = 0 increased with 0.12 for every 1-point increase in stress scores at t = -1 (p = .019). T = 0 stress scores were not associated with change in t = -1 fullness scores. No associations between concurrent symptom scores were found for HCs. CONCLUSIONS: Concurrent and preceding stress scores are positively associated with fullness scores in patients with FD, but not in HCs. These findings indicate that increased levels of stress may precede feelings of fullness in patients with FD. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT04204421.
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Dispepsia , Adulto , Dispepsia/diagnóstico , Avaliação Momentânea Ecológica , Feminino , Nível de Saúde , Humanos , Inquéritos e QuestionáriosRESUMO
Hesperidin and naringin are citrus flavonoids with known anti-oxidative and anti-inflammatory properties. Evidence from previous studies indicates that both these compounds and the metabolites that are formed during intestinal metabolism are able to exert beneficial effects on intestinal barrier function and inflammation. However, so far, studies investigating the relative contributions of the various compounds are lacking. Therefore, we assessed the effect of citrus flavonoids and their intestinal metabolites on immune-mediated barrier disruption in an in vitro co-culture model. Caco-2 cell monolayers were placed in co-culture with phorbol 12-myristate 13-acetate-stimulated THP-1-Blue™ NF-κB cells for 30 h. At baseline, the citrus flavonoids and their metabolites were added to the apical compartment (50 or 100 µM per compound). After 24 h, THP-1 cells were incubated with lipopolysaccharide (LPS) in the basolateral compartment for 6 h. Incubation with citrus flavonoids and their metabolites did not induce changes in transepithelial electrical resistance, fluorescein isothiocyanate-dextran 4 kDa permeation or gene expression of barrier-related genes for any of the compounds tested. After LPS stimulation, NF-κB activity was significantly inhibited by all compounds (100 µM) except for one metabolite (all P ≤ 0·03). LPS-induced production of the cytokines IL-8, TNF-α and IL-6 was inhibited by most compounds (all P < 0·05). However, levels of IL-1ß were increased, which may contribute to the lack of an improved barrier effect. Overall, these results suggest that citrus flavonoids may decrease intestinal inflammation via reduction of NF-κB activity and that the parent compounds and their metabolites formed during intestinal metabolism are able to exert comparable effects.
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Citrus , Flavonoides , Humanos , NF-kappa B/metabolismo , Células CACO-2 , Técnicas de Cocultura , Citrus/metabolismo , Lipopolissacarídeos/efeitos adversos , Inflamação/induzido quimicamente , Mucosa Intestinal/metabolismoRESUMO
PURPOSE: The Irritable Bowel Syndrome Quality of Life (IBS-QoL) questionnaire is a commonly used and validated IBS-specific QoL instrument. However, this questionnaire is in contrast to the EQ-5D-5L, not preference-based and as such does not allow calculation of QALYs. The objective of this study was to describe the convergent- and known-group validity of both questionnaires and to develop a mapping algorithm from EQ-5D-5L which enable IBS-QoL scores to be transformed into utility scores for use in economic evaluations. METHODS: We used data from two multicenter randomized clinical trials, which represented the estimation and external validation dataset. The convergent validity was investigated by examining correlations between the EQ-5D-5L and IBS-QoL and the known-group validity by calculating effect sizes. Ordinary least squares (OLS), censored least absolute deviations (CLAD), and mixture models were used in this mapping approach. RESULTS: 283 IBS patients were included (n = 189 vs. n = 84). Mean IBS-QoL score was 71.13 (SD 15.66) and mean EQ-5D-5L utility score was 0.73 (SD 0.19). The overall sensitivity of the IBS-QoL and EQ-5D-5L to discriminate between patient and disease characteristics was similar. CLAD model 4, containing the total IBS-QoL score and squared IBS-SSS (IBS severity scoring system), was chosen as the most appropriate model to transform IBS-QoL scores into EQ-5D-5L utility scores. CONCLUSION: This study reports the development of an algorithm where the condition-specific questionnaire IBS-QoL can be used to calculate utility values for use in economic evaluations. Including a clinical measure, IBS-SSS, in the model improved the performance of the algorithm.
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Síndrome do Intestino Irritável , Qualidade de Vida , Análise Custo-Benefício , Humanos , Qualidade de Vida/psicologia , Anos de Vida Ajustados por Qualidade de Vida , Inquéritos e QuestionáriosRESUMO
BACKGROUND AND STUDY AIMS: We conducted a systematic review and meta-analysis of population-based studies to explore pooled prevalence and magnitude of electrolyte changes after bowel preparation for colonoscopy based on the most recent guidelines. PATIENTS AND METHODS: PubMed and Cochrane were queried for population-based studies examining changes in electrolyte values after bowel preparation, published by July 1, 2021. We report prevalences of serum hypokalemia, hyponatremia, hyperphosphatemia, and hypocalcemia after bowel preparation and changes in mean electrolyte values after vs. before bowel preparation using sodium phosphate (NaP) and polyethylene glycol (PEG). RESULTS: Thirteen studies met the inclusion criteria; 2386 unique patients were included. Overall, hypokalemia was found in 17.2% (95% CI 6.7, 30.9) in the NaP group vs. 4.8% (95% CI 0.27, 13.02) in the PEG group. The magnitude of potassium decrease after NaP bowel preparation was significantly increased compared to PEG (mean difference -0.38; 95% CI -0.49 to -0.27, P < 0.001). No study reported on major complications. CONCLUSIONS: Hypokalemia was found in 17.2% of patients after bowel preparation with NaP and in 4.8% of patients with PEG, a finding that is clinically relevant with respect to choosing the type of bowel preparation. The magnitude of the potassium decrease after NaP was significantly higher compared to PEG. These data provide the evidence that supports the recommendation of the European Society of Gastrointestinal Endoscopy against routine use of NaP for bowel preparation.
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Hipopotassemia , Catárticos/efeitos adversos , Colonoscopia/efeitos adversos , Colonoscopia/métodos , Eletrólitos/efeitos adversos , Humanos , Polietilenoglicóis/efeitos adversos , PotássioRESUMO
Intestinal barrier dysfunction is a pathogenic hallmark in Crohn's disease (CD). Identifying key players that regulate intestinal barrier may provide novel leads for therapeutic intervention. Interleukin-28A (IL-28A) is a newly identified IL-10/interferon cytokine family member, with its most implicated function being antiviral and anti-proliferative properties. However, the role and underlying mechanisms of IL-28A in the regulation of epithelial barrier in CD remain so far unexplored. IL-28A levels were measured in the plasma and biopsies of CD patients and healthy subjects. CD patient-derived intestinal organoids were characterized by differentiation gene markers and then exposed to TNF-α, IFN-γ, IL-1ß or LPS, or IL-28A with or without GLPG0634 (filgotinib). Epithelial permeability was assessed by FITC-D4 flux. Expression of junctional components was analyzed by qRT-PCR, immunofluorescence staining, or Western blotting. JAK-STAT activity was analyzed by Western blotting. IL-28A levels were significantly increased in the plasma and biopsies from active patients with CD as compared with healthy subjects. IL-28A and its receptor complex IL-28AR/IL-10R2 were detected in CD patient-derived intestinal organoids and showed a selective response to IFN-γ exposure. IL-28A triggered epithelial barrier disruption and accompanied by reduced ZO-1 and E-cadherin expression. This effect was mediated by JAK-STAT1 pathway. Pre-incubation with the JAK1 inhibitor filgotinib ameliorated the barrier dysfunction induced by IL-28A. These results identified IL-28A as a novel regulator of epithelial barrier function and could be a putative target for CD treatment. We provide novel basic evidence that restoring intestinal barrier is a potential mechanism that contributes to the clinical benefits of JAK1 inhibitor in patients with CD.NEW & NOTEWORTHY IL-28A levels were significantly increased in the plasma and biopsies from active patients with CD as compared with healthy subjects. IFN-γ exposure stimulated IL-28A expression in intestinal organoids. Partially mimicking the effect of IFN-γ, IL-28A impaired epithelial barrier function and disrupted junctional components through the activation of JAK-STAT1 signaling, whereas JAK1 inhibitor ameliorated the above-mentioned effects of IL-28A. These findings highlight the newly identified cytokine IL-28A as a novel contributor to CD pathogenesis and could be a putative target for CD treatment. We also provide new evidence for potential applications of JAK inhibition in CD therapy.
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Doença de Crohn/metabolismo , Interleucinas/farmacologia , Mucosa Intestinal/efeitos dos fármacos , Organoides/efeitos dos fármacos , Doença de Crohn/patologia , Humanos , Interferon gama/farmacologia , Interleucina-1beta/farmacologia , Interleucinas/sangue , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Lipopolissacarídeos/farmacologia , Organoides/metabolismo , Organoides/patologia , Transdução de Sinais/efeitos dos fármacos , Fator de Necrose Tumoral alfa/farmacologiaRESUMO
BACKGROUND & AIMS: Peppermint oil is frequently used to treat irritable bowel syndrome (IBS), despite a lack of evidence for efficacy from high-quality controlled trials. We studied the efficacy and safety of small-intestinal-release peppermint oil in patients with IBS and explored the effects of targeted ileocolonic-release peppermint oil. METHODS: We performed a double-blind trial of 190 patients with IBS (according to Rome IV criteria) at 4 hospitals in The Netherlands from August 2016 through March 2018; 189 patients were included in the intent-to-treat analysis (mean age, 34.0 years; 77.8% female; 57.7% in primary care), and 178 completed the study. Patients were randomly assigned to groups given 182 mg small-intestinal-release peppermint oil, 182 mg ileocolonic-release peppermint oil, or placebo for 8 weeks. The primary endpoint was abdominal pain response, as defined by the US Food and Drug Administration: at least a 30% decrease in the weekly average of worst daily abdominal pain compared with baseline in at least 4 weeks. The co-primary endpoint was overall relief of IBS symptoms, as defined by the European Medicines Agency. Secondary endpoints included abdominal pain, discomfort, symptom severity, and adverse events. RESULTS: Abdominal pain response did not differ significantly between the peppermint oil and placebo groups: 29 of 62 patients in the small-intestinal-release peppermint oil group had a response (46.8%, P = .170 vs placebo), 26 of 63 patients in the ileocolonic-release peppermint oil group had a response (41.3%, P = .385 vs placebo), and 22 of 64 patients in the placebo group had a response (34.4%). We did not find differences among the groups in overall relief (9.7%, P = .317 and 1.6%, P = .351 vs 4.7% for placebo). The small intestinal peppermint oil did, however, produce greater improvements than placebo in secondary outcomes of abdominal pain (P = .016), discomfort (P = .020), and IBS severity (P = .020). Adverse events, although mild, were more common in both peppermint oil groups (P < .005). CONCLUSIONS: In a randomized trial of patients with IBS, we found that neither small-intestinal-release nor ileocolonic-release peppermint oil (8 weeks) produced statistically significant reductions in abdominal pain response or overall symptom relief, when using US Food and Drug Administration/European Medicines Agency recommended endpoints. The small-intestinal-release peppermint oil did, however, significantly reduce abdominal pain, discomfort, and IBS severity. These findings do not support further development of ileocolonic-release peppermint oil for treatment of IBS. Clinicaltrials.gov, Number: NCT02716285.
Assuntos
Dor Abdominal/tratamento farmacológico , Analgésicos/administração & dosagem , Síndrome do Intestino Irritável/tratamento farmacológico , Óleos de Plantas/administração & dosagem , Dor Abdominal/diagnóstico , Dor Abdominal/etiologia , Administração Oral , Adolescente , Adulto , Idoso , Analgésicos/efeitos adversos , Cápsulas , Método Duplo-Cego , Feminino , Humanos , Mucosa Intestinal/efeitos dos fármacos , Síndrome do Intestino Irritável/complicações , Síndrome do Intestino Irritável/diagnóstico , Masculino , Mentha piperita , Pessoa de Meia-Idade , Países Baixos , Medição da Dor , Índice de Gravidade de Doença , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND AND AIMS: With the introduction of the national bowel cancer screening program, the detection of sessile and flat colonic lesions ≥20 mm in size, defined as large nonpedunculated colorectal polyps (LNPCPs), has increased. The aim of this study was to examine the quality of endoscopic treatment of LNPCPs in the Dutch screening program. METHODS: This investigation comprised 2 related, but separate, substudies (1 with a cross-sectional design and 1 with a longitudinal design). The first examined prevalence and characteristics of LNPCPs in data from the national Dutch screening cohort from February 2014 until January 2017. The second, with screening data from 5 endoscopy units in the Southern part of the Netherlands from February 2014 until August 2015, examined performance on important quality indicators (technical and clinical successes, recurrence rate, adverse event rate, and surgery referral rate). All patients were part of the national Dutch screening cohort. RESULTS: In the national cohort, an LNPCP was detected in 8% of participants. Technical and clinical success decreased with increasing LNPCP size, from 93% and 96% in 20- to 29-mm lesions to 85% and 86% in 30- to 39-mm lesions and to 74% and 81% in ≥40-mm lesions (P < .001; P = .034). The cumulative recurrence rate at 12 months increased with LNPCP size, from 9% to 22% and 26% in the respective size groups (P = .095). The adverse event rate was 5%. The overall surgical referral rate for noninvasive LNPCPs was 7%. CONCLUSIONS: In this performance of 2 substudies, it was shown that quality parameters for endoscopic resection of large polyps in the Dutch screening cohort are not reached, especially in ≥30-mm polyps. Endoscopic resection of large polyps could benefit from additional training, quality monitoring, and centralization either within or between centers.
Assuntos
Pólipos do Colo , Neoplasias Colorretais , Pólipos do Colo/diagnóstico , Pólipos do Colo/cirurgia , Colonoscopia , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/cirurgia , Estudos Transversais , Detecção Precoce de Câncer , Humanos , Indicadores de Qualidade em Assistência à SaúdeRESUMO
BACKGROUND: Optical diagnosis of colorectal polyps remains challenging. Image-enhancement techniques such as narrow-band imaging and blue-light imaging (BLI) can improve optical diagnosis. We developed and prospectively validated a computer-aided diagnosis system (CADx) using high-definition white-light (HDWL) and BLI images, and compared the system with the optical diagnosis of expert and novice endoscopists. METHODS: CADx characterized colorectal polyps by exploiting artificial neural networks. Six experts and 13 novices optically diagnosed 60 colorectal polyps based on intuition. After 4 weeks, the same set of images was permuted and optically diagnosed using the BLI Adenoma Serrated International Classification (BASIC). RESULTS: CADx had a diagnostic accuracy of 88.3â% using HDWL images and 86.7â% using BLI images. The overall diagnostic accuracy combining HDWL and BLI (multimodal imaging) was 95.0â%, which was significantly higher than that of experts (81.7â%, Pâ=â0.03) and novices (66.7â%, Pâ<â0.001). Sensitivity was also higher for CADx (95.6â% vs. 61.1â% and 55.4â%), whereas specificity was higher for experts compared with CADx and novices (95.6â% vs. 93.3â% and 93.2â%). For endoscopists, diagnostic accuracy did not increase when using BASIC, either for experts (intuition 79.5â% vs. BASIC 81.7â%, Pâ=â0.14) or for novices (intuition 66.7â% vs. BASIC 66.5â%, Pâ=â0.95). CONCLUSION: CADx had a significantly higher diagnostic accuracy than experts and novices for the optical diagnosis of colorectal polyps. Multimodal imaging, incorporating both HDWL and BLI, improved the diagnostic accuracy of CADx. BASIC did not increase the diagnostic accuracy of endoscopists compared with intuitive optical diagnosis.
Assuntos
Adenoma , Pólipos do Colo , Neoplasias Colorretais , Adenoma/diagnóstico por imagem , Pólipos do Colo/diagnóstico por imagem , Colonoscopia , Neoplasias Colorretais/diagnóstico por imagem , Computadores , Humanos , Imagem de Banda EstreitaRESUMO
BACKGROUND AND AIMS: Alcohol-related liver disease is the most frequent cause of cirrhosis and a major indication for liver transplantation. Several alcohol use biomarkers have been developed in recent years and are already in use in several centers. However, in patients with liver disease their diagnostic performance might be influenced by altered biomarker formation by hepatic damage, altered excretion by kidney dysfunction and diuretics use, and altered deposition in hair and nails. We systematically reviewed studies on the diagnostic accuracy of biomarkers of alcohol use in patients with liver disease and performed a detailed study quality assessment. METHODS: A structured search in PubMed/Medline/Embase databases was performed for relevant studies, published until April 28, 2019. The risk of bias and applicability concerns was assessed according to the adapted quality assessment of diagnostic accuracy studies-2 (QUADAS-2) checklist. RESULTS: Twelve out of 6,449 studies met inclusion criteria. Urinary ethyl glucuronide and urinary ethyl sulfate showed high sensitivity (70 to 89 and 73 to 82%, respectively) and specificity (93 to 99 and 86 to 89%, respectively) for assessing any amount of alcohol use in the past days. Serum carbohydrate-deficient transferrin showed low sensitivity but higher specificity (40 to 79 and 57 to 99%, respectively) to detect excessive alcohol use in the past weeks. Whole blood phosphatidylethanol showed high sensitivity and specificity (73 to 100 and 90 to 96%, respectively) to detect any amount of alcohol use in the previous weeks. Scalp hair ethyl glucuronide showed high sensitivity (85 to 100%) and specificity (97 to 100%) for detecting chronic excessive alcohol use in the past 3 to 6 months. Main limitations of the current evidence are the lack of an absolute gold standard to assess alcohol use, heterogeneous study populations, and the paucity of studies. CONCLUSIONS: Urinary and scalp hair ethyl glucuronide are currently the most validated alcohol use biomarkers in patients with liver disease with good diagnostic accuracies. Phosphatidylethanol is a highly promising alcohol use biomarker, but so far less validated in liver patients. Alcohol use biomarkers can complement each other regarding diagnostic time window. More validation studies on alcohol use biomarkers in patients with liver disease are needed.