IMPORTANCE: Diagnostic yield of upper gastrointestinal (GI) tract endoscopy for uninvestigated dyspepsia is low, and its clinical implications are limited. There is an unmet need for better ...strategies to reduce the volume of upper GI tract endoscopic procedures for dyspepsia. OBJECTIVE: To study the effectiveness of a web-based educational intervention as a tool to reduce upper GI tract endoscopy in uninvestigated dyspepsia. DESIGN, SETTING, AND PARTICIPANTS: This open-label, multicenter, randomized clinical trial enrolled participants between November 1, 2017, and March 31, 2019, with follow-up 52 weeks after randomization, at 4 teaching hospitals in the Netherlands. Participants included patients with uninvestigated dyspeptic symptoms who were referred for upper GI tract endoscopy by their general health care clinician without prior consultation of a gastroenterologist. A total of 119 patients, aged 18 to 69 years, were included. Patients were excluded if any of the following red flag symptoms were present: (indirect) signs of upper GI tract hemorrhage (hematemesis, melena, hematochezia, or anemia), unintentional weight loss of 5% or higher of normal body weight during a period of 6 to 12 months, persistent vomiting, dysphagia, or jaundice. INTERVENTIONS: Patients were randomly assigned (1:1) to education (intervention) or upper GI tract endoscopy (control). Education consisted of a self-managed web-based educational intervention, containing information on gastric function, dyspepsia, and upper GI tract endoscopy. MAIN OUTCOMES AND MEASURES: Difference in the proportion of upper GI tract endoscopy procedures between those who received access to the web-based educational intervention and those who did not at 12 weeks and 52 weeks after randomization, analyzed in the intention-to-treat population. Secondary outcomes included quality of life (Nepean Dyspepsia Index) and symptom severity (Patient Assessment of Gastrointestinal Disorders Symptom Severity Index) measured at baseline and 12 weeks. RESULTS: Of 119 patients included (median age, 48 years interquartile range, 37-56 years; 48 men 40%), 62 were randomized to web-based education (intervention) and 57 to upper GI tract endoscopy (control). Significantly fewer patients compared with controls underwent upper GI tract endoscopy after using the web-based educational intervention: 24 (39%) vs 47 (82%) (relative risk, 0.46; 95% CI, 0.33-0.64; P < .001). Symptom severity and quality of life improved equivalently in both groups. One additional patient in the intervention group required upper GI tract endoscopy during follow-up. CONCLUSIONS AND RELEVANCE: Findings of this study indicate that web-based patient education is an effective tool to decrease the need for upper GI tract endoscopy in uninvestigated dyspepsia. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03205319
Abstract
Background and Aims
The COVID-19 risk and disease course in inflammatory bowel disease IBD patients remains uncertain. Therefore, we aimed to assess the clinical presentation, disease ...course, and outcomes of COVID-19 in IBD patients. Second, we determined COVID-19 incidences in IBD patients and compared this with the general population.
Methods
We conducted a multicentre, nationwide IBD cohort study in The Netherlands and identified patients with COVID-19. First, we assessed the COVID-19 disease course and outcomes. Second, we compared COVID-19 incidences between our IBD study cohort and the general Dutch population.
Results
We established an IBD cohort of 34 763 patients. COVID-19 was diagnosed in 100/34 763 patients 0.29%; 20/100 of these patients 20% had severe COVID-19 defined as admission to the intensive care unit, mechanical ventilation, and/or death. Hospitalisation occurred in 59/100 59.0% patients and 13/100 13.0% died. All patients who died had comorbidities and all but one were ≥65 years old. In line, we identified ≥1 comorbidity as an independent risk factor for hospitalisation (odds ratio OR 4.20, 95% confidence interval CI 1.58–11.17,; p = 0.004). Incidences of COVID-19 between the IBD study cohort and the general population were comparable (287.6 95% CI 236.6–349.7 versus 333.0 95% CI 329.3–336.7 per 100000 patients, respectively; p = 0.15).
Conclusions
Of 100 cases with IBD and COVID-19, 20% developed severe COVID-19, 59% were hospitalised and 13% died. A comparable COVID-19 risk was found between the IBD cohort 100/34 763 = 0.29% and the general Dutch population. The presence of ≥1 comorbidities was an independent risk factor for hospitalisation due to COVID-19.
Endoscopic dilation (ED) is still the mainstay of therapeutic management of benign esophageal strictures (BESs). This study aimed to establish risk factors for refractory BESs and assess long-term ...clinical outcomes of ED.
We performed a retrospective study in 891 patients who underwent ED from 2003 to 2018 for BESs. We searched electronic medical records in 6 tertiary care centers in the Netherlands for data on clinical outcome of ED. Median follow-up was 39 months. The primary endpoint was risk factors for refractory BESs, defined as factors associated with an increased number of ED sessions during follow-up. Secondary endpoints were time from first to last ED session and adverse events.
Dilation up to 13 to 15 mm was associated with a higher number of ED sessions than dilation up to 16 to 18 mm (5.0 vs 4.1; hazard ratio HR, 1.4; P = .001). Compared with peptic strictures, anastomotic (4.9 vs 3.6; HR, 2.1; P < .001), radiation (5.0 vs 3.6; HR, 3.0; P < .001), caustic (7.2 vs 3.6; HR, 2.7; P < .001), and postendotherapy (3.9 vs 3.6; HR, 1.8; P = .005) strictures were associated with a higher number of ED sessions. After 1 year of follow-up, the proportions of patients who remained free of ED was 75% in anastomotic, 71% in radiation, 70% in peptic, 83% in postendotherapy, and 62% in caustic strictures. Esophageal perforation occurred in 23 ED sessions (.4%) in 22 patients (2.4%).
More than 60% of patients with BESs remain free of ED after 1 year of follow-up. Because dilation up to 16 to 18 mm diameter was associated with fewer ED sessions during follow-up, we suggest that clinicians should consider dilation up to at least 16 mm to reduce the number of ED sessions in these patients.
Objective:
The use and impact of antibiotics and the impact of causative pathogens on clinical outcomes in a large real-world cohort covering the entire clinical spectrum of necrotizing pancreatitis ...remain unknown.
Summary Background Data:
International guidelines recommend broad-spectrum antibiotics in patients with suspected infected necrotizing pancreatitis. This recommendation is not based on high-level evidence and clinical effects are unknown.
Materials and Methods:
This study is a post-hoc analysis of a nationwide prospective cohort of 401 patients with necrotizing pancreatitis in 15 Dutch centers (2010-2019). Across the patient population from the time of admission to 6 months postadmission, multivariable regression analyses were used to analyze (1) microbiological cultures and (2) antibiotic use.
Results:
Antibiotics were started in 321/401 patients (80%) administered at a median of 5 days (P25-P75: 1-13) after admission. The median duration of antibiotics was 27 days (P25-P75: 15-48). In 221/321 patients (69%) infection was not proven by cultures at the time of initiation of antibiotics. Empirical antibiotics for infected necrosis provided insufficient coverage in 64/128 patients (50%) with a pancreatic culture. Prolonged antibiotic therapy was associated with
Enterococcus
infection (OR 1.08 95% CI 1.03-1.16,
P
=0.01).
Enterococcus
infection was associated with new/persistent organ failure (OR 3.08 95% CI 1.35-7.29,
P
<0.01) and mortality (OR 5.78 95% CI 1.46-38.73,
P
=0.03). Yeast was found in 30/147 cultures (20%).
Discussion:
In this nationwide study of patients with necrotizing pancreatitis, the vast majority received antibiotics, typically administered early in the disease course and without a proven infection. Empirical antibiotics were inappropriate based on pancreatic cultures in half the patients. Future clinical research and practice must consider antibiotic selective pressure due to prolonged therapy and coverage of
Enterococcus
and yeast. Improved guidelines on antimicrobial diagnostics and therapy could reduce inappropriate antibiotic use and improve clinical outcomes.
Summary
Background
Azathioprine (AZA) and mercaptopurine (MP) are the cornerstone of steroid‐sparing strategies in autoimmune hepatitis (AIH). Up to 20% of patients do not tolerate or respond to ...these regimens.
Aim
To evaluate retrospectively the tolerability and efficacy of tioguanine (thioguanine) (TG) therapy in selected patients with AIH and AIH variant syndromes.
Methods
Records of 52 patients who received TG therapy were retrieved from nine hospitals in the Netherlands. Indications for TG treatment were intolerable side effects on AZA or MP (n = 38), insufficient response (n = 11) or first‐line treatment (n = 3). Treatment efficacy was defined as normalisation of serum aminotransferases and serum immunoglobulin G.
Results
No serious adverse events occurred in patients treated with TG during a median follow‐up of 18 months (range 1‐194). Treatment was well tolerated in 41 patients (79%), whereas four had tolerable (8%) and seven (13%) intolerable side effects. Thirty‐eight patients were treated with TG after intolerable side effects on AZA or MP; 29 patients continued TG therapy of whom 24 (83%) achieved complete biochemical remission, four (14%) had incomplete and one (3%) had no response; nine discontinued treatment. Seven of 11 patients with insufficient response to AZA or MP were responsive to TG, three with complete and four with incomplete biochemical remission; four discontinued due to intolerance (n = 2) and non‐response (n = 2). TG was effective in all AIH patients as first‐line maintenance treatment.
Conclusion
In our retrospective review of TG therapy in selected patients with AIH or AIH variants who previously failed on AZA or MP, TG appeared tolerable with biochemical efficacy.
Surveillance of pancreatic cysts focuses on the detection of (mostly morphologic) features warranting surgery. European guidelines consider elevated CA19.9 as a relative indication for surgery. We ...aimed to evaluate the role of CA19.9 monitoring for early detection and management in a cyst surveillance population.
The PACYFIC-registry is a prospective collaboration that investigates the yield of pancreatic cyst surveillance performed at the discretion of the treating physician. We included participants for whom at least one serum CA19.9 value was determined by a minimum follow-up of 12 months.
Of 1865 PACYFIC participants, 685 met the inclusion criteria for this study (mean age 67 years, SD 10; 61% female). During a median follow-up of 25 months (IQR 24, 1966 visits), 29 participants developed high-grade dysplasia (HGD) or pancreatic cancer. At baseline, CA19.9 ranged from 1 to 591 kU/L (median 10 kU/L IQR 14), and was elevated (≥37 kU/L) in 64 participants (9%). During 191 of 1966 visits (10%), an elevated CA19.9 was detected, and these visits more often led to an intensified follow-up (42%) than those without an elevated CA19.9 (27%; p < 0.001). An elevated CA19.9 was the sole reason for surgery in five participants with benign disease (10%). The baseline CA19.9 value was (as continuous or dichotomous variable at the 37 kU/L threshold) not independently associated with HGD or pancreatic cancer development, whilst a CA19.9 of ≥ 133 kU/L was (HR 3.8, 95% CI 1.1-13, p = 0.03).
In this pancreatic cyst surveillance cohort, CA19.9 monitoring caused substantial harm by shortening surveillance intervals (and performance of unnecessary surgery). The current CA19.9 cutoff was not predictive of HGD and pancreatic cancer, whereas a higher cutoff may decrease false-positive values. The role of CA19.9 monitoring should be critically appraised prior to implementation in surveillance programs and guidelines.
Abstract
Background
Patients suffering from inflammatory bowel diseases (IBD) and treated with originator infliximab are increasingly being switched to biosimilars. Some patients, however, are ...“reverse switched” to treatment with the originator. Here we assess the prevalence of reverse switching, including its indication and outcomes.
Methods
In this retrospective multicenter cohort study, data on patients with IBD from 9 hospitals in the Netherlands were collected. All adult patients with IBD were included if they previously had been switched from originator infliximab to the biosimilar CT-P13 and had a follow-up time of at least 52 weeks after the initial switch. The reasons for reverse switching were categorized into worsening gastrointestinal symptoms, adverse effects, or loss of response to CT-P13. Drug persistence was analyzed through survival analyses.
Results
A total of 758 patients with IBD were identified. Reverse switching was observed in 75 patients (9.9%). Patients with reverse switching were predominantly female (70.7%). Gastrointestinal symptoms (25.5%) and dermatological symptoms (21.8%) were the most commonly reported reasons for reverse switching. In 9 patients (12.0%), loss of response to CT-P13 was the reason for reverse switching. Improvement of reported symptoms was seen in 73.3% of patients after reverse switching and 7 out of 9 patients (77.8%) with loss of response regained response. Infliximab persistence was equal between patients who were reverse-switched and those who were maintained on CT-P13.
Conclusions
Reverse switching occurred in 9.9% of patients, predominantly for biosimilar-attributed adverse effects. Switching back to originator infliximab seems effective in patients who experience adverse effects, worsening gastrointestinal symptoms, or loss of response after switching from originator infliximab to CT-P13.
Background. Chronic hepatitis C virus (HCV) infection is associated with liver dysfunction and hepatocellular carcinoma. In patients with normal kidney function, treatment with pegylated interferon ...(PEG-IFN) and ribavirin (RBV) frequently leads to eradication of HCV. Treatment in dialysis patients has long been controversial and until recently, the use of RBV was considered to be contra-indicated. We used plasma trough levels of RBV to promote tolerance, safety and efficacy. PEG-IFN alfa-2a (40 kD) was chosen because it is cleared predominantly via hepatic metabolism. Methods. Seven haemodialysis patients with chronic HCV infection were eligible and started with 135 μg PEG-IFN alfa-2a (40 kD) weekly and 200 mg RBV every other day. Dose adaptations were allowed following study guidelines. Genotypes 1 and 4 (five patients) were treated for 48 weeks and genotypes 2 and 3 (two patients) for 24 weeks. HCV-RNA was determined after 12, 24 and 48 weeks (and at 72 weeks for genotypes 1 and 4). RBV trough plasma levels were monitored regularly by HPLC-technique. Results. All patients completed the treatment. In two patients, the PEG-IFN dose had to be reduced to 90 μg/week because of adverse events. To achieve the target range (1.5–2.5 μg/ml) of the plasma trough level, the mean RBV dose was increased to a dose between 133 and 200 mg each day in five patients. Despite an increase of the weekly erythropoietin (Epo) dose, two to a max of four red cell transfusions were given to four patients. A sustained viral response (SVR) was reached in five patients (3/5 with genotype 1/4 and 2/2 with genotype 2/3). Conclusion. In our series of seven patients, we were able to use RBV monitoring drug levels in combination with PEG-IFN alfa-2a (40 kD) and achieve high sustained response rates. However, Epo and transfusion requirements may increase. In two patients adverse events were observed, but manageable with dose reduction of PEG-IFN.
Barrett's esophagus, with gastroesophageal reflux disease and obesity as risk factors, predisposes to esophageal adenocarcinoma (EAC). Recently a British genome wide association study identified two ...Barrett's esophagus susceptibility loci mapping within the major histocompatibility complex (MHC; rs9257809) and closely to the Forkhead‐F1 (FOXF1; rs9936833) coding gene. An interesting issue is whether polymorphisms associated with Barrett's esophagus, are also implicated in esophageal carcinoma (EC), and more specifically EAC genesis. Assessing the individual genetic susceptibility can help identify high risk patients more prone to benefit from surveillance programs. Our hypothesis: Barrett associated MHC and FOXF1 variants modify EC risk in Caucasians. In a Dutch case‐control study, 431 patients with EC and 605 healthy controls were included. Polymorphisms at chromosomes 6p21 (MHC) and 16q24 (FOXF1) were determined by means of real‐time polymerase chain reaction (RT‐PCR). Logistic regression analysis was used to calculate odds ratios with 95% confidence intervals. The FOXF1 rs9936833 variant C allele was associated with an increased EAC susceptibility; OR, 95% CI; 1.21, 0.99–1.47. A sex‐stratified analysis revealed a similar association in males; 1.24 1.00–1.55. The variant MHC rs9257809 G allele as well as the MHC heterozygous AG genotype significantly increased ESCC risk; 1.76 1.16–2.66 and 1.74 1.08–2.80, respectively. Sex‐stratification showed that the variant G allele was especially present in female patients; 2.32 1.04–5.20. In conclusion, this study provides evidence that MHC rs9257809 and FOXF1 rs9936833 variants, associated with Barrett's esophagus, also increase ESCC and EAC susceptibility in Caucasians. FOX proteins are transcription factors involved in organogenesis of the GI tract, while MHC haplotypes are strongly associated with smoking behavior, a crucial risk factor for ESCC. Assessing the individual genetic susceptibility can help identify high risk patients more prone to benefit from (Barrett) surveillance programs.
What's new?
Identifying patients with genetic variants that heighten susceptibility to carcinoma of the esophagus could make esophageal cancer surveillance programs more effective. Here, two variations, Barrett‐associated MHC rs9257809 and FOXF1 rs9936833, are reported to increase esophageal adenocarcinoma (ECA) and squamous cell carcinoma (ESCC) susceptibility in Caucasians. Both have plausible mechanisms to support their involvement, with FOX proteins known to be associated with in organogenesis of the gastrointestinal tract and certain major histocompatibility (MHC) haplotypes associated with smoking behavior, a crucial risk factor for ESCC.
Background
Anti-tumor necrosis factor (TNF) therapy is effective for the treatment of Crohn’s disease. Cessation may be considered in patients with a low risk of relapse. We aimed to externally ...validate and update our previously developed prediction model to estimate the risk of relapse after cessation of anti-TNF therapy.
Methods
We performed a retrospective cohort study in 17 Dutch hospitals. Crohn’s disease patients in clinical, biochemical or endoscopic remission were included after anti-TNF cessation. Primary outcome was a relapse necessitating treatment. Discrimination and calibration of the previously developed model were assessed. After external validation, the model was updated. The performance of the updated prediction model was assessed in internal-external validation and by using decision curve analysis.
Results
486 patients were included with a median follow-up of 1.7 years. Relapse rates were 35 and 54% after 1 and 2 years. At external validation, the discriminative ability of the prediction model was equal to that found at the development of the model c-statistic 0.58 (95% confidence interval (CI) 0.54–0.62), though the model was not well-calibrated on our cohort calibration slope: 0.52 (0.28–0.76). After an update, a c-statistic of 0.60 (0.58–0.63) and calibration slope of 0.89 (0.69–1.09) were reported in internal-external validation.
Conclusion
Our previously developed and updated prediction model for the risk of relapse after cessation of anti-TNF in Crohn’s disease shows reasonable performance. The use of the model may support clinical decision-making to optimize patient selection in whom anti-TNF can be withdrawn. Clinical validation is ongoing in a prospective randomized trial.
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