Objective: To compare the long-term outcomes of immediate drainage versus the postponed-drainage approach in patients with infected necrotizing pancreatitis.Background: In the randomized POINTER... Show moreObjective: To compare the long-term outcomes of immediate drainage versus the postponed-drainage approach in patients with infected necrotizing pancreatitis.Background: In the randomized POINTER trial, patients assigned to the postponed-drainage approach using antibiotic treatment required fewer interventions, as compared with immediate drainage, and over a third were treated without any intervention.Methods: Clinical data of those patients alive after the initial 6-month follow-up were re-evaluated. The primary outcome was a composite of death and major complications.Results: Out of 104 patients, 88 were re-evaluated with a median follow-up of 51 months. After the initial 6-month follow-up, the primary outcome occurred in 7 of 47 patients (15%) in the immediate-drainage group and 7 of 41 patients (17%) in the postponed-drainage group (RR 0.87, 95% CI 0.33–2.28; P=0.78). Additional drainage procedures were performed in 7 patients (15%) versus 3 patients (7%) (RR 2.03; 95% CI 0.56–7.37; P=0.34). The median number of additional interventions was 0 (IQR 0–0) in both groups (P=0.028). In the total follow-up, the median number of interventions was higher in the immediate-drainage group than in the postponed-drainage group (4 vs. 1, P=0.001). Eventually, 14 of 15 patients (93%) in the postponed-drainage group who were successfully treated in the initial 6-month follow-up with antibiotics and without any intervention remained without intervention. At the end of follow-up, pancreatic function and quality of life were similar.Conclusions: Also, during long-term follow-up, a postponed-drainage approach using antibiotics in patients with infected necrotizing pancreatitis results in fewer interventions as compared with immediate drainage and should therefore be the preferred approach. Show less
BackgroundEarly aspirin withdrawal, also known as P2Y12-inhibitor monotherapy, following percutaneous coronary intervention (PCI) for non-ST-segment elevation acute coronary syndrome (NSTE-ACS) can... Show moreBackgroundEarly aspirin withdrawal, also known as P2Y12-inhibitor monotherapy, following percutaneous coronary intervention (PCI) for non-ST-segment elevation acute coronary syndrome (NSTE-ACS) can reduce bleeding without a trade-off in efficacy. Still the average daily bleeding risk is highest during the first months and it remains unclear if aspirin can be omitted immediately following PCI.MethodsThe LEGACY study is an open-label, multicenter randomized controlled trial evaluating the safety and efficacy of immediate P2Y12-inhibitor monotherapy versus dual antiplatelettherapy (DAPT) for 12 months in 3,090 patients. Patients are randomized immediately following successful PCI for NSTE-ACS to 75-100 mg aspirin once daily versus no aspirin. The primary hypothesis is that immediately omitting aspirin is superior to DAPT with respect to major or minor bleeding defined as Bleeding Academic Research Consortium type 2, 3, or 5 bleeding, while maintaining noninferiority for the composite of all-cause mortality, myocardial infarction and stroke compared to DAPT.ConclusionsThe LEGACY study is the first randomized study that is specifically designed to evaluate the impact of immediately omitting aspirin, and thus treating patients with P2Y12-inhibitor monotherapy, as compared to DAPT for 12 months on bleeding and ischemic events within 12 months following PCI for NSTE-ACS. Show less
Objective: Routine urgent endoscopic retrograde cholangiopancreatography (ERCP) with endoscopic biliary sphincterotomy (ES) does not improve outcome in patients with predicted severe acute biliary... Show moreObjective: Routine urgent endoscopic retrograde cholangiopancreatography (ERCP) with endoscopic biliary sphincterotomy (ES) does not improve outcome in patients with predicted severe acute biliary pancreatitis. Improved patient selection for ERCP by means of endoscopic ultrasonography (EUS) for stone/sludge detection may challenge these findings. Design: A multicentre, prospective cohort study included patients with predicted severe acute biliary pancreatitis without cholangitis. Patients underwent urgent EUS, followed by ERCP with ES in case of common bile duct stones/sludge, within 24 hours after hospital presentation and within 72 hours after symptom onset. The primary endpoint was a composite of major complications or mortality within 6 months after inclusion. The historical control group was the conservative treatment arm (n=113) of the randomised APEC trial (Acute biliary Pancreatitis: urgent ERCP with sphincterotomy versus conservative treatment, patient inclusion 2013-2017) applying the same study design. Results: Overall, 83 patients underwent urgent EUS at a median of 21 hours (IQR 17-23) after hospital presentation and at a median of 29 hours (IQR 23-41) after start of symptoms. Gallstones/sludge in the bile ducts were detected by EUS in 48/83 patients (58%), all of whom underwent immediate ERCP with ES. The primary endpoint occurred in 34/83 patients (41%) in the urgent EUS-guided ERCP group. This was not different from the 44% rate (50/113 patients) in the historical conservative treatment group (risk ratio (RR) 0.93, 95% CI 0.67 to 1.29; p=0.65). Sensitivity analysis to correct for baseline differences using a logistic regression model also showed no significant beneficial effect of the intervention on the primary outcome (adjusted OR 1.03, 95% CI 0.56 to 1.90, p=0.92). Conclusion: In patients with predicted severe acute biliary pancreatitis without cholangitis, urgent EUS-guided ERCP with ES did not reduce the composite endpoint of major complications or mortality, as compared with conservative treatment in a historical control group. Show less
Frequin, H.L.; Schouten, J.; Verschuur, C.V.M.; Suwijn, S.R.; Boel, J.A.; Post, B.; ... ; LEAP Study Grp 2023
Background and ObjectivesThe Levodopa in EArly Parkinson's Disease (LEAP) study enabled us to conduct post hoc analyses concerning the effects of levodopa in patients with early Parkinson disease... Show moreBackground and ObjectivesThe Levodopa in EArly Parkinson's Disease (LEAP) study enabled us to conduct post hoc analyses concerning the effects of levodopa in patients with early Parkinson disease.MethodsThe LEAP study was a double-blind, placebo-controlled, randomized, delayed-start trial in which patients with early Parkinson disease were randomized to receive levodopa/carbidopa 300/75 mg daily for 80 weeks (early-start group) or to placebo for 40 weeks followed by levodopa/carbidopa 300/75 mg daily for 40 weeks (delayed-start group). We analyzed the effect of levodopa with the Unified Parkinson's Disease Rating Scale on bradykinesia, rigidity, and tremor. At week 80, participants answered 3 questions regarding motor response fluctuations.ResultsA total of 222 patients were randomized to the early-start group (mean ± SD age at baseline 64.8 ± 8.7 years; 71% male) and 223 to the delayed-start group (mean ± SD age at baseline 65.5 ± 8.8 years; 69% male). The difference between the early- and delayed-start groups in mean change from baseline to week 4, expressed as Hedges g effect size, was −0.33 for bradykinesia, −0.29 for rigidity, and −0.25 for tremor (for all symptoms indicating a small effect in favor of the early-start group); from baseline to week 22, respectively, −0.49, −0.36, and −0.44 (small to medium effect); and from baseline to week 40, respectively, −0.32, −0.19, and −0.27 (small effect). At 80 weeks, fewer patients in the early-start group (46 of 205 patients, 23%) experienced motor response fluctuations than patients in the delayed-start group (81 of 211, 38%; p < 0.01).DiscussionIn patients with early Parkinson disease, levodopa improves bradykinesia, rigidity, and tremor to the same order of magnitude. For all 3 symptoms, effects were larger at 22 weeks compared with 4 weeks. At 80 weeks, there were fewer patients with motor response fluctuations in the group that had started levodopa earlier. Show less
Background & Aims: Primary sclerosing cholangitis (PSC) is a progressive, cholestatic liver disease which greatly impacts the lives of individuals. Burden of disease due to shortened life... Show moreBackground & Aims: Primary sclerosing cholangitis (PSC) is a progressive, cholestatic liver disease which greatly impacts the lives of individuals. Burden of disease due to shortened life expectancy and impaired quality of life is ill-described. The aim of this study was to assess long-term disease burden in a large population-based registry with regard to survival, clinical course, quality adjusted life years (QALYs), medical consumption and work productivity loss. Methods: All PSC patients living in a geographically defined area covering similar to 50% of the Netherlands were included, together with patients from the three liver transplant centres. Survival was estimated by competing risk analysis. Proportional shortfall of QALYs during disease course was measured relative to a matched reference cohort using validated questionnaires. Work productivity loss and medical consumption were evaluated over time. Results: A total of 1208 patients were included with a median follow-up of 11.2 year. Median liver transplant-free survival was 21.0 years. Proportional shortfall of QALYs increased to 48% >25 years after diagnosis. Patients had on average 12.4 hospital contact days among which 3.17 admission days per year, annual medical costs were (sic)12 169 and mean work productivity loss was 25%. Conclusions: Our data quantify for the first time disease burden in terms of QALYs lost, clinical events, medical consumption, costs as well as work productivity loss, and show that all these are substantial and increase over time. Show less
Background & AimsPrimary sclerosing cholangitis (PSC) is a progressive, cholestatic liver disease which greatly impacts the lives of individuals. Burden of disease due to shortened life... Show moreBackground & AimsPrimary sclerosing cholangitis (PSC) is a progressive, cholestatic liver disease which greatly impacts the lives of individuals. Burden of disease due to shortened life expectancy and impaired quality of life is ill-described. The aim of this study was to assess long-term disease burden in a large population-based registry with regard to survival, clinical course, quality adjusted life years (QALYs), medical consumption and work productivity loss.MethodsAll PSC patients living in a geographically defined area covering ~50% of the Netherlands were included, together with patients from the three liver transplant centres. Survival was estimated by competing risk analysis. Proportional shortfall of QALYs during disease course was measured relative to a matched reference cohort using validated questionnaires. Work productivity loss and medical consumption were evaluated over time.ResultsA total of 1208 patients were included with a median follow-up of 11.2 year. Median liver transplant-free survival was 21.0 years. Proportional shortfall of QALYs increased to 48% >25 years after diagnosis. Patients had on average 12.4 hospital contact days among which 3.17 admission days per year, annual medical costs were €12 169 and mean work productivity loss was 25%.ConclusionsOur data quantify for the first time disease burden in terms of QALYs lost, clinical events, medical consumption, costs as well as work productivity loss, and show that all these are substantial and increase over time. Show less
Huinink, S.T.; Jong, D.C. de; Nieboer, D.; Thomassen, D.; Steyerberg, E.W.; Dijkgraaf, M.G.W.; ... ; Vries, A.C. de 2022
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... Show moreBackground 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. Show less
BACKGROUND & AIMS: Previous randomized trials, including the Transluminal Endoscopic Step-Up Approach Versus Minimally Invasive Surgical Step-Up Approach in Patients With Infected Pancreatic... Show moreBACKGROUND & AIMS: Previous randomized trials, including the Transluminal Endoscopic Step-Up Approach Versus Minimally Invasive Surgical Step-Up Approach in Patients With Infected Pancreatic Necrosis (TENSION) trial, demonstrated that the endoscopic step-up approach might be preferred over the surgical step-up approach in patients with infected necrotizing pancreatitis based on favorable short-term outcomes. We compared long-term clinical outcomes of both step-up approaches after a period of at least 5 years. METHODS: In this long-term follow-up study, we reevaluated all clinical data on 83 patients (of the originally 98 included patients) from the TENSION trial who were still alive after the initial 6-month follow-up. The primary end point, similar to the TENSION trial, was a composite of death and major complications. Secondary end points included individual major complications, pancreaticocutaneous fistula, reinterventions, pancreatic insufficiency, and quality of life. RESULTS: After a mean followup period of 7 years, the primary end point occurred in 27 patients (53%) in the endoscopy group and in 27 patients (57%) in the surgery group (risk ratio [RR], 0.93; 95% confidence interval [CI], 0.65-1.32; P = .688). Fewer pancreaticocutaneous fistulas were identified in the endoscopy group (8% vs 34%; RR, 0.23; 95% CI, 0.08-0.83). After the initial 6-month follow-up, the endoscopy group needed fewer reinterventions than the surgery group (7% vs 24%; RR, 0.29; 95% CI, 0.09-0.99). Pancreatic insufficiency and quality of life did not differ between groups. CONCLUSIONS: At long-term follow-up, the endoscopic step-up approach was not superior to the surgical step-up approach in reducing death or major complications in patients with infected necrotizing pancreatitis. However, patients assigned to the endoscopic approach developed overall fewer pancreaticocutaneous fistulas and needed fewer reinterventions after the initial 6-month follow-up. Show less
Background & AimsPrevious randomized trials, including the Transluminal Endoscopic Step-Up Approach Versus Minimally Invasive Surgical Step-Up Approach in Patients With Infected Pancreatic Necrosis... Show moreBackground & AimsPrevious randomized trials, including the Transluminal Endoscopic Step-Up Approach Versus Minimally Invasive Surgical Step-Up Approach in Patients With Infected Pancreatic Necrosis (TENSION) trial, demonstrated that the endoscopic step-up approach might be preferred over the surgical step-up approach in patients with infected necrotizing pancreatitis based on favorable short-term outcomes. We compared long-term clinical outcomes of both step-up approaches after a period of at least 5 years.MethodsIn this long-term follow-up study, we reevaluated all clinical data on 83 patients (of the originally 98 included patients) from the TENSION trial who were still alive after the initial 6-month follow-up. The primary end point, similar to the TENSION trial, was a composite of death and major complications. Secondary end points included individual major complications, pancreaticocutaneous fistula, reinterventions, pancreatic insufficiency, and quality of life.ResultsAfter a mean follow-up period of 7 years, the primary end point occurred in 27 patients (53%) in the endoscopy group and in 27 patients (57%) in the surgery group (risk ratio [RR], 0.93; 95% confidence interval [CI], 0.65–1.32; P = .688). Fewer pancreaticocutaneous fistulas were identified in the endoscopy group (8% vs 34%; RR, 0.23; 95% CI, 0.08–0.83). After the initial 6-month follow-up, the endoscopy group needed fewer reinterventions than the surgery group (7% vs 24%; RR, 0.29; 95% CI, 0.09–0.99). Pancreatic insufficiency and quality of life did not differ between groups.ConclusionsAt long-term follow-up, the endoscopic step-up approach was not superior to the surgical step-up approach in reducing death or major complications in patients with infected necrotizing pancreatitis. However, patients assigned to the endoscopic approach developed overall fewer pancreaticocutaneous fistulas and needed fewer reinterventions after the initial 6-month follow-up. Netherlands Trial Register no: NL8571. Show less
BACKGROUND AND PURPOSE: Endovascular treatment for acute ischemic stroke has been proven clinically effective, but evidence of the cost-effectiveness based on real-world data is scarce. The aim of... Show moreBACKGROUND AND PURPOSE: Endovascular treatment for acute ischemic stroke has been proven clinically effective, but evidence of the cost-effectiveness based on real-world data is scarce. The aim of this study was to assess whether endovascular therapy plus usual care is cost-effective in comparison to usual care alone in acute ischemic stroke patients. METHODS: An economic evaluation was performed from a societal perspective with a 2-year time horizon. Empirical data on health outcomes and the use of resources following endovascular treatment were gathered parallel to the MR CLEAN trial (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands) and its 2-year follow-up study. Incremental cost-effectiveness ratios were calculated as the extra costs per additional patient with functional independence (modified Rankin Scale score 0-2) and the extra cost per quality-adjusted life year gained. RESULTS: The mean costs per patient in the intervention group were $126 494 versus $143 331 in the control group (mean difference, -$16 839 [95% CI, -$38 113 to $5456]). Compared with patients in the control group, more patients in the intervention group achieved functional independence, 37.2% versus 23.9% (absolute difference, 13.3% [95% CI, 4.0%-22.0%]) and they generated more quality-adjusted life years, 0.99 versus 0.83 (mean difference of 0.16 [95% CI, 0.04-0.29]). Endovascular treatment dominated standard treatment with $18 233 saved per extra patient with a good outcome and $105 869 saved per additional quality-adjusted life year. CONCLUSIONS: Endovascular treatment added to usual care is clinically effective, and cost saving in comparison to usual care alone in patients with acute ischemic stroke. Registration: URL: ; Unique identifier: NL695. URL: ; Unique identifier: ISRCTN10888758. Show less
Verschuur, C.V.M.; Suwijn, S.R.; Haan, R.J. de; Boel, J.A.; Post, B.; Bloem, B.R.; ... ; Bie, R.M.A. de 2022
Background: In the Levodopa in EArly Parkinson's disease (LEAP) study, 445 patients were randomized to levodopa/carbidopa 100/25 mg three times per day for 80 weeks (early-start) or placebo for 40... Show moreBackground: In the Levodopa in EArly Parkinson's disease (LEAP) study, 445 patients were randomized to levodopa/carbidopa 100/25 mg three times per day for 80 weeks (early-start) or placebo for 40 weeks followed by levodopa/carbidopa 100/25 mg three times per day for 40 weeks (delayed-start). Objective: This paper reports the results of the economic evaluation performed alongside the LEAP-study.Methods: Early-start treatment was evaluated versus delayed-start treatment, in which the cost-effectiveness analysis (CEA) and the cost-utility analysis (CUA) were performed from the societal perspective, including health care costs among providers, non-reimbursable out-of-pocket expenses of patients, employer costs of sick leave, and lowered productivity while at work. The outcome measure for the CEA was the extra cost per unit decrease on the Unified Parkinson's Disease Rating Scale 80 weeks after baseline. The outcome measure for the CUA was the extra costs per additional quality adjusted life year (QALY) during follow-up. Results: 212 patients in the early-start and 219 patients in the delayed-start group reported use of health care resources. With savings of D 59 per patient (BCa 95% CI: -829, 788) in the early-start compared to the delayed-start group, societal costs were balanced. The early-start group showed a mean of 1.30 QALYs (BCa 95% CI: 1.26, 1.33) versus 1.30 QALYs (BCa 95% CI: 1.27, 1.33) for the delayed-start group. Because of this negligible difference, incremental cost-effectiveness and cost-utility ratios were not calculated. Conclusion: From an economic point of view, this study suggests that early treatment with levodopa is not more expensive than delayed treatment with levodopa. Show less
Voorst, H. van; Kunz, W.G.; Berg, L.A. van den; Kappelhof, M.; Pinckaers, F.M.E.; Goyal, M.; ... ; Majoie, C.B.L.M. 2021
Background The effectiveness of endovascular treatment (EVT) for large vessel occlusion (LVO) stroke severely depends on time to treatment. However, it remains unclear what the value of faster... Show moreBackground The effectiveness of endovascular treatment (EVT) for large vessel occlusion (LVO) stroke severely depends on time to treatment. However, it remains unclear what the value of faster treatment is in the years after index stroke. The aim of this study was to quantify the value of faster EVT in terms of health and healthcare costs for the Dutch LVO stroke population. Methods A Markov model was used to simulate 5-year follow-up functional outcome, measured with the modified Rankin Scale (mRS), of 69-year-old LVO patients. Post-treatment mRS was extracted from the MR CLEAN Registry (n=2892): costs per unit of time and Quality-Adjusted Life Years (QALYs) per mRS sub-score were retrieved from follow-up data of the MR CLEAN trial (n=500). Net Monetary Benefit (NMB) at a willingness to pay of euro80 000 per QALY was reported as primary outcome, and secondary outcome measures were days of disability-free life gained and costs. Results EVT administered 1 min faster resulted in a median NMB of euro309 (IQR: 226;389), 1.3 days of additional disability-free life (IQR: 1.0;1.6), while cumulative costs remained largely unchanged (median: -euro15, IQR: -65;33) over a 5-year follow-up period. As costs over the follow-up period remained stable while QALYs decreased with longer time to treatment, which this results in a near-linear decrease of NMB. Since patients with faster EVT lived longer, they incurred more healthcare costs. Conclusion One-minute faster EVT increases QALYs while cumulative costs remain largely unaffected. Therefore, faster EVT provides better value of care at no extra healthcare costs. Show less
Background Rapid weight loss is a major risk factor for the formation of cholesterol gallstones. Consequently, patients with morbid obesity undergoing bariatric surgery frequently develop... Show moreBackground Rapid weight loss is a major risk factor for the formation of cholesterol gallstones. Consequently, patients with morbid obesity undergoing bariatric surgery frequently develop symptomatic gallstone disease. This trial assessed the efficacy of ursodeoxycholic acid versus placebo for the prevention of symptomatic gallstone disease after bariatric surgery.Methods This multicentre, double-blind, randomised, placebo-controlled superiority trial enrolled patients with an intact gallbladder scheduled for laparoscopic Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy in three hospitals in the Netherlands. Patients were randomly assigned (1:1) by a web-based randomisation module to receive 900 mg ursodeoxycholic acid daily for 6 months or matched placebo. Randomisation was stratified by the presence of asymptomatic gallstones at baseline and type of surgery. Patients, clinicians, and study staff were masked to treatment allocation. The primary endpoint was symptomatic gallstone disease within 24 months, assessed in the modified intention-to-treat population (all randomly assigned eligible patients with any postrandomisation measurement). Prespecified subgroup analyses were done based on the stratification groups. Safety was assessed in all patients who took at least one dose of the study drug. This trial is registered with the Netherlands Trial Register, NL5954.Findings Between Jan 11, 2017, and Oct 22, 2018, 985 patients were randomly assigned to receive either ursodeoxycholic acid (n=492) or placebo (n=493). 967 patients were included in the modified intention-to-treat population, of whom 959 had data available for primary endpoint assessment. 189 (20%) patients had asymptomatic gallstones at baseline and 78 (8%) received a sleeve gastrectomy. Symptomatic gallstone disease occurred in 31 (6.5%) of 475 patients in the ursodeoxycholic acid group and in 47 (9.7%) of 484 patients in the placebo group (relative risk 0.67, 95% CI 0.43-1.04, p=0.071). Logistic regression showed a significant interaction between ursodeoxycholic acid and the presence of asymptomatic gallstones at baseline (p=0.046), with an effect of ursodeoxycholic acid in patients without (0.47, 0.27-0.84, p=0.0081), and no effect in patients with asymptomatic gallstones at baseline (1.22, 0.61-2.47, p=0.57). The effect was stronger in patients without gallstones at baseline undergoing RYGB (0.37, 0.20-0.71, p=0.0016), whereas the subgroup of patients undergoing sleeve gastrectomy was too small to draw clear conclusions. Adverse events were rare. In the ursodeoxycholic acid group, diarrhoea occurred in four (0.9%) of 444 patients and skin rash in two (0.5%) patients. In the placebo group, diarrhoea occurred in two (0.4%) of 453 patients and skin rash in two (0.4%) patients. The total number of serious adverse events did not significantly differ between the trial groups (75 [17%] in 444 patients in the ursodeoxycholic acid group and 102 [23%] in 453 patients in the placebo group). The most common serious adverse events were abdominal pain and internal hernia. No serious adverse event was attributed to the study drug.Interpretation Ursodeoxycholic acid prophylaxis did not significantly reduce the occurrence of symptomatic gallstone disease in all patients after bariatric surgery. In patients without gallstones before RYGB surgery, ursodeoxycholic acid treatment reduced the occurrence of symptomatic gallstone disease compared with placebo. Further research is needed to assess the efficacy of ursodeoxycholic acid after sleeve gastrectomy. Copyright (C) 2021 Elsevier Ltd. All rights reserved. Show less
BACKGROUNDInfected necrotizing pancreatitis is a potentially lethal disease that is treated with the use of a step-up approach, with catheter drainage often delayed until the infected necrosis is... Show moreBACKGROUNDInfected necrotizing pancreatitis is a potentially lethal disease that is treated with the use of a step-up approach, with catheter drainage often delayed until the infected necrosis is encapsulated. Whether outcomes could be improved by earlier catheter drainage is unknown.METHODSWe conducted a multicenter, randomized superiority trial involving patients with infected necrotizing pancreatitis, in which we compared immediate drainage within 24 hours after randomization once infected necrosis was diagnosed with drainage that was postponed until the stage of walled-off necrosis was reached. The primary end point was the score on the Comprehensive Complication Index, which incorporates all complications over the course of 6 months of follow-up.RESULTSA total of 104 patients were randomly assigned to immediate drainage (55 patients) or postponed drainage (49 patients). The mean score on the Comprehensive Complication Index (scores range from 0 to 100, with higher scores indicating more severe complications) was 57 in the immediate-drainage group and 58 in the postponed-drainage group (mean difference, -1; 95% confidence interval [CI], -12 to 10; P=0.90). Mortality was 13% in the immediate-drainage group and 10% in the postponed-drainage group (relative risk, 1.25; 95% CI, 0.42 to 3.68). The mean number of interventions (catheter drainage and necrosectomy) was 4.4 in the immediate-drainage group and 2.6 in the postponed-drainage group (mean difference, 1.8; 95% CI, 0.6 to 3.0). In the postponed-drainage group, 19 patients (39%) were treated conservatively with antibiotics and did not require drainage; 17 of these patients survived. The incidence of adverse events was similar in the two groups.CONCLUSIONSThis trial did not show the superiority of immediate drainage over postponed drainage with regard to complications in patients with infected necrotizing pancreatitis. Patients randomly assigned to the postponed-drainage strategy received fewer invasive interventions. Show less
Aims This study was performed to develop and externally validate prediction models for appropriate implantable cardioverter-defibrillator (ICD) shock and mortality to identify subgroups with... Show moreAims This study was performed to develop and externally validate prediction models for appropriate implantable cardioverter-defibrillator (ICD) shock and mortality to identify subgroups with insufficient benefit from ICD implantation.Methods and results We recruited patients scheduled for primary prevention ICD implantation and reduced left ventricular function. Bootstrapping-based Cox proportional hazards and Fine and Gray competing risk models with likely candidate predictors were developed for all-cause mortality and appropriate ICD shock, respectively. Between 2014 and 2018, we included 1441 consecutive patients in the development and 1450 patients in the validation cohort. During a median follow-up of 2.4 (IQR 2.1-2.8) years, 109 (7.6%) patients received appropriate ICD shock and 193 (13.4%) died in the development cohort. During a median follow-up of 2.7 (IQR 2.0-3.4) years, 105 (7.2%) received appropriate ICD shock and 223 (15.4%) died in the validation cohort. Selected predictors of appropriate ICD shock were gender, NSVT, ACE/ARB use, atrial fibrillation history, Aldosterone-antagonist use, Digoxin use, eGFR, (N)OAC use, and peripheral vascular disease. Selected predictors of all-cause mortality were age, diuretic use, sodium, NT-pro-BNP, and ACE/ARB use. C-statistic was 0.61 and 0.60 at respectively internal and external validation for appropriate ICD shock and 0.74 at both internal and external validation for mortality.Conclusion Although this cohort study was specifically designed to develop prediction models, risk stratification still remains challenging and no large group with insufficient benefit of ICD implantation was found. However, the prediction models have some clinical utility as we present several scenarios where ICD implantation might be postponed. Show less
Ooijevaar, R.E.; Nood, E. van; Goorhuis, A.; Terveer, E.M.; Prehn, J. van; Verspaget, H.W.; ... ; Keller, J.J. 2021
Fecal microbiota transplantation (FMT) has become a well-established treatment for recurrent Clostridioides difficile infection (rCDI). While short-term outcomes and adverse events relating to FMT... Show moreFecal microbiota transplantation (FMT) has become a well-established treatment for recurrent Clostridioides difficile infection (rCDI). While short-term outcomes and adverse events relating to FMT have been well documented, there still is a paucity of data with regard to long-term safety. In this report, we describe the long-term follow-up of the prospective cohort of the first randomized controlled trial of FMT for rCDI, and review the existing literature. A total of 34 patients were treated with FMT for rCDI. Seven patients were still alive after a follow-up of more than 10 years and three patients were lost to follow-up. None of the 34 patients had experienced a new-onset autoimmune, gastrointestinal, or malignant disorder during follow-up. We did not find any deterioration or amelioration of pre-existing medical conditions. Furthermore, no deaths directly attributable to FMT could be identified. These findings are in accordance with the data in available literature. In conclusion, no long-term adverse events or complications directly attributable to FMT were found in our prospective cohort. Review of the available literature does not point to long-term risks associated with FMT in this elderly population, provided that carefully screened fecal suspensions are being used. No firm conclusion on the long-term safety of FMT in younger patients could be drawn. Show less
Bousema, J.E.; Hoeijmakers, F.; Dijkgraaf, M.G.W.; Annema, J.T.; Broek, F.J.C. van den; Akker-van Marle, M.E. van den; MEDIASTrial Study Grp 2021
Background: Variability in practice and ongoing debate on optimal invasive mediastinal staging of patients with resectable non-small cell lung cancer (NSCLC) are widely described in the literature.... Show moreBackground: Variability in practice and ongoing debate on optimal invasive mediastinal staging of patients with resectable non-small cell lung cancer (NSCLC) are widely described in the literature. Patients' preferences on this topic have, however, been underexposed so far. Methods: An internet-based questionnaire was distributed among MEDIASTrial partici-pants (NTR6528, randomization of patients to mediastinoscopy or not in the case of negative endosonography). Literature, expert opinion and patient interviews resulted in five attributes: the risk of a futile lung resection (oncologically futile in case of unforeseen N2 disease), the length of the staging period, resection of the primary tumor, complications of staging procedures and the mediastinoscopy scar. The relative importance (RI) of each attribute was assessed by using adaptive conjoint analysis and hierarchical Bayes estimation. treatment trade-off was used to examine the acceptable proportion of avoided futile lung resections to cover the burden of confirmatory mediastinoscopy. Results: Ninety-seven patients completed the questionnaire (57%). The length of the staging period was significantly the most important attribute (RI 26.24; 95% CI: 25.05-27.43), followed by the risk of a futile surgical lung resection (RI 23.44; 95% CI: 22.28-24.60) and resection of the primary tumor (RI 22.21; 95% CI: 21.09-23.33). Avoidance of 7% (IQR 1- >14%) futile lung resections would cover the burden of confirmatory mediastinoscopy, with a dichotomy among patients always (39%) or never (38%) willing to undergo confirmatory mediastinoscopy after N2 and N3-negative endosonography. Conclusion: Although a strong dichotomy among patients always or never willing to undergo confirmatory mediastinoscopy was found, the length of the staging period was the most important attribute in invasive mediastinal staging according to patients with resectable NSCLC. Trial Not Show less
Terveer, E.M.; Vendrik, K.E.W.; Ooijevaar, R.E.; Lingen, E. van; Boeije-Koppenol, E.; Nood, E. van; ... ; Keller, J.J. 2020
Background The Netherlands Donor Feces Bank provides standardized ready-to-use donor faecal suspensions for faecal microbiota transplantation treatment of patients with recurrentClostridioides... Show moreBackground The Netherlands Donor Feces Bank provides standardized ready-to-use donor faecal suspensions for faecal microbiota transplantation treatment of patients with recurrentClostridioides difficileinfection. Objective The purpose of this study was evaluation of safety, feasibility and outcome of faecal microbiota transplantation facilitated by a national stool bank. Methods The methods used included: observational cohort study of donors and recipients of faecal suspensions; assessment of donor screening and patient selection performed by an expert panel of medical microbiologists, gastroenterologists and infectious disease specialists; and patient outcome evaluated at different timepoints after faecal microbiota transplantation. Results Of 871 volunteers who registered as a potential faeces donor, 16 (2%) became active donors. Nine donors stopped or were excluded after a mean donation period of 5.7 months. In 2016-2019, 47 (27%) of 176 requests for faecal microbiota transplantations were deemed not indicated by the expert panel. In total, 129 patients with recurrentC. difficileinfection were treated with 143 faecal suspensions in 40 different hospitals. The cure rate at two months after a single infusion was 89% (107/120). Of 84 patients, long-term follow-up (median 42 weeks) was available and sustained cure was achieved in 61 (73%). EarlyC. difficileinfection relapses (within two months after faecal microbiota transplantation) and late recurrences (after more than two months) occurred more frequently in patients who received non-C. difficileantibiotics within three weeks after faecal microbiota transplantation and in moderately to severely immunocompromised patients. Of 21 patients withC. difficileinfection after faecal microbiota transplantation, 14 were cured with anti-C. difficileantibiotics and seven with a second transplantation. No faecal microbiota transplantation-related serious adverse events were observed, but gastro-intestinal complaints (nausea, abdominal pain or diarrhoea) persisted in 32% of the treated patients at long-term follow-up. Conclusion Faecal suspensions provided by a centralized stool bank, supported by a multidisciplinary expert team, resulted in effective, appropriate and safe application of faecal microbiota transplantation for recurrentC. difficileinfection. Show less
Introduction Cirrhotic patients with portal hypertension can suffer from variceal bleeding or refractory ascites and can benefit from a transjugular intrahepatic portosystemic shunt (TIPS). Post... Show moreIntroduction Cirrhotic patients with portal hypertension can suffer from variceal bleeding or refractory ascites and can benefit from a transjugular intrahepatic portosystemic shunt (TIPS). Post-TIPS hepatic encephalopathy (HE) is a common (20%-54%) and often severe complication. A prophylactic strategy is lacking.Methods and analysis The Prevention of hepatic Encephalopathy by Administration of Rifaximin and Lactulose in patients with liver cirrhosis undergoing placement of a TIPS (PEARL) trial, is a multicentre randomised, double blind, placebo controlled trial. Patients undergoing covered TIPS placement are prescribed either rifaximin 550 mg two times per day and lactulose 25 mL two times per day (starting dose) or placebo 550 mg two times per day and lactulose 25 mL two times per day from 72 hours before and until 3 months after TIPS placement. Primary endpoint is the development of overt HE (OHE) within 3 months (according to West Haven criteria). Secondary endpoints include 90-day mortality; development of a second episode of OHE; time to development of episode(s) of OHE; development of minimal HE; molecular changes in peripheral and portal blood samples; quality of life and cost-effectiveness. The total sample size is 238 patients and recruitment period is 3 years in six hospitals in the Netherlands and one in Belgium.Ethics and dissemination This study protocol was approved in the Netherlands by the Medical Research Ethics Committee of the Academic Medical Centre, Amsterdam (2018-332), in Belgium by the Ethics Committee Research UZ/KU Leuven (S62577) and competent authorities. This study will be conducted in accordance with Good Clinical Practice guidelines and the principles of the Declaration of Helsinki. Study results will be submitted for publication in a peer-reviewed journal. Show less
Verschuur, C.V.M.; Suwijn, S.R.; Boel, J.A.; Post, B.; Bloem, B.R.; Hilten, J.J. van; ... ; LEAP Study Grp 2019
