Impact of 18FFDG-PET/CT and Laparoscopy in Staging of Locally Advanced Gastric Cancer: A Cost Analysis in the Prospective Multicenter PLASTIC-Study.

BACKGROUND: Unnecessary D2-gastrectomy and associated costs can be prevented after detecting non-curable gastric cancer, but impact of staging on treatment costs is unclear. This study determined the cost impact of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18FFDG-PET/CT) and staging laparoscopy (SL) in gastric cancer staging. MATERIALS AND METHODS: In this cost analysis, four staging strategies were modeled in a decision tree: (1) 18FFDG-PET/CT first, then SL, (2) SL only, (3) 18FFDG-PET/CT only, and (4) neither SL nor 18FFDG-PET/CT. Costs were assessed on the basis of the prospective PLASTIC-study, which evaluated adding 18FFDG-PET/CT and SL to staging advanced gastric cancer (cT3-4 and/or cN+) in 18 Dutch hospitals. The Dutch Healthcare Authority provided 18FFDG-PET/CT unit costs. SL unit costs were calculated bottom-up. Gastrectomy-associated costs were collected with hospital claim data until 30 days postoperatively. Uncertainty was assessed in a probabilistic sensitivity analysis (1000 iterations). RESULTS: 18FFDG-PET/CT costs were €1104 including biopsy/cytology. Bottom-up calculations totaled €1537 per SL. D2-gastrectomy costs were €19,308. Total costs per patient were €18,137 for strategy 1, €17,079 for strategy 2, and €19,805 for strategy 3. If all patients undergo gastrectomy, total costs were €18,959 per patient (strategy 4). Performing SL only reduced costs by €1880 per patient. Adding 18FFDG-PET/CT to SL increased costs by €1058 per patient; IQR €870-1253 in the sensitivity analysis. CONCLUSIONS: For advanced gastric cancer, performing SL resulted in substantial cost savings by reducing unnecessary gastrectomies. In contrast, routine 18FFDG-PET/CT increased costs without substantially reducing unnecessary gastrectomies, and is not recommended due to limited impact with major costs. TRIAL REGISTRATION: NCT03208621. This trial was registered prospectively on 30-06-2017.

The EORTC QLU-C10D is a valid cancer-specific preference-based measure for cost-utility and health technology assessment in the Netherlands.

BACKGROUND: Cost-utility analysis typically relies on preference-based measures (PBMs). While generic PBMs are widely used, disease-specific PBMs can capture aspects relevant for certain patient populations. Here the EORTC QLU-C10D, a cancer-specific PBM based on the QLQ-C30, is validated using Dutch trial data with the EQ-5D-3L as a generic comparator measure. METHODS: We retrospectively analysed data from four Dutch randomised controlled trials (RCTs) comprising the EORTC QLQ-C30 and the EQ-5D-3L. Respective Dutch value sets were applied. Correlations between the instruments were calculated for domains and index scores. Bland-Altman plots and intra-class correlations (ICC) displayed agreement between the measures. Independent and paired t-tests, effect sizes and relative validity indices were used to determine the instruments' performance in detecting clinically known-group differences and health changes over time. RESULTS: We analysed data from 602 cancer patients from four different trials. In overall, the EORTC QLU-C10D showed good relative validity with the EQ-5D-3L as a comparator (correlations of index scores r = 0.53-0.75, ICCs 0.686-0.808, conceptually similar domains showed higher correlations than dissimilar domains). Most importantly, it detected 63% of expected clinical group differences and 50% of changes over time in patients undergoing treatment. Both instruments showed poor performance in survivors. Detection rate and measurement efficiency were clearly higher for the QLU-C10D than for the EQ-5D-3L. CONCLUSIONS: The Dutch EORTC QLU-C10D showed good comparative validity in patients undergoing treatment. Our results underline the benefit that can be achieved by using a cancer-specific PBM for generating health utilities for cancer patients from a measurement perspective.

EAES rapid guideline: updated systematic review, network meta-analysis, CINeMA and GRADE assessment, and evidence-informed European recommendations on the management of common bile duct stones.

BACKGROUND: Choledocholithiasis presents in a considerable proportion of patients with gallbladder disease. There are several management options, including preoperative or intraoperative endoscopic cholangiopancreatography (ERCP), and laparoscopic common bile duct exploration (LCBDE). OBJECTIVE: To develop evidence-informed, interdisciplinary, European recommendations on the management of common bile duct stones in the context of intact gallbladder with a clinical decision to intervene to both the gallbladder and the common bile duct stones. METHODS: We updated a systematic review and network meta-analysis of LCBDE, preoperative, intraoperative, and postoperative ERCP. We formed evidence summaries using the GRADE and the CINeMA methodology, and a panel of general surgeons, gastroenterologists, and a patient representative contributed to the development of a GRADE evidence-to-decision framework to select among multiple interventions. RESULTS: The panel reached unanimous consensus on the first Delphi round. We suggest LCBDE over preoperative, intraoperative, or postoperative ERCP, when surgical experience and expertise are available; intraoperative ERCP over LCBDE, preoperative or postoperative ERCP, when this is logistically feasible in a given healthcare setting; and preoperative ERCP over LCBDE or postoperative ERCP, when intraoperative ERCP is not feasible and there is insufficient experience or expertise with LCBDE (weak recommendation). The evidence summaries and decision aids are available on the platform MAGICapp ( https://app.magicapp.org/#/guideline/nJ5zyL ). CONCLUSION: We developed a rapid guideline on the management of common bile duct stones in line with latest methodological standards. It can be used by healthcare professionals and other stakeholders to inform clinical and policy decisions. GUIDELINE REGISTRATION NUMBER: IPGRP-2022CN170.

Individuals' Preferences for Esophageal Cancer Screening: A Discrete Choice Experiment.

OBJECTIVES: The increasing incidence of esophageal adenocarcinoma (EAC) and the dismal prognosis has stimulated interest in the early detection of EAC. Our objective was to determine individuals' preferences for EAC screening and to assess to what extent procedural characteristics of EAC screening tests predict willingness for screening participation. METHODS: A discrete choice experiment questionnaire was sent by postal mail to 1000 subjects aged 50 to 75 years who were randomly selected from the municipal registry in the Netherlands. Each subject answered 12 discrete choice questions of 2 hypothetical screening tests comprising 5 attributes: EAC-related mortality risk reduction, procedure-related pain and discomfort, screening location, test specificity, and costs. A multinomial logit model was used to estimate individuals' preferences for each attribute level and to calculate expected rates of uptake. RESULTS: In total, 375 individuals (37.5%) completed the questionnaire. Test specificity, pain and discomfort, mortality reduction, and out-of-pocket costs all had a significant impact on respondents' preferences. The average expected uptake of EAC screening was 62.8% (95% confidence interval [CI] 61.1-64.5). Severe pain and discomfort had the largest impact on screening uptake (-22.8%; 95% CI -26.8 to -18.7). Male gender (ß 2.81; P < .001), cancer worries (ß 1.96; P = .01), endoscopy experience (ß 1.46; P = .05), and upper gastrointestinal symptoms (ß 1.50; P = .05) were significantly associated with screening participation. CONCLUSIONS: EAC screening implementation should consider patient preferences to maximize screening attendance uptake. Based on our results, an optimal screening test should have high specificity, cause no or mild to moderate pain or discomfort, and result in a decrease in EAC-related mortality.

ESGE and ESGENA Position Statement on gastrointestinal endoscopy and the COVID-19 pandemic.

We are currently living in the throes of the COVID-19 pandemic that imposes a significant stress on health care providers and facilities. Europe is severely affected with an exponential increase in incident infections and deaths. The clinical manifestations of COVID-19 can be subtle, encompassing a broad spectrum from asymptomatic mild disease to severe respiratory illness. Health care professionals in endoscopy units are at increased risk of infection from COVID-19. Infection prevention and control has been shown to be dramatically effective in assuring the safety of both health care professionals and patients. The European Society of Gastrointestinal Endoscopy (www.esge.com) and the European Society of Gastroenterology and Endoscopy Nurses and Associates (www.esgena.org) are joining forces to provide guidance during this pandemic to help assure the highest level of endoscopy care and protection against COVID-19 for both patients and endoscopy unit personnel. This guidance is based upon the best available evidence regarding assessment of risk during the current status of the pandemic and a consensus on which procedures to perform and the priorities on resumption. We appreciate the gaps in knowledge and evidence, especially on the proper strategy(ies) for the resumption of normal endoscopy practice during the upcoming phases and end of the pandemic and therefore a list of potential research questions is presented. New evidence may result in an updated statement.

Endosheath ultrathin transnasal endoscopy is a cost-effective method for screening for Barrett's esophagus in patients with GERD symptoms.

BACKGROUND AND AIMS: Barrett's esophagus (BE) screening is currently not considered to be cost effective in the general population but may be effective in high-risk subgroups, such as 50-year-old white men with chronic reflux disease (GERD). A new modality for screening is unsedated transnasal endoscopy using endosheath technology (uTNE), which has been shown to be safe and effective in clinical practice. In this study, we determined the cost-utility of uTNE in a high-risk subgroup compared with no screening or screening with standard endoscopy. METHODS: A Markov model was used to simulate screening of 50-year-old white men with symptoms of GERD with either uTNE or standard endoscopy compared with no screening, over a lifetime horizon. Input variables were based on the literature and recent data on uTNE screening for BE. The study was designed from a healthcare payer perspective by using direct costs. Primary outcome measures were costs, quality-adjusted life years (QALYs), and the incremental cost-utility ratio (ICUR) of uTNE and standard endoscopy compared with no screening. Sensitivity analysis was performed for several factors, such as prevalence of BE. RESULTS: Costs of uTNE, standard endoscopy, and no screening were estimated at, $2495, $2957, and $1436, respectively. Compared with no screening, uTNE screening resulted in an overall QALY increase of 0.039 (95% percentile 0.018; 0.063) and an ICUR of $29,446 per QALY gained (95% confidence interval [CI], 18.516-53.091), whereas standard endoscopy compared with no screening resulted in a QALY increase of 0.034 (95% CI, 0.015-0.056) and an ICUR of $47,563 (95% CI, 31,036-82,970). CONCLUSION: Both uTNE and standard endoscopy seem to be cost-effective screening methods in a screening cohort of 50-year-old white men with GERD at a willingness-to-pay cutoff of $50,000.

Evolution of Costs of Inflammatory Bowel Disease over Two Years of Follow-Up.

BACKGROUND: With the increasing use of anti-TNF therapy in inflammatory bowel disease (IBD), a shift of costs has been observed with medication costs replacing hospitalization and surgery as major cost driver. We aimed to explore the evolution of IBD-related costs over two years of follow-up. METHODS AND FINDINGS: In total 1,307 Crohn's disease (CD) patients and 915 ulcerative colitis (UC) patients were prospectively followed for two years by three-monthly web-based questionnaires. Changes of healthcare costs, productivity costs and out-of-pocket costs over time were assessed using mixed model analysis. Multivariable logistic regression analysis was used to identify costs drivers. In total 737 CD patients and 566 UC were included. Total costs were stable over two years of follow-up, with annual total costs of €7,835 in CD and €3,600 in UC. However, within healthcare costs, the proportion of anti-TNF therapy-related costs increased from 64% to 72% in CD (p<0.01) and from 31% to 39% in UC (p < 0.01). In contrast, the proportion of hospitalization costs decreased from 19% to 13% in CD (p<0.01), and 22% to 15% in UC (p < 0.01). Penetrating disease course predicted an increase of healthcare costs (adjusted odds ratio (adj. OR) 1.95 (95% CI 1.02-3.37) in CD and age <40 years in UC (adj. OR 4.72 (95% CI 1.61-13.86)). CONCLUSIONS: BD-related costs remained stable over two years. However, the proportion of anti-TNF-related healthcare costs increased, while hospitalization costs decreased. Factors associated with increased costs were penetrating disease course in CD and age <40 in UC.

Self-reported Health Care Utilization of Patients with Inflammatory Bowel Disease Correlates Perfectly with Medical Records.

BACKGROUND: Studies on the costs of health care in patients with inflammatory bowel disease (IBD) are increasingly conducted through the collection of self-reported data. We aimed to assess the concordance between estimated annual costs based on self-reported health care utilization and administrative data in IBD. METHODS: Consecutive patients with Crohn's disease or ulcerative colitis visiting the outpatient clinic were enrolled. Participants were asked to fill out a questionnaire on their IBD-specific health care utilization over the past year. Registered health care utilization over the same time period was extracted from medical records. Health care resources were multiplied by their unit prices to obtain costs. Cost estimates were compared, and correlation, sensitivity, and specificity were calculated. RESULTS: In total, 101 patients (70 Crohn's disease, 31 ulcerative colitis) were enrolled. Mean direct health care costs were &OV0556;4758 per year according to self-reported data and &OV0556;4866 according to administrative data (r = 0.97). Hospitalizations and diagnostics were relatively underreported with a sensitivity of 75% and 88%, and a specificity of 100% and 88%, respectively. One of 7 surgical procedures was overreported, and only 1 of 25 patients did not report the use of anti-tumor necrosis factor compounds. Suffering from a flare or having a pouch predicted a decreased recall with an adjusted odds ratio of 3.5 (95% confidence interval, 1.3-9.6) and 10.7 (95% confidence interval, 1.1-107.6), respectively. CONCLUSIONS: We report a high concordance between costs of self-reported health care utilization and administrative data over the past year in IBD. Self-reported health care utilization reliably measures the consumption of health care in IBD.

The "golden retriever" study: improving polyp retrieval rates by providing education and competitive feedback.

BACKGROUND AND AIMS: Although optical diagnosis of small colorectal polyps can be achieved at expert centers, accurate prediction of histopathological outcomes has not been achieved in all practice settings. It is therefore important that resected polyps are retrieved for histology. The aims of this study were to evaluate the effect of education and competitive feedback on the overall polyp retrieval rate and to determine which polyp-related and procedure-related factors are associated with retrieval. METHODS: We prospectively included consecutive colonoscopies performed at a single center between April 1, 2013 and April 1, 2014. Patients with inflammatory bowel disease or familial polyposis syndromes were excluded from analysis. Six months after the start of the study, all endoscopists were educated on the importance of polyp retrieval, and a competition was started by publicly providing feedback on the retrieval rate of all endoscopists and the monthly best 3 performers (or "golden retrievers") in particular. We compared overall retrieval rates in the 6 months before and after the start of the competition. RESULTS: The overall polyp retrieval rate improved from 88% (525/594) to 93% (978/1047), comparing consecutive colonoscopies performed in the 6 months before and during the polyp retrieval competition (P < .01). The histopathological outcomes of retrieved polyps were not different before and during the competition. The retrieval rate of right-sided polyps increased from 85% to 95% during the competition (odds ratio [OR], 3.3; 95% confidence interval [CI], 2.0-5.4), whereas the left-sided retrieval rate remained 92%. On multivariable analysis, polyp size greater than 5 mm (OR, 4.1; 95% CI, 1.8-9.6) and in competition resection (OR, 1.8; 95% CI, 1.3-2.6) were significantly associated with polyp retrieval, respectively. CONCLUSION: Providing education and competitive feedback to endoscopists will improve polyp retrieval rates, especially for clinically relevant, right-sided polyps.

Comparison of Costs and Quality of Life in Ulcerative Colitis Patients with an Ileal Pouch-Anal Anastomosis, Ileostomy and Anti-TNFα Therapy.

BACKGROUND AND AIMS: More data are warranted on the economic impact of different treatment strategies in ulcerative colitis (UC) patients. We compared the costs and quality of life of UC patients with a pouch reconstruction, an ileostomy or anti-tumour necrosis factor α (TNFα) therapy. METHODS: UC patients filled out 3-monthly questionnaires for 2 years. Differences in 3-monthly healthcare costs, productivity costs and patient costs were tested using mixed model analysis. Quality of life was assessed employing the ) and the inflammatory bowel disease questionnaire (IBDQ). RESULTS: Out of 915 UC patients, 81 (9%) had a pouch and 48 (5%) an ileostomy, and 34 (4%) were on anti-TNFα therapy. Anti-TNFα-treated patients reported high UC related-healthcare costs per 3 months (€5350). Medication use accounted for 92% of healthcare costs. UC-attributable healthcare costs were 3-fold higher in ileostomy patients compared with pouch patients (€1581 versus €407; p < 0.01). Main cost drivers in ileostomy patients were healthcare costs and ileostomy supplies (2 and 23% of healthcare costs, respectively). In pouch patients, the main cost driver was hospitalization, accounting for 50% of healthcare costs. Productivity loss did not differ between pouch and ileostomy patients (€483 versus €377; p < 0.23), but was significantly higher in anti-TNFα-treated patients (€1085). No difference was found in IBDQ scores, but pouch patients were found to have higher quality-adjusted life years than ileostomy patients and anti-TNFα-treated patients (0.90 [interquartile range 0.78-1.00] versus 0.84 [0.78-1.00] and 0.84 [0.69-1.00], respectively; p < 0.01). CONCLUSION: Patients receiving anti-TNFα therapy reported the highest healthcare cost, in which medication use was the major cost driver. Ileostomy patients were three times more expensive than pouch patients due to frequent hospitalization and ileostomy supplies.

Cost Efficacy of Metal Stents for Palliation of Extrahepatic Bile Duct Obstruction in a Randomized Controlled Trial.

BACKGROUND & AIMS: Endoscopic stents are placed for palliation of extrahepatic bile duct obstruction. Although self-expandable metal stents (SEMS) remain patent longer than plastic stents, they are more expensive. We aimed to evaluate which type of stent (plastic, uncovered SEMS [uSEMS], or partially covered SEMS [pcSEMS]) is the most effective and we assessed costs. METHODS: We performed a multicenter randomized trial in 219 patients at 18 hospitals in The Netherlands from February 2008 through February 2013. Patients were assigned randomly for placement of a plastic stent (n = 73), uSEMS (n = 75), or pcSEMS (n = 71) during endoscopic retrograde cholangiopancreatography. Patients were followed up for up to 1 year. Researchers were not blinded to groups. The main study end points included functional stent time and costs. RESULTS: The mean functional stent times were 172 days for plastic stents, 288 days for uSEMS, and 299 days for pcSEMS (P < .005 for uSEMS and pcSEMS vs plastic). The initial placement of plastic stents (€1042 or $1106) cost significantly less than placement of SEMS (€1973 or $2094) (P = .001). However, the total cost per patient at the end of the follow-up period did not differ significantly between plastic stents (€7320 or $7770) and SEMS (€6932 or $7356) (P = .61). Furthermore, in patients with short survival times (≤3 mo) or metastatic disease, the total cost per patient did not differ between plastic stents and SEMS. No differences in costs were found between pcSEMS and uSEMS. CONCLUSIONS: Although placement of SEMS (uncovered or partially covered) for palliation of extrahepatic bile duct obstruction initially is more expensive than placement of plastic stents, SEMS have longer functional time. The total costs after 1 year do not differ significantly with stent type. Dutch Clinical Trial Registration no: NTR1361.

Constipation-related direct medical costs in 16 887 patients newly diagnosed with chronic constipation.

BACKGROUND: Chronic constipation is a common condition, but the exact impact on healthcare budgets in Western Europe is poorly documented. OBJECTIVES: The aim of this study was to (a) investigate chronic constipation-related direct medical costs in patients with newly diagnosed chronic constipation and (b) study differences in costs according to natural history. PATIENTS AND METHODS: We identified 16 887 patients newly diagnosed with chronic constipation in a Dutch health insurance database (∼1.3 million patients) in 2006-2009. Individuals with chronic constipation were selected on the basis of chronic laxative use (≥90 days/year) and diagnostic related groups for chronic constipation. On the basis of the episodes of laxative use and diagnostic related groups, individuals were categorized as having persistent, episodic, and nonrecurrent disease. Unadjusted costs for laxatives and hospital care for chronic constipation and constipation-related comorbidities were assessed and compared between patients with nonrecurrent, episodic, and persistent disease. Factors associated with costs were identified using Cox regression analyses. RESULTS: The mean total chronic constipation-related direct medical costs in the first year after diagnosis were &OV0556;310±845 and consisted of laxatives (45%) and hospital care for chronic constipation (26%) as well as constipation-related comorbidities (29%). Costs were highest in patients with persistent disease (&OV0556;367±882) compared with patients with episodic (&OV0556;292±808) and nonrecurrent (&OV0556;263±613) disease (P<0.01). Male sex was associated with higher costs, whereas increasing age, diabetes, and use of opioids were associated with lower costs. CONCLUSION: Pharmacy costs and hospital care costs for chronic constipation-related comorbidities were the largest cost drivers for total constipation-related direct medical costs in patients with newly diagnosed chronic constipation. Direct medical costs differed according to patient characteristics.

Open-access flexible sigmoidoscopy frequently leads to additional colonoscopy in symptomatic patients over 50 years.

BACKGROUND & AIMS: General practitioners (GPs) in the Netherlands have open access to flexible sigmoidoscopy (FS) for patients with lower gastrointestinal symptoms, but not to colonoscopy. This study was performed to investigate the yield of FS in GP-referred patients, to evaluate the proportion of patients in whom additional colonoscopy was performed and to investigate whether there was a subgroup of patients referred for symptoms with a low risk of detecting significant findings. METHODS: All patients undergoing FS in 2008 and 2009 who were referred by GPs were analyzed. Indications for additional colonoscopy were the presence of polyps and/or colorectal cancer (CRC), polyp screening or surveillance, incomplete FS or other reasons. RESULTS: In total, 916 patients underwent FS. A cause for the symptoms was found in 44.2% of patients. In patients aged 50 years or older, additional colonoscopy was more frequently performed than in younger patients (27.5% vs. 9.6%, OR=3.6 [95% CI 2.4-5.4]), mainly due to a higher prevalence of adenomatous polyps (29.9% vs. 10.5%, OR=3.6 [95% CI 2.4-5.4]) and CRC (7.5% vs. 1.3%, OR=6.2 [95% CI 2.2-17.5]) during FS. In 7.8% patients undergoing FS for abdominal pain as the presenting symptom, a probable cause for the symptoms was found, mainly diverticular disease. CONCLUSION: Due to the high prevalence of polyps and CRC in symptomatic patients aged 50 years or older undergoing FS, an additional colonoscopy is performed frequently. In patients referred with abdominal pain, FS is unlikely to reveal a relevant cause for the symptoms.

Effect of aging on healthcare costs of inflammatory bowel disease: a glimpse into the future.

BACKGROUND: Population aging is expected to result in a substantial additional burden on healthcare resources in the near future. We aimed to assess the current and future impact of aging on direct healthcare costs (DHC) attributed to inflammatory bowel disease (IBD). METHODS: Patients with IBD from a Dutch multicenter cohort filled out 3-monthly questionnaires for 2 years. Elderly (≥60 yr) and younger patients (18-60 yr) IBD were analyzed for differences in 3-monthly DHC, productivity losses, and out-of-pocket costs. Prevalence rates were obtained from a health insurance database. Estimates of annual DHC and prevalence rates were applied to the total Dutch adult population in 2011 and then projected to 2040, using predicted changes in population demography, prices, and volume. RESULTS: IBD-attributable DHC were lower in elderly than in younger patients with IBD with respect to 3-monthly DHC (&OV0556;359 versus &OV0556;978, P < 0.01), productivity losses (&OV0556;108 versus &OV0556;456, P < 0.01), and out-of-pocket costs (&OV0556;40 versus &OV0556;57, P < 0.01). Between 2011 and 2040, the percentage of elderly IBD patients in the Netherlands has been projected to rise from 24% to 35%. Between 2011 and 2040, DHC of the total IBD population in the Netherlands are projected to increase from &OV0556;161 to &OV0556;661 million. Population aging accounted for 1% of this increase, next to rising prices (29%), and volume growth (70%). CONCLUSIONS: Population aging has a negligible effect on IBD-attributable DHC of the IBD population in the near future, because the average costs incurred by elderly patients with IBD are considerably lower than those incurred by younger patients with IBD.

Healthcare costs of inflammatory bowel disease have shifted from hospitalisation and surgery towards anti-TNFα therapy: results from the COIN study.

OBJECTIVE: The introduction of anti tumour necrosis factor-α (anti-TNFα) therapy might impact healthcare expenditures, but there are limited data regarding the costs of inflammatory bowel diseases (IBD) following the introduction of these drugs. We aimed to assess the healthcare costs and productivity losses in a large cohort of IBD patients. DESIGN: Crohn's disease (CD) and ulcerative colitis (UC) patients from seven university hospitals and seven general hospitals were invited to fill-out a web-based questionnaire. Cost items were derived from a 3 month follow-up questionnaire and categorised in outpatient clinic, diagnostics, medication, surgery and hospitalisation. Productivity losses included sick leave of paid and unpaid work. Costs were expressed as mean 3-month costs per patients with a 95% CI obtained using non-parametric bootstrapping. RESULTS: A total of 1315 CD patients and 937 UC patients were included. Healthcare costs were almost three times higher in CD as compared with UC, €1625 (95% CI €1476 to €1775) versus €595 (95% CI €505 to €685), respectively (p<0.01). Anti-TNFα use was the main costs driver, accounting for 64% and 31% of the total cost in CD and UC. Hospitalisation and surgery together accounted for 19% and <1% of the healthcare costs in CD and 23% and 1% in UC, respectively. Productivity losses accounted for 16% and 39% of the total costs in CD and UC. CONCLUSIONS: We showed that healthcare costs are mainly driven by medication costs, most importantly by anti-TNFα therapy. Hospitalisation and surgery accounted only for a minor part of the healthcare costs.

Optimizing screening for tuberculosis and hepatitis B prior to starting tumor necrosis factor-α inhibitors in Crohn's disease.

BACKGROUND AND AIMS: Treatment with tumor necrosis factor-α (TNF-α) inhibitors in patients with Crohn's disease (CD) is associated with potentially serious infections, including tuberculosis (TB) and hepatitis B virus (HBV). We assessed the cost-effectiveness of extensive TB screening and HBV screening prior to initiating TNF-α inhibitors in CD. METHODS: We constructed two Markov models: (1) comparing tuberculin skin test (TST) combined with chest X-ray (conventional TB screening) versus TST and chest X-ray followed by the interferon-gamma release assay (extensive TB screening) in diagnosing TB; and (2) HBV screening versus no HBV screening. Our base-case included an adult CD patient starting with infliximab treatment. Input parameters were extracted from the literature. Direct medical costs were assessed and discounted following a third-party payer perspective. The main outcome was the incremental cost-effectiveness ratio (ICER). Sensitivity and Monte Carlo analyses were performed over wide ranges of probability and cost estimates. RESULTS: At base-case, the ICERs of extensive screening and HBV screening were €64,340 and €75,760 respectively to gain one quality-adjusted life year. Sensitivity analyses concluded that extensive TB screening was a cost-effective strategy if the latent TB prevalence is more than 12 % or if the false positivity rate of TST is more than 20 %. HBV screening became cost-effective if HBV reactivation or HBV-related mortality is higher than 37 and 62 %, respectively. CONCLUSIONS: Extensive TB screening and HBV screening are not cost-effective compared with conventional TB screening and no HBV screening, respectively. However, when targeted at high-risk patient groups, these screening strategies are likely to become cost-effective.

Nurse-led follow-up at home vs. conventional medical outpatient clinic follow-up in patients with incurable upper gastrointestinal cancer: a randomized study.

CONTEXT: Upper gastrointestinal cancer is associated with a poor prognosis. The multidimensional problems of incurable patients require close monitoring and frequent support, which cannot sufficiently be provided during conventional one to two month follow-up visits to the outpatient clinic. OBJECTIVES: To compare nurse-led follow-up at home with conventional medical follow-up in the outpatient clinic for patients with incurable primary or recurrent esophageal, pancreatic, or hepatobiliary cancer. METHODS: Patients were randomized to nurse-led follow-up at home or conventional medical follow-up in the outpatient clinic. Outcome parameters were quality of life (QoL), patient satisfaction, and health care consumption, measured by different questionnaires at one and a half and four months after randomization. As well, cost analyses were done for both follow-up strategies in the first four months. RESULTS: In total, 138 patients were randomized, of which 66 (48%) were evaluable. At baseline, both groups were similar with respect to clinical and sociodemographic characteristics and health-related QoL. Patients in the nurse-led follow-up group were significantly more satisfied with the visits, whereas QoL and health care consumption within the first four months were comparable between the two groups. Nurse-led follow-up was less expensive than conventional medical follow-up. However, the total costs for the first four months of follow-up in this study were higher in the nurse-led follow-up group because of a higher frequency of visits. CONCLUSION: The results suggest that conventional medical follow-up is interchangeable with nurse-led follow-up. A cost utility study is necessary to determine the preferred frequency and duration of the home visits.

Early surgery versus optimal current step-up practice for chronic pancreatitis (ESCAPE): design and rationale of a randomized trial.

BACKGROUND: In current practice, patients with chronic pancreatitis undergo surgical intervention in a late stage of the disease, when conservative treatment and endoscopic interventions have failed. Recent evidence suggests that surgical intervention early on in the disease benefits patients in terms of better pain control and preservation of pancreatic function. Therefore, we designed a randomized controlled trial to evaluate the benefits, risks and costs of early surgical intervention compared to the current stepwise practice for chronic pancreatitis. METHODS/DESIGN: The ESCAPE trial is a randomized controlled, parallel, superiority multicenter trial. Patients with chronic pancreatitis, a dilated pancreatic duct (≥5 mm) and moderate pain and/or frequent flare-ups will be registered and followed monthly as potential candidates for the trial. When a registered patient meets the randomization criteria (i.e. need for opioid analgesics) the patient will be randomized to either early surgical intervention (group A) or optimal current step-up practice (group B). An expert panel of chronic pancreatitis specialists will oversee the assessment of eligibility and ensure that allocation to either treatment arm is possible. Patients in group A will undergo pancreaticojejunostomy or a Frey-procedure in case of an enlarged pancreatic head (≥4 cm). Patients in group B will undergo a step-up practice of optimal medical treatment, if needed followed by endoscopic interventions, and if needed followed by surgery, according to predefined criteria. Primary outcome is pain assessed with the Izbicki pain score during a follow-up of 18 months. Secondary outcomes include complications, mortality, total direct and indirect costs, quality of life, pancreatic insufficiency, alternative pain scales, length of hospital admission, number of interventions and pancreatitis flare-ups. For the sample size calculation we defined a minimal clinically relevant difference in the primary endpoint as a difference of at least 15 points on the Izbicki pain score during follow-up. To detect this difference a total of 88 patients will be randomized (alpha 0.05, power 90%, drop-out 10%). DISCUSSION: The ESCAPE trial will investigate whether early surgery in chronic pancreatitis is beneficial in terms of pain relief, pancreatic function and quality of life, compared with current step-up practice. TRIAL REGISTRATION: ISRCTN: ISRCTN45877994.

Robot-assisted minimally invasive thoraco-laparoscopic esophagectomy versus open transthoracic esophagectomy for resectable esophageal cancer, a randomized controlled trial (ROBOT trial).

BACKGROUND: For esophageal cancer patients, radical esophagolymphadenectomy is the cornerstone of multimodality treatment with curative intent. Transthoracic esophagectomy is the preferred surgical approach worldwide allowing for en-bloc resection of the tumor with the surrounding lymph nodes. However, the percentage of cardiopulmonary complications associated with the transthoracic approach is high (50 to 70%).Recent studies have shown that robot-assisted minimally invasive thoraco-laparoscopic esophagectomy (RATE) is at least equivalent to the open transthoracic approach for esophageal cancer in terms of short-term oncological outcomes. RATE was accompanied with reduced blood loss, shorter ICU stay and improved lymph node retrieval compared with open esophagectomy, and the pulmonary complication rate, hospital stay and perioperative mortality were comparable. The objective is to evaluate the efficacy, risks, quality of life and cost-effectiveness of RATE as an alternative to open transthoracic esophagectomy for treatment of esophageal cancer. METHODS/DESIGN: This is an investigator-initiated and investigator-driven monocenter randomized controlled parallel-group, superiority trial. All adult patients (age ≥ 18 and ≤ 80 years) with histologically proven, surgically resectable (cT1-4a, N0-3, M0) esophageal carcinoma of the intrathoracic esophagus and with European Clinical Oncology Group performance status 0, 1 or 2 will be assessed for eligibility and included after obtaining informed consent. Patients (n = 112) with resectable esophageal cancer are randomized in the outpatient department to either RATE (n = 56) or open three-stage transthoracic esophageal resection (n = 56). The primary outcome of this study is the percentage of overall complications (grade 2 and higher) as stated by the modified Clavien-Dindo classification of surgical complications. DISCUSSION: This is the first randomized controlled trial designed to compare RATE with open transthoracic esophagectomy as surgical treatment for resectable esophageal cancer. If our hypothesis is proven correct, RATE will result in a lower percentage of postoperative complications, lower blood loss, and shorter hospital stay, but with at least similar oncologic outcomes and better postoperative quality of life compared with open transthoracic esophagectomy. The study started in January 2012. Follow-up will be 5 years. Short-term results will be analyzed and published after discharge of the last randomized patient. TRIAL REGISTRATION: Dutch trial register: NTR3291 ClinicalTrial.gov: NCT01544790.

Social inequalities and mortality in Europe--results from a large multi-national cohort.

BACKGROUND: Socio-economic inequalities in mortality are observed at the country level in both North America and Europe. The purpose of this work is to investigate the contribution of specific risk factors to social inequalities in cause-specific mortality using a large multi-country cohort of Europeans. METHODS: A total of 3,456,689 person/years follow-up of the European Prospective Investigation into Cancer and Nutrition (EPIC) was analysed. Educational level of subjects coming from 9 European countries was recorded as proxy for socio-economic status (SES). Cox proportional hazard model's with a step-wise inclusion of explanatory variables were used to explore the association between SES and mortality; a Relative Index of Inequality (RII) was calculated as measure of relative inequality. RESULTS: Total mortality among men with the highest education level is reduced by 43% compared to men with the lowest (HR 0.57, 95% C.I. 0.52-0.61); among women by 29% (HR 0.71, 95% C.I. 0.64-0.78). The risk reduction was attenuated by 7% in men and 3% in women by the introduction of smoking and to a lesser extent (2% in men and 3% in women) by introducing body mass index and additional explanatory variables (alcohol consumption, leisure physical activity, fruit and vegetable intake) (3% in men and 5% in women). Social inequalities were highly statistically significant for all causes of death examined in men. In women, social inequalities were less strong, but statistically significant for all causes of death except for cancer-related mortality and injuries. DISCUSSION: In this European study, substantial social inequalities in mortality among European men and women which cannot be fully explained away by accounting for known common risk factors for chronic diseases are reported.