Hospital utilisation and the costs associated with complications of ICD implantation in a contemporary primary prevention cohort.

INTRODUCTION: Implantation of an implantable cardioverter defibrillator (ICD) is standard care for primary prevention of sudden cardiac death. However, ICD-related complications are increasing as the population of ICD recipients grows. METHODS: ICD-related complications in a national DO-IT Registry cohort of 1442 primary prevention ICD patients were assessed in terms of additional use of hospital care resources and costs. RESULTS: During a median follow-up of 28.7 months (IQR 25.2-33.7) one or more complications occurred in 13.5% of patients. A complication resulted in a surgical intervention in 53% of cases and required on average 3.65 additional hospital days. The additional hospital costs were €6,876 per complication or €8,110 per patient, to which clinical re-interventions and additional hospital days contributed most. Per category of complications, infections required most hospital utilisation and were most expensive at an average of €22,892. The mean costs were €5,800 for lead-related complications, €2,291 for pocket-related complications and €5,619 for complications due to other causes. We estimate that the total yearly incidence-based costs in the Netherlands for hospital management of ICD-related complications following ICD implantation for primary prevention are €2.7 million. CONCLUSION: Complications following ICD implantation are related to a substantial additional need for hospital resources. When performing cost-effectiveness analyses of ICD implantation, including the costs associated with complications, one should be aware that real-world complication rates may deviate from trial data. Considering the economic implications, strategies to reduce the incidence of complications are encouraged.

Optimal postoperative pain management after VATS lung resection by thoracic epidural analgesia, continuous paravertebral block or single-shot intercostal nerve block (OPtriAL): study protocol of a three-arm multicentre randomised controlled trial.

BACKGROUND: Adequate pain control after video-assisted thoracoscopic surgery (VATS) for lung resection is important to improve postoperative mobilisation, recovery, and to prevent pulmonary complications. So far, no consensus exists on optimal postoperative pain management after VATS anatomic lung resection. Thoracic epidural analgesia (TEA) is the reference standard for postoperative pain management following VATS. Although the analgesic effect of TEA is clear, it is associated with patient immobilisation, bladder dysfunction and hypotension which may result in delayed recovery and longer hospitalisation. These disadvantages of TEA initiated the development of unilateral regional techniques for pain management. The most frequently used techniques are continuous paravertebral block (PVB) and single-shot intercostal nerve block (ICNB). We hypothesize that using either PVB or ICNB is non-inferior to TEA regarding postoperative pain and superior regarding quality of recovery (QoR). Signifying faster postoperative mobilisation, reduced morbidity and shorter hospitalisation, these techniques may therefore reduce health care costs and improve patient satisfaction. METHODS: This multi-centre randomised study is a three-arm clinical trial comparing PVB, ICNB and TEA in a 1:1:1 ratio for pain (non-inferiority) and QoR (superiority) in 450 adult patients undergoing VATS anatomic lung resection. Patients will not be eligible for inclusion in case of contraindications for TEA, PVB or ICNB, chronic opioid use or if the lung surgeon estimates a high probability that the operation will be performed by thoracotomy. PRIMARY OUTCOMES: (1) the proportion of pain scores ≥ 4 as assessed by the numerical rating scale (NRS) measured during postoperative days (POD) 0-2; and (2) the QoR measured with the QoR-15 questionnaire on POD 1 and 2. Secondary outcome measures are cumulative use of opioids and analgesics, postoperative complications, hospitalisation, patient satisfaction and degree of mobility. DISCUSSION: The results of this trial will impact international guidelines with respect to perioperative care optimization after anatomic lung resection performed through VATS, and will determine the most cost-effective pain strategy and may reduce variability in postoperative pain management. Trial registration The trial is registered at the Netherlands Trial Register (NTR) on February 1st, 2021 (NL9243). The NTR is no longer available since June 24th, 2022 and therefore a revised protocol has been registered at ClinicalTrials.gov on August 5th, 2022 (NCT05491239). PROTOCOL VERSION: version 3 (date 06-05-2022), ethical approval through an amendment (see ethical proof in the Study protocol proof).

Cost-effectiveness of immediate total-body CT in patients with severe trauma (REACT-2 trial).

BACKGROUND: The effect of immediate total-body CT (iTBCT) on health economic aspects in patients with severe trauma is an underreported issue. This study determined the cost-effectiveness of iTBCT compared with conventional radiological imaging with selective CT (standard work-up (STWU)) during the initial trauma evaluation. METHODS: In this multicentre RCT, adult patients with a high suspicion of severe injury were randomized in-hospital to iTBCT or STWU. Hospital healthcare costs were determined for the first 6 months after the injury. The probability of iTBCT being cost-effective was calculated for various levels of willingness-to-pay per extra patient alive. RESULTS: A total of 928 Dutch patients with complete clinical follow-up were included. Mean costs of hospital care were €25 809 (95 per cent bias-corrected and accelerated (bca) c.i. €22 617 to €29 137) for the iTBCT group and €26 155 (€23 050 to €29 344) for the STWU group, a difference per patient in favour of iTBCT of €346 (€4987 to €4328) (P = 0.876). Proportions of patients alive at 6 months were not different. The proportion of patients alive without serious morbidity was 61.6 per cent in the iTBCT group versus 66.7 per cent in the STWU group (difference -5.1 per cent; P = 0.104). The probability of iTBCT being cost-effective in keeping patients alive remained below 0.56 for the whole group, but was higher in patients with multiple trauma (0.8-0.9) and in those with traumatic brain injury (more than 0.9). CONCLUSION: Economically, from a hospital healthcare provider perspective, iTBCT should be the diagnostic strategy of first choice in patients with multiple trauma or traumatic brain injury.

Observational versus antibiotic treatment for uncomplicated diverticulitis: an individual-patient data meta-analysis.

BACKGROUND: Two RCTs (AVOD and DIABOLO) demonstrated no difference in recovery or adverse outcomes when antibiotics for acute uncomplicated diverticulitis were omitted. Both trials showed non-significantly higher rates of complicated diverticulitis and surgery in the non-antibiotic groups. This meta-analysis of individual-patient data aimed to explore adverse outcomes and identify patients at risk who may benefit from antibiotic treatment. METHODS: Individual-patient data from those with uncomplicated diverticulitis from two RCTs were pooled. Risk factors for adverse outcomes and the effect of observational management were assessed using logistic regression analyses. P < 0·025 was considered statistically significant owing to multiple testing adjustment. RESULTS: In total, 545 patients in the observational group and 564 in the antibiotics group were included. No statistical differences were found in 1-year follow-up rates of ongoing diverticulitis (7·2 versus 5·0 per cent in observation versus antibiotics groups respectively; P = 0·062), recurrent diverticulitis (8·6 versus 9·6 per cent; P = 0·610), complicated diverticulitis (4·0 versus 2·1 per cent; P = 0·079) and sigmoid resection (5·0 versus 2·5 per cent; P = 0·214). An initial pain score greater than 7, white blood cell count exceeding 13·5 × 109 /l and previous diverticulitis at presentation were risk factors for adverse outcomes. Antibiotic treatment did not prevent adverse outcomes in patients at high risk of adverse events. CONCLUSION: Observational management of acute uncomplicated diverticulitis is safe. Some statistical uncertainty remains, depending on the thresholds of clinical relevance, owing to small differences, but no subgroup that would benefit from antibiotic treatment was apparent.

ANTECEDENTES: Dos ensayos clínicos aleatorizados y controlados (randomized controlled trials, RCTc) (AVOD y DIABOLO) no mostraron diferencias en la recuperación ni en los resultados adversos al tratar la diverticulitis aguda no complicada sin antibióticos. Ambos ensayos mostraron tasas más altas, estadísticamente no significativas, de diverticulitis complicada y cirugía en los grupos sin antibióticos. Este metaanálisis de datos individuales de pacientes tuvo como objetivo explorar resultados adversos e identificar pacientes en riesgo que pudieran beneficiarse del tratamiento con antibióticos. MÉTODOS: Se agruparon los datos individuales de pacientes con diverticulitis no complicada de dos RCT. Los factores de riesgo para los resultados adversos y el efecto del tratamiento observacional (sin antibióticos) se evaluaron mediante un análisis de regresión logística. Una P < 0,025 se consideró estadísticamente significativa debido al ajuste de múltiples comparaciones. RESULTADOS: En total, se incluyeron 545 pacientes en el grupo de observación y 564 pacientes en el grupo de tratamiento antibiótico. No se encontraron diferencias estadísticamente significativas (observación versus antibióticos, respectivamente) en el seguimiento a 1 año en los porcentajes de diverticulitis persistente (7,2% versus 5,0%; P = 0,062), diverticulitis recurrente (8,6% versus 9,6%; P = 0,610), diverticulitis complicada (4,0% versus 2,1%; P = 0,079) y resección sigmoidea (5,0% versus 2,5%; P = 0,214). Una puntuación de dolor inicial > 7, un recuento leucocitario > 13,5 x 109 /L y los antecedentes de diverticulitis fueron factores de riesgo para un resultado adverso. El tratamiento con antibióticos no previno los resultados adversos en pacientes con alto riesgo. CONCLUSIÓN: El tratamiento de la diverticulitis aguda no complicada basado en la observación es seguro. No obstante, persiste una cierta incertidumbre desde el punto de vista estadístico, dependiendo de los umbrales de relevancia clínica, debido a pequeñas diferencias, pero no fue evidente ningún subgrupo que se pudiera beneficiar del tratamiento con antibióticos.

Protocol of a randomized open label multicentre trial comparing continuous intrajejunal levodopa infusion with deep brain stimulation in Parkinson's disease - the INfusion VErsus STimulation (INVEST) study.

BACKGROUND: Both Deep Brain Stimulation (DBS) and Continuous intrajejunal Levodopa Infusion (CLI) are effective therapies for the treatment of Parkinson's disease (PD). To our knowledge, no direct head-to-head comparison of DBS and CLI has been performed, whilst the costs probably differ significantly. In the INfusion VErsus STimulation (INVEST) study, costs and effectiveness of DBS and CLI are compared in a randomized controlled trial (RCT) in patients with PD, to study whether higher costs of one of the therapies are justified by superiority of that treatment. METHODS: A prospective open label multicentre RCT is being performed, with ancillary patient preference observational arms. Patients with PD who, despite optimal pharmacological treatment, have severe response fluctuations, bradykinesia, dyskinesias, or painful dystonia are eligible for inclusion. A total of 66 patients will be randomized. There is no minimal inclusion in the patient preference arms. The primary health economic outcomes are costs per unit on the Parkinson's Disease Questionnaire-39 (PDQ-39) and costs per unit Quality-Adjusted Life Year (QALY) at 12 months. The main clinical outcome is patient-reported quality of life measured with the PDQ-39 at 12 months. Patients will additionally be followed during 36 months after initiation of the study treatment. DISCUSSION: The INVEST trial directly compares the costs and effectiveness of the advanced therapies DBS and CLI. TRIAL REGISTRATION: Dutch Trial Register identifier 4753, registered November 3rd, 2014; EudraCT number 2014-001501-32, Clinicaltrials.gov: NCT02480803.

Costs and quality of life in a randomized trial comparing minimally invasive and open distal pancreatectomy (LEOPARD trial).

BACKGROUND: Minimally invasive distal pancreatectomy decreases time to functional recovery compared with open distal pancreatectomy, but the cost-effectiveness and impact on disease-specific quality of life have yet to be established. METHODS: The LEOPARD trial randomized patients to minimally invasive (robot-assisted or laparoscopic) or open distal pancreatectomy in 14 Dutch centres between April 2015 and March 2017. Use of hospital healthcare resources, complications and disease-specific quality of life were recorded up to 1 year after surgery. Unit costs of hospital healthcare resources were determined, and cost-effectiveness and cost-utility analyses were performed. Primary outcomes were the costs per day earlier functional recovery and per quality-adjusted life-year. RESULTS: All 104 patients who had a distal pancreatectomy (48 minimally invasive and 56 open) in the trial were included in this study. Patients who underwent a robot-assisted procedure were excluded from the cost analysis. Total medical costs were comparable after laparoscopic and open distal pancreatectomy (mean difference €-427 (95 per cent bias-corrected and accelerated confidence interval €-4700 to 3613; P = 0·839). Laparoscopic distal pancreatectomy was shown to have a probability of at least 0·566 of being more cost-effective than the open approach at a willingness-to-pay threshold of €0 per day of earlier recovery, and a probability of 0·676 per additional quality-adjusted life-year at a willingness-to-pay threshold of €80 000. There were no significant differences in cosmetic satisfaction scores (median 9 (i.q.r. 5·75-10) versus 7 (4-8·75); P = 0·056) and disease-specific quality of life after minimally invasive (laparoscopic and robot-assisted procedures) versus open distal pancreatectomy. CONCLUSION: Laparoscopic distal pancreatectomy was at least as cost-effective as open distal pancreatectomy in terms of time to functional recovery and quality-adjusted life-years. Cosmesis and quality of life were similar in the two groups 1 year after surgery.

Long-Term Effects of Omitting Antibiotics in Uncomplicated Acute Diverticulitis.

BACKGROUND: Traditionally uncomplicated acute diverticulitis was routinely treated with antibiotics, although evidence for this strategy was lacking. Recently, two randomized clinical trials (AVOD trial and DIABOLO trial) published short-term results of omitting antibiotics compared to routine antibiotic treatment. Both showed no significant differences regarding recovery from the initial episode, as well as rates of complicated or recurrent diverticulitis and sigmoid resection. However, both studies showed a trend of higher rates of sigmoid resection in the observational groups. Here, the long-term effects of omitting antibiotics in first episode uncomplicated acute diverticulitis were assessed. METHODS: A total of 528 patients with CT-proven, primary, left-sided, uncomplicated acute diverticulitis were randomized to either an observational or an antibiotic treatment strategy (DIABOLO trial). Outcome measures were complicated diverticulitis, recurrent diverticulitis and sigmoid resection at 24 months' follow up. Differences between the groups were explored and risk factors were identified using multivariable logistic regression. RESULTS: Complete case analyses showed no difference in rates of recurrent diverticulitis (15.4% in the observational group versus 14.9% in the antibiotic group; p = 0.885), complicated diverticulitis (4.8% versus 3.3%; p = 0.403) and sigmoid resection (9.0% versus. 5.0%; p = 0.085). Young patients (<50 years) and patients with a pain score at presentation of 8 or higher on a visual analogue pain scale were at risk for complicated or recurrent diverticulitis. In this multivariable analysis, treatment type (with or without antibiotics) was not an independent predictor for complicated or recurrent diverticulitis. CONCLUSION: Omitting antibiotics in the treatment of uncomplicated acute diverticulitis did not result in more complicated diverticulitis, recurrent diverticulitis or sigmoid resections at long-term follow up. As the DIABOLO trial was not powered for these secondary outcome measures, some uncertainty remains whether (small) non-significant differences could be true associations.

Meta-analysis of in-hospital delay before surgery as a risk factor for complications in patients with acute appendicitis.

BACKGROUND: The traditional fear that every case of acute appendicitis will eventually perforate has led to the generally accepted emergency appendicectomy with minimized delay. However, emergency and thereby sometimes night-time surgery is associated with several drawbacks, whereas the consequences of surgery after limited delay are unclear. This systematic review aimed to assess in-hospital delay before surgery as risk factor for complicated appendicitis and postoperative morbidity in patients with acute appendicitis. METHODS: PubMed and EMBASE were searched from 1990 to 2016 for studies including patients who underwent appendicectomy for acute appendicitis, reported in two or more predefined time intervals. The primary outcome measure was complicated appendicitis after surgery (perforated or gangrenous appendicitis); other outcomes were postoperative surgical-site infection and morbidity. Adjusted odds ratios (ORs) were pooled using forest plots if possible. Unadjusted data were pooled using generalized linear mixed models. RESULTS: Forty-five studies with 152 314 patients were included. Pooled adjusted ORs revealed no significantly higher risk for complicated appendicitis when appendicectomy was delayed for 7-12 or 13-24 h (OR 1·07, 95 per cent c.i. 0·98 to 1·17, and OR 1·09, 0·95 to 1·24, respectively). Meta-analysis of unadjusted data supported these findings by yielding no increased risk for complicated appendicitis or postoperative complications with a delay of 24-48 h. CONCLUSION: This meta-analysis demonstrates that delaying appendicectomy for presumed uncomplicated appendicitis for up to 24 h after admission does not appear to be a risk factor for complicated appendicitis, postoperative surgical-site infection or morbidity. Delaying appendicectomy for up to 24 h may be an acceptable alternative for patients with no preoperative signs of complicated appendicitis.

A randomized controlled trial of a skills training for oncologists and a communication aid for patients to stimulate shared decision making about palliative systemic treatment (CHOICE): study protocol.

BACKGROUND: Systemic treatment for advanced cancer offers uncertain and sometimes little benefit while the burden can be high. Hence, treatment decisions require Shared Decision Making (SDM). The CHOICE trial examines the separate and combined effect of oncologist training and a patient communication aid on SDM in consultations about palliative systemic treatment. METHODS: A RCT design with four parallel arms will be adopted. Patients with metastatic or irresectable cancer with a median life expectancy <12 months who meet with a medical oncologist to discuss the start or continuation of palliative systemic treatment are eligible. A total of 24 oncologists (in training) and 192 patients will be recruited. The oncologist training consists of a reader, two group sessions (3.5 h; including modelling videos and role play), a booster feedback session (1 h) and a consultation room tool. The patient communication aid consists of a home-sent question prompt list and a value clarification exercise to prepare patients for SDM in the consultation. The control condition consists of care as usual. The primary outcome is observed SDM in audio-recorded consultations. Secondary outcomes include patient and oncologist evaluation of communication and decision-making, the decision made, quality of life, potential adverse outcomes such as anxiety and hopelessness, and consultation duration. Patients fill out questionnaires at baseline (T0), before (T1) and after the consultation (T2) and at 3 and 6 months (T3 and T4). All oncologists participate in two standardized patient assessments (before-after training) prior to the start of patient inclusion. They will fill out a questionnaire before and after these assessments, as well as after each of the recorded consultations in clinical practice. DISCUSSION: The CHOICE trial will enable evidence-based choices regarding the investment in SDM interventions targeting either oncologists, patients or both in the advanced cancer setting. The trial takes into account the immediate effect of the interventions on observed communication, but also on more distal and potential adverse patient outcomes. Also, the trial provides evidence regarding the assumption that SDM about palliative cancer treatment results in less aggressive treatment and more quality of life in the final period of life. TRIAL REGISTRATION: Netherlands Trial Registry number NTR5489 (prospective; 15 Sep 2015).

Randomized clinical trial of observational versus antibiotic treatment for a first episode of CT-proven uncomplicated acute diverticulitis.

BACKGROUND: Antibiotics are advised in most guidelines on acute diverticulitis, despite a lack of evidence to support their routine use. This trial compared the effectiveness of a strategy with or without antibiotics for a first episode of uncomplicated acute diverticulitis. METHODS: Patients with CT-proven, primary, left-sided, uncomplicated, acute diverticulitis were included at 22 clinical sites in the Netherlands, and assigned randomly to an observational or antibiotic treatment strategy. The primary endpoint was time to recovery during 6 months of follow-up. Main secondary endpoints were readmission rate, complicated, ongoing and recurrent diverticulitis, sigmoid resection and mortality. Intention-to-treat and per-protocol analyses were done. RESULTS: A total of 528 patients were included. Median time to recovery was 14 (i.q.r. 6-35) days for the observational and 12 (7-30) days for the antibiotic treatment strategy, with a hazard ratio for recovery of 0·91 (lower limit of 1-sided 95 per cent c.i. 0·78; P = 0·151). No significant differences between the observation and antibiotic treatment groups were found for secondary endpoints: complicated diverticulitis (3·8 versus 2·6 per cent respectively; P = 0·377), ongoing diverticulitis (7·3 versus 4·1 per cent; P = 0·183), recurrent diverticulitis (3·4 versus 3·0 per cent; P = 0·494), sigmoid resection (3·8 versus 2·3 per cent; P = 0·323), readmission (17·6 versus 12·0 per cent; P = 0·148), adverse events (48·5 versus 54·5 per cent; P = 0·221) and mortality (1·1 versus 0·4 per cent; P = 0·432). Hospital stay was significantly shorter in the observation group (2 versus 3 days; P = 0·006). Per-protocol analyses were concordant with the intention-to-treat analyses. CONCLUSION: Observational treatment without antibiotics did not prolong recovery and can be considered appropriate in patients with uncomplicated diverticulitis. Registration number: NCT01111253 (http://www.clinicaltrials.gov).

High rates of clinically relevant incidental findings by total-body CT scanning in trauma patients; results of the REACT-2 trial.

OBJECTIVES: To determine whether there is a difference in frequency and clinical relevance of incidental findings detected by total-body computed tomography scanning (TBCT) compared to those by the standard work-up (STWU) with selective computed tomography (CT) scanning. METHODS: Trauma patients from five trauma centres were randomized between April 2011 and January 2014 to TBCT imaging or STWU consisting of conventional imaging with selective CT scanning. Incidental findings were divided into three categories: 1) major finding, may cause mortality; 2) moderate finding, may cause morbidity; and 3) minor finding, hardly relevant. Generalized estimating equations were applied to assess differences in incidental findings. RESULTS: In total, 1083 patients were enrolled, of which 541 patients (49.9 %) were randomized for TBCT and 542 patients (50.1 %) for STWU. Major findings were detected in 23 patients (4.3 %) in the TBCT group compared to 9 patients (1.7 %) in the STWU group (adjusted rate ratio 2.851; 95%CI 1.337-6.077; p < 0.007). Findings of moderate relevance were detected in 120 patients (22.2 %) in the TBCT group compared to 86 patients (15.9 %) in the STWU group (adjusted rate ratio 1.421; 95%CI 1.088-1.854; p < 0.010). CONCLUSIONS: Compared to selective CT scanning, more patients with clinically relevant incidental findings can be expected by TBCT scanning. KEY POINTS: • Total-body CT scanning in trauma results in 1.5 times more incidental findings. • Evaluation by TBCT in trauma results in more patients with incidental findings. • In every category of clinical relevance, TBCT detects more incidental findings.

Home visits as part of a new care pathway (iAID) to improve quality of care and quality of life in ostomy patients: a cluster-randomized stepped-wedge trial.

AIM: Morbidity in patients with an ostomy is high. A new care pathway, including perioperative home visits by enterostomal therapists, was studied to assess whether more elaborate education and closer guidance could reduce stoma-related complications and improve quality of life (QoL), at acceptable cost. METHOD: Patients requiring an ileostomy or colostomy, for any inflammatory or malignant bowel disease, were included in a 15-centre cluster-randomized 'stepped-wedge' study. Primary outcomes were stoma-related complications and QoL, measured using the Stoma-QOL, 3 months after surgery. Secondary outcomes included costs of care. RESULTS: The standard pathway (SP) was followed by 113 patients and the new pathway (NP) by 105 patients. Although the overall number of stoma-related complications was similar in both groups (SP 156, NP 150), the proportion of patients experiencing one or more stoma-related complications was significantly higher in the NP (72% vs 84%, risk difference 12%; 95% CI: 0.3-23.3%). Although in the NP more patients had stoma-related complications, QoL scores were significantly better (P < 0.001). In the SP more patients required extra care at home for their ostomy than in the NP (60.6% vs 33.7%, respectively; risk difference 26.9%, 95% CI: 13.5-40.4%). Stoma revision was done more often in the SP (n = 11) than in the NP (n = 2). Total costs in the SP did not differ significantly from the NP. CONCLUSION: The NP did not reduce the number of stoma-related complications but did lead to improved quality of care and life, against similar costs. Based on these results the NP, including perioperative home visits by an enterostomal therapist, can be recommended.

Dutch outcome in implantable cardioverter-defibrillator therapy (DO-IT): registry design and baseline characteristics of a prospective observational cohort study to predict appropriate indication for implantable cardioverter-defibrillator.

BACKGROUND: Implantable cardioverter-defibrillators (ICDs) are widely used for the prevention of sudden cardiac death. At present, both clinical benefit and cost-effectiveness of ICD therapy in primary prevention patients are topics of discussion, as only a minority of these patients will eventually receive appropriate ICD therapy. METHODS/DESIGN: The DO-IT Registry is a nationwide prospective cohort with a target enrolment of 1,500 primary prevention ICD patients with reduced left ventricular function in a setting of structural heart disease. The primary outcome measures are death and appropriate ICD therapy for ventricular tachyarrhythmias. Secondary outcome measures are inappropriate ICD therapy, death of any cause, hospitalisation for ICD related complications and for cardiovascular reasons. As of December 2016, data on demographic, clinical, and ICD characteristics of 1,468 patients have been collected. Follow-up will continue up to 24 months after inclusion of the last patient. During follow-up, clinical and ICD data are collected based on the normal follow-up of these patients, assuming ICD interrogations take place every six months and clinical follow-up is once a year. At baseline, the mean age was 66 (standard deviation [SD] 10) years and 27% were women. CONCLUSION: The DO-IT Registry represents a real-world nationwide cohort of patients receiving ICDs for primary prevention of sudden cardiac death with reduced left ventricular function in a setting of structural heart disease. The registry investigates the efficacy of the current practice and aims to develop prediction rules to identify subgroups who will not (sufficiently) benefit from ICD implantation and to provide results regarding costs and budget impact of targeted supply of primary preventions ICDs.

A multicentre comparative prospective blinded analysis of EUS and MRI for screening of pancreatic cancer in high-risk individuals.

OBJECTIVE: Endoscopic ultrasonography (EUS) and MRI are promising tests to detect precursors and early-stage pancreatic ductal adenocarcinoma (PDAC) in high-risk individuals (HRIs). It is unclear which screening technique is to be preferred. We aimed to compare the efficacy of EUS and MRI in their ability to detect clinically relevant lesions in HRI. DESIGN: Multicentre prospective study. The results of 139 asymptomatic HRI (>10-fold increased risk) undergoing first-time screening by EUS and MRI are described. Clinically relevant lesions were defined as solid lesions, main duct intraductal papillary mucinous neoplasms and cysts ≥10 mm. Results were compared in a blinded, independent fashion. RESULTS: Two solid lesions (mean size 9 mm) and nine cysts ≥10 mm (mean size 17 mm) were detected in nine HRI (6%). Both solid lesions were detected by EUS only and proved to be a stage I PDAC and a multifocal pancreatic intraepithelial neoplasia 2. Of the nine cysts ≥10 mm, six were detected by both imaging techniques and three were detected by MRI only. The agreement between EUS and MRI for the detection of clinically relevant lesions was 55%. Of these clinically relevant lesions detected by both techniques, there was a good agreement for location and size. CONCLUSIONS: EUS and/or MRI detected clinically relevant pancreatic lesions in 6% of HRI. Both imaging techniques were complementary rather than interchangeable: contrary to EUS, MRI was found to be very sensitive for the detection of cystic lesions of any size; MRI, however, might have some important limitations with regard to the timely detection of solid lesions.

Cost-effectiveness of same-admission versus interval cholecystectomy after mild gallstone pancreatitis in the PONCHO trial.

BACKGROUND: Same-admission cholecystectomy is indicated after gallstone pancreatitis to reduce the risk of recurrent disease or other gallstone-related complications, but its impact on overall costs is unclear. This study analysed the cost-effectiveness of same-admission versus interval cholecystectomy after mild gallstone pancreatitis. METHODS: In a multicentre RCT (Pancreatitis of biliary Origin: optimal timiNg of CHOlecystectomy; PONCHO) patients with mild gallstone pancreatitis were randomized before discharge to either cholecystectomy within 72 h (same-admission cholecystectomy) or cholecystectomy after 25-30 days (interval cholecystectomy). Healthcare use of all patients was recorded prospectively using clinical report forms. Unit costs of resources used were determined, and patients completed multiple Health and Labour Questionnaires to record pancreatitis-related absence from work. Cost-effectiveness analyses were performed from societal and healthcare perspectives, with the costs per readmission prevented as primary outcome with a time horizon of 6 months. RESULTS: All 264 trial participants were included in the present analysis, 128 randomized to same-admission cholecystectomy and 136 to interval cholecystectomy. Same-admission cholecystectomy reduced the risk of acute readmission for recurrent gallstone-related complications from 16·9 to 4·7 per cent (P = 0·002). Mean total costs from a societal perspective were €234 (95 per cent c.i. -1249 to 738) less per patient in the same-admission cholecystectomy group. Same-admission cholecystectomy was superior to interval cholecystectomy, with a societal incremental cost-effectiveness ratio of -€1918 to prevent one readmission for gallstone-related complications. CONCLUSION: In mild biliary pancreatitis, same-admission cholecystectomy was more effective and less costly than interval cholecystectomy.

A multi-centred randomised trial of radical surgery versus adjuvant chemoradiotherapy after local excision for early rectal cancer.

BACKGROUND: Rectal cancer surgery is accompanied with high morbidity and poor long term functional outcome. Screening programs have shown a shift towards more early staged cancers. Patients with early rectal cancer can potentially benefit significantly from rectal preserving therapy. For the earliest stage cancers, local excision is sufficient when the risk of lymph node disease and subsequent recurrence is below 5 %. However, the majority of early cancers are associated with an intermediate risk of lymph node involvement (5-20 %) suggesting that local excision alone is not sufficient, while completion radical surgery, which is currently standard of care, could be a substantial overtreatment for this group of patients. METHODS/STUDY DESIGN: In this multicentre randomised trial, patients with an intermediate risk T1-2 rectal cancer, that has been locally excised using an endoluminal technique, will be randomized between adjuvant chemo-radiotherapylimited to the mesorectum and standard completion total mesorectal excision (TME). To strictly monitor the risk of locoregional recurrence in the experimental arm and enable early salvage surgery, there will be additional follow up with frequent MRI and endoscopy. The primary outcome of the study is three-year local recurrence rate. Secondary outcomes are morbidity, disease free and overall survival, stoma rate, functional outcomes, health related quality of life and costs. The design is a non inferiority study with a total sample size of 302 patients. DISCUSSION: The results of the TESAR trial will potentially demonstrate that adjuvant chemoradiotherapy is an oncological safe treatment option in patients who are confronted with the difficult clinical dilemma of a radically removed intermediate risk early rectal cancer by polypectomy or transanal surgery that is conventionally treated with subsequent radical surgery. Preserving the rectum using adjuvant radiotherapy is expected to significantly improve morbidity, function and quality of life if compared to completion TME surgery. TRIAL REGISTRATION: NCT02371304 , registration date: February 2015.

A randomized controlled trial to compare a restrictive strategy to usual care for the effectiveness of cholecystectomy in patients with symptomatic gallstones (SECURE trial protocol).

BACKGROUND: Five to 22 % of the adult Western population has gallstones. Among them, 13 to 22 % become symptomatic during their lifetime. Cholecystectomy is the preferred treatment for symptomatic cholecystolithiasis. Remarkably, cholecystectomy provides symptom relief in only 60-70 % of patients. The objective of this trial is to compare the effectiveness of usual (operative) care with a restrictive strategy using a standardized work-up with stepwise selection for cholecystectomy in patients with gallstones and abdominal complaints. DESIGN AND METHODS: The SECURE-trial is designed as a multicenter, randomized, parallel-arm, non-inferiority trial in patients with abdominal symptoms and ultrasound proven gallstones or sludge. If patients meet the inclusion criteria they will be randomized to either usual care or the restrictive strategy. Patients in the usual care group will be treated according to the physician's knowledge and preference. Patients in the restrictive care group will be treated with interval evaluation and stepwise selection for laparoscopic cholecystectomy. In this stepwise selection, patients strictly meeting the preselected criteria for symptomatic cholecystolithiasis will be offered a cholecystectomy. Patients not meeting these criteria will be assessed for other diagnoses and re-evaluated at 3-monthly intervals. Follow-up consists of web-based questionnaires at 3, 6, 9 and 12 months. The main end point of this trial is defined as the proportion of patients being pain-free at 12 months follow-up. Pain will be assessed with the Izbicki Pain Score and Gallstone Symptom Score. Secondary endpoints will be the proportion of patients with complications due to gallstones or cholecystectomy, the association between the patients' symptoms and treatment and work performance, and ultimately, cost-effectiveness. DISCUSSION: The SECURE trial is the first randomized controlled trial examining the effectiveness of usual care versus restrictive care in patients with symptomatic gallstones. The outcome of this trial will inform clinicians whether a more restrictive strategy can minimize persistent pain in post-operative patients at least as good as usual care does, but at a lower cholecystectomy rate. (The Netherlands National Trial Register NTR4022, 17th December 2012) TRIAL REGISTRATION: The Netherlands National Trial Register NTR4022 http://www.zonmw.nl/nl/projecten/project-detail/scrutinizing-inefficient-use-of-cholecystectomy-a-randomized-trial-concerning-variation-in-practi/samenvatting/.

Comparison of Imaging Strategies with Conditional versus Immediate Contrast-Enhanced Computed Tomography in Patients with Clinical Suspicion of Acute Appendicitis.

OBJECTIVES: To compare the diagnostic accuracy of conditional computed tomography (CT), i.e. CT when initial ultrasound findings are negative or inconclusive, and immediate CT for patients with suspected appendicitis. METHODS: Data were collected within a prospective diagnostic accuracy study on imaging in adults with acute abdominal pain. All patients underwent ultrasound and CT, read by different observers who were blinded from the other modality. Only patients with clinical suspicion of appendicitis were included. An expert panel assigned a final diagnosis to each patient after 6 months of follow-up (clinical reference standard). RESULTS: A total of 422 patients were included with final diagnosis appendicitis in 251 (60 %). For 199 patients (47 %), ultrasound findings were inconclusive or negative. Conditional CT imaging correctly identified 241 of 251 (96 %) appendicitis cases (95 %CI, 92 % to 98 %), versus 238 (95 %) with immediate CT (95 %CI, 91 % to 97 %). The specificity of conditional CT imaging was lower: 77 % (95 %CI, 70 % to 83 %) versus 87 % for immediate CT (95 %CI, 81 % to 91 %). CONCLUSION: A conditional CT strategy correctly identifies as many patients with appendicitis as an immediate CT strategy, and can halve the number of CTs needed. However, conditional CT imaging results in more false positives. KEY POINTS: • Conditional CT (CT after negative/inconclusive ultrasound findings) can be used for suspected appendicitis. • Half the number of CT examinations is needed with a conditional strategy. • Conditional CT correctly identifies as many patients with appendicitis as immediate CT. • Conditional imaging results in more false positive appendicitis cases.

Early reconstruction of the leaking ileal pouch-anal anastomosis: a novel solution to an old problem.

AIM: The study aimed to determine the effectiveness and direct medical costs of early surgical closure of the anastomotic defect after a short course of Endo-sponge® therapy of the presacral cavity, compared with conventional treatment in patients with anastomotic leakage after ileal pouch-anal anastomosis (IPAA). METHOD: Patients with anastomotic leakage after IPAA undergoing early surgical closure of the anastomotic defect after a short Endo-sponge® treatment were prospectively followed and compared with a consecutive cohort of patients with an anastomotic leak treated by creation of a loop ileostomy and occasional drainage of the presacral cavity. RESULTS: A total of 15 patients were treated with early surgical closure and 29 were treated conventionally. In the early surgical closure group, the Endo-sponge® treatment was continued for a median of 12 days [interquartile range (IQR) 7-15 days] with a median of 3 (IQR 2-4) Endo-sponge® changes. Secondary anastomotic healing was achieved in all patients (n = 15) in the early surgical closure group compared with 52% (n = 16) in the conventional treatment group (P = 0.003). Closure of the anastomotic defect was achieved after a median of 48 (25-103) days in the early surgical closure group compared with 70 (IQR 49-175) days in the conventional treatment group (P = 0.013). A functional pouch was seen in 93% and 86% of the patients in each group. There was no significant difference in direct medical cost. CONCLUSION: Early surgical closure after a short period of Endo-sponge® treatment is highly effective in treating anastomotic leakage after IPAA without increasing cost.

Long-term results of palliative stent placement for acute malignant colonic obstruction.

BACKGROUND: Endoscopic placement of self-expanding-metal-stents (SEMS) is widely performed as palliative treatment for acute malignant colonic obstruction. There is ongoing debate regarding risks and benefits associated with SEMS placement. This study aimed to evaluate long-term outcomes of palliative SEMS placement in patients presenting with acute malignant colonic obstruction. METHODS: A prospectively collected patient cohort (2005-2013) from a general teaching hospital was used. In this hospital, all consecutive patients presenting with acute malignant large bowel obstruction are treated with endoscopic SEMS placement. Only colon cancer patients who underwent palliative SEMS placement were selected. RESULTS: In total, 48 patients were included. The technical and short-term clinical success rates were 91 % (44/48) and 85 % (36/48), respectively. SEMS-related mortality occurred in 6/48 patients (13 %) (early n = 4, late n = 2) and was caused by SEMS-related perforation in all cases. The SEMS-related morbidity rate was 38 % (18/48) (early n = 7, late n = 11). Endoscopic re-intervention was performed 14 times and 13 patients eventually underwent surgical treatment during follow-up. The stoma-formation rate was 15 % (7/48). Long-term clinical success was 48 % (23/48). The estimated stent patency rate (95 % confidence interval) was 69 % (52-79) at 1 month, 54 % (37-66) at 6 months and 50 % (33-62) at 12 months. CONCLUSION: Palliative SEMS placement provides rapid relief of obstruction and avoids a stoma in most patients with acute colonic obstruction caused by incurable or inoperable colon cancer. However, these benefits should be weighed against mortality and morbidity related to SEMS placement.