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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. Patients' preferences on this topic have, however, been underexposed so far. Methods: An internet-based questionnaire was distributed among MEDIASTrial participants (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. A 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 Registration: Not applicable. [ABSTRACT FROM AUTHOR]

Background: The acute abdomen is a frequent entity at the Emergency Department (ED), which usually needs rapid and accurate diagnostic work-up. Diagnostic work-up with imaging can consist of plain X-ray, ultrasonography (US), computed tomography (CT) and even diagnostic laparoscopy. However, no evidence-based guidelines exist in current literature. The actual diagnostic work-up of a patient with acute abdominal pain presenting to the ED varies greatly between hospitals and physicians. The OPTIMA study was designed to provide the evidence base for constructing an optimal diagnostic imaging guideline for patients with acute abdominal pain at the ED. Methods/design: Thousand consecutive patients with abdominal pain > 2 hours and < 5 days will be enrolled in this multicentre trial. After clinical history, physical and laboratory examination all patients will undergo a diagnostic imaging protocol, consisting of plain X-ray (upright chest and supine abdomen), US and CT. The reference standard will be a post hoc assignment of the final diagnosis by an expert panel. The focus of the analysis will be on the added value of the imaging modalities over history and clinical examination, relative to the incremental costs. Discussion: This study aims to provide the evidence base for the development of a diagnostic algorithm that can act as a guideline for ED physicians to evaluate patients with acute abdominal pain. [ABSTRACT FROM AUTHOR]

Background: For the evaluation of severely injured trauma patients a variety of total body computed tomography (CT) scanning protocols exist. Frequently multiple pass protocols are used. A split bolus contrast protocol can reduce the number of passes through the body, and thereby radiation exposure, in this relatively young and vitally threatened population.Purpose: To evaluate three protocols for single pass total body scanning in 64-slice multidetector CT (MDCT) on optimal image quality.Material and Methods: Three total body CT protocols were prospectively evaluated in three series of 10 consecutive trauma patients. In Group A unenhanced brain and cervical spine CT was followed by chest-abdomen-pelvis CT in portovenous phase after repositioning of the arms. Group B underwent brain CT followed without arm repositioning by a one-volume contrast CT from skull base to the pubic symphysis. Group C was identical to Group A, but the torso was scanned with a split bolus technique. Three radiologists independently evaluated protocol quality scores (5-point Likert scale), parenchymal and vascular enhancement and artifacts.Results: Overall image quality was good (4.10) in Group A, more than satisfactory (3.38) in Group B, and nearly excellent (4.75) in Group C (P < 0.001). Interfering artifacts were mostly reported in Group B in the liver and spleen.Conclusion: In single pass total body CT scanning a split bolus technique reached the highest overall image quality compared to conventional total body CT and one-volume contrast CT. [ABSTRACT FROM AUTHOR]

Long-term complications and associated conditions of type 1 Gaucher Disease (GD) can include splenectomy, bone complications, pulmonary hypertension, Parkinson disease and malignancies. Enzyme replacement therapy (ERT) reverses cytopenia and reduces organomegaly. To study the effects of ERT on long-term complications and associated conditions, the course of Gaucher disease was modelled. [ABSTRACT FROM AUTHOR]

Background: The cost-effectiveness of enzyme replacement therapy (ERT) compared to standard medical care was evaluated in the Dutch cohort of patients with Fabry disease. Methods: Cost-effectiveness analysis was performed using a life-time state-transition model. Transition probabilities, effectiveness data and costs were derived from retrospective data and prospective follow-up of the Dutch study cohort consisting of males and females aged 5-78 years. Intervention with ERT (either agalsidase alfa or agalsidase beta) was compared to the standard medical care. The main outcome measures were years without end organ damage (renal, cardiac en cerebrovascular complications), quality adjusted life years (QALYs), and costs. Results: Over a 70 year lifetime, an untreated Fabry patient will generate 55.0 years free of end-organ damage (53.5 years in males, 56.9 years in females) and 48.6 QALYs (47.8 in males, 49.7 in females). Starting ERT in a symptomatic patient increases the number of years free of end-organ damage by 1.5 year (1.6 in males, 1.3 in females), while the number of QALYs gained increases by a similar amount (1.7 in males, 1.4 in females). The costs of ERT starting in the symptomatic stage are between €9 - €10 million (£ 7.9 - £ 8.8 million, $13.0- $14.5 million) during a patient's lifetime. Consequently, the extra costs per additional year free of end-organ damage and the extra costs per additional QALY range from €5.5 - €7.5 million (£ 4.8 - £ 6.6 million, $ 8.0 - $ 10.8 million), undiscounted. Conclusions: In symptomatic patients with Fabry disease, ERT has limited effect on quality of life and progression to end organ damage. The pharmaco-economic evaluation shows that this modest effectiveness drives the costs per QALY and the costs per year free of end-organ damage to millions of euros. Differentiation of patients who may benefit from ERT should be improved to enhance cost-effectiveness. [ABSTRACT FROM AUTHOR]

Summary: Background: Anal cancer is an increasing issue in HIV-positive men who have sex with men (MSM). Screening for its precursor, anal intraepithelial neoplasia (AIN), is subject of discussion. Current treatment options are suboptimum and have not been compared in a prospective trial. We compared efficacy and side-effects of imiquimod, topical fluorouracil, and electrocautery for the treatment of AIN. Methods: In this open-label randomised trial, we included HIV-positive MSM older than 18 years visiting the HIV outpatient clinic of the Academic Medical Center, Amsterdam, Netherlands. Patients with histologically confirmed AIN were randomly assigned to receive either 16 weeks of imiquimod (three times a week), 16 weeks of topical fluorouracil (twice a week), or monthly electrocautery for 4 months. Randomisation was done with random block sizes of three and six, stratified for AIN grade (AIN grades 1, 2, or 3) and AIN location (peri-anal or intra-anal). Participants were assessed by high-resolution anoscopy 4 weeks after treatment. Responding patients returned for follow-up 24 weeks, 48 weeks, and 72 weeks after treatment. The primary endpoint was histological resolution of AIN measured 4 weeks after treatment and AIN recurrence at week 24, week 48, and week 72 after treatment. The primary analysis was done in a modified intention-to-treat population, including all patients who had received their assigned treatment at least once. The trial is registered at the Netherlands Trial Register, number NTR1236. Findings: Between Aug 12, 2008, and Dec 1, 2010, we screened 388 HIV-positive MSM for AIN by high resolution anoscopy. Of the 246 (63%) patients who had AIN, 156 (63%) were randomly assigned to either receive imiquimod (54 patients), topical fluorouracil (48 patients), or electrocautery (46 patients) following withdrawing of consent by eight patients. Modified intention-to-treat analysis showed a complete response in 13 (24%, 95% CI 15–37) patients in the imiquimod group, eight (17%, 8–30) of patients in the fluorouracil group, and 18 (39%, 26–54) of patients in the electrocautery group (p=0·027). At week 24, 11 (22%) of 50 responders had recurrence; at week 48, 22 (46%) of 48 had recurred; and at week 72, 30 (67%) of 45 had recurred. Recurrence was observed at 72 weeks in 10 (71%) of 14 patients treated with imiquimod, seven (58%) of 12 patients treated with fluorouracil, and 13 (68%) of 19 patients treated with electrocautery. Grade 3–4 side-effects were noted in 23 (43%) of 53 patients in the imiquimod group, 13 (27%) of 48 patients in the fluorouracil group, and eight (18%) patients in the electrocautery group (p=0·019). The most common side-effects were pain, bleeding, and itching. Seven serious adverse events occurred, all not related to the study. Interpretation: Electrocautery is better than imiquimod and fluorouracil in the treatment of AIN, but recurrence rates are substantial. Funding: Anna Maurits de Cock foundation provided funding for the video colposcope. [ABSTRACT FROM AUTHOR]

OBJECTIVES:Drug-induced pancreatitis (DIP) is considered a relative rare disease entity, perhaps due to lack of recognition. The objective of this study was to evaluate the prevalence of pancreatitis-associated drugs in a Dutch cohort of patients admitted for acute pancreatitis (AP) and to identify the proportion AP possibly attributable to the use of drugs.METHODS:This was a multicenter observational study (EARL study). Etiology, disease course, use of pancreatitis-associated drugs at hospital admittance, and discontinuation of these drugs were evaluated. Drugs were scored by means of an evidence-based DIP classification system.RESULTS:The first documented hospital admissions of 168 patients were analyzed. In all, 70 out of 168 (41.6%; 95% confidence interval (CI): 34.5-49.2%) patients used pancreatitis-associated drugs at admission. In 26.2% (44/168; 95% CI: 20.1-33.3%) of cases, at least one class I pancreatitis-associated drug was used. Possibly DIP was present in 12.5% (21/168; 95% CI: 8.3-18.4%); in less than half of these patients (9/21 or 42.9%; 95% CI: 24.5-63.5%), the prescribed drugs were actually discontinued, with no recurrence of AP later on. Among the remaining 12 patients without discontinuation of their drugs use and in absence of an alternative etiologic cause of AP, 8 patients used a class I pancreatitis-associated drug, representing 4.8% (8/168, 95% CI: 2.4-9.1%) of the total study population.CONCLUSIONS:In this series, a remarkably high percentage of patients who were admitted because of an attack of AP used pancreatitis-associated drugs. Physicians should be more aware of the possibility of DIP in patients with otherwise unexplained AP and act appropriately by discontinuation of the drug. [ABSTRACT FROM AUTHOR]

Summary: Background: Pulsed high-dose dexamethasone induced long-lasting remission in patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) in a pilot study. The PREDICT study aimed to compare remission rates in patients with CIDP treated with high-dose dexamethasone with rates in patients treated with standard oral prednisolone. Methods: In eight neuromuscular centres in the Netherlands and one in the UK, patients aged 18 years or older who had newly diagnosed definite or probable CIDP were randomly assigned to a treatment regimen of either pulsed high-dose dexamethasone or standard oral prednisolone. Randomisation was done with a random number generator. The primary outcome measure was remission at 12 months, defined as improvement of at least three points on the Rivermead mobility index and improvement of at least one point on the inflammatory neuropathy cause and treatment disability scale. Analysis was by intention to treat. This trial is registered with Current Controlled Trials, number ISRCTN07779236. Findings: Between December, 2003, and December, 2008, 40 patients were treated: 24 received dexamethasone and 16 received prednisolone. At 12 months, 16 patients were in remission: ten in the dexamethasone group and six in the prednisolone group (odds ratio [OR] 1·2, 95% CI 0·3–4·4). Most adverse events were minor and did not differ substantially between treatment groups; however, sleeplessness and Cushing''s face occurred more often in the prednisolone group. Interpretation: Pulsed high-dose dexamethasone treatment did not induce remission more often than prednisolone treatment. A substantial proportion of patients were in remission at 12 months in both treatment groups. High-dose dexamethasone could be considered as induction therapy in CIDP, but comparison with intravenous immunoglobulin treatment is needed. Funding: The Prinses Beatrix Fonds (MAR01-0213) and the Department of Neurology, Academic Medical Center. [Copyright &y& Elsevier]

Background: The peritoneum is the second most common site of recurrence in colorectal cancer. Early detection of peritoneal carcinomatosis (PC) by imaging is difficult. Patients eventually presenting with clinically apparent PC have a poor prognosis. Median survival is only about five months if untreated and the benefit of palliative systemic chemotherapy is limited. Only a quarter of patients are eligible for curative treatment, consisting of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CR/HIPEC). However, the effectiveness depends highly on the extent of disease and the treatment is associated with a considerable complication rate. These clinical problems underline the need for effective adjuvant therapy in high-risk patients to minimize the risk of outgrowth of peritoneal micro metastases. Adjuvant hyperthermic intraperitoneal chemotherapy (HIPEC) seems to be suitable for this purpose. Without the need for cytoreductive surgery, adjuvant HIPEC can be performed with a low complication rate and short hospital stay.Methods/design: The aim of this study is to determine the effectiveness of adjuvant HIPEC in preventing the development of PC in patients with colon cancer at high risk of peritoneal recurrence. This study will be performed in the nine Dutch HIPEC centres, starting in April 2015. Eligible for inclusion are patients who underwent curative resection for T4 or intra-abdominally perforated cM0 stage colon cancer. After resection of the primary tumour, 176 patients will be randomized to adjuvant HIPEC followed by routine adjuvant systemic chemotherapy in the experimental arm, or to systemic chemotherapy only in the control arm. Adjuvant HIPEC will be performed simultaneously or shortly after the primary resection. Oxaliplatin will be used as chemotherapeutic agent, for 30 min at 42-43 °C. Just before HIPEC, 5-fluorouracil and leucovorin will be administered intravenously. Primary endpoint is peritoneal disease-free survival at 18 months. Diagnostic laparoscopy will be performed routinely after 18 months postoperatively in both arms of the study in patients without evidence of disease based on routine follow-up using CT imaging and CEA.Discussion: Adjuvant HIPEC is assumed to reduce the expected 25 % absolute risk of PC in patients with T4 or perforated colon cancer to a risk of 10 %. This reduction is likely to translate into a prolonged overall survival.Trial Registration Number: NCT02231086 (Clinicaltrials.gov). [ABSTRACT FROM AUTHOR]

Background: Liver surgery in perihilar cholangiocarcinoma (PHC) is associated with high postoperative morbidity because the tumor typically causes biliary obstruction. Preoperative biliary drainage is used to create a safer environment prior to liver surgery, but biliary drainage may be harmful when severe drainage-related complications deteriorate the patients' condition or increase the risk of postoperative morbidity. Biliary drainage can cause cholangitis/cholecystitis, pancreatitis, hemorrhage, portal vein thrombosis, bowel wall perforation, or dehydration. Two methods of preoperative biliary drainage are mostly applied: endoscopic biliary drainage, which is currently used in most regional centers before referring patients for surgical treatment, and percutaneous transhepatic biliary drainage. Both methods are associated with severe drainage-related complications, but two small retrospective series found a lower incidence in the number of preoperative complications after percutaneous drainage compared to endoscopic drainage (18-25% versus 38-60%, respectively). The present study randomizes patients with potentially resectable PHC and biliary obstruction between preoperative endoscopic or percutaneous transhepatic biliary drainage.Methods/design: The study is a multi-center trial with an "all-comers" design, randomizing patients between endoscopic or percutaneous transhepatic biliary drainage. All patients selected to potentially undergo a major liver resection for presumed PHC are eligible for inclusion in the study provided that the biliary system in the future liver remnant is obstructed (even if they underwent previous inadequate endoscopic drainage). Primary outcome measure is the total number of severe preoperative complications between randomization and exploratory laparotomy. The study is designed to detect superiority of percutaneous drainage: a provisional sample size of 106 patients is required to detect a relative decrease of 50% in the number of severe preoperative complications (alpha = 0.95; beta = 0.8). Interim analysis after inclusion of 53 patients (50%) will provide the definitive sample size. Secondary outcome measures encompass the success of biliary drainage, quality of life, and postoperative morbidity and mortality.Discussion: The DRAINAGE trial is designed to identify a difference in the number of severe drainage-related complications after endoscopic and percutaneous transhepatic biliary drainage in patients selected to undergo a major liver resection for perihilar cholangiocarcinoma.Trial Registration: Netherlands Trial Register [ NTR4243 , 11 October 2013]. [ABSTRACT FROM AUTHOR]

Background: Stroke is a leading cause of death worldwide. Infections after stroke occur in 30% of stroke patients and are strongly associated with unfavourable outcome. Preventive antibiotic therapy lowers infection rate in patients after stroke, however, the effect of preventive antibiotic treatment on functional outcome after stroke has not yet been investigated.The Preventive Antibiotics in Stroke Study (PASS) is an ongoing, multicentre, prospective, randomised, open-label, blinded end point trial of preventive antibiotic therapy in acute stroke. Patients are randomly assigned to either ceftriaxone at a dose of 2 g, given every 24 hours intravenously for four-days, in addition to stroke-unit care, or standard stroke-unit care without preventive antibiotic therapy. Aim of the study is to assess whether preventive antibiotic treatment improves functional outcome at three months by preventing infections.Results: To date, 2,470 patients have been included in PASS. Median stroke severity of the first 2,133 patients (second interim analysis) is 5 (IQR 3 to 9) on the National Institutes of Health Stroke Scale (NIHSS). Due to the PROBE design, no outcome data are available yet. In the initial trial protocol we proposed a dichotomisation of the mRS as primary analysis of outcome and ordinal regression analysis as secondary analysis of primary outcome, requiring a sample size of 3,200 patients. However, ordinal analysis of outcome data is becoming increasingly more common in acute stroke trials, as it increases statistical power. For PASS, funding is insufficient for inclusion of 3,200 patients with the overall inclusion rate of 15 patients per week. Therefore we change the analysis of our primary outcome from dichotomisation to ordinal regression analysis on the mRS. Power analysis showed that with similar assumptions 2,550 patients are needed using ordinal regression analysis. We expect to complete follow-up in June 2014. A full statistical analysis plan will be submitted for publication before treatment allocation will be unblinded.Conclusion: The data from PASS will establish whether preventive antibiotic therapy in acute stroke improves functional outcome by preventing infection. In this update, we changed our primary outcome analysis from dichotomisation to ordinal regression analysis.Trial Registration: Current controlled trials; ISRCTN66140176. Date of registration: 6 April 2010. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the cost-effectiveness of enzyme replacement therapy (ERT) compared to standard medical care without ERT in the Dutch cohort of patients with type 1 Gaucher disease (GD I).Design: Cost-effectiveness analysis was performed using a life-time state-transition model of the disease's natural course. Transition probabilities, effectiveness data and costs were derived from retrospective data and prospective follow-up of the Dutch study cohort.Setting: The tertiary referral center for Gaucher disease in the Netherlands.Participants: The Dutch cohort of patients with GD I.Intervention: ERT versus standard medical care without ERT in symptomatic patients.Main Outcome Measures: Years free of end organ damage (YFEOD) (splenectomy, bone complication, malignancy, multiple complications), quality adjusted life years (QALY), and costs.Results: Over an 85 year lifetime, an untreated GD I patient will generate 48.9 YFEOD and 55.86 QALYs. Starting ERT in a symptomatic patient increases the YFEOD by 12.8 years, while the number of QALYs gained increases by 6.27. The average yearly ERT medication costs range between € 124,000 and € 258,000 per patient. The lifetime costs of ERT starting in the symptomatic stage are € 5,716,473 against € 171,780 without ERT, a difference of € 5,544,693. Consequently, the extra costs per additional YFEOD or per additional QALY are € 434,416 and € 884,994 respectively. After discounting effects by 1.5% and costs by 4% and under a reasonable scenario of ERT unit cost reduction by 25%, these incremental cost-effectiveness ratios could decrease to € 149,857 and € 324,812 respectively.Discussion: ERT is a highly potential drug for GD I with substantial health gains. The conservatively estimated incremental cost-effectiveness ratios are substantially lower than for Pompe and Fabry disease. We suggest that the high effectiveness has contributed importantly to acceptance of reimbursement of ERT for GD I. The present study may further support discussions on acceptable price limits for ultra-orphan products. [ABSTRACT FROM AUTHOR]

Background: The cost-effectiveness of enzyme replacement therapy (ERT) compared to standard medical care was evaluated in the Dutch cohort of patients with Fabry disease.Methods: Cost-effectiveness analysis was performed using a life-time state-transition model. Transition probabilities, effectiveness data and costs were derived from retrospective data and prospective follow-up of the Dutch study cohort consisting of males and females aged 5-78 years. Intervention with ERT (either agalsidase alfa or agalsidase beta) was compared to the standard medical care. The main outcome measures were years without end organ damage (renal, cardiac en cerebrovascular complications), quality adjusted life years (QALYs), and costs.Results: Over a 70 year lifetime, an untreated Fabry patient will generate 55.0 years free of end-organ damage (53.5 years in males, 56.9 years in females) and 48.6 QALYs (47.8 in males, 49.7 in females). Starting ERT in a symptomatic patient increases the number of years free of end-organ damage by 1.5 year (1.6 in males, 1.3 in females), while the number of QALYs gained increases by a similar amount (1.7 in males, 1.4 in females). The costs of ERT starting in the symptomatic stage are between €9 - €10 million (£ 7.9 - £ 8.8 million, $13.0- $14.5 million) during a patient's lifetime. Consequently, the extra costs per additional year free of end-organ damage and the extra costs per additional QALY range from €5.5 - €7.5 million (£ 4.8 - £ 6.6 million, $ 8.0 - $ 10.8 million), undiscounted.Conclusions: In symptomatic patients with Fabry disease, ERT has limited effect on quality of life and progression to end organ damage. The pharmaco-economic evaluation shows that this modest effectiveness drives the costs per QALY and the costs per year free of end-organ damage to millions of euros. Differentiation of patients who may benefit from ERT should be improved to enhance cost-effectiveness. [ABSTRACT FROM AUTHOR]

Background: Adverse drug events (ADEs) are a considerable cause of inhospital morbidity and mortality. Patient flow differs substantially for surgical and nonsurgical patients: surgical patients are subjected to multiple medication changes related to surgical intervention or postoperative care. The objective of this study is to systematically review the occurrence and nature of ADEs in surgical patients. Also, a comparison with nonsurgical patients was made.Methods: A search was conducted in Embase and Medline identifying studies that reported observational data on the occurrence and nature of ADEs in surgical hospitalised adult patients. If sufficient data were available, the occurrence of (preventable) ADEs was compared between surgical and nonsurgical patients.Results: Six studies fulfilled the inclusion criteria. The occurrence of ADEs in surgical patients ranged from 2.0 to 27.7 per 100 admissions, from 4.7 to 8.9 per 1,000 patient days, or involved 8.9% of the patients. Proportions of preventable ADEs in surgical patients were 18% and 54%, described in two studies. A head-to-head comparison of surgical patients and nonsurgical patients was possible for five of six studies. The occurrence of ADEs in nonsurgical patients was significantly higher than in surgical patients in three studies.Conclusions: ADEs are a relevant problem in surgical patients and nonsurgical patients, with a high proportion of preventable ADEs. The occurrence of ADEs appears to be higher in nonsurgical patients than in surgical patients. However, studies lack details on the differences in nature of ADEs between hospital populations. To improve medication safety this knowledge is essential. [ABSTRACT FROM AUTHOR]

Background: A medical tests may influence the health of patients by guiding clinical decisions, such as treatment in case of a positive test result. However, a medical test can influence the health of patients through other mechanisms as well, like giving reassurance. To make a clinical recommendation about a medical test, we should be aware of the full range of effects of that test on patients. This requires an understanding of the range of effects that medical testing can have on patients. This study evaluates the mechanisms through which medical testing can influence patients' health, other than the effect on clinical management, from a gynecologist's perspective.Methods: A qualitative study in which explorative focus groups were conducted with gynecologists, gynecological residents and gynecological M.D. researchers (n = 43). Discussions were transcribed verbatim. Transcriptions were coded inductively and analyzed by three researchers.Results: All participants contributed various clinical examples in which medical testing had influenced patients' health. Clinical examples illustrated that testing, in itself or in interaction with contextual factors, may provoke a wide range of effects on patients. Our data showed that testing can influence the doctor's perceptions of the patients' appraisal of their illness, their perceived control, or the doctor-patient relationship. This may lead to changes in psychological, behavioral, and/or medical outcomes, both favorably or unfavorably. The data were used to construct a conceptual framework of effects of medical testing on patients.Conclusions: Besides supporting clinical decision making, medical testing may have favorable or unfavorable effects on patients' health though several mechanisms. [ABSTRACT FROM AUTHOR]

Background: Infected necrotising pancreatitis is a potentially lethal disease that nearly always requires intervention. Traditionally, primary open necrosectomy has been the treatment of choice. In recent years, the surgical step-up approach, consisting of percutaneous catheter drainage followed, if necessary, by (minimally invasive) surgical necrosectomy has become the standard of care. A promising minimally invasive alternative is the endoscopic transluminal step-up approach. This approach consists of endoscopic transluminal drainage followed, if necessary, by endoscopic transluminal necrosectomy. We hypothesise that the less invasive endoscopic step-up approach is superior to the surgical step-up approach in terms of clinical and economic outcomes.Methods/design: The TENSION trial is a randomised controlled, parallel-group superiority multicenter trial. Patients with (suspected) infected necrotising pancreatitis with an indication for intervention and in whom both treatment modalities are deemed possible, will be randomised to either an endoscopic transluminal or a surgical step-up approach. During a 4 year study period, 98 patients will be enrolled from 24 hospitals of the Dutch Pancreatitis Study Group. The primary endpoint is a composite of death and major complications within 6 months following randomisation. Secondary endpoints include complications such as pancreaticocutaneous fistula, exocrine or endocrine pancreatic insufficiency, need for additional radiological, endoscopic or surgical intervention, the need for necrosectomy after drainage, the number of (re-)interventions, quality of life, and total direct and indirect costs.Discussion: The TENSION trial will answer the question whether an endoscopic step-up approach reduces the combined primary endpoint of death and major complications, as well as hospital stay and related costs compared with a surgical step-up approach in patients with infected necrotising pancreatitis. [ABSTRACT FROM AUTHOR]

Background: Posttraumatic osteoarthritis can develop after an intra-articular extremity fracture, leading to pain and loss of function. According to international guidelines, anatomical reduction and fixation are the basis for an optimal functional result. In order to achieve this during fracture surgery, an optimal view on the position of the bone fragments and fixation material is a necessity. The currently used 2D-fluoroscopy does not provide sufficient insight, in particular in cases with complex anatomy or subtle injury, and even an 18-26% suboptimal fracture reduction is reported for the ankle and foot. More intra-operative information is therefore needed.Recently the 3D-RX-system was developed, which provides conventional 2D-fluoroscopic images as well as a 3D-reconstruction of bony structures. This modality provides more information, which consequently leads to extra corrections in 18-30% of the fracture operations. However, the effect of the extra corrections on the quality of the anatomical fracture reduction and fixation as well as on patient relevant outcomes has never been investigated.The objective of this study protocol is to investigate the effectiveness of the intra-operative use of the 3D-RX-system as compared to the conventional 2D-fluoroscopy in patients with traumatic intra-articular fractures of the wrist, ankle and calcaneus. The effectiveness will be assessed in two different areas: 1) the quality of fracture reduction and fixation, based on the current golden standard, Computed Tomography. 2) The patient-relevant outcomes like functional outcome range of motion and pain. In addition, the diagnostic accuracy of the 3D-RX-scan will be determined in a clinical setting and a cost-effectiveness as well as a cost-utility analysis will be performed.Methods/design: In this protocol for an international multicenter randomized clinical trial, adult patients (age > 17 years) with a traumatic intra-articular fracture of the wrist, ankle or calcaneus eligible for surgery will be subjected to additional intra-operative 3D-RX. In half of the patients the surgeon will be blinded to these results, in the other half the surgeon may use the 3D-RX results to further optimize fracture reduction. In both randomization groups a CT-scan will be performed postoperatively. Based on these CT-scans the quality of fracture reduction and fixation will be determined. During the follow-up visits after hospital discharge at 6 and 12 weeks and 1 year postoperatively the patient relevant outcomes will be determined by joint specific, health economic and quality of life questionnaires. In addition a follow up study will be performed to determine the patient relevant outcomes and prevalence of posttraumatic osteoarthritis at 2 and 5 years postoperatively.Discussion: The results of the study will provide more information on the effectiveness of the intra-operative use of 3D-imaging during surgical treatment of intra-articular fractures of the wrist, ankle and calcaneus. A randomized design in which patients will be allocated to a treatment arm during surgery will be used because of its high methodological quality and the ability to detect incongruences in the reduction and/or fixation that occur intra-operatively in the blinded arm of the 3D-RX. An alternative, pragmatic design could be to randomize before the start of the surgery, then two surgical strategies would be compared. This resembles clinical practice better, but introduces more bias and does not allow the assessment of incongruences that would have been detected by 3D-RX in the blinded arm.Trial Registration: Dutch Trial Register NTR 1902. [ABSTRACT FROM AUTHOR]