Comparative Efficacy of Subcutaneous and Intravenous Infliximab and Vedolizumab for Maintenance Treatment of TNF-naive Adult Patients with Inflammatory Bowel Disease: A Systematic Literature Review and Network Meta-analysis.

BACKGROUND: Infliximab and vedolizumab are widely used to treat Crohn's disease (CD) and ulcerative colitis (UC). AIMS: This systematic review and network meta-analysis evaluated comparative efficacy of various regimens for intravenous or subcutaneous infliximab and vedolizumab during maintenance treatment in CD and UC. METHODS: Parallel-group randomized controlled trials (RCTs) were identified by a systematic literature review (CRD42022383401) and included if they evaluated therapeutics of interest for maintenance treatment of adults with moderate-to-severe luminal CD or UC and assessed clinical remission between Weeks 30 and 60. Clinical remission rates in CD or UC and mucosal healing rates in UC were analyzed in a Bayesian network meta-analysis model. Endoscopic outcomes in CD were synthesized by proportional meta-analysis. RESULTS: Overall, 13 RCTs were included in the analyses. All vedolizumab studies randomized induction responders to maintenance treatment; infliximab studies used a treat-through design. Subcutaneous infliximab 120 mg every 2 weeks had the highest odds ratio (OR) [95% credible interval] versus placebo for clinical remission during the maintenance phase (CD: 5.90 [1.90-18.2]; UC: 5.45 [1.94-15.3]), with surface under the cumulative ranking curve (SUCRA) values of 0.91 and 0.82, respectively. For mucosal healing in UC, subcutaneous infliximab 120 mg every 2 weeks showed the highest OR (4.90 [1.63-14.1]), with SUCRA value of 0.73, followed by intravenous vedolizumab 300 mg every 4 weeks (SUCRA value, 0.70). Endoscopic outcomes in CD were better with subcutaneous infliximab 120 mg every 2 weeks than intravenous infliximab 5 mg/kg every 8 weeks. CONCLUSIONS: Subcutaneous infliximab showed a favorable efficacy profile for achieving clinical remission and endoscopic outcomes during maintenance treatment in CD or UC.

Another gastrointestinal lesion amendable for ablation.

A 79-year-old patient, with a history of redoendoscopic ampullectomy (low grade dysplasia), was referred to our hospital with cholestatic liver function abnormalities and dilation of the common bile duct. Diagnostic endoscopic ultrasound (EUS) was performed (Figure 1, left), as well as upper gastrointestinal endoscopy (Figure 1, right). What is the final diagnosis and which treatment would you propose?

Clinical added value of MRI to CT in patients scheduled for local therapy of colorectal liver metastases (CAMINO): study protocol for an international multicentre prospective diagnostic accuracy study.

BACKGROUND: Abdominal computed tomography (CT) is the standard imaging method for patients with suspected colorectal liver metastases (CRLM) in the diagnostic workup for surgery or thermal ablation. Diffusion-weighted and gadoxetic-acid-enhanced magnetic resonance imaging (MRI) of the liver is increasingly used to improve the detection rate and characterization of liver lesions. MRI is superior in detection and characterization of CRLM as compared to CT. However, it is unknown how MRI actually impacts patient management. The primary aim of the CAMINO study is to evaluate whether MRI has sufficient clinical added value to be routinely added to CT in the staging of CRLM. The secondary objective is to identify subgroups who benefit the most from additional MRI. METHODS: In this international multicentre prospective incremental diagnostic accuracy study, 298 patients with primary or recurrent CRLM scheduled for curative liver resection or thermal ablation based on CT staging will be enrolled from 17 centres across the Netherlands, Belgium, Norway, and Italy. All study participants will undergo CT and diffusion-weighted and gadoxetic-acid enhanced MRI prior to local therapy. The local multidisciplinary team will provide two local therapy plans: first, based on CT-staging and second, based on both CT and MRI. The primary outcome measure is the proportion of clinically significant CRLM (CS-CRLM) detected by MRI not visible on CT. CS-CRLM are defined as liver lesions leading to a change in local therapeutical management. If MRI detects new CRLM in segments which would have been resected in the original operative plan, these are not considered CS-CRLM. It is hypothesized that MRI will lead to the detection of CS-CRLM in ≥10% of patients which is considered the minimal clinically important difference. Furthermore, a prediction model will be developed using multivariable logistic regression modelling to evaluate the predictive value of patient, tumor and procedural variables on finding CS-CRLM on MRI. DISCUSSION: The CAMINO study will clarify the clinical added value of MRI to CT in patients with CRLM scheduled for local therapy. This study will provide the evidence required for the implementation of additional MRI in the routine work-up of patients with primary and recurrent CRLM for local therapy. TRIAL REGISTRATION: The CAMINO study was registered in the Netherlands National Trial Register under number NL8039 on September 20th 2019.

Discriminating complicated from uncomplicated appendicitis by ultrasound imaging, computed tomography or magnetic resonance imaging: systematic review and meta-analysis of diagnostic accuracy.

BACKGROUND: Discriminating complicated from uncomplicated appendicitis is crucial. Patients with suspected complicated appendicitis are best treated by emergency surgery, whereas those with uncomplicated appendicitis may be treated with antibiotics alone. This study aimed to obtain summary estimates of the accuracy of ultrasound imaging, CT and MRI in discriminating complicated from uncomplicated appendicitis. METHODS: A systematic literature review was conducted by an electronic search in PubMed, Embase and the Cochrane Library for studies describing the diagnostic accuracy of complicated versus uncomplicated appendicitis. Studies were included if the population comprised adults, and surgery or pathology was used as a reference standard. Risk of bias and applicability were assessed with QUADAS-2. Bivariable logitnormal random-effect models were used to estimate mean sensitivity and specificity. RESULTS: Two studies reporting on ultrasound imaging, 11 studies on CT, one on MRI, and one on ultrasonography with conditional CT were included. Summary estimates for sensitivity and specificity in detecting complicated appendicitis could be calculated only for CT, because of lack of data for the other imaging modalities. For CT, mean sensitivity was 78 (95 per cent c.i. 64 to 88) per cent, and mean specificity was 91 (85 to 99) per cent. At a median prevalence of 25 per cent, the positive predictive value of CT for complicated appendicitis would be 74 per cent and its negative predictive value 93 per cent. CONCLUSION: Ultrasound imaging, CT and MRI have limitations in discriminating between complicated and uncomplicated appendicitis. Although CT has far from perfect sensitivity, its negative predictive value for complicated appendicitis is high.

Systematic review of reporting benefits and harms of surgical interventions in randomized clinical trials.

BACKGROUND: Standardized reporting methods facilitate comparisons between studies. Reporting of data on benefits and harms of treatments in surgical RCTs should support clinical decision-making. Correct and complete reporting of the outcomes of clinical trials is mandatory to appreciate available evidence and to inform patients properly before asking informed consent. METHODS: RCTs published between January 2005 and January 2017 in 15 leading journals comparing a surgical treatment with any other treatment were reviewed systematically. The CONSORT checklist, including the extension for harms, was used to appraise the publications. Beneficial and harmful treatment outcomes, their definitions and their precision measures were extracted. RESULTS: Of 1200 RCTs screened, 88 trials were included. For the differences in effect size of beneficial outcomes, 68 per cent of the trials reported a P value only but not a 95 per cent confidence interval. For harmful effects, this was 67 per cent. Only five of the 88 trials (6 per cent) reported a number needed to treat, and no study a number needed to harm. Only 61 per cent of the trials reported on both the beneficial and harmful outcomes of the intervention studied in the same paper. CONCLUSION: Despite CONSORT guidelines, current reporting of benefits and harms in surgical trials does not facilitate clear communication of treatment outcomes with patients. Researchers, reviewers and journal editors should ensure proper reporting of treatment benefits and harms in trials.

ANTECEDENTES: Los métodos para la estandarización en la descripción de los resultados facilitan la comparación entre estudios. La toma de decisiones clínicas debe estar respaldada por los resultados que se obtienen en los ensayos clínicos aleatorizados (randomized clinical trials, RCTs) quirúrgicos sobre los efectos beneficiosos y nocivos de los tratamientos. Es obligado que la descripción de los resultados de los ensayos clínicos sea correcta y completa a fin de estimar la evidencia disponible y poder informar a los pacientes de forma adecuada antes de solicitar el consentimiento informado. MÉTODOS: Se revisaron de forma sistemática los RCTs publicados entre enero de 2005 y enero de 2017 en las 15 revistas principales en los que se comparaba un tratamiento quirúrgico con cualquier otro. Para evaluar las publicaciones, se utilizó la guía de comprobación del CONsolidated Standard of Reporting Trials (CONSORT), haciéndola extensiva también a los efectos nocivos. Se obtuvieron los resultados sobre los efectos beneficiosos y nocivos del tratamiento, sus definiciones y sus medidas de precisión. RESULTADOS: De 1.200 RCTs seleccionados, se incluyeron 88 ensayos. Para comparar las diferencias de los efectos beneficiosos de los resultados, en el 68% de los ensayos se aportó sólo un valor de la P pero no el intervalo de confianza del 95%. Para efectos nocivos, el porcentaje fue del 67%. En sólo 5 de 88 ensayos (6%) se informó del número de pacientes que es necesario tratar (number needed to treat, NNT), y en ningún estudio se precisó el número de pacientes que es necesario para perjudicar (number needed to harm, NNH). En sólo el 61% de los ensayos se informó de los resultados beneficiosos y nocivos de la intervención analizada en el mismo artículo. CONCLUSIÓN: A pesar de la guía CONSORT, la descripción actual de los efectos beneficiosos y nocivos en los ensayos quirúrgicos no permite obtener una clara información del resultado del tratamiento obtenido en los pacientes. Los investigadores, los revisores y los editores de las revistas deben garantizar una descripción adecuada los beneficios y efectos nocivos del tratamiento en los ensayos clínicos.

An economic analysis of preimplantation genetic testing for aneuploidy by polar body biopsy in advanced maternal age.

OBJECTIVE: What are the cost per live birth and the incremental cost of preventing a miscarriage with preimplantation genetic testing for aneuploidy (PGT-A) by polar body biopsy and array-based comprehensive genome hybridisation (aCGH) versus regular IVF/ICSI without PGT-A for infertility treatment in women 36-40 years of age? DESIGN: Decision tree model. POPULATION: A randomised clinical trial on PGT-A (ESTEEM study). METHODS: Two treatment strategies were compared: one cycle of IVF/ICSI with or without PGT-A. Costs and effects were analysed with this model for four different cost scenarios: high-, higher medium, lower medium and low-cost. Base case, sensitivity, threshold, and probabilistic sensitivity analyses were used to examine the cost-effectiveness implications of PGT-A. RESULTS: PGT-A increased the cost per live birth by approximately 15% in the high-cost scenario to approximately 285% in the low-cost scenario. Threshold analysis revealed that PGT-A would need to be associated with an absolute increase in pregnancy rate by 6% to >39% or, alternatively, would need to be US$2,969 (high-cost scenario) to US$4,888 (low-cost scenario) cheaper. The incremental cost to prevent one miscarriage by PGT-A using the base case assumptions was calculated to be US$34,427 (high-cost scenario) to US$51,146 (low-cost scenario). A probabilistic sensitivity analysis showed cost-effectiveness for PGT-A from 1.9% (high-cost scenario) to 0.0% (low-cost scenario) of calculated samples. CONCLUSIONS: While avoiding unnecessary embryo transfers and miscarriages are important goals, patients and doctors need to be aware of the high-cost implications of applying PGT-A using aCGH on polar bodies. TWEETABLE ABSTRACT: PGT-A by polar body biopsy and comprehensive genome hybridisation increases cost per live birth and requires high financial spending per miscarriage averted.

Ulcerative colitis treatment : an insight into daily clinical practice.

BACKGROUND: The natural history of ulcerative colitis (UC) is unpredictable. Factors associated with the need for different types of step-up therapy in UC patients failing on 5-aminosalicylic acid (5-ASA) or corticosteroids are understudied. AIMS: Describe step-up therapy in patients with UC the first year after failing on 5-ASA or corticosteroids. METHODS: A Belgian, multi-center, prospective, non-interventional observational study comprising adult UC patients failing on 5-ASA or corticosteroids and naïve to immunomodulators/ biologicals. During a 12 months follow-up, patient characteristics, demography, medical therapy, biomarkers, therapy adherence and quality of life (QoL) were assessed. RESULTS: After 1 year, 35% of the patients were on biological therapy. Use of anti-TNF differed depending on baseline treatment: corticosteroid-refractory patients (55.8%), 5-ASA refractory (20.0%), and corticosteroid-dependent (16.0%) patients (p<0.001). The decision to start a line of therapy was based on the Mayo combined severity but not on biomarkers like faecal calprotectin, haemoglobin, CRP, albumin, platelets, and number of extraintestinal manifestations. At year 1, 84.2% of the patients had only mild UC or remission and a significant improvement of fatigue (p=0.004) and IBDQ scores (p<0.001) were observed implying an improved QoL. CONCLUSION: Treatment step-up, based on clinical scores in immunomodulatory and anti-TNF naïve patients with UC, provides good clinical outcomes and QoL.

Relationship between type of unprovoked venous thromboembolism and cancer location: An individual patient data meta-analysis.

BACKGROUND: Unprovoked venous thromboembolism (VTE) may be the first manifestation of an underlying cancer. We aimed to assess the period prevalence of occult cancer detection stratified by VTE location (deep vein thrombosis [DVT], pulmonary embolism [PE] or both) and the anatomical relationship between occult cancer and VTE. METHODS: Post-hoc analysis of a systematic review and individual patient data meta-analysis of adults with unprovoked VTE with at least 12 months of follow-up. Cancer types were grouped according to thoracic, abdomino-pelvic, or other locations. RESULTS: A total of 2300 patients were eligible including 1218 with DVT only (53%), 719 with PE only (31%), and 363 with both PE and DVT (16%). The pooled 12-month period prevalence of cancer in DVT only, PE only, and DVT + PE was 5.6% (95% CI, 4.4 to 7.2), 4.3% (95% CI, 2.7 to 6.9), and 5.6% (95% CI, 1.7 to 15.5), respectively. Most occult cancers were located in the abdomen (68.4%). The proportion of patients with an abdomino-pelvic cancer was not different in patients with DVT + PE (81%; 95% CI, 54 to 96) than in those with DVT (68%; 95% CI, 57 to 78) or PE alone (65%; 95% CI, 48 to 79). CONCLUSION: The 12-month prevalence of occult cancer was similar in patients with DVT only, PE only, or both. Most cancers were located in the abdomen, and there was no relationship between VTE type and cancer location.

Efficacy of switching to infliximab in patients with Crohn's disease with loss of response to adalimumab.

BACKGROUND AND STUDY AIMS: Anti-TNF monoclonal antibodies are a cornerstone in the treatment of Crohn's disease. Prospective data on switching from the subcutaneous and human adalimumab (ADM) to the intravenous and chimeric infliximab (IFX) are scarce. PATIENTS AND METHODS: In this prospective, observational, multicentre cohort study we included 21 patients with loss of response to ADM despite at least 4 consecutive weekly injections. Clinical response (CDAI drop≥70 points) and remission (CDAI≤150) were assessed after switching from ADM to IFX after 10 weeks, 6 and 12 months. Predictive factors of response/remission, the need for therapy intensification, discontinuation and safety were investigated. RESULTS: Short-term response and remission (10 weeks) were seen in 57% and 48% respectively. Mid- and long-term clinical response and remission were achieved in 40% and 25% after 6 months and in 45% and 20% after 12 months respectively. At 12 months, 81% still were on IFX. IFX therapy intensification was needed in half of the patients at 6 months and three quarter of patients at 12 months. Undetectable ADM trough levels (despite weekly injections) were a predictive factor for short-term response and remission to IFX. About half of the patients with response at week 10 maintained response at 6 and 12 months. CONCLUSIONS: Switching from ADM to IFX can be efficacious in patients with loss of response, in particular in case of undetectable ADM trough levels. The majority of patients however will need IFX therapy intensification during their first year of treatment.

Evaluation of an online family history tool for identifying hereditary and familial colorectal cancer.

Identifying a hereditary colorectal cancer (CRC) syndrome or familial CRC (FCC) in a CRC patient may enable the patient and relatives to enroll in surveillance protocols. As these individuals are insufficiently recognized, we evaluated an online family history tool, consisting of a patient-administered family history questionnaire and an automated genetic referral recommendation, to facilitate the identification of patients with hereditary CRC or FCC. Between 2015 and 2016, all newly diagnosed CRC patients in five Dutch outpatient clinics, were included in a trial with a stepped-wedge design, when first visiting the clinic. Each hospital continued standard procedures for identifying patients at risk (control strategy) and then, after a predetermined period, switched to offering the family history tool to included patients (intervention strategy). After considering the tool-based recommendation, the health care provider could decide on and arrange the referral. Primary outcome was the relative number of CRC patients who received screening or surveillance recommendations for themselves or relatives because of hereditary CRC or FCC, provided by genetic counseling. The intervention effect was evaluated using a logit-linear model. With the tool, 46/489 (9.4%) patients received a screening or surveillance recommendation, compared to 35/292 (12.0%) in the control group. In the intention-to-treat-analysis, accounting for time trends and hospital effects, this difference was not statistically significant (p = 0.58). A family history tool does not necessarily assist in increasing the number of CRC patients and relatives enrolled in screening or surveillance recommendations for hereditary CRC or FCC. Other interventions should be considered.

IVF or IUI as first-line treatment in unexplained subfertility: the conundrum of treatment selection markers.

STUDY QUESTION: Are there treatment selection markers that could aid in identifying couples, with unexplained or mild male subfertility, who would have better chances of a healthy child with IVF with single embryo transfer (IVF-SET) than with IUI with ovarian stimulation (IUI-OS)? SUMMARY ANSWER: We did not find any treatment selection markers that were associated with better chances of a healthy child with IVF-SET instead of IUI-OS in couples with unexplained or mild male subfertility. WHAT IS KNOWN ALREADY: A recent trial, comparing IVF-SET to IUI-OS, found no evidence of a difference between live birth rates and multiple pregnancy rates. It was suggested that IUI-OS should remain the first-line treatment instead of IVF-SET in couples with unexplained or mild male subfertility and female age between 18 and 38 years. The question remains whether there are some couples that may have higher pregnancy chances if treated with IVF-SET instead of IUI. STUDY DESIGN, SIZE, DURATION: We performed our analyses on data from the INeS trial, where couples with unexplained or mild male subfertility and an unfavourable prognosis for natural conception were randomly allocated to IVF-SET, IVF in a modified natural cycle or IUI-OS. In view of the aim of this study, we only used data of the comparison between IVF-SET (201 couples) and IUI-OS (207 couples). PARTICIPANTS/MATERIALS, SETTING, METHODS: We pre-defined the following baseline characteristics as potential treatment selection markers: female age, ethnicity, smoking status, type of subfertility (primary/secondary), duration of subfertility, BMI, pre-wash total motile count and Hunault prediction score. For each potential treatment selection marker, we explored the association with the chances of a healthy child after IVF-SET and IUI-OS and tested if there was an interaction with treatment. Given the exploratory nature of our analysis, we used a P-value of 0.1. MAIN RESULTS AND THE ROLE OF CHANCE: None of the markers were associated with higher chances of a healthy child from IVF-SET compared to IUI-OS (P-value for interaction >0.10). LIMITATIONS, REASONS FOR CAUTION: Since this is the first large study that looked at potential treatment selection markers for IVF-SET compared to IUI-OS, we had no data on which to base a power calculation. The sample size was limited, making it difficult to detect any smaller associations. WIDER IMPLICATIONS OF THE FINDINGS: We could not identify couples with unexplained or mild male subfertility who would have had higher chances of a healthy child from immediate IVF-SET than from IUI-OS. As in the original trial IUI-OS had similar effectiveness and was less costly compared to IVF-SET, IUI-OS should remain the preferred first-line treatment in these couples. STUDY FUNDING/COMPETING INTEREST(S): The study was supported by a grant from the Netherlands Organization for Health Research and Development, and a grant from the Netherlands' association of health care insurers. There are no conflicts of interest. TRIAL REGISTRATION NUMBER: The trial was registered at the Dutch trial registry (NTR939).

Prediction of disease-free survival using relative change in FDG-uptake early during neoadjuvant chemoradiotherapy for potentially curable esophageal cancer: A prospective cohort study.

18F-Fluorodeoxyglucose positron emission tomography (FDG-PET) has been investigated as a tool for monitoring response to neoadjuvant chemo- and chemoradiotherapy (CT and CRT, respectively) and as a predictor for survival in patients with esophageal cancer. In contrast to patients who undergo neoadjuvant CT, it is not known whether patients who are clinically identified as responders after neoadjuvant CRT show better disease-free survival (DFS) than patients identified as nonresponders. The aim of the study was to determine the predictive value of FDG-uptake measured prior to and early during neoadjuvant CRT. Patients treated with neoadjuvant CRT between 2004 and 2009 within a randomized trial were included. FDG-uptake was measured at baseline and after 14 days of CRT. According to the PERCIST-criteria, patients were allocated to have metabolic response, stable disease, or progression. Patients were followed until recurrence of disease or death. The predictive value of FDG-PET was determined with univariable and multivariable analysis in patients who underwent potentially curative surgery. One-hundred and six patients were included in the analysis. Minimal follow-up for surviving patients was 60 months. No significant differences in DFS were found between patients with metabolic response, stable disease, or progression, with 5-year DFS rates of 66%, 53%, and 67%, respectively (P = 0.39). Relative change in FDG uptake after 14 days of CRT is not associated with DFS in patients with esophageal cancer undergoing neoadjuvant chemoradiotherapy followed by surgery. These measurements should not be used for prognostication in this specific group of patients.

A randomised comparison of two faecal immunochemical tests in population-based colorectal cancer screening.

OBJECTIVE: Colorectal cancer screening programmes are implemented worldwide; many are based on faecal immunochemical testing (FIT). The aim of this study was to evaluate two frequently used FITs on participation, usability, positivity rate and diagnostic yield in population-based FIT screening. DESIGN: Comparison of two FITs was performed in a fourth round population-based FIT-screening cohort. Randomly selected individuals aged 50-74 were invited for FIT screening and were randomly allocated to receive an OC -Sensor (Eiken, Japan) or faecal occult blood (FOB)-Gold (Sentinel, Italy) test (March-December 2014). A cut-off of 10 µg haemoglobin (Hb)/g faeces (ie, 50 ng Hb/mL buffer for OC-Sensor and 59 ng Hb for FOB-Gold) was used for both FITs. RESULTS: In total, 19 291 eligible invitees were included (median age 61, IQR 57-67; 48% males): 9669 invitees received OC-Sensor and 9622 FOB-Gold; both tests were returned by 63% of invitees (p=0.96). Tests were non-analysable in 0.7% of participants using OC-Sensor vs 2.0% using FOB-Gold (p<0.001). Positivity rate was 7.9% for OC-Sensor, and 6.5% for FOB-Gold (p=0.002). There was no significant difference in diagnostic yield of advanced neoplasia (1.4% for OC-Sensor vs 1.2% for FOB-Gold; p=0.15) or positive predictive value (PPV; 31% vs 32%; p=0.80). When comparing both tests at the same positivity rate instead of cut-off, they yielded similar PPV and detection rates. CONCLUSIONS: The OC-Sensor and FOB-Gold were equally acceptable to a screening population. However, FOB-Gold was prone to more non-analysable tests. Comparison between FIT brands is usually done at the same Hb stool concentration. Our findings imply that for a fair comparison on diagnostic yield between FIT's positivity rate rather than Hb concentration should be used. TRIAL REGISTRATION NUMBER: NTR5385; Results.

MisoREST: surgical versus expectant management in women with an incomplete evacuation of the uterus after misoprostol treatment for miscarriage: a randomized controlled trial.

STUDY QUESTION: Is curettage more effective than expectant management in case of an incomplete evacuation after misoprostol treatment for first trimester miscarriage? SUMMARY ANSWER: Curettage leads to a higher chance of complete evacuation but expectant management is successful in at least 76% of women with an incomplete evacuation of the uterus after misoprostol treatment for first trimester miscarriage. WHAT IS KNOWN ALREADY: In 5-50% of the women treated with misoprostol, there is a suspicion of incomplete evacuation of the uterus on sonography. Although these women generally have minor symptoms, such a finding often leads to additional curettage. STUDY DESIGN, SIZE, DURATION: From June 2012 until July 2014, we conducted a nationwide multicenter randomized controlled trial (RCT). Women who had had primary misoprostol treatment for miscarriage with sonographic evidence of incomplete evacuation of the uterus were randomly allocated to either curettage or expectant management (1:1), using a web-based application. PARTICIPANTS/MATERIALS, SETTING, METHODS: We included 59 women in 27 hospitals; 30 were allocated to curettage and 29 were allocated to expectant management. A successful outcome was defined as sonographic finding of an empty uterus 6 weeks after randomization. MAIN RESULTS AND THE ROLE OF CHANCE: Baseline characteristics of both groups were comparable. Empty uterus on sonography or uneventful clinical follow-up was seen in 29/30 women (97%) allocated to curettage compared with 22/29 women (76%) allocated to expectant management (RR 1.3, 95% CI 1.03-1.6) with complication rates of 10% versus 10%, respectively (RR 0.97, 95% CI 0.21-4.4). In the group allocated to curettage, no woman required re-curettage, while two women (6.7%) underwent hysteroscopy (for other or unknown reasons). In the women allocated to expectant management, curettage was performed in four women (13.8%) and three women (10.3%) underwent hysteroscopy. LIMITATIONS, REASONS FOR CAUTION: Due to a strong patient preference, mainly for expectant management, the targeted sample size could not be included and the trial was stopped prematurely. WIDER IMPLICATIONS OF THE FINDINGS: In women suspected of incomplete evacuation of the uterus after misoprostol, curettage is more effective than expectant management. However, expectant management is equally safe and prevents curettage for most of the women. This finding could further restrain the use of curettage in the treatment of first trimester miscarriage. STUDY FUNDING/COMPETING INTERESTS: This study was funded by ZonMw, a Dutch organization for Health Research and Development, project number 80-82310-97-12066. There were no conflicts of interests. TRIAL REGISTRATION NUMBER: Dutch Trial Register NTR3310, http://www.trialregister.nl TRIAL REGISTRATION DATE: 27 February 2012. DATE OF FIRST PATIENT'S ENROLMENT: 12 June 2012.

PO-07 - Excluding pulmonary embolism in cancer patients using the Wells rule and age-adjusted D-dimer testing: an individual patient data meta-analysis.

INTRODUCTION: Among patients with clinically suspected pulmonary embolism (PE), imaging and anticoagulant treatment can be safely withheld in approximately one-third of patients based on the combination of a "PE unlikely" Wells score and a D-dimer below the age-adjusted threshold. The clinical utility of this diagnostic approach in cancer patients is less clear. AIM: To evaluate the efficiency and failure rate of the original and simplified Wells rules in combination with age-adjusted D-dimer testing in patients with active cancer. MATERIALS AND METHODS: Individual patient data were used from 6 large prospective studies in which the diagnostic management of PE was guided by the original Wells rule and D-dimer testing. Study physicians classified patients as having active cancer if they had new, recurrent, or progressive cancer (excluding basal-cell or squamous-cell skin carcinoma), or cancer requiring treatment in the last 6 months. We evaluated the dichotomous Wells rule and its simplified version (Table). The efficiency of the algorithm was defined as the proportion of patients with a "PE unlikely" Wells score and a negative age-adjusted D-dimer, defined by a D-dimer below the threshold of a patient's age times 10 µg/L in patients aged ≥51 years. A diagnostic failure was defined as a patient with a "PE unlikely" Wells score and negative age-adjusted D-dimer who had symptomatic venous thromboembolism during 3 months follow-up. A one-stage random effects meta-analysis was performed to estimate the efficiency and failure. RESULTS: The dataset comprised 938 patients with active cancer with a mean age of 63 years. The most frequent cancer types were breast (13%), gastrointestinal tract (11%), and lung (8%). The type of cancer was not specified in 42%. The pooled PE prevalence was 29% (95% CI 25-32). PE could be excluded in 122 patients based on a "PE unlikely" Wells score and a negative age-adjusted D-dimer (efficiency 13%; 95% CI 11-15). Two of 122 patients were diagnosed with non-fatal symptomatic venous thromboembolism during follow-up (failure rate 1.5%; 95% CI 0.13-14.8). The simplified Wells score in combination with a negative age-adjusted D-dimer had an efficiency of 3.9% (95% CI 2.0-7.6) and a failure rate of 2.4% (95% CI 0.3-15). CONCLUSIONS: Among cancer patients with clinically suspected PE, imaging and anticoagulant treatment can be withheld in 1 out of every 8 patients by the original Wells rule and age-adjusted D-dimer testing. The simplified Wells rule was neither efficient nor safe in this population.

Adding family history to faecal immunochemical testing increases the detection of advanced neoplasia in a colorectal cancer screening programme.

BACKGROUND: Faecal immunochemical testing (FIT) for colorectal cancer (CRC) screening has suboptimal sensitivity for detecting advanced neoplasia. To increase its performance, FIT could be combined with other risk factors. AIM: To evaluate the incremental yield of a screening programme using a positive FIT or a CRC family history, to offer a diagnostic colonoscopy. METHODS: For this post hoc analysis, data were collected in the colonoscopy arm of a colonoscopy or colonography for screening study. In this study, 6600 randomly selected, asymptomatic men and women (50-75 years) were invited for screening colonoscopy. 1112 Participants completed a FIT and a questionnaire prior to colonoscopy. We compared the yield of FIT-only and FIT combined with CRC family history, defined as having one or more first-degree relatives with CRC. RESULTS: At a 10 µg Hb/g faeces FIT-positivity threshold the combined strategy would increase the yield from 36 (3.2%; CI: 2.4-4.5%) to 53 (4.8%; CI: 3.7-6.2%) cases of advanced neoplasia, at the expense of 148 additional negative colonoscopies. Sensitivity in detecting advanced neoplasia would increase from 36% (CI: 26-46%) to 52% (CI: 42-63%), whereas specificity would decrease from 93% (CI: 92-95%) to 79% (CI: 76-81%). The strategy will be preferred if one accepts 8.8 false positives for every additional participant in whom advanced neoplasia can be detected. CONCLUSIONS: Offering colonoscopy to those with a positive FIT or CRC family history increases the yield of a FIT-based screening programme. Depending on the number of negative colonoscopies one accepts, this combined approach can be considered for improving CRC screening.

Smoking status informs about the risk of advanced serrated polyps in a screening population.

BACKGROUND AND STUDY AIMS: Evidence has accumulated that approximately 15 % to 30 % of colorectal cancers (CRC) arise from serrated polyps (SP). Population screening, therefore, should be designated to detect advanced SP, in addition to advanced adenomas and CRC. We aimed to evaluate whether CRC risk factors also act as risk factors for advanced SP. PATIENTS AND METHODS: Data were collected in the colonoscopy arm of a multicenter randomized trial comparing colonoscopy with CT-colonography for primary population screening. Information on risk factors was obtained by screening participants before colonoscopy with a validated risk questionnaire. Advanced SP were defined as SP ≥ 10 mm and/or with dysplasia. Endoscopists were instructed to resect all detected lesions. Odds ratios (OR) for the detection of advanced SP as most advanced lesion were calculated using multiple logistic regression analysis. RESULTS: Of 6 600 invited participants, 1 426 underwent a colonoscopy and 1 236 also completed the questionnaire. In 40 participants an advanced SP was the most advanced lesion detected. Multivariate analysis demonstrated a strong association between current smoking and the presence of at least one advanced SP (OR 4.50; 95 % CI 2.23 - 8.89; P < 0.001). A significant association was also demonstrated for higher fiber intake (OR 1.36 per 20 gram intake; CI 1.07 - 1.73; P = 0.01). Other clinical CRC risk factors did not show a significant association with the presence of at least one advanced SP in the univariate analyses. Fecal haemoglobin levels were also not significantly associated with the presence of advanced SPs (OR 1.00 per 10 ng/mL CI 0.97 - 1.03, P = 0.99). CONCLUSIONS: Current smoking is a strong clinical risk factor for the presence of advanced SPs. As such, smoking status could contribute to risk stratification in targeted CRC population screening. Dutch Trial Register: NTR1829 (www.trialregister.nl).

Participation, yield, and interval carcinomas in three rounds of biennial FIT-based colorectal cancer screening.

BACKGROUND: The effectiveness of colorectal cancer screening programs based on the fecal immunochemical test (FIT) is influenced by program adherence during consecutive screening rounds. We aimed to evaluate the participation rate, yield, and interval cancers in a third round of biennial CRC screening using FIT and to compare those with the first and the second screening round. METHODS: A total of 3566 average-risk individuals aged 50-75 years were invited to participate in a third round of biennial FIT-based CRC screening. All FIT positives were recommended to undergo colonoscopy. We merged our data with the national cancer registry in the Netherlands to identify all non-screen-detected cancers in our cohort. RESULTS: Of the invitees, 2142 (60%) returned the FIT in this third screening round, compared to 56% in the second round and 57% in the first round. Overall, 153 of the third-round participants (7.1%) had a positive FIT result, versus 7.9% in the second round and 8.1% in the first round (P=0.05). Of all FIT positives, 123 (80%) underwent colonoscopy. Within this group, 33 persons had advanced neoplasia. The predictive value of FIT positivity for advanced neoplasia was 27% (33/123), compared to 42% in the second round and 54% in the first round - a significant decline (P<0.01). CONCLUSION: In an FIT-based screening program, participation rates remained stable over consecutive biennial screening rounds, while the FIT positivity rate and positive predictive value for advanced neoplasia gradually declined. Cancers in non-participants are significantly more advanced in staging than cancers in participants in the first round of screening.

Validation of an online questionnaire for identifying people at risk of familial and hereditary colorectal cancer.

We developed and validated an online questionnaire to document familial cancer history, in order to facilitate the detection of persons with a familial or hereditary colorectal cancer (CRC) risk. The development of the self-administered online questionnaire for the assessment of familial and hereditary CRC risk was based on nationwide criteria for referral to genetic specialists due to a Lynch syndrome suspicion, as well as existing criteria for surveillance colonoscopies because of an increased risk of familial CRC. The questionnaire was validated at a private colonoscopy center. Patients scheduled for colonoscopy were enrolled (n = 150). Performance of the questionnaire was assessed by comparing referrals based on questionnaire data against referral decisions based on full pedigree data. In a second validation phase, referrals based on questionnaire data were compared with referrals based on data collected in a telephone interview. We also calculated inter-observer agreement in referral decisions. In the first validation phase, the questionnaire had a sensitivity of 90% (95% CI 55-98%) at a specificity of 98% (95% CI 87-100%) in identifying persons qualifying for referral. In the second validation phase, sensitivity was 100% (95% CI 63-100) at a specificity of 97% (95% CI 91-99%). In both validation phases an inter-observer agreement of 100% in referral decisions was achieved. The online questionnaire has a high sensitivity and specificity in identifying persons qualifying for referral because of suspected Lynch syndrome or familial CRC. Implementation of this tool in colonoscopy clinics can facilitate the detection of patients with hereditary or familial CRC.

A decision aid regarding treatment options for patients with an asymptomatic abdominal aortic aneurysm: a randomised clinical trial.

OBJECTIVE: Abdominal aortic aneurysm patients tend to be informed inconsistently and incompletely about their disorder and the treatment options open to them. The objective of this trial was to evaluate whether these patients are better informed and experience less decisional conflict regarding their treatment options after viewing a decision aid. DESIGN: A six-centre, randomised clinical trial comparing a decision aid plus regular information versus regular information from the surgeon. METHODS: Included patients had recently been diagnosed with an asymptomatic abdominal aortic aneurysm at least 4 cm in diameter. The decision aid consisted of a one-time viewing of an interactive CD-ROM elaborating on elective surgery versus watchful waiting. Generally, the decision aid advised patients with aneurysms less than 5.5 cm to agree to watchful waiting, for larger aneurysms the decision aid provided insight into the balance of benefit and harm of surgical and conservative approaches, taking into account age, co-morbidity and size of the aneurysm. The primary outcome was patient decisional conflict measured at 1 month follow-up (Decisional Conflict Scale). Secondary outcomes were patient knowledge, anxiety and satisfaction. RESULTS: In 178 aneurysm patients, decisional conflict scores did not differ significantly between the decision aid and the regular information groups (22 vs. 24 on the 0-100 Decisional Conflict Scale; p = .33). Patients in the decision aid group had significantly better knowledge (10.0 vs. 9.4 out of 13 points; p = .04), whereas anxiety levels (4.4 and 5.0 on a 0-21 scale; p = .73) and satisfaction scores (74 and 73 on a 0-100 scale; p = .81) were similar in both groups. CONCLUSION: In addition to regular patient-surgeon communication, a decision aid helps to share treatment decisions with abdominal aortic aneurysm patients by increasing their knowledge about the disorder and available treatment options without raising anxiety levels; however, it does not reduce decisional conflict, nor does it improve satisfaction.