| 1. |
- de Vries, Paul S., et al.
(författare)
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Multiancestry Genome-Wide Association Study of Lipid Levels Incorporating Gene-Alcohol Interactions
- 2019
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Ingår i: American Journal of Epidemiology. - : Oxford University Press. - 0002-9262 .- 1476-6256. ; 188:6, s. 1033-1054
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Tidskriftsartikel (refereegranskat)abstract
- A person's lipid profile is influenced by genetic variants and alcohol consumption, but the contribution of interactions between these exposures has not been studied. We therefore incorporated gene-alcohol interactions into a multiancestry genome-wide association study of levels of high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides. We included 45 studies in stage 1 (genome-wide discovery) and 66 studies in stage 2 (focused follow-up), for a total of 394,584 individuals from 5 ancestry groups. Analyses covered the period July 2014-November 2017. Genetic main effects and interaction effects were jointly assessed by means of a 2-degrees-of-freedom (df) test, and a 1-df test was used to assess the interaction effects alone. Variants at 495 loci were at least suggestively associated (P < 1 x 10(-6)) with lipid levels in stage 1 and were evaluated in stage 2, followed by combined analyses of stage 1 and stage 2. In the combined analysis of stages 1 and 2, a total of 147 independent loci were associated with lipid levels at P < 5 x 10(-8) using 2-df tests, of which 18 were novel. No genome-wide-significant associations were found testing the interaction effect alone. The novel loci included several genes (proprotein convertase subtilisin/kexin type 5 (PCSK5), vascular endothelial growth factor B (VEGFB), and apolipoprotein B mRNA editing enzyme, catalytic polypeptide 1 (APOBEC1) complementation factor (A1CF)) that have a putative role in lipid metabolism on the basis of existing evidence from cellular and experimental models.
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| 2. |
- Feitosa, Mary F., et al.
(författare)
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Novel genetic associations for blood pressure identified via gene-alcohol interaction in up to 570K individuals across multiple ancestries
- 2018
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Ingår i: PLOS ONE. - : Public library science. - 1932-6203. ; 13:6
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Tidskriftsartikel (refereegranskat)abstract
- Heavy alcohol consumption is an established risk factor for hypertension; the mechanism by which alcohol consumption impact blood pressure (BP) regulation remains unknown. We hypothesized that a genome-wide association study accounting for gene-alcohol consumption interaction for BP might identify additional BP loci and contribute to the understanding of alcohol-related BP regulation. We conducted a large two-stage investigation incorporating joint testing of main genetic effects and single nucleotide variant (SNV)-alcohol consumption interactions. In Stage 1, genome-wide discovery meta-analyses in approximate to 131 K individuals across several ancestry groups yielded 3,514 SNVs (245 loci) with suggestive evidence of association (P <1.0 x 10(-5)). In Stage 2, these SNVs were tested for independent external replication in individuals across multiple ancestries. We identified and replicated (at Bonferroni correction threshold) five novel BP loci (380 SNVs in 21 genes) and 49 previously reported BP loci (2,159 SNVs in 109 genes) in European ancestry, and in multi-ancestry meta-analyses (P < 5.0 x 10(-8)). For African ancestry samples, we detected 18 potentially novel BP loci (P< 5.0 x 10(-8)) in Stage 1 that warrant further replication. Additionally, correlated meta-analysis identified eight novel BP loci (11 genes). Several genes in these loci (e.g., PINX1, GATA4, BLK, FTO and GABBR2 have been previously reported to be associated with alcohol consumption. These findings provide insights into the role of alcohol consumption in the genetic architecture of hypertension.
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| 3. |
- Sung, Yun Ju, et al.
(författare)
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A multi-ancestry genome-wide study incorporating gene-smoking interactions identifies multiple new loci for pulse pressure and mean arterial pressure
- 2019
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Ingår i: Human Molecular Genetics. - : Oxford University Press. - 0964-6906 .- 1460-2083. ; 28:15, s. 2615-2633
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Tidskriftsartikel (refereegranskat)abstract
- Elevated blood pressure (BP), a leading cause of global morbidity and mortality, is influenced by both genetic and lifestyle factors. Cigarette smoking is one such lifestyle factor. Across five ancestries, we performed a genome-wide gene–smoking interaction study of mean arterial pressure (MAP) and pulse pressure (PP) in 129 913 individuals in stage 1 and follow-up analysis in 480 178 additional individuals in stage 2. We report here 136 loci significantly associated with MAP and/or PP. Of these, 61 were previously published through main-effect analysis of BP traits, 37 were recently reported by us for systolic BP and/or diastolic BP through gene–smoking interaction analysis and 38 were newly identified (P < 5 × 10−8, false discovery rate < 0.05). We also identified nine new signals near known loci. Of the 136 loci, 8 showed significant interaction with smoking status. They include CSMD1 previously reported for insulin resistance and BP in the spontaneously hypertensive rats. Many of the 38 new loci show biologic plausibility for a role in BP regulation. SLC26A7 encodes a chloride/bicarbonate exchanger expressed in the renal outer medullary collecting duct. AVPR1A is widely expressed, including in vascular smooth muscle cells, kidney, myocardium and brain. FHAD1 is a long non-coding RNA overexpressed in heart failure. TMEM51 was associated with contractile function in cardiomyocytes. CASP9 plays a central role in cardiomyocyte apoptosis. Identified only in African ancestry were 30 novel loci. Our findings highlight the value of multi-ancestry investigations, particularly in studies of interaction with lifestyle factors, where genomic and lifestyle differences may contribute to novel findings.
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| 4. |
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| 5. |
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| 6. |
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| 7. |
- Haraldsson, E, et al.
(författare)
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Endoscopic classification of the papilla of Vater. Results of an inter- and intraobserver agreement study
- 2017
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Ingår i: United European Gastroenterology Journal. - : Wiley. - 2050-6406 .- 2050-6414. ; 5:4, s. 504-510
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Tidskriftsartikel (refereegranskat)abstract
- Background: Many endoscopists acknowledge that the appearance of the papilla of Vater seems to affect biliary cannulation. To assess the association between the macroscopic appearance of the papilla and biliary cannulation and other related clinical issues, a system is needed to define the appearance of the papilla. Objective: The purpose of this study was to validate an endoscopic classification of the papilla of Vater by assessing the interobserver and intraobserver agreements among endoscopist with varying experience. Methods: An endoscopic classification, based on pictures captured from 140 different papillae, containing four types of papillae was proposed. The four types are (a) Type 1: regular papilla, no distinctive features, ‘classic appearance’; (b) Type 2: small papilla, often flat, with a diameter ≤ 3 mm (approximately 9 Fr); (c) Type 3: protruding or pendulous papilla, a papilla that is standing out, protruding or bulging into the duodenal lumen or sometimes hanging down, pendulous with the orifice oriented caudally; and (d) Type 4: creased or ridged papilla, where the ductal mucosa seems to extend distally, rather out of the papillary orifice, either on a ridge or in a crease. To assess the level of interobserver agreement, a web-based survey was sent out to 18 endoscopists, containing 50 sets of still images of the papilla, distributed between the four different types. Three months later a follow-up survey, with images from the first survey was sent to the same endoscopists. Results: Interobserver agreement was substantial (κ = 0.62, 95% confidence interval (CI) 0.58–0.65) and were similar for both experts and non-experts. The intraobserver agreement assessed with the second survey was also substantial (κ = 0.66, 95% CI 0.59–0.72). Conclusion: The proposed endoscopic classification of the papilla of Vater seems to be easy to use, irrespective of the level of experience of the endoscopist. It carries a substantial inter- and intraobserver agreement and now the clinical relevance of the four different papilla types awaits to be determined.
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| 8. |
- Koulaouzidis, Anastasios, et al.
(författare)
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Association Between Fecal Calprotectin Levels and Small-bowel Inflammation Score in Capsule Endoscopy : A Multicenter Retrospective Study
- 2016
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Ingår i: Digestive Diseases and Sciences. - : Springer Science and Business Media LLC. - 1573-2568 .- 0163-2116. ; 61:7, s. 2033-2040
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Accurate inflammation reporting in capsule endoscopy (CE) is important for diagnosis and monitoring of treatment of inflammatory bowel disease (IBD). Fecal calprotectin (FC) is a highly specific biomarker of gut inflammation. Lewis score (LS) was developed to standardize quantification of inflammation in small-bowel (SB) CE images.GOALS: Multicenter retrospective study aiming to investigate correlation between LS and FC in a large group of patients undergoing CE for suspected or known small-bowel IBD, and to develop a model for prediction of CE results (LS) based on FC levels.STUDY: Five academic centers and a district general hospital offering CE in UK, Finland, Sweden, Canada, and Israel. In total, 333 patients were recruited. They had small-bowel CE and FC done within 3 months.RESULTS: Overall, correlation between FC and LS was weak (r s: 0.232, P < 0.001). When two clinically significant FC thresholds (100 and 250 μg/g) were examined, the r s between FC and LS was 0.247 (weak) and 0.337 (moderate), respectively (P = 0.307). For clinically significant (LS ≥ 135) or negative (LS < 135) for SB inflammation, ROC curves gave an optimum cutoff point of FC 76 μg/g with sensitivity 0.59 and specificity 0.41.LIMITATIONS: Retrospective design.CONCLUSIONS: LS appears to show low correlation with FC as well as other serology markers of inflammation. FC does not appear to be a reliable biomarker for significant small-bowel inflammation. Nevertheless, FC level ≥ 76 μg/g may be associated with appreciable visual inflammation on small-bowel CE in patients with negative prior diagnostic workup.
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| 9. |
- Koulaouzidis, Anastasios, et al.
(författare)
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KID Project : an internet-based digital video atlas of capsule endoscopy for research purposes
- 2017
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Ingår i: Endoscopy International Open. - : Georg Thieme Verlag KG. - 2364-3722 .- 2196-9736. ; 5:6, s. 477-483
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND AIMS: Capsule endoscopy (CE) has revolutionized small-bowel (SB) investigation. Computational methods can enhance diagnostic yield (DY); however, incorporating machine learning algorithms (MLAs) into CE reading is difficult as large amounts of image annotations are required for training. Current databases lack graphic annotations of pathologies and cannot be used. A novel database, KID, aims to provide a reference for research and development of medical decision support systems (MDSS) for CE.METHODS: Open-source software was used for the KID database. Clinicians contribute anonymized, annotated CE images and videos. Graphic annotations are supported by an open-access annotation tool (Ratsnake). We detail an experiment based on the KID database, examining differences in SB lesion measurement between human readers and a MLA. The Jaccard Index (JI) was used to evaluate similarity between annotations by the MLA and human readers.RESULTS: The MLA performed best in measuring lymphangiectasias with a JI of 81 ± 6 %. The other lesion types were: angioectasias (JI 64 ± 11 %), aphthae (JI 64 ± 8 %), chylous cysts (JI 70 ± 14 %), polypoid lesions (JI 75 ± 21 %), and ulcers (JI 56 ± 9 %).CONCLUSION: MLA can perform as well as human readers in the measurement of SB angioectasias in white light (WL). Automated lesion measurement is therefore feasible. KID is currently the only open-source CE database developed specifically to aid development of MDSS. Our experiment demonstrates this potential.
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| 10. |
- Koulaouzidis, Anastasios, et al.
(författare)
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Macroscopic findings in collagenous colitis : A multi-center, retrospective, observational cohort study
- 2017
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Ingår i: Annals of Gastroenterology. - : Hellenic Society of Gastroenterology. - 1108-7471 .- 1792-7463. ; 30:3, s. 309-314
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Tidskriftsartikel (refereegranskat)abstract
- Background Collagenous colitis (CC) is by definition a histological diagnosis. However, colonoscopy often reveals characteristic endoscopic findings. The aim of this study was to evaluate the frequency and type of endoscopic findings in patients diagnosed with CC in 4 participating centers. Methods This was a retrospective study; the databases of 2 university hospitals in Edinburgh (Scotland) and Malmö (Sweden), and 2 district general hospitals in Tomelloso (Spain) and Gateshead (England) were interrogated for patients diagnosed with CC between May 2008 and August 2013. Endoscopy reports and images were retrieved and reviewed; data on lesions, sedation, bowel preparation and endoscopist experience were abstracted. Categorical data are reported as mean±SD. Fischer’s exact, chi-square and t (unpaired) tests were used to compare datasets. A two-tailed P-value of <0.05 was considered statistically significant. Results 607 patients (149 male, mean age 66.9±12.25 years) were diagnosed with CC. A total of 108/607 (17.8%) patients had one or more suggestive endoscopy findings: i.e., mucosal erythema/edema, 91/607 (15%); linear colonic mucosal defects, 12/607 (2%); or mucosal scarring, 5/607 (0.82%). For colonic mucosa erythema, there was no difference in the odds of finding erythema with the use of different bowel preparation methods (P=0.997). For colonic mucosal defects there was some evidence (P=0.005) that patients colonoscoped by experienced endoscopists had 87% less odds of developing such defects. Moreover, there was evidence that analgesia reduced the odds of developing mucosal defects by 84%. Conclusion A significant minority of patients with CC have endoscopic findings in colonoscopy. The description of such findings appears to be related to the endoscopist’s experience.
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| 11. |
- Koulaouzidis, Anastasios, et al.
(författare)
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Novel experimental and software methods for image reconstruction and localization in capsule endoscopy
- 2018
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Ingår i: Endoscopy International Open. - : Georg Thieme Verlag KG. - 2364-3722 .- 2196-9736. ; 6:2, s. 205-210
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Tidskriftsartikel (refereegranskat)abstract
- Background and study aims : Capsule endoscopy (CE) is invaluable for minimally invasive endoscopy of the gastrointestinal tract; however, several technological limitations remain including lack of reliable lesion localization. We present an approach to 3D reconstruction and localization using visual information from 2D CE images.Patients and methods : Colored thumbtacks were secured in rows to the internal wall of a LifeLike bowel model. A PillCam SB3 was calibrated and navigated linearly through the lumen by a high-precision robotic arm. The motion estimation algorithm used data (light falling on the object, fraction of reflected light and surface geometry) from 2D CE images in the video sequence to achieve 3D reconstruction of the bowel model at various frames. The ORB-SLAM technique was used for 3D reconstruction and CE localization within the reconstructed model. This algorithm compared pairs of points between images for reconstruction and localization.Results: As the capsule moved through the model bowel 42 to 66 video frames were obtained per pass. Mean absolute error in the estimated distance travelled by the CE was 4.1 ± 3.9 cm. Our algorithm was able to reconstruct the cylindrical shape of the model bowel with details of the attached thumbtacks. ORB-SLAM successfully reconstructed the bowel wall from simultaneous frames of the CE video. The "track" in the reconstruction corresponded well with the linear forwards-backwards movement of the capsule through the model lumen.Conclusion: The reconstruction methods, detailed above, were able to achieve good quality reconstruction of the bowel model and localization of the capsule trajectory using information from the CE video and images alone.
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| 12. |
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| 13. |
- Toth, Ervin, et al.
(författare)
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Video capsule colonoscopy in routine clinical practice
- 2017
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Ingår i: Annals of Translational Medicine. - : AME Publishing Company. - 2305-5839 .- 2305-5847. ; 5:9
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Tidskriftsartikel (refereegranskat)abstract
- Background: Colon capsule endoscopy (CCE) offers direct mucosal visualisation without sedation or gas insufflation required in conventional colonoscopy (CC). However, evidence for the role of CCE as an adjunct or alternative to CC remains equivocal. In this observational cohort study, we report our experience of using CCE to investigate patients with suspected colon pathology at a tertiary referral centre. Methods: From 2007-2015, consecutive patients requiring colonoscopy were recruited from a tertiary care centre in Malmo, Sweden. Data collected: patient demographics, indication for CCE, findings, bowel cleansing, colon transit time (CTT) and completeness of colon examination. Results: Seventy-seven patients (57 F/20 F, median age 56 years) were included. The reason for CCE was previously incomplete or refused CC in 39 and 26 cases, and follow up of previous findings in 12 cases, respectively. The main clinical indications were gastrointestinal (GI) bleeding (n=28; 36%) and suspected inflammatory bowel disease (IBD) or follow-up of known IBD (n=23; 30%). CCE was complete in 58/77 (75%) patients. In 3 patients the colon was not reached; in the other 16, the capsule reached the rectum (n=4), sigmoid (n=6), descending colon (n=5) and transverse colon (n=1). Findings were: normal CCE (n=15; 19%) colonic diverticula (n=29; 38%), polyps (n=17; 22%), active IBD (n=12; 16%), haemorrhoids (n=8; 10%), colonic angioectasia (n=4; 5%) and cancer (n=1; 1%). Small-bowel findings were recorded in 8 (10%) patients. All patients tolerated bowel preparation and CCE well. Two patients with an ulcerated small-bowel stricture and cancer respectively experienced temporary capsule retention with spontaneous resolution. Conclusions: CCE is a well-tolerated alternative to CC, but requires technological improvement and optimisation of clinical practice to meet current reference standards. Although further technical development is required, CCE may complement or even replace CC for certain clinical indications.
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| 14. |
- Vasilakakis, Michael, et al.
(författare)
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Follow-up on: optimizing lesion detection in small bowel capsule endoscopy and beyond: from present problems to future solutions
- 2019
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Ingår i: Expert Review of Gastroenterology and Hepatology. - : Informa UK Limited. - 1747-4124 .- 1747-4132. ; 13:2, s. 129-141
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: This review presents noteworthy advances in clinical and experimental Capsule Endoscopy (CE), focusing on the progress that has been reported over the last 5 years since our previous review on the subject. Areas covered: This study presents the commercially available CE platforms, as well as the advances made in optimizing the diagnostic capabilities of CE. The latter includes recent concept and prototype capsule endoscopes, medical approaches to improve diagnostic yield, and progress in software for enhancing visualization, abnormality detection, and lesion localization. Expert commentary: Currently, moving through the second decade of CE evolution, there are still several open issues and remarkable challenges to overcome.
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| 15. |
- Yung, Diana E., et al.
(författare)
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Capsule endoscopy in young patients with iron deficiency anaemia and negative bidirectional gastrointestinal endoscopy
- 2017
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Ingår i: United European Gastroenterology Journal. - : Wiley. - 2050-6406 .- 2050-6414. ; 5:7, s. 974-981
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Tidskriftsartikel (refereegranskat)abstract
- Background: Recent data imply young patients (age ≤50 years) undergoing small-bowel (SB) capsule endoscopy (CE) for iron deficiency anaemia (IDA) show higher diagnostic yield (DY) for sinister pathology. We aimed to investigate DY of CE in a large cohort of young IDA patients, and evaluate factors predicting significant SB pathology. Materials and methods: This was a retrospective, multicentre study (2010–2015) in consecutive, young patients (≤50 years) from 18 centres/12 countries, with negative bidirectional gastrointestinal (GI) endoscopy undergoing SBCE for IDA. Exclusion criteria: previous/ongoing obscure-overt GI bleeding; age <19 or >50 years; comorbidities associated with IDA. Data retrieved: SBCE indications; prior investigations; medications; SBCE findings; final diagnosis. Clinical and laboratory data were analysed by multivariate logistic regression. Results: Data on 389 young IDA patients were retrieved. In total, 169 (43.4%) were excluded due to incomplete clinical data; data from 220 (122F/98M; mean age 40.5 ± 8.6 years) patients were analysed. Some 71 patients had at least one clinically significant SBCE finding (DY: 32.3%). They were divided into two groups: neoplastic pathology (10/220; 4.5%), and non-neoplastic but clinically significant pathology (61/220; 27.7%). The most common significant but non-neoplastic pathologies were angioectasias (22/61) and Crohn’s disease (15/61). On multivariate analysis, weight loss and lower mean corpuscular volume(MCV) were associated with significant SB pathology (OR: 3.87; 95%CI: 1.3–11.3; p = 0.01; and OR: 0.96; 95%CI: 0.92–0.99; p = 0.03; respectively). Our model also demonstrates association between use of antiplatelets and significant SB pathology, although due to the small number of patients, definitive conclusions cannot be drawn. Conclusion: In IDA patients ≤50 years with negative bidirectional GI endoscopy, overall DY of SBCE for clinically significant findings was 32.3%. Some 5% of our cohort was diagnosed with SB neoplasia; lower MCV or weight loss were associated with higher DY for SB pathology.
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| 16. |
- Yung, Diana E., et al.
(författare)
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Clinical outcomes of negative small-bowel capsule endoscopy for small-bowel bleeding : A systematic review and meta-analysis
- 2017
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Ingår i: Gastrointestinal Endoscopy. - : Elsevier BV. - 0016-5107. ; 85:2, s. 2-317
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Tidskriftsartikel (refereegranskat)abstract
- Background and Aims: Small-bowel bleeding is the primary indication for capsule endoscopy (CE). Many experts advocate a "watch-and-wait" policy in negative CE. This meta-analysis examines the odds of rebleeding after negative index CE and the impact on long-term follow-up. Methods: A comprehensive literature search identified articles examining the rebleeding rate after negative CE. Demographic and clinical information with emphasis on outcomes was retrieved, pooled, and analyzed. Heterogeneity among studies was assessed using the I2 statistic. A random effects model was used as the pooling method because of high heterogeneity. Risk of bias was assessed using the quality assessment of diagnostic accuracy studies (QUADAS-2) tool. The primary outcome evaluated was the pooled odds ratios (ORs) for rebleeding after a negative CE for obscure GI bleeding (OGIB). Results: Twenty-six studies with 3657 patients were included. The pooled rate of rebleeding after negative CE was .19 (95% CI, .14-.25; . P < .0001). The pooled OR of rebleeding was .59 (95% CI, .37-.95; . P < .001). The effect was more pronounced in studies with a short follow-up (OR, .47; 95% CI, .24-.94; . P < .001). There was no statistically significant difference in rebleeding after CE for occult and overt OGIB. Prospective studies showed a lower OR of rebleeding of .24 (95% CI, .08-.73; . P = .01). Most studies were high quality. Conclusions: Our analysis shows that negative CE provides adequate evidence of a subsequently low risk of rebleeding. Such patients can therefore be safely managed with watchful waiting. However, patients who rebleed after 2 years may need to be investigated for a new source of blood loss.
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| 17. |
- Yung, Diana E, et al.
(författare)
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Clinical validity of flexible spectral imaging color enhancement (FICE) in small-bowel capsule endoscopy : a systematic review and meta-analysis
- 2017
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Ingår i: Endoscopy. - : Georg Thieme Verlag KG. - 0013-726X .- 1438-8812. ; 49:3, s. 258-269
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Forskningsöversikt (refereegranskat)abstract
- Patients and methods A comprehensive literature search was conducted. We measured pooled rate of lesion visualization improvement and improvement in lesion detection comparing FICE settings 1 – 3 and WLE, for angioectasias and ulcers/erosions. Pooled results were derived using the random-effects model because of high heterogeneity as measured by I 2. Repeated-measures analysis of variance (ANOVA) was used to measure differences in lesion detection between WLE and the three FICE modes. Results 13 studies were analyzed. All studies used the PillCam SB 1 and/or SB 2 devices. Most used experienced readers. Improvement in delineation had been investigated in 4 studies; in the 3 studies entered into the meta-analysis, using FICE setting 1, 89 % of angioectasias and 45 % of ulcer/erosions were considered to show improved delineation. For FICE settings 2 and 3, small proportions of images showed improved delineation. Heterogeneity of studies was high with I 2 > 90 % in 4/6 analyses. Lesion detection had been investigated in 10 studies; meta-analysis included 5 studies. Lesion detection did not differ significantly between any of the FICE modes and WLE. Conclusions Overall, the use of the three FICE modes did not significantly improve delineation or detection rate in SBCE. In pigmented lesions, FICE setting 1 performed better in lesion delineation and detection.
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