D Turner

Hebrew University of Jerusalem, Yerushalayim, Jerusalem District, Israel

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Publications (27)130.36 Total impact

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    ABSTRACT: OBJECTIVE: Data to support treatment algorithms in ambulatory paediatric UC are scarce. We aimed to explore the 1 year outcome in an inception cohort of paediatric UC patients and to identify early predictors of good outcome that might serve as short term treatment targets. DESIGN: A chart review of 115 children with new onset UC was performed (age 11±4.1 years; 58 (50%) males; 86 (75%) extensive colitis; 70 (61%) moderate-severe disease; 63 (55%) received steroids at baseline). We assessed the Paediatric Ulcerative Colitis Activity Index (PUCAI) and laboratory variables at the time of diagnosis and at 3 months, and endoscopy at diagnosis. RESULTS: The 3 month PUCAI was the strongest predictor of 1 year sustained steroid free remission (SSFR) (area under the receiver operating characteristic curve (AUROC)=0.7 (95% CI 0.6 to 0.8) and colectomy by 2 years (AUROC=0.75 (0.6 to 0.89)). SSFR was achieved in 9/54 (17%) children who had active disease (PUCAI ≥10) at 3 months (negative predictive value (NPV)=83%) and by 4/46 (8.6%) of those with a PUCAI score >10; (NPV=91%, positive predictive value=52%; p<0.001), implying that PUCAI >10 at 3 months has a probability of 9% for achieving SSFR versus 48% with a PUCAI value of ≤10. None of the variables at baseline was predictive of SSFR or colectomy (endoscopic severity, disease extent, age, PUCAI or C reactive protein/erythrocyte sedimentation rate/albumin/haemoglobin; all AUROC<0.6, p>0.05) but baseline PUCAI predicted subsequent acute severe colitis and the need for salvage medical therapy. CONCLUSIONS: Completeness of the early response appears more important than baseline UC severity for predicting outcome in children, and supports using PUCAI<10 as a feasible treatment goal. Our data suggest that treatment escalation should be considered with a PUCAI value of ≥10 at 3 months.
    Gut 04/2015; 64(4):580-8. · 13.32 Impact Factor
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    ABSTRACT: Background In the treatment of Crohn's disease (CD), mucosal healing has become a major goal, with the hope of avoiding intestinal damage from chronic inflammation. Magnetic resonance enterography (MRE) has emerged as a non-invasive means of monitoring inflammation and damage.AimsAs part of the development of MRE-based multi-item measures of inflammation and damage for paediatric studies, we carried out a systematic review and meta-analysis to identify MRE variables used to describe these two distinct concepts.Methods2501 studies of MRI and CD were identified. Studies written in any language reporting individual MRE signs for patients diagnosed with CD were included. Two-hundred-and-forty-four studies were fully reviewed and 62 were included (inflammation, n = 51; damage, n = 24). Sensitivity, specificity and associated confidence intervals were calculated, and hierarchical summary ROC curves were constructed for each MRE sign.ResultsA total of 22 MRE signs were used to reflect inflammation, and 9 to reflect damage. Diagnostic accuracy of MRE signs of inflammation and damage was heterogeneous; however, wall enhancement, mucosal lesions and wall T2 hyperintensity were the most consistently useful for inflammation (most sensitivities >80% and specificities >90%), and detection of abscess and fistula were most consistently useful for damage (most sensitivities >90%, specificities >95%).Conclusions Identifying the best MRE variables to reflect inflammation and damage will maximise the utility of this rapidly emerging technique and is the first stage of constructing MRE-based indices for evaluating inflammation and intestinal damage.
    Alimentary Pharmacology & Therapeutics 11/2014; DOI:10.1111/apt.13024 · 4.55 Impact Factor
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    ABSTRACT: BACKGROUND: Current guidelines recommend performance of oesophago-gastro-duodenoscopy at the time of diagnosis of hepatic cirrhosis to screen for oesophageal varices. These guidelines require people to undergo an unpleasant invasive procedure repeatedly with its attendant risks, despite the fact that half of the people do not have identifiable oesophageal varices 10 years after the initial diagnosis of cirrhosis. Video capsule endoscopy is a non-invasive test proposed as an alternative method for the diagnosis of oesophageal varices. OBJECTIVES: To determine the diagnostic accuracy of capsule endoscopy for the diagnosis of oesophageal varices in children or adults with chronic liver disease or portal vein thrombosis, irrespective of the aetiology. To investigate the accuracy of capsule endoscopy as triage or replacement of oesophago-gastro-duodenoscopy. SEARCH METHODS: We searched the Cochrane Hepato-Biliary Group Diagnostic Test Accuracy Studies Register (October 2013), MEDLINE (Ovid SP) (1950 to October 2013), EMBASE (Ovid SP) (1980 to October 2013), ACP Journal Club (Ovid SP) (1991 to October 2013), Database of Abstracts of Reviews of Effects (DARE) (Ovid SP) (third quarter), Health Technology Assessment (HTA) (Ovid SP) (third quarter), NHS Economic Evaluation Database (NHSEED) (Ovid SP) (third quarter), and Science Citation Index Expanded (SCI-EXPANDED) (ISI Web of Knowledge) (1955 to October 2013). We applied no language or document type restrictions. SELECTION CRITERIA: Studies that evaluated the diagnostic accuracy of capsule endoscopy for the diagnosis of oesophageal varices using oesophago-gastro-duodenoscopy as the reference standard in children or adults of any age, with chronic liver disease or portal vein thrombosis. DATA COLLECTION AND ANALYSIS: We followed the available guidelines provided in the Cochrane Handbook for Diagnostic Test of Accuracy Reviews. We calculated the pooled estimates of sensitivity and specificity using the bivariate model due to the absence of a negative correlation in the receiver operating characteristic (ROC) space and of a threshold effect. MAIN RESULTS: The search identified 16 eligible studies, in which only adults with cirrhosis were included. In one study, people with portal thrombosis were also included. We classified most of the studies at high risk of bias for the 'Participants selection' and the 'Flow and timing' domains. One study assessed the accuracy of capsule endoscopy for the diagnosis of large (high-risk) oesophageal varices. In the remaining15 studies that assessed the accuracy of capsule endoscopy for the diagnosis of oesophageal varices of any size in people with cirrhosis, 936 participants were included; the pooled estimate of sensitivity was 84.8% (95% confidence interval (CI) 77.3% to 90.2%) and of specificity 84.3% (95% CI 73.1% to 91.4%). Eight of these studies included people with suspected varices or people with already diagnosed or even treated varices, or both, introducing a selection bias. Seven studies including only people with suspected but unknown varices were at low risk of bias; the pooled estimate of sensitivity was 79.7% (95% CI 73.1% to 85.0%) and of specificity 86.1% (95% CI 64.5% to 95.5%). Six studies assessed the diagnostic accuracy of capsule endoscopy for the diagnosis of large oesophageal varices, associated with a higher risk of bleeding; the pooled sensitivity was 73.7% (95% CI 52.4% to 87.7%) and of specificity 90.5% (95% CI 84.1% to 94.4%). Two studies also evaluated the presence of red marks, which are another marker of high risk of bleeding; the estimates of sensitivity and specificity varied widely. Two studies obtained similar results with the use of a modified device as index test (string capsule). Due to the absence of data, we could not perform all planned subgroup analyses. Interobserver agreement in the interpretation of capsule endoscopy results and any adverse event attributable to capsule endoscopy were poorly assessed and reported. Only four studies evaluated the interobserver agreement in the interpretation of capsule endoscopy results: the concordance was moderate. The participants' preferences for capsule endoscopy or oesophago-gastro-duodenoscopy were reported differently but seemed in favour of capsule endoscopy in nine of 10 studies. In 10 studies, participants reported some minor discomfort on swallowing the capsule. Only one study identified other significant adverse events, including impaction of the capsule due to previously unidentified oesophageal strictures in two participants. No adverse events were reported as a consequence of the reference standard. AUTHORS' CONCLUSIONS: We cannot support the use of capsule endoscopy as a triage test in adults with cirrhosis, administered before oesophago-gastro-duodenoscopy, despite the low incidence of adverse events and participant reports of being better tolerated. Thus, we cannot conclude that oesophago-gastro-duodenoscopy can be replaced by capsule endoscopy for the detection of oesophageal varices in adults with cirrhosis. We found no data assessing capsule endoscopy in children and in people with portal thrombosis.
    Cochrane database of systematic reviews (Online) 10/2014; 10(CD008760). DOI:10.1002/14651858.CD008760.pub2. · 5.94 Impact Factor
  • Journal of Crohn s and Colitis 09/2014; 8:S410. DOI:10.1016/S1873-9946(14)50062-1 · 3.56 Impact Factor
  • Journal of Crohn s and Colitis 09/2014; 8:S406. DOI:10.1016/S1873-9946(14)50046-3 · 3.56 Impact Factor
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    Journal of Crohn s and Colitis 09/2014; 8:S422. DOI:10.1016/S1873-9946(14)50096-7 · 3.56 Impact Factor
  • M.L. Greer, D. Turner
    Journal of Crohn s and Colitis 09/2014; 8:S406. DOI:10.1016/S1873-9946(14)50048-7 · 3.56 Impact Factor
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    ABSTRACT: Thiopurines are effective for maintenance of remission in inflammatory bowel disease (IBD) in only about half of patients. Predictors of response may assist in selecting the most appropriate patients for thiopurine therapy. Thiopurines inhibit Rac1, a GTPase that exerts an anti-apoptotic effect on T-lymphocytes. A genetic association was recently demonstrated between a Rac1 single nucleotide polymorphism (SNP) and poorer response to thiopurines in adult patients with Crohn's disease. We aimed to determine whether Rac1 SNPs are associated with response to thiopurines in children with IBD. Children with IBD treated with thiopurines were prospectively followed for one year and were genotyped for three Rac1 SNPs previously found to be relevant to IBD: rs10951982, rs4720672 and rs34932801. The rate of sustained steroid-free remission (SSFR) without treatment escalation by 12 months was compared between wild types and heterozygotes. 59 patients were studied (63% male, 80% Crohn's, mean age 13 ± 4.1). 19/41 wild type (46%) and 9/15 (60%) heterozygotes for rs10951982 were in SSFR (p = 0.55). Similarly, 21/45 (47%) WT and 8/12 (67%) heterozygotes for rs4720672 were in remission (p = 0.33). Finally, 21/45 (47%) WT and 3/5 (60%) heterozygotes for rs34932801 were in remission (p = 0.66). All three comparisons remained non-significant in a sensitivity analysis of only the Crohn's disease patients. We did not find an association between three Rac1 SNPs and thiopurine effectiveness by 12 months in a prospective study of children with IBD. Other predictors of response should be sought in order to optimize patient selection for thiopurine therapy.
    Journal of Crohn s and Colitis 09/2014; 8:S428. DOI:10.1016/S1873-9946(14)50117-1 · 3.56 Impact Factor
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    ABSTRACT: Children and adolescents with Crohn's disease (CD) present often with a more complicated disease course compared to adult patients. In addition, the potential impact of CD on growth, pubertal and emotional development of patients underlines the need for a specific management strategy of pediatric-onset CD. To develop the first evidenced based and consensus driven guidelines for pediatric-onset CD an expert panel of 33 IBD specialists was formed after an open call within the European Crohn's and Colitis Organisation and the European Society of Pediatric Gastroenterolog, Hepatology and Nutrition. The aim was to base on a thorough review of existing evidence a state of the art guidance on the medical treatment and long term management of children and adolescents with CD, with individualized treatment algorithms based on a benefit-risk analysis according to different clinical scenarios. In children and adolescents who did not have finished their growth, exclusive enteral nutrition (EEN) is the induction therapy of first choice due to its excellent safety profile, preferable over corticosteroids, which are equipotential to induce remission. The majority of patients with pediatric-onset CD require immunomodulator based maintenance therapy. The experts discuss several factors potentially predictive for poor disease outcome (such as severe perianal fistulizing disease, severe stricturing/penetrating disease, severe growth retardation, panenteric disease, persistent severe disease despite adequate induction therapy), which may incite to an anti-TNF-based top down approach. These guidelines are intended to give practical (whenever possible evidence-based) answers to (pediatric) gastroenterologists who take care of children and adolescents with CD; they are not meant to be a rule or legal standard, since many different clinical scenario exist requiring treatment strategies not covered by or different from these guidelines.
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    ABSTRACT: Data to support treatment algorithms in ambulatory paediatric UC are scarce. We aimed to explore the 1 year outcome in an inception cohort of paediatric UC patients and to identify early predictors of good outcome that might serve as short term treatment targets.
    Journal of Crohn s and Colitis 02/2014; 8:S9. DOI:10.1136/gutjnl-2014-306999 · 3.56 Impact Factor
  • Journal of Crohn s and Colitis 02/2013; 7:S123-S124. DOI:10.1016/S1873-9946(13)60306-2 · 3.56 Impact Factor
  • Digestive and Liver Disease 10/2012; 44:S284. DOI:10.1016/S1590-8658(12)60725-7 · 2.89 Impact Factor
  • R Lev-Tzion, D Turner
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    ABSTRACT: The incidence of pediatric inflammatory bowel disease (IBD) continues to rise in most countries. Approximately 20-25% of IBD patients present before the age of 20, and their management is associated with many unique challenges. These challenges stem both from the inherent differences between children and adults, and from the differences in the nature and course of the disease. Children with IBD are more likely than adults to present with extensive disease ‑ both in Crohn's disease (CD) and ulcerative colitis (UC). Diagnosis requires a high index of suspicion, as children may present with less typical signs such as poor growth and delayed puberty. In the very young patients with inflammatory bowel disease, the pediatric clinician must consider a broader range of immunological and allergic disorders. Optimal management requires recognition of pediatric patterns of presentation, efficacy and adverse-effect profiles, and understanding monitoring aspects unique to pediatrics. These aspects include pediatric disease-related psychological issues, adherence to therapy and transition to adult care. Inadequate attention to growth, puberty or bone health in childhood can result in long-term consequences, such as impaired adult height and increased risk of fractures. Management of pediatric IBD and prevention of adverse long-term consequences relies on a variety of therapies well-known to the adult practitioner, along with therapies that are not widespread in adults, most notably exclusive enteral nutrition (EEN). The latter is as effective as corticosteroids in achieving clinical remission in children, while achieving better results than corticosteroids with regard to mucosal healing and growth. This review discusses the broad variety of issues that form the basis for management of pediatric IBD.
    Minerva gastroenterologica e dietologica 06/2012; 58(2):137-50.
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    ABSTRACT: Assessment of fecal calprotectin, a surrogate marker of mucosal inflammation, is a promising means to monitor therapeutic response in pediatric inflammatory bowel disease, especially if the result is readily available. We tested the performance of a novel calprotectin rapid test, Quantum Blue, versus the conventional enzyme-linked immunosorbent assay in 134 stool samples from 56 pediatric patients with Crohn disease. The intraclass correlation coefficient analysis reflected good agreement (intraclass correlation coefficient 0.97 [95% confidence interval 0.95-0.98]) but agreement was better in lower values, where dilutions were not required. Using a cutoff of 100 μg/g for normal values, the percentage agreement between the 2 tests was 87%. The optimal cutoff values to guide clinical decisions in the therapy of inflammatory bowel disease have yet to be determined.
    Journal of pediatric gastroenterology and nutrition 03/2012; 55(4):436-439. DOI:10.1097/MPG.0b013e318253cff1 · 2.87 Impact Factor
  • Journal of Crohn s and Colitis 02/2012; 6:S84. DOI:10.1016/S1873-9946(12)60208-6 · 3.56 Impact Factor
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    ABSTRACT: There are no current recommendations for bowel cleansing before colonoscopy in children. The Israeli Society of Pediatric Gastroenterology and Nutrition (ISPGAN) established an iterative working group to formulate evidence-based guidelines for bowel cleansing in children prior to colonoscopy. Data were collected by systematic review of the literature and via a national-based survey of all endoscopy units in Israel. Based on the strength of evidence, the Committee reached consensus on six recommended protocols in children. Guidelines were finalized after an open audit of ISPGAN members. Data on 900 colonoscopies per year were accrued, which represents all annual pediatric colonoscopies performed in Israel. Based on the literature review, the national survey, and the open audit, several age-stratified pediatric cleansing protocols were proposed: two PEG-ELS protocols (polyethylene-glycol with electrolyte solution); Picolax-based protocol (sodium picosulphate with magnesium citrate); sodium phosphate protocol (only in children over the age of 12 years who are at low risk for renal damage); stimulant laxative-based protocol (e. g. bisacodyl); and a PEG 3350-based protocol. A population-based analysis estimated that the acute toxicity rate of oral sodium phosphate is at most 3/7320 colonoscopies (0.041 %). Recommendations on diet and enema use are provided in relation to each proposed protocol. There is no ideal bowel cleansing regimen and, thus, various protocols are in use. We propose several evidence-based protocols to optimize bowel cleansing in children prior to colonoscopy and minimize adverse events.
    Endoscopy 12/2010; 42(12):1063-70. DOI:10.1055/s-0030-1255646 · 5.20 Impact Factor
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    ABSTRACT: To compare four faecal markers for their ability to predict steroid refractoriness in severe paediatric ulcerative colitis (UC). Construct validity and responsiveness to change were also assessed. This was a prospective multicentre cohort study. Stool samples from 101 children (13.3 + or - 3.6 years; Pediatric UC Activity Index (PUCAI) at admission 72 + or - 12 points) were obtained at the third day of intravenous steroid therapy. Repeated samples at discharge were obtained from 24 children. Predictive validity was assessed using diagnostic utility statistics to predict steroid failure (ie, the need for salvage treatment). Concurrent validity was assessed using correlational analysis with the following constructs: PUCAI, Lindgren and Seo scores, physician's global assessment, albumin, erythrocyte sedimentation rate and C-reactive protein (CRP). Responsiveness was assessed using test utility and correlational strategies. Median values (IQR) were very high at baseline for all four markers (calprotectin 4215 microg/g (2297-8808); lactoferrin 212 microg/g (114-328); M2-pyruvate kinase (M2-PK) 363 U/g (119-3104); and S100A12 469 microg/g (193-1112)). M2-PK was numerically superior to the other three markers and CRP in predicting response to corticosteroid treatment (area under the receiver operating characteristic (ROC) curve 0.75 (95% CI 0.64 to 0.85; p<0.001) vs <0.65 for the others). However, it did not add to the predictive ability of the PUCAI (area under the ROC 0.81 (95% CI 0.73 to 0.89)). M2-PK also had the highest construct validity but with a modest mean correlation with all constructs (r=0.3; p<0.05). None of the markers was responsive to change (Spearman's rho correlation with change in the PUCAI <0.1; p>0.05, area under the ROC curve <0.65; p>0.05). The four markers were greatly elevated in severe paediatric UC. Only M2-PK had good construct and predictive validity, and none was responsive to change. The PUCAI, a simple clinical index, performed better than the faecal markers in predicting outcome following a course of intravenous corticosteroids in severe UC.
    Gut 09/2010; 59(9):1207-12. DOI:10.1136/gut.2010.211755 · 13.32 Impact Factor
  • Cochrane database of systematic reviews (Online) 01/2010; · 5.70 Impact Factor
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    ABSTRACT: Comparison of bowel preparation for colonoscopy in children with either Pico-Salax (sodium picosulphate with magnesium citrate) or polyethylene glycol with electrolyte solution (PEG-ELS). In this investigator-blinded, randomized controlled trial, 83 children (12.5 +/- 3.1 years) requiring elective colonoscopy at a referral hospital were randomly allocated to Pico-Salax (n = 43) or PEG-ELS (n = 40), and an intention-to treat analysis was applied. Pico-Salax was administered in two doses, one the evening before and one on the morning of the procedure. PEG-ELS was administered over 4 hours. Efficacy was scored using the Ottawa scale and other constructs. Tolerability and toxicity were measured by patient and nursing questionnaires and serum biochemistry. 35 of Pico-Salax patients (81 %) were satisfied or very satisfied with the cleanout, compared with 19 (48 %) in the PEG-ELS group (P = 0.001). No differences were found in bowel cleanout effectiveness, as judged by the Ottawa score (P = 0.24), completion rates (P = 0.69), colonoscopy duration (P = 0.59), need for enemas (P = 0.25), or physician's global impression (P = 0.7). Except for one case of mild dehydration in the Pico-Salax group, no clinically significant adverse events were recorded. Serum biochemistry results were similar between groups except for more hypermagnesemia associated with Pico-Salax and hypokalemia with PEG-ELS; neither was clinically significant. Children tolerate Pico-Salax better than PEG-ELS for bowel cleanout before colonoscopy. This study did not demonstrate superiority of effectiveness or safety for either regimen.
    Endoscopy 12/2009; 41(12):1038-45. DOI:10.1055/s-0029-1215333 · 5.20 Impact Factor
  • Inflammatory Bowel Diseases 09/2009; 3(1):5-5. DOI:10.1016/S1873-9954(09)70023-0 · 5.48 Impact Factor

Publication Stats

305 Citations
130.36 Total Impact Points

Institutions

  • 2010–2014
    • Hebrew University of Jerusalem
      • Shaare Zedek Medical Center
      Yerushalayim, Jerusalem District, Israel
  • 2006–2014
    • Shaare Zedek Medical Center
      • Department of Pediatrics
      Yerushalayim, Jerusalem District, Israel
  • 2012
    • Washington University in St. Louis
      San Luis, Missouri, United States
  • 2007–2008
    • SickKids
      • Division of Gastroenterology, Hepatology and Nutrition
      Toronto, Ontario, Canada
    • University of Toronto
      • Hospital for Sick Children
      Toronto, Ontario, Canada