Person: Moss, Alan
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Moss
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Alan
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Moss, Alan
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Publication Outcomes after escalation of infliximab therapy in ambulatory patients with moderately active ulcerative colitis(Wiley, 2012-01-13) Rostholder, E; Ahmed, A; Cheifetz, AS; Moss, AlanBackground Infliximab (IFX) therapy escalation during maintenance treatment occurs frequently in clinical practice in patients with ulcerative colitis (UC). Outcomes for these patients have not been described. Aim To describe the prevalence of, and outcomes after, IFX escalation during maintenance therapy in patients with moderate-severe UC. Methods Retrospective observational study of clinical outcomes in ambulatory patients with moderate-severe UC treated with maintenance IFX. Results Fifty-six ambulatory patients received IFX for moderate-severe UC; fifty (89%) responded and proceeded to maintenance therapy. Mean duration of maintenance therapy was 14 months, with mean follow-up of 38 months. Twenty-seven patients (54%) required IFX therapy escalation after a mean of 6 maintenance infusions. Clinical remission was noted in 36% of the entire cohort (18/50) at 12 months; 19% in the escalation group, and 56% in the non-escalation group. Patients who required IFX escalation were less likely to be in clinical remission at 12 months (OR 0.2, 95% CI 0.1-0.6, p=0.01) when compared to those who did not. During the follow-up period, 27% of patients required a colectomy, and the mean time to colectomy was 17 months. Patients in the escalation group required a colectomy in 33% of cases, compared with 21% of non-escalation patients. Conclusions A significant proportion of ambulatory patients with UC treated with maintenance IFX required therapy escalation over time. This was associated with lower remission, and higher colectomy, rates.Publication Meta-analysis: the impact of disease activity at conception on disease activity during pregnancy in patients with inflammatory bowel disease(Wiley, 2013-07-15) Abhyankar, A; Ham, M; Moss, AlanBackground The rate of IBD exacerbation during pregnancy varies in the published literature. Aim We sought to perform a systematic review and meta-analysis of the effects of disease activity at conception on disease course during pregnancy in women with IBD. Methods Published studies and abstracts from standard sources were screened for appropriate studies. Data was pooled and analyzed using funnel and forest plots. Quality assessment scores were given using GRADE criteria. Results Fourteen studies were eligible for inclusion; ten studies contained patients with UC (N=1130), and six studies contained patients with CD (N=590). In patients with UC there was a significantly higher risk ratio of active disease during pregnancy in patients who commenced pregnancy with active disease (55%), when compared with those in remission at conception (36%) (RR 2.0, 95% CI: 1.5–3, p<0.001). This risk was also higher in patients with CD, (RR 2.0, 95% CI: 1.2–3.4, p=0.006). Thirteen of the studies rated “low” in all domains of a quality assessment, and there was significant statistical heterogeneity. Conclusions Patients with IBD who conceive when their disease is active are more likely to have active disease during pregnancy than those who conceive when in remission. All studies used in this analysis had a high risk of bias therefore further studies are required.Publication Cause for controversy? Infliximab in the treatment of ulcerative colitis: an update(Dove Press, 2009-12-09) Lawlor, GO; Moss, AlanInfliximab is a monoclonal antibody against tumor necrosis factor (TNF) which has become an established therapy for Crohn’s disease over the last 10 years. Given the similarities between Crohn’s disease and ulcerative colitis (UC), it is no surprise that gastroenterologists have used infliximab in patients with UC who have failed other therapies. Although the initial controlled trials with infliximab in steroid-refractory disease were unimpressive, subsequent controlled trials have demonstrated the efficacy of infliximab in both moderate to severe disease, and as rescue-therapy to avoid colectomy. The long-term remission rates, colectomy-sparing effects, and the impact of concomitant immunomodulator therapy, remain to be determined in these patients. Whether infliximab is a superior strategy to cyclosporine in patients with steroid-refractory disease is controversial. This review examines the data on the efficacy and safety of infliximab as an induction and maintenance agent for UC.Publication Novel treatment options for ulcerative colitis(OMICS Publishing Group, 2013) Vaughn, Byron P; Moss, AlanThe approved treatment options for patients with ulcerative colitis (UC) are currently limited to mesalamine or immunosuppressants. Patients who do not respond to mesalamine-based therapy can be treated with immunomodulators or anti-TNF antibody therapy. Failure or adverse reactions to these medications leaves the patient with little choice other than colectomy. However, novel insights into the pathogenic drivers of UC have led to new developments in drugs that promise clinical efficacy via modulation of targeted pathways. Given the impending expansion of therapeutic options for patients with UC, clinicians and researchers should be familiar with these mechanisms of action. In addition, the typical ‘step-up’ treatment paradigm for UC will likely need to be reshaped to allow for a more personalized approach to treating UC.Publication The Burden of Inflammatory Bowel Disease: A Patient-Reported Qualitative Analysis and Development of a Conceptual Model(Ovid Technologies (Wolters Kluwer Health), 2014) Devlen, Jennifer; Beusterien, Kathleen; Yen, Linnette; Ahmed, Awais; Cheifetz, Adam S.; Moss, AlanBackground The aim of this study was to describe the impacts of inflammatory bowel disease (IBD) from the patients’ perspective, and to inform the development of a conceptual model. Methods Focus groups and one-on-one interviews were undertaken in adult patients with IBD. Transcripts from the focus groups and interviews were analyzed to identify themes and links between themes, assisted by qualitative data software MaxQDA. Themes from the qualitative research were supplemented with those reported in the literature and concepts included in IBD-specific patient-reported outcome (PRO) measures. Results Twenty-seven patients participated. Key physical symptoms included pain, bowel-related symptoms such as frequency, urgency, incontinence, diarrhea, passing blood, and systemic symptoms such as weight loss and fatigue. Participants described continuing and variable symptom experiences. IBD symptoms caused immediate disruption of activities but also had ongoing impacts on daily activities, including dietary restrictions, lifestyle changes, and maintaining close proximity to a toilet. More distal impacts included interference with work, school, parenting, social and leisure activities, relationships, and psychological well-being. The inconvenience of rectal medications, refrigerated biologics, and medication refills emerged as novel burdens not identified in existing PRO measures. Conclusions IBD symptoms cause immediate disruption in activities, but patients may continue to experience some symptoms on a chronic basis. The conceptual model presented here may be useful for identifying target concepts for measurement in future studies in IBD.Publication Iron Replacement in Patients with Inflammatory Bowel Disease – A Systematic Review and Meta-Analysis(Oxford University Press (OUP), 2015-08) Abhyankar, Anita; Moss, AlanBackground A number of controlled trials and prospective studies have compared intravenous (IV) to oral (PO) iron for the treatment of IDA, with mixed results. Methods We conducted a systematic review of trials published to 2014 that compared IV to PO iron to treat iron deficiency in patients with IBD. Meta-analysis was performed to generate effect estimates. Quality assessment was also performed according to GRADE criteria. Results Five studies met our inclusion criteria, enrolling 694 patients. For the primary outcome of ‘response’ (Hb rise >2g/dl), there was no significant difference between IV or PO iron; risk ratio (RR) for response with IV was 1.08 (95% CI 0.9, 1.2, p=0.2). For the secondary outcome of mean change in Hb (g/dl), the mean difference between PO and IV iron was not statistically significant (mean difference 0.6g/dL, 96% CI −0.1, 1.3, p=0.08). IV iron was associated with a significantly greater initial rise in serum ferritin compared to PO iron (mean difference 89ng/ml, 95% CI 29, 148, p=0.003). There was a lower risk of withdrawal due to adverse events in these trials in the IV iron cohorts when compared to PO iron (RR 0.4, 95% CI 0.1, 1.0, p=0.05). Conclusions We found no significant difference between IV and PO iron in correcting iron-deficiency anemia in patients with IBD in this meta-analysis. Patients who received IV iron had a greater rise in serum ferritin, and were less likely to stop treatment due to adverse events, when compared to those who received PO iron.Publication Characteristics of Inflammatory Bowel Disease Serology in Patients With Indeterminate Colitis(Ovid Technologies (Wolters Kluwer Health), 2014) Sura, Siddharth P.; Ahmed, Awais; Cheifetz, Adam S.; Moss, AlanGoals and Background Inflammatory bowel disease (IBD) serology testing is often used in patients with indeterminate colitis (IC) to help distinguish between ulcerative colitis (UC) and Crohn’s disease (CD). We investigated the performance of serology testing in predicting future diagnosis in this setting. Study Observational study of individuals with IC at a single center who underwent IBD serology testing (pANCA, ASCA and anti-OmpC) and had at least 12 months follow-up from time of serology result. Results 117 individuals with IC and 1 year follow-up data were enrolled. All IC patients had endoscopic and histologic evidence of colitis at enrollment. One year after serology testing, 58 (50%) individuals with IC were diagnosed with UC, 49 (42%) with CD, and 10 (9%) remained labeled with IC. The sensitivity/specificity of an initial positive pANCA for a subsequent diagnosis of UC was 78%/44%. For ASCA and anti-OmpC, the results were 18%/84% and 27%/75%, respectively, for a subsequent diagnosis of CD. A positive pANCA test was associated with a likelihood ratio (LR) of 1.4 (95% CI: 1.1–1.8) for a subsequent diagnosis of UC at 1 year. Neither positive ASCA (LR 1.1; 95% CI: 0.5–2.5) nor anti-OmpC (LR 1.1; 95% CI: 0.6–2.0) was associated with a subsequent diagnosis CD in patients with IC. Conclusions The disease phenotype in the majority of individuals initially labeled with IC evolved to be more consistent with either UC or CD on follow-up. pANCA, ASCA, and anti-OmpC, individually, were of limited utility in predicting a patient’s subsequent disease phenotype.Publication In Silico Promoter Analysis can Predict Genes of Functional Relevance in Cell Proliferation: Validation in a Colon Cancer Model(Sage, 2007-02) Moss, Alan; Doran, P; MacMathuna, P.Specific combinations of transcription-factor binding sites in the promoter regions of genes regulate gene expression, and thus key functional processes in cells. Analysis of such promoter regions in specific functional contexts can be used to delineate novel disease-associated genes based on shared phenotypic properties. The aim of this study was to utilize promoter analysis to predict cell proliferation-associated genes and to test this method in colon cancer cell lines. We used freely-available bioinformatic techniques to identify cell-proliferation-associated genes expressed in colon cancer, extract a shared promoter module, and identify novel genes that also contain this module in the human genome. An EGRF/ETSF promoter module was identified as prevalent in proliferation-associated genes from a colon cancer cDNA library. We detected 30 other genes, from the known promoters of the human genome, which contained this proliferation-associated module. This group included known proliferation-associated genes, such as HERG1 and MCM7, and a number of genes not previously implicated in cell proliferation in cancer, such as TSPAN3, Necdin and APLP2. Suppression of TSPAN3 and APLP2 by siRNA was performed and confirmed by RT-PCR. Inhibition of these genes significantly inhibited cell proliferation in colon cancer cell lines. This study demonstrates that promoter analysis can be used to identify novel cancer-associated genes based on shared functional processes.Publication Prevention of post-operative recurrence of Crohn’s disease(Baishideng Publishing Group Inc., 2014) Vaughn, Byron; Moss, AlanEndoscopic and clinical recurrence of Crohn’s disease (CD) is a common occurrence after surgical resection. Smokers, those with perforating disease, and those with myenteric plexitis are all at higher risk of recurrence. A number of medical therapies have been shown to reduce this risk in clinical trials. Metronidazole, thiopurines and anti-tumour necrosis factors (TNFs) are all effective in reducing the risk of endoscopic or clinical recurrence of CD. Since these are preventative agents, the benefits of prophylaxis need to be weighed-against the risk of adverse events from, and costs of, therapy. Patients who are high risk for post-operative recurrence should be considered for early medical prophylaxis with an anti-TNF. Patients who have few to no risk factors are likely best served by a three-month course of antibiotics followed by tailored therapy based on endoscopy at one year. Clinical recurrence rates are variable, and methods to stratify patients into high and low risk populations combined with prophylaxis tailored to endoscopic recurrence would be an effective strategy in treating these patients.Publication Nephrolithiasis in patients with inflammatory bowel disease in the community(Dove Medical Press, 2013) Cury, Dídia Bismara; Moss, Alan; Schor, NestorBackground: Inflammatory bowel disease (IBD) has been associated with renal stone formation. The objective of this study was to determine prospectively the prevalence of nephrolithiasis in a community-based population of patients with IBD and to analyze factors associated with renal calculus formation. Methods: Screening renal ultrasound was performed in a well characterized cohort of patients seen between 2009 and 2012 at an IBD clinic. We enrolled 168 patients, including 93 with Crohn’s disease and 75 with ulcerative colitis. Clinical and phenotypic variables associated with asymptomatic nephrolithiasis were determined. Results: Nephrolithiasis was detected in 36 patients with Crohn’s disease and in 28 patients with ulcerative colitis (38% for both). Although none of the patients had been previously hospitalized for symptomatic nephrolithiasis, nine with Crohn’s disease and five with ulcerative colitis had recurrent urinary tract infections or hydronephrosis. In patients with Crohn’s disease, ileocolonic (L3) disease was associated with a greater risk of nephrolithiasis than was ileal (L1) or colonic (L2) disease (odds ratio [OR] 2.3, 95% confidence interval [CI] 1.8–7). Active ulcerative colitis (regardless of severity) represented a significant risk factor for formation of renal calculi (OR 4.2, 95% CI 1.1–15, P = 0.02). Conclusion: In surgery-naïve patients with IBD in the community, asymptomatic nephrolithiasis is common and should be considered when renal dysfunction or infection is detected.