37 results on '"Loftus, E"'
Search Results
2. Physical cluster theory of point defect interactions. II. Application to AgCl doped with CdCl2.
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Allnatt, A. R. and Loftus, E.
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- 1973
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3. A17 EFFICACY AND SAFETY OF FILGOTINIB AS MAINTENANCE THERAPY FOR PATIENTS WITH MODERATELY TO SEVERELY ACTIVE ULCERATIVE COLITIS: RESULTS FROM THE PHASE 2B/3 SELECTION STUDY.
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Peyrin-Biroulet, L, Loftus, E V, Danese, S, Vermeire, S, Sandborn, W J, Fogel, R, Nijhawan, S, Kempinski, R, Filip, R, Hospodarskyy, I, McNally, J, Yun, C, Zhao, S, Liu, X, Tasset, C, Besuyen, R, Watanabe, M, Schreiber, S, Rogler, G, and Hibi, T
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- 2021
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4. A15 EFFICACY AND SAFETY OF FILGOTINIB AS INDUCTION THERAPY FOR PATIENTS WITH MODERATELY TO SEVERELY ACTIVE ULCERATIVE COLITIS: RESULTS FROM THE PHASE 2B/3 SELECTION STUDY.
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Feagan, B G, Loftus, E V, Danese, S, Vermeire, S, Sandborn, W J, Ritter, T, Mehta, R, Seidler, U, Seibold, F, Beales, I, Kim, H, McNally, J, Yun, C, Zhao, S, Liu, X, Tasset, C, Besuyen, R, Watanabe, M, Schreiber, S, and Rogler, G
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- 2021
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5. Immune modulator therapy for microscopic colitis in a case series of 73 patients.
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Cotter, T. G., Kamboj, A. K., Hicks, S. B., Tremaine, W. J., Loftus, E. V., and Pardi, D. S.
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COLITIS treatment ,DIARRHEA ,THERAPEUTICS ,IMMUNOLOGICAL adjuvants ,ADRENOCORTICAL hormones ,MEDICAL microscopy - Abstract
Background Microscopic colitis ( MC) is a common cause of chronic diarrhoea. Various treatment options have been described, but there are limited data describing outcomes of corticosteroid-sparing treatments. Aim To evaluate the outcomes of patients with active MC treated with immune modulators. Methods All patients seen at Mayo Clinic, Rochester between January 1, 1997 and November 30, 2016 with a histological diagnosis of MC were identified. Patients treated with an immune modulator of interest were selected and clinical outcomes recorded. Results Seventy-three MC patients (50 collagenous colitis and 23 lymphocytic colitis) with a median disease duration of 24 months (range, 7-60) were included. The indications for treatment were budesonide-refractoriness in 66%, budesonide dependence in 29%, and budesonide intolerance in 5%. Median age was 51.8 years (range, 43.4-63.1) and 61 (84%) were female. Thiopurines were used in 49 patients (67%) for a median of 4 months (range, 1.5-15). Complete and partial response occurred in 43% and 22% respectively. Adverse effects resulting in therapy cessation occurred in 17 patients (35%). Twelve patients (16%) were treated with methotrexate for a median of 14 months (3-18.8). Complete and partial response occurred in 58% and 17%, respectively. Anti- TNF therapy was used in 10 patients (14%) for a median of 4 months (range, 2.3-5.5). Complete response occurred in four patients and partial response in four patients. Conclusions The majority of patients with active MC responded to thiopurines, methotrexate, or anti- TNF therapy. Larger controlled studies are required to confirm the efficacy and safety of these medications in MC. [ABSTRACT FROM AUTHOR]
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- 2017
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6. Comparative effectiveness and safety of infliximab and adalimumab in patients with ulcerative colitis.
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Singh, S., Heien, H. C., Sangaralingham, L. R., Schilz, S. R., Kappelman, M. D., Shah, N. D., and Loftus, E. V.
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INFLIXIMAB ,ADALIMUMAB ,MEDICATION safety ,DRUG efficacy ,ULCERATIVE colitis ,COLITIS treatment ,THERAPEUTICS - Abstract
Background Real-world comparative benefits and risks of infliximab ( IFX) and adalimumab ( ADA) in patients with ulcerative colitis ( UC) are unclear. Aim To evaluate the comparative effectiveness and safety of IFX and ADA in patients with UC who were new users of anti- TNF agents. Methods Using an administrative claims database (Optum Labs Data Warehouse), we identified patients who received first anti- TNF ( IFX, ADA) prescription after a 12-month period without any anti- TNF treatment (baseline), and with a minimum 6-month follow-up after anti- TNF initiation. Primary outcome measures were: all-cause and UC-related hospitalisation, abdominal surgery, corticosteroid use >60 days after starting anti- TNF, and serious infections. We performed 2:1 propensity-score matched Cox proportional hazard analysis, and inverse probability-of-treatment weight ( IPTW) analysis, accounting for healthcare utilisation, comorbidities and use of UC-related medication. Results We included 1400 new users of anti- TNF agents (age, 43 ± 15 years; 52% males), from 2006 to 2014. On propensity-score matched analysis, there was no significant difference in the risk of UC-related hospitalisation [ IFX vs. ADA; adjusted hazard ratio ( aHR), 1.04; 95% confidence interval ( CI) 0.71-1.51], corticosteroid use ( aHR, 0.85; 95% CI, 0.68-1.06) and serious infections ( aHR, 0.62; 95% CI, 0.29-1.34) between IFX- and ADA-treated patients; the number of surgical events was very small. On IPTW analysis, risk of corticosteroid use was significantly lower in IFX - as compared to ADA - treated patients ( aHR, 0.82; 95% CI, 0.68-0.99). Results were stable on multiple sensitivity analyses. Conclusions In a large retrospective cohort of patients with UC who were new users of anti- TNF agents, IFX-treated patients may have lower corticosteroid use than ADA-treated patients, but risk of hospitalisation and serious infections were comparable. [ABSTRACT FROM AUTHOR]
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- 2016
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7. Review article: recent advances in pharmacogenetics and pharmacokinetics for safe and effective thiopurine therapy in inflammatory bowel disease.
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Moon, W. and Loftus, E. V.
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AZATHIOPRINE ,INFLAMMATORY bowel diseases ,PHARMACOKINETICS ,PHARMACOGENOMICS ,NUCLEOTIDES - Abstract
Background Azathioprine and mercaptopurine have a pivotal role in the treatment of inflammatory bowel disease ( IBD). However, because of their complex metabolism and potential toxicities, optimal use of biomarkers to predict adverse effects and therapeutic response is paramount. Aim To provide a comprehensive review focused on pharmacogenetics and pharmacokinetics for safe and effective thiopurine therapy in IBD. Methods A literature search up to July 2015 was performed in PubMed using a combination of relevant Me SH terms. Results Pre-treatment thiopurine S-methyltransferase typing plus measurement of 6-tioguanine nucleotides and 6-methylmercaptopurine ribonucleotides levels during treatment have emerged with key roles in facilitating safe and effective thiopurine therapy. Optimal use of these tools has been shown to reduce the risk of adverse effects by 3-7%, and to improve efficacy by 15-30%. For the introduction of aldehyde oxidase ( AOX) into clinical practice, the association between AOX activity and AZA dose requirements should be positively confirmed. Inosine triphosphatase assessment associated with adverse effects also shows promise. Nucleoside diphosphate-linked moiety X-type motif 15 variants have been shown to predict myelotoxicity on thiopurines in East Asian patients. However, the impact of assessments of xanthine oxidase, glutathione S-transferase, hypoxanthine guanine phosphoribosyltransferase and inosine monophosphate dehydrogenase appears too low to favour incorporation into clinical practice. Conclusions Measurement of thiopurine-related enzymes and metabolites reduces the risk of adverse effects and improves efficacy, and should be considered part of standard management. However, this approach will not predict or avoid all adverse effects, and careful clinical and laboratory monitoring of patients receiving thiopurines remains essential. [ABSTRACT FROM AUTHOR]
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- 2016
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8. Systematic review with meta-analysis: faecal diversion for management of perianal Crohn's disease.
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Singh, S., Ding, N. S., Mathis, K. L., Dulai, P. S., Farrell, A. M., Pemberton, J. H., Hart, A. L., Sandborn, W. J., and Loftus, E. V.
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CROHN'S disease ,META-analysis ,INFLAMMATORY bowel diseases ,ILEOSTOMY ,REFRACTORY materials - Abstract
Background Temporary faecal diversion is sometimes used for management of refractory perianal Crohn's disease ( CD) with variable success. Aims To perform a systematic review with meta-analysis to evaluate the effectiveness, long-term outcomes and factors associated with success of temporary faecal diversion for perianal CD. Methods Through a systematic literature review through 15 July 2015, we identified 16 cohort studies (556 patients) reporting outcomes after temporary faecal diversion. We estimated pooled rates [with 95% confidence interval ( CI)] of early clinical response, attempted and successful restoration of bowel continuity after temporary faecal diversion (without symptomatic relapse), and rates of re-diversion (in patients with attempted restoration) and proctectomy (with or without colectomy and end-ileostomy). We identified factors associated with successful restoration of bowel continuity. Results On meta-analysis, 63.8% (95% CI: 54.1-72.5) of patients had early clinical response after faecal diversion for refractory perianal CD. Restoration of bowel continuity was attempted in 34.5% (95% CI: 27.0-42.8) of patients, and was successful in only 16.6% (95% CI: 11.8-22.9). Of those in whom restoration was attempted, 26.5% (95% CI: 14.1-44.2) required re-diversion because of severe relapse. Overall, 41.6% (95% CI: 32.6-51.2) of patients required proctectomy after failure of temporary faecal diversion. There was no difference in the successful restoration of bowel continuity after temporary faecal diversion in the pre-biological or biological era (13.7% vs. 17.6%, P = 0.60), in part due to selection bias. Absence of rectal involvement was the most consistent factor associated with restoration of bowel continuity. Conclusions Temporary faecal diversion may improve symptoms in approximately two-thirds of patients with refractory perianal Crohn's disease, but bowel restoration is successful in only 17% of patients. [ABSTRACT FROM AUTHOR]
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- 2015
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9. Systematic review: colitis associated with anti- CTLA-4 therapy.
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Gupta, A., De Felice, K. M., Loftus, E. V., and Khanna, S.
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COLITIS ,CYTOTOXIC T cells ,DIARRHEA ,T cells ,MELANOMA - Abstract
Background Cytotoxic T-lymphocyte-associated protein-4 ( CTLA-4) has an important role in T-cell regulation, proliferation and tolerance. Anti- CTLA-4 agents, such as ipilimumab and tremelimumab, have been shown to prolong overall survival in patients with metastatic melanoma, and their use is being investigated in the treatment of other malignancies. Their novel immunostimulatory mechanism, however, predisposes patients to immune-related adverse effects, of which gastrointestinal effects such as diarrhoea and colitis are the most common. Aims To discuss the existing literature and summarise the epidemiology, pathogenesis and clinical features of anti- CTLA-4-associated colitis, and to present a management algorithm for it. Methods We searched PubMed for studies published through October 2014 using the terms 'anti- CTLA,' 'ipilimumab,' 'tremelimumab,' 'colitis,' 'gastrointestinal,' 'immune-related adverse effect,' 'immunotherapy,' 'melanoma,' and 'diarrhoea.' Results Watery diarrhoea is commonly associated with anti- CTLA-4 therapy (27-54%), and symptoms occur within a few days to weeks of therapy. Diffuse acute and chronic colitis are the most common findings on endoscopy (8-22%). Concomitant infectious causes of diarrhoea must be evaluated. Most cases may be successfully managed with discontinuation of anti- CTLA-4 and conservative therapy. Those with persistent grade 2 and grade 3/4 diarrhoea should undergo endoscopic evaluation and require corticosteroid therapy. Corticosteroid-resistant cases may respond to anti-tumour necrosis factor-alpha therapy such as infliximab. Surgery is reserved for patients with bowel perforation or failure of medical therapy. Conclusion Given the increasing use of anti- CTLA-4 therapy, clinicians must be aware of related adverse events and their management. [ABSTRACT FROM AUTHOR]
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- 2015
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10. Efficacy and safety of certolizumab pegol for Crohn's disease in clinical practice.
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Moon, W., Pestana, L., Becker, B., Loftus, E. V., Hanson, K. A., Bruining, D. H., Tremaine, W. J., and Kane, S. V.
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CROHN'S disease ,FISTULA ,DRUG efficacy ,BIOLOGICAL decontamination ,ADALIMUMAB - Abstract
Background Certolizumab pegol ( CZP) is Food and Drug Administration ( FDA)-approved to treat Crohn's disease ( CD). However, the efficacy and safety of CZP outside clinical trials are not well established. Aim To report the efficacy, safety and predictors of response to CZP in CD patients treated during a 6-year period since FDA-approval at a tertiary care centre. Methods All CD patients who received CZP at our institution between 2008 and 2013 were evaluated through retrospective medical record-based review of steroid-free complete response ( SCR), loss of response and safety. Results A total of 358 patients were included. One hundred twelve patients (31.3%) and 189 (52.8%) received CZP as their second and third biological agent, respectively. The probability of SCR at 26 week was 19.9% (95% CI, 15.9-24.5). The probability of survival free of loss of response at 2 year was 45.7% (95% CI, 32.5-59.5). A predictor of SCR was age at CD diagnosis of >40 years old (hazard ratio, HR relative to those <17, 4.69; 95% CI, 1.75-12.61). Negative predictors included present perianal fistula ( HR, 0.39; 95% CI, 0.16-0.98) and prior primary nonresponse to adalimumab (ADA; HR relative to secondary loss of response, 0.18; 95% CI, 0.04-0.76). Twenty-three patients (6.4%) experienced serious adverse events and 19 patients (5.3%) discontinued CZP due to adverse events. Conclusions Certolizumab pegol was both effective and well tolerated for the treatment of Crohn's disease in this large tertiary care centre enriched with biologics-exposed patients. It may be more effective in patients without early-aged Crohn's disease diagnosis, prior primary nonresponse to adalimumab and present perianal fistula. [ABSTRACT FROM AUTHOR]
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- 2015
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11. Clinical and demographic characteristics predictive of treatment outcomes for certolizumab pegol in moderate to severe Crohn's disease: analyses from the 7-year PRECiSE 3 study.
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Sandborn, W. J., Melmed, G. Y., McGovern, D. P. B., Loftus, E. V., Choi, J. M., Cho, J. H., Abraham, B., Gutierrez, A., Lichtenstein, G., Lee, S. D., Randall, C. W., Schwartz, D. A., Regueiro, M., Siegel, C. A., Spearman, M., Kosutic, G., Pierre‐Louis, B., Coarse, J., and Schreiber, S.
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CROHN'S disease ,DEMOGRAPHIC characteristics ,TREATMENT effectiveness ,SURGERY ,INFLAMMATORY bowel diseases - Abstract
Background Clinical factors were previously identified as predictors of short-term treatment efficacy in Crohn's disease (CD). The PRECiSE 3 (P3) 7-year trial provides an opportunity to study predictors of short- and long-term clinical remission among CD patients treated with certolizumab pegol (CZP). Aim To identify factors that influence long-term remission of CD with CZP treatment. Methods Patients who had completed placebo-controlled studies (PRECiSE 1/PRECiSE 2, P1/P2) enrolled in P3 and received open-label CZP 400 mg every 4 weeks up to 7 years. Baseline predictors included, but were not limited to, smoking status, disease duration, prior inflammatory bowel disease (IBD) surgery, Harvey-Bradshaw Index (HBI), albumin, haematocrit and CZP exposure; association with time to initial remission (HBI ≤4) was tested for patients who received CZP in P1/P2; time to loss of remission/frequency of maintenance of remission was also tested. Univariate analyses and multivariate Cox or logistic regression models were used. Results Predictors for initial remission (N = 377) included age, haematocrit, prior IBD surgery and entry HBI (P < 0.05 for all). Predictors for loss of remission (N = 437) included HBI, serum albumin concentration, haematocrit, smoking status and exposure. Predictors of maintenance of remission (N = 437) included haematocrit, IBD surgery, HBI, disease duration, serum albumin concentration and exposure. Significant predictors were confirmed with stepwise multivariate regression models. Conclusions These analyses identified several influential parameters for short-and long-term remission of Crohn's disease with certolizumab pegol treatment. The data yield valuable hypotheses regarding factors that influence certolizumab pegol treatment. More investigation is needed. (ClinicalTrials.gov identifier NCT00552058). [ABSTRACT FROM AUTHOR]
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- 2015
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12. Letter: comparative efficacy of biological therapy in patients with ulcerative colitis.
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Singh, S., Garg, S. K., Wang, Z., Murad, M. H., and Loftus, E. V.
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COLITIS treatment ,ULCERATIVE colitis ,TUMOR necrosis factors - Abstract
A letter to the editor is presented in response to the article "Systematic review with network meta-analysis: the efficacy of anti-tumour necrosis factor-alpha (TNF) agents for the treatment of ulcerative colitis (UC)" by R. W. Stidham and colleagues in the 2014 issue.
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- 2014
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13. Detection rate and outcome of colonic serrated epithelial changes in patients with ulcerative colitis or Crohn's colitis.
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Johnson, D. H., Khanna, S., Smyrk, T. C., Loftus, E. V., Anderson, K. S., Mahoney, D. W., Ahlquist, D. A., and Kisiel, J. B.
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COLON diseases ,CROHN'S disease ,ULCERATIVE colitis ,DISEASE prevalence ,COLONOSCOPY ,PATHOLOGY ,DISEASE risk factors - Abstract
Background Chronic ulcerative colitis ( CUC) and colonic Crohn's disease ( CD) increase colorectal neoplasia ( CRN) risk. While sessile serrated polyp ( SSP) is a known cancer precursor, serrated epithelial changes ( SEC) are of uncertain prevalence and neoplastic risk. Aim To assess the serrated lesion detection rates in CUC and CD and documented incidence of subsequent CRN in a retrospective, single-centre cohort study. Methods Patients were identified by a central diagnostic index and pathology review confirmed SEC, SSP, CUC and CD diagnoses from 2006-12. Matched controls were identified from among all CUC and CD patients having colonoscopy during the second half of the time period. All were followed for incident CRN, estimated by the Kaplan-Meier method. Results Between 2006 and 2012, 79 SEC and 10 SSP cases were identified. Detection rates were estimated to be 10/1000 and 2/1000 patients, for SEC and SSP respectively, among 4208 unique CUC or CD patients having colonoscopy from 2010-12. With only 10 cases, SSP patients were not further analysed. Cumulative incidence of subsequent CRN at 1 and 3 years was 12% (95% CI, 0-30%) and 30% (3-57%), respectively, in SEC patients compared to 4% (0-12%) and 9% (0-23%), respectively, in CUC or CD controls ( P = 0.047, log-rank). However, this statistical difference was not significant after patients were stratified for history of prior or synchronous dysplasia ( P = 0.09). Conclusions Serrated epithelial changes and sessile serrated polyps are uncommonly detected by colonoscopy in chronic ulcerative colitis and Crohn's disease patients. Histology with changes of serrated epithelium may be associated with risk of subsequent colorectal neoplasia, however further studies are needed to explore this relationship. [ABSTRACT FROM AUTHOR]
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- 2014
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14. The fate of indefinite and low-grade dysplasia in ulcerative colitis and primary sclerosing cholangitis colitis before and after liver transplantation.
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Eaton, J. E., Smyrk, T. C., Imam, M., Pardi, D. S., Loftus, E. V., Owens, V. L., and Talwalkar, J. A.
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DYSPLASIA ,ULCERATIVE colitis ,LIVER transplantation ,DISEASE progression ,RETROSPECTIVE studies ,COLON diseases - Abstract
Background Patients with primary sclerosing cholangitis ( PSC) and ulcerative colitis ( UC) are at an increased risk of colorectal neoplasia, but it is unknown if liver transplantation ( LT) alters neoplasia progression. Aim To examine the natural history of indefinite dysplasia ( IND) and low-grade dysplasia ( LGD) that develop in patients with PSC- UC with and without LT. Methods We performed a retrospective review of patients with PSC and UC evaluated at our institution between 1993 and 2011 who were diagnosed with IND or LGD before or after LT for PSC. The primary end point was neoplasia progression or persistent LGD. Results Ninety-six patients (non- LT n = 63, LT n = 33) were examined. For the IND group, multifocal lesions were significantly associated with time to neoplasia progression [hazard ratio ( HR), 3.5; 95% confidence interval ( CI), 1.3-9.7], while 5-aminosalicylate (5- ASA) use was protective ( HR, 0.2; 95% CI, 0.1-0.6). For patients with LGD, multifocal lesions were significantly associated with the primary end point ( HR, 7.1; 95% CI, 1.7-28.3), while LT was protective ( HR, 0.3; 95% CI, 0.1-0.9). Conclusions In PSC- UC patients with IND, 5- ASA use was associated with a decreased the risk of neoplasia progression, regardless of transplant status. In contrast, multifocal IND and LGD were associated with neoplasia progression or persistent LGD. Patients who developed LGD following LT for PSC were less likely to have progressive neoplasia or persistent LGD, compared with those who had not been transplanted. [ABSTRACT FROM AUTHOR]
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- 2013
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15. Meta-analysis: serological markers and the risk of acute and chronic pouchitis.
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Singh, S., Sharma, P. K., Loftus, E. V., and Pardi, D. S.
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NEUTROPHILS ,SACCHAROMYCES cerevisiae ,COLITIS treatment ,ULCERATIVE colitis ,META-analysis ,IMMUNOGLOBULINS - Abstract
Background Serological markers such as anti-neutrophil cytoplasmic antibody ( ANCA) and anti- Saccharomyces cerevisiae antibody ( ASCA) may be associated with pouchitis after ileal pouch-anal anastomosis ( IPAA). Aim To perform a systematic review with meta-analysis of studies evaluating the association of ANCA and ASCA status with risk of acute and chronic pouchitis after IPAA. Methods We searched multiple databases (upto September 2012) for studies reporting ANCA and/or ASCA status along with risk of acute or chronic pouchitis after IPAA in adults with ulcerative colitis ( UC). We abstracted odds ratio ( OR) or raw data from the individual studies to calculate summary OR estimates with 95% CIs using random-effects model. Results Eight studies reporting 184 cases of acute pouchitis and six studies reporting 151 cases of chronic pouchitis were included. The odds of chronic pouchitis were 76% higher in ANCA-positive patients than ANCA-negative (six studies; OR: 1.76; 95% CI: 1.19-2.61; P < 0.01). ASCA-positivity was not associated with the risk of chronic pouchitis (three studies; OR: 0.89; 95% CI: 0.49-1.59; P = 0.68). Neither ANCA (eight studies; OR: 1.54; 95% CI: 0.79-3.02; P = 0.21) nor ASCA-positivity (two studies; OR: 1.28; 95% CI: 0.25-6.54; P = 0.77) were associated with the risk of acute pouchitis. Conclusions The risk of chronic pouchitis after IPAA is higher in ANCA-positive patients, but the risk of acute pouchitis is unaffected by ANCA status. ASCA status was not associated with the risk of acute or chronic pouchitis. This information may be used to counsel UC patients regarding their risk of pouchitis after IPAA. [ABSTRACT FROM AUTHOR]
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- 2013
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16. Stool DNA testing for the detection of colorectal neoplasia in patients with inflammatory bowel disease.
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Kisiel, J. B., Yab, T. C., Nazer Hussain, F. T., Taylor, W. R., Garrity‐Park, M. M., Sandborn, W. J., Loftus, E. V., Wolff, B. G., Smyrk, T. C., Itzkowitz, S. H., Rubin, D. T., Zou, H., Mahoney, D. W., and Ahlquist, D. A.
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COLON diseases ,INFLAMMATORY bowel diseases ,GENETIC markers ,METHYLATION ,CROHN'S disease ,DYSPLASIA - Abstract
Background Current approaches to the detection of colorectal neoplasia associated with inflammatory bowel disease ( IBD- CRN) are suboptimal. Aim To test the feasibility of using stool assay of exfoliated DNA markers to detect IBD- CRN. Methods This investigation comprised tissue and stool studies. In the tissue study, gene sequencing and methylation assays were performed on candidate genes using tissue DNA from 25 IBD- CRNs and from 25 IBD mucosae without CRN. Mutations on p53, APC, KRAS, BRAF or PIK3 CA genes were insufficiently informative, but several aberrantly methylated genes were highly discriminant. In the stool study, we evaluated candidate methylated genes ( vimentin, EYA4, BMP3, NDRG4) in a prospective blinded study on buffered stools from 19 cases with known IBD- CRN and 35 age- and sex-matched IBD controls without CRN. From stool-extracted DNA, target genes were assayed using quantitative allele-specific real-time target and signal amplification method. Results IBD- CRN cases included 17 with ulcerative colitis ( UC) and two with Crohn's disease ( CD); nine had cancer and 10 had dysplasia. Controls included 25 with UC and 10 with CD. Individually, BMP3, vimentin, EYA4 and NDRG4 markers showed high discrimination in stools with respective areas under the ROC curve of 0.91, 0.91, 0.85 and 0.84 for total IBD- CRN and of 0.97, 0.97, 0.95 and 0.85 for cancer. At 89% specificity, the combination of BMP3 and mNDRG4 detected 9/9 (100%) of CRC and 80% of dysplasia, 4/4 (100%) of high grade and 4/6 (67%) of low grade. Conclusion These findings demonstrate the feasibility of stool DNA testing for non-invasive detection of colorectal neoplasia associated with inflammatory bowel disease. [ABSTRACT FROM AUTHOR]
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- 2013
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17. Anti-tumour necrosis factor treatment of inflammatory bowel disease in liver transplant recipients.
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Mohabbat, A. B., Sandborn, W. J., Loftus, E. V., Wiesner, R. H., and Bruining, D. H.
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ULCERATIVE colitis ,CROHN'S disease ,LIVER transplantation ,IMMUNOSUPPRESSIVE agents ,MUCOUS membranes ,CLOSTRIDIUM ,PATIENTS - Abstract
Background Ulcerative colitis ( UC) and Crohn's disease can sometimes relapse and be refractory to standard treatment following orthotopic liver transplantation ( OLT) despite post-transplantation immunosuppressive therapy. Aim To evaluate the efficacy and safety of anti-tumour necrosis factor (anti- TNF) agents for the management of IBD following OLT. Methods We reviewed the records of patients with a diagnosis of IBD who underwent OLT at Mayo Clinic Rochester between 1985 and 2009. Patients were included if they had received anti- TNF therapy post- OLT. Clinical response was defined as a physician's assessment of improvement after 12 weeks of anti- TNF usage, and mucosal healing was defined as the absence of ulcerations on follow-up endoscopy. Results The median age of the eight study patients was 42.0 years and 37.5% were female patients. All had been diagnosed with IBD prior to OLT ( UC in three and Crohn's disease in five). Indication for OLT was cirrhotic stage primary sclerosing cholangitis ( PSC), and three concomitantly had cholangiocarcinoma. Clinical response was demonstrated in seven of eight patients (87.5%) and mucosal healing was demonstrated in three of seven (42.9%). Four infections (oral candidiasis, Clostridium difficile colitis, bacterial pneumonia and cryptosporidiosis) in three patients were reported. One patient developed an Epstein- Barr virus-positive post-transplant lympho-proliferative disorder. One death occurred due to complications from recurrent PSC. Conclusions Starting Anti- TNF therapy following orthotopic liver transplantation appears to be a potential option for inflammatory bowel disease management. Additional studies are needed, however, to confirm these findings and to further assess risks associated with this treatment strategy. [ABSTRACT FROM AUTHOR]
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- 2012
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18. Evolving Molecular Targets in the Treatment of Nonmalignant Gastrointestinal Diseases.
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Katzka, D A, Loftus, E V, and Camilleri, M
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GASTROINTESTINAL disease treatment ,GASTROESOPHAGEAL reflux ,SHORT bowel syndrome ,HEALTH outcome assessment ,CROHN'S disease ,PHARMACODYNAMICS - Abstract
Novel treatments for gastrointestinal (GI) diseases are based on molecular targets. Novel pharmacologic and biological agents with greater selectivity and specificity are being developed for a variety of epithelial diseases, including eosinophilic esophagitis (EoE), gastroesophageal reflux disease (GERD), celiac disease, short bowel syndrome (SBS), and inflammatory bowel diseases (IBDs; Crohn's disease and ulcerative colitis). Motility and secretory agents are being developed for gastroparesis, irritable bowel syndrome (IBS), functional constipation, and diarrhea. Here we focus on data from clinical trials involving validated pharmacodynamic or patient response outcomes. [ABSTRACT FROM AUTHOR]
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- 2012
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19. Die Rolle der D�nndarmendoskopie beim Management von Patienten mit chronisch-entz�ndlichen Darmerkrankungen: ein internationaler OMED-ECCO-Konsensus.
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Bourreille, A., Ignjatovic, A., Aabakken, L., Loftus, E. V., Eliakim, R., Pennazio, M., Bouhnik, Y., Seidman, E., Keuchel, M., Albert, J. G., Ardizzone, S., Bar-Meir, S., Bisschops, R., Despott, E. J., Fortun, P. F., Heuschkel, R., Kammermeier, J., Leighton, J. A., Mantzaris, G. J., and Moussata, D.
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- 2009
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20. Age at onset of inflammatory bowel disease and the risk of surgery for non-neoplastic bowel disease.
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TREMAINE, W. J., TIMMONS, L. J., LOFTUS, E. V., PARDI, D. S., SANDBORN, W. J., HARMSEN, W. S., THAPA, P., and ZINSMEISTER, A. R.
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CROHN'S disease ,INFLAMMATORY bowel diseases ,GASTROENTERITIS ,COLON diseases ,INTESTINAL diseases ,SURGICAL therapeutics - Abstract
Background There is conflicting data regarding the response to medical and surgical therapy for inflammatory bowel disease with respect to age at disease onset. Aim To determine if the age at onset of Crohn's disease and ulcerative colitis is a risk factor for surgery for non-neoplastic bowel disease. Methods This was a case–control study of patients evaluated between 1998 and 2001. Cases had undergone an initial operation for bowel disease. Controls were matched 1:1 for gender, disease subtype, date of first visit (±2 years), time from diagnosis prior to first visit (±3 years) and duration of follow-up. Association with age, disease extent, smoking history, medication use and co-morbidities vs. case/control status was assessed using multiple variable conditional logistic regression to estimate the odds ratio (OR) and 95% confidence intervals (CI) for undergoing surgery. Results Among 132 Crohn’s patients, older patients had lower odds for surgery (OR per 5 years, 0.86; 95% CI: 0.75–0.98). The rate of surgery for non-neoplastic bowel disease was not significantly associated with disease distribution, co-morbidities or cigarette smoking. Among 234 ulcerative colitis patients, the rate of surgery was unrelated to age, disease extent, co-morbidities or cigarette smoking, Conclusions For Crohn’s disease, but not ulcerative colitis, the risk of surgery for non-neoplastic bowel disease decreases with increasing age at diagnosis, irrespective of disease distribution and history of cigarette smoking. [ABSTRACT FROM AUTHOR]
- Published
- 2007
- Full Text
- View/download PDF
21. Systematic review Short-term adverse effects of 5-aminosalicylic acid agents in the treatment of ulcerative colitis.
- Author
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Loftus, E. V., Kane, S. V., and Bjorkman, D.
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ULCERATIVE colitis ,SALICYLIC acid ,PLACEBOS ,AMINO acids ,CLINICAL trials - Abstract
: To determine whether there is a difference in short-term adverse events in patients with ulcerative colitis treated with mesalazine, olsalazine or balsalazide. : MEDLINE was searched for articles published until 2002. Randomized trials of oral mesalazine, olsalazine or balsalazide for the treatment of active disease or the maintenance of remission were included. Outcomes of interest were the frequencies of patients experiencing adverse events and those withdrawn due to adverse events. : Forty-six trials were included. One study of mesalazine vs. sulfasalazine for active colitis showed significantly fewer patients with adverse events with mesalazine. Both balsalazide vs. sulfasalazine studies for active disease showed significantly fewer withdrawals with balsalazide. One trial of balsalazide vs. sulfasalazine for maintenance showed significantly fewer patients with adverse events with balsalazide. Otherwise, no significant differences in safety outcomes were noted. : All three 5-aminosalicylic acid agents are safe in the short term. In mesalazine-treated patients, the frequencies of adverse events or withdrawals due to adverse events were comparable with those in placebo-treated patients and lower than those in sulfasalazine-treated patients. Overall, adverse events or withdrawals were not significantly more frequent with olsalazine than with placebo or sulfasalazine. Adverse events and study withdrawals on balsalazide were less frequent than those on sulfasalazine. [ABSTRACT FROM AUTHOR]
- Published
- 2004
- Full Text
- View/download PDF
22. Repifermin (keratinocyte growth factor-2) for the treatment of active ulcerative colitis: a randomized, double-blind, placebo-controlled, dose-escalation trial.
- Author
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Sandborn, W. J., Sands, B. E., Wolf, D. C., Valentine, J. F., Safdi, M., Katz, S., Isaacs, K. L., Wruble, L. D., Katz, J., Present, D. H., Loftus, E. V., Graeme‐Cook, F., Odenheimer, D. J., and Hanauer, S. B.
- Subjects
KERATINOCYTES ,INFLAMMATION ,ULCERATIVE colitis - Abstract
Summary Background: Repifermin (keratinocyte growth factor-2) has been shown to reduce inflammation in animal models of colitis. Aim: To evaluate repifermin for the treatment of active ulcerative colitis. Methods: Eighty-eight patients with active ulcerative colitis were enrolled in a 6-week, double-blind trial. Patients were randomized to receive treatment for five consecutive days with intravenous repifermin at a dose of 1, 5, 10, 25 or 50 μg/kg, or placebo. The primary objective of the study was to evaluate the safety of repifermin. The primary efficacy outcome was clinical remission at week 4, defined as a score of zero on the endoscopic appearance and stool blood components of the Mayo score and a score of zero or unity on the stool frequency and physician's global assessment components. Results: At week 4, the rates of clinical remission in the 1, 5, 10, 25 and 50 μg/kg repifermin groups were 19%, 9%, 0%, 0% and 0%, respectively, and 11% for the placebo group (P = 0.32 for repifermin vs. placebo). The frequencies of commonly occurring adverse events and severe adverse events were similar in both groups. Conclusions: Intravenous repifermin at a dose of 1–50 μg/kg was very well tolerated, but there was no evidence that repifermin was effective for the treatment of active ulcerative colitis at these doses. An additional study to determine the efficacy of repifermin at doses of > 50 μg/kg or for a longer treatment duration may be warranted, as the maximally tolerated dose was not reached in the present study. [ABSTRACT FROM AUTHOR]
- Published
- 2003
- Full Text
- View/download PDF
23. The epidemiology and natural history of Crohn’s disease in population-based patient cohorts from North America: a systematic review.
- Author
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Loftus, E. V., Schoenfeld, P., and Sandborn, W. J.
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CROHN'S disease ,ADRENOCORTICAL hormones ,DRUG efficacy - Abstract
Aim: To quantify, through systematic review, the epidemiology and natural history of Crohn’s disease in North America. Methods: The selected articles contained: (i) population-based samples of patients followed from the time of diagnosis; and (ii) objective diagnostic criteria for disease. Studies on the natural history of Crohn’s disease also contained sufficient follow-up. Data collection and analysis: For prevalence studies, data on the incidence, prevalence, gender and age at diagnosis were extracted. For natural history studies, data on the disease activity, use of medications and surgery were extracted. Main results: The prevalence of Crohn’s disease in North America ranges from 26.0 to 198.5 cases per 100 000 persons. The incidence rates range from 3.1 to 14.6 cases per 100 000 person-years. Most patients have a chronic intermittent disease course, while 13% have an unremitting disease course and 10% have a prolonged remission. Less than half require corticosteroids at any point. During any given year, approximately 10% are treated with corticosteroids and 30% are treated with 5-aminosalicylates. Up to 57% of patients require at least one surgical resection. Conclusions: Between 400 000 and 600 000 patients in North America have Crohn’s disease, and the natural history is marked by frequent exacerbations requiring treatment with corticosteroids, 5-aminosalicylate products and surgery. [ABSTRACT FROM AUTHOR]
- Published
- 2002
- Full Text
- View/download PDF
24. Leucopenia resulting from a drug interaction between azathioprine or 6-mercaptopurine and mesalamine, sulphasalazine, or balsalazide.
- Author
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Lowry, P. W., Franklin, C. L., Weaver, A. L., Szumlanski, C. L., Mays, D. C., Loftus, E. V., Tremaine, W. J., Lipsky, J. J., Weinshilboum, R. M., and Sandborn, W. J.
- Published
- 2001
25. Pediatric "PSC-IBD": a descriptive report of associated inflammatory bowel disease among pediatric patients with psc.
- Author
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Faubion Jr., W. A., Loftus, E. V., Sandborn, W. J., Freese, D. K., Perrault, J., and Faubion, W A Jr
- Published
- 2001
26. Interexaminer agreement in the measurement of periodontal disease.
- Author
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Feldman, R. S., Douglass, C. W., Loftus, E. K., Kapur, K. K., and Chauncey, H. H.
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DENTAL prophylaxis ,PERIODONTAL disease ,DENTAL pathology ,PERIODONTICS ,PATHOLOGY ,PREVENTIVE medicine ,DENTAL calculus - Abstract
Six variables of periodontal pathology were independently measured by two periodontists in a study of healthy male adult participants from the VA Dental Longitudinal Study. Two examination sets containing a total of 50 volunteers were compared to establish interexaminer agreement. Measures of gingival recession, tooth mobility, calculus accumulation, and plaque accumulation exhibited high interexaminer correlation. The measures or periodontal pocket depth and gingival health also showed good levels of agreement, but reflected the examination order; the second examiner consistently scored more severe disease because of the invasive nature of these measures. Establishment of the reproducibility of periodontal pathology measurements is essential for studies which involve more than one examiner. This investigation demonstrated a high confidence level of reproducibility for the six measure utilized and showed that recalibration enhanced the initial training procedure and increased examiner agreement above the initial level. [ABSTRACT FROM AUTHOR]
- Published
- 1982
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27. Cytomegalovirus as an exacerbating factor in ulcerative colitis.
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Loftus, Edward V., Alexander, Glenn L., Carpenter, Herschel A., Loftus, E V Jr, Alexander, G L, and Carpenter, H A
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- 1994
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28. Cross-sectional and longitudinal tooth survival characteristics of a healthy male population.
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LOFTUS, EDWARD R., ALMAN, JOHN E., FELDMAN, ROY S., WAYLER, ALAN H., KAPUR, KRISHAN K., CHAUNCEY, HOWARD H., Loftus, E R, Alman, J E, Feldman, R S, Wayler, A H, Kapur, K K, and Chauncey, H H
- Published
- 1982
- Full Text
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29. Cigarette smoking and oral leukoplakia in healthy males.
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LOFTUS, EDWARD R., BARIC, JEAN M., KAPUR, KRISHAN K., CHAUNCEY, HOWARD H., Loftus, E R, Baric, J M, Kapur, K K, and Chauncey, H H
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- 1981
- Full Text
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30. Balancing the risks and benefits of infliximab in the treatment of inflammatory bowel disease.
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Sandborn, W. J. and Loftus, E. V.
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INFLIXIMAB ,CROHN'S disease ,ULCERATIVE colitis ,PLACEBOS ,IMMUNOGLOBULINS ,CLINICAL trials - Abstract
Infliximab, a monoclonal antibody to tumor necrosis factor α, is an important advance in the treatment of Crohn's disease. The efficacy of infliximab for the treatment of ulcerative colitis is still unclear. All patients in the study initially received at least one induction dose of infliximab. Thus safety data in patients with Crohn's disease treated only with placebo who were naive to infliximab was available in only 34 of 1081 patients enrolled in placebo controlled trials.
- Published
- 2004
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31. Erratum: Physical cluster theory of point defect interactions. II. Application to AgCl doped with CdCl2.
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Allnatt, A. R. and Loftus, E.
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- 1979
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32. FORUM.
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Morgan, Jim, Liss, Jeffrey M., Kolesar, Paul, Kline, Gertrude G., Allen, Brian, Bode, Kirk W., Berry, David S., Church, Lou, Buelna, Joseph L., Scott, Catherine, Kearney, Michael J., Richardson, Cordell P., Caroline, Peter H., McPherson, John C., McCracken, Allen C., Swenson, Thomas J., Nelson, Hermione, Khan, Gertrude, Sviatko, Anthony V., and Loftus, E. A.
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LETTERS to the editor ,TIME'S Person of the Year selections ,REFERENDUM ,GUN laws ,FASHION design - Abstract
Several letters to the editor are presented in response to articles in the previous issues including the call for nominations for the "Time" magazine's Man of the Year selection, an article on handgun confiscation referendum of Massachusetts in the November 15, 1976 issue, and another on the latest fashion designs from Paris.
- Published
- 1976
33. Letter: anti- CTLA-4-associated colitis and inflammatory bowel disease pathogenesis - authors' reply.
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Gupta, A., De Felice, K. M., Loftus, E. V., and Khanna, S.
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COLITIS treatment ,CYTOTOXIC T lymphocyte-associated molecule-4 ,INFLAMMATORY bowel diseases - Abstract
A response from the authors of the article "Systematic review: colitis associated with anti-CTLA-4 therapy" in the 2015 issue is presented.
- Published
- 2015
- Full Text
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34. Letter: cytomegalovirus colitis in a patient treated with ipilimumab for metastatic melanoma - authors' reply.
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Gupta, A., Loftus, E. V., De Felice, K. M., and Khanna, S.
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CYTOMEGALOVIRUS disease treatment ,IPILIMUMAB ,MELANOMA treatment - Abstract
A letter to the editor is presented in response to the article "Letter: cytomegalovirus colitis in a patient treated with ipilimumab for metastatic melanoma," by F. Bossa and colleagues in the 2015 issue.
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- 2016
- Full Text
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35. EARLY RHEUMATIC MYOCARDITIS.
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Wigram, Loftus E.
- Published
- 1928
36. Letter: effectiveness of split-dose certolizumab pegol for Crohn's disease.
- Author
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Kane, S. V., Neis, B., Becker, B. D., Bruining, D., Faubion, W. A., Kisiel, J., Loftus, E. V., Pardi, D., Raffals, L., Schroeder, K., and Tremaine, W. J.
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INFLAMMATORY bowel disease treatment ,INFLAMMATORY bowel diseases - Abstract
A letter to the editor is presented on the use of certolizumab pegol for the treatment of Crohn's disease.
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- 2013
- Full Text
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37. Markov model projection of remission status for early versus delayed step-up adalimumab use in moderate to severe crohn's disease.
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Loftus, E V, Chao, J, Yang, M, Pollack, P F, Li, Z, Thakkar, R B, and Mulani, P M
- Abstract
Introduction No randomised clinical trials have compared early treatment with anti-TNF agents and conventional delayed step-up treatment for patients with moderate to severe Crohn's disease (CD). The goal of this study was to project remission rates in patients with moderate to severe CD with early versus delayed step-up use of adalimumab (ADA) using a Markov model. Methods The Markov model considered 4 states: remission, no remission but response, no remission and no response, and discontinuation. Each treatment cycle was 4 weeks. In the early treatment arm, patients with shorter disease duration (onset ≤2 years) would start ADA without prior use of immunomodulators (IMMs). In the step-up treatment arm, patients with longer disease duration (onset >2 years) would be treated with IMMs before switching to ADA owing to lack of response for 2 consecutive months. Transitional probabilities for patients on ADA were estimated using a multinomial logistic model using data from the CHARM trial, specifically the treatment arm of ADA 40 mg every other week. Transitional probabilities for patients on IMM treatment in the step-up treatment arm were derived from literature. One-year remission rates with early and step-up use of ADA were projected with the estimated transitional probabilities. Results The multinomial logistic model estimated that patients in the early ADA treatment arm had a higher probability of transitioning from moderate/severe disease to remission during the induction cycle (weeks 0–4) than did patients in the step-up arm (54.8% vs 30.4%, p=0.0106). After achieving remission, early use patients had a higher probability of staying in remission than did step-up patients (91.5% vs 78.2%, p<0.0001). Using the estimated transitional probabilities, the Markov model projected early use patients to have a remission rate of 46.2% at the end of 1 year, with cumulative time in remission of 0.57 years. For step-up patients, the model projected a remission rate of 37.5% at the end of 1 year, with cumulative time in remission of 0.36 years. Conclusion Early initiation with ADA was projected in a 1-year Markov model to result in higher remission rates and longer time in remission than delayed step-up therapy. [ABSTRACT FROM PUBLISHER]
- Published
- 2011
- Full Text
- View/download PDF
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