Publications by authors named "Mona Akbari"

24 Publications

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Salivary profile and dental status of patients with multiple sclerosis.

Dent Med Probl 2020 Jan-Mar;57(1):25-29

Department of Oral and Maxillofacial Surgery, School of Dentistry, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Background: Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system. The MS patients may display biochemical changes in their cerebrospinal fluid, peripheral blood and saliva. Since the salivary profile plays a critical role in maintaining oral health and function, the analysis of saliva in the MS patients would be beneficial to prevent oral diseases, such as dental caries.

Objectives: The aim of this study was to evaluate the dental status and salivary profile of the MS patients.

Material And Methods: The study involved 25 MS patients and 25 healthy controls who were examined with regard to the calcium and phosphorus level, pH and flow rate of saliva as well as the decayed, missing and filled teeth (DMFT) index for permanent first molars. Student's t-test, the χ2 test and the Mann-Whitney test were utilized to compare the study groups.

Results: Significantly lower salivary flow rates were observed in the MS patients as compared to the controls. The salivary calcium and phosphorus levels were significantly higher in the case group during the first 6 years of the disease and 6-11 years after the onset of the disease, respectively, in comparison with the controls; however, there was no significant difference between the groups in terms of pH. The DMFT index for permanent first molars was higher in the MS patients than in the healthy controls, but not significantly. The number of carious and missing permanent first molars was significantly higher in the MS patients.

Conclusions: Multiple sclerosis appears to significantly change the salivary profile and dental status of the patients.
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http://dx.doi.org/10.17219/dmp/112576DOI Listing
November 2020

Association between CYP19A

Int J Mol Cell Med 2019 20;8(2):162-168. Epub 2019 Jul 20.

Department of Internal Medicine, Medical School, Kermanshah University of Medical Sciences, Kermanshah, Iran.

Acne vulgaris (AV) is a common skin disease that causes physical and psychological problems for the affected individual. In addition to systemic changes in hormone levels, overproduction of local steroids, especially androgens are associated with AV. Cytochrome (CYP) 19 is involved in the synthesis of estrogens. The aim of the present study was to investigate the influence of CYP19A
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http://dx.doi.org/10.22088/IJMCM.BUMS.8.2.162DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7081083PMC
July 2019

The Insulin-like Growth Factor-1 (G>A) and 5,10-methylenetetrahydrofolate Reductase (C677T) Gene Variants and the Serum Levels of Insulin-like Growth Factor-1, Insulin, and Homeostasis Model Assessment in Patients with .

Iran J Pathol 2020 ;15(1):23-29

Department of Internal Medicine, Medical School, Kermanshah University of Medical Sciences, Kermanshah, Iran.

Background & Objective: To find an association between gene variants of insulin-like growth factor-1 (IGF-1) and 5,10-methylenetetrahydrofolate reductase (MTHFR) with the risk of acne vulgaris (AV).

Methods: In a case-control study, we investigated 150 AV patients and 148 healthy individuals (aged 18-25 years) for the IGF-1 G>A and MTHFR C677T polymorphisms, as well as the serum levels of IGF-1, insulin, and the homeostasis model assessment of insulin resistance (HOMA-IR). The serum biochemical parameters and the genotypes of IGF-1 G>A and MTHFR C677T were detected by using appropriate kits and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methods, respectively.

Results: The frequencies of IGF-1 and the MTHFR polymorphisms were not significantly different comparing patients and controls. The serum level of IGF-1 was 179.8±72.8 µg/L in AV patients compared to 164.6±63.7 µg/L in controls (=0.056). The serum level of insulin in female patients was significantly higher than controls. The HOMA was 3.54±5.6 in patients compared to 1.16±1.4 (<0.001) in controls. Significantly higher levels of fasting blood sugar (FBS), total cholesterol, and low-density lipoprotein-cholesterol (LDL-C) were detected in female patients than controls. However, the level of estradiol was significantly lower in female patients than in controls. In females, the presence of the MTHFR T allele was associated with significantly higher levels of FBS and LDL-C, as well as a significantly lower level of estradiol compared to those carriers of the C allele.

Conclusion: We found the absence of an association between IGF-1 and MTHFR polymorphisms with the risk of AV. However, increased insulin, IGF-1, and HOMA levels in AV patients indicated the effect of insulin and insulin resistance in the risk of AV and its severity.
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http://dx.doi.org/10.30699/IJP.2019.105695.2098DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6995677PMC
January 2020

Vedolizumab for prevention of graft-versus-host disease after allogeneic hematopoietic stem cell transplantation.

Blood Adv 2019 12;3(23):4136-4146

Center for International Blood and Marrow Transplant Research, Minneapolis, MN.

Acute graft-versus-host disease (aGVHD) remains a significant complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Vedolizumab could help prevent aGVHD by inhibiting the migration of both naive and activated lymphocytes into gut-associated lymphoid tissues and the lamina propria. We carried out a phase 1b, open-label, dose-finding study in adults undergoing allo-HSCT to evaluate the tolerability, safety, and pharmacokinetics of vedolizumab, and its effectiveness in reducing aGVHD. IV vedolizumab was administered on day -1, +13, and +42 with respect to allo-HSCT, starting at 75 mg and with dose escalation guided by tolerability and pharmacokinetics. A total of 24 participants was enrolled, and no dose-limiting toxicities were observed in either the 75-mg cohort (n = 3) or the dose-escalated 300-mg cohort (n = 21). Treatment-emergent adverse events related to vedolizumab occurred in 8 participants. Overall, 4 deaths occurred during the 12 months following allo-HSCT. No participants in the 75-mg cohort developed modified Glucksberg grade II to IV aGVHD by 100 days after allo-HSCT. Four participants (19.0%) in the 300-mg cohort developed grade II to IV aGVHD by 100 days after allo-HSCT, including 3 participants who developed stage 1 aGVHD of the lower-intestinal tract. Vedolizumab IV 300 mg was well tolerated as aGVHD prevention, and the incidence of overall and lower-intestinal aGVHD was low. These findings support further evaluation of vedolizumab in this patient population. This trial was registered at www.clinicaltrials.gov as #NCT02728895.
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http://dx.doi.org/10.1182/bloodadvances.2019000893DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6963235PMC
December 2019

Microfluidic-assisted preparation of PLGA nanoparticles for drug delivery purposes: experimental study and computational fluid dynamic simulation.

Res Pharm Sci 2019 Oct 4;14(5):459-470. Epub 2019 Oct 4.

Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, I.R. Iran.

This study, for the first time, tries to provide a simultaneous experimental and computational fluid dynamic (CFD) simulation investigation for production of uniform, reproducible, and stable polylactic-co-glycolic acid (PLGA) nanoparticles. CFD simulation was carried out to observe fluid flow behavior and micromixing in microfluidic system and improve our understanding about the governing fluid profile. The major objective of such effort was to provide a carrier for controlled and sustained release profile of different drugs. Different experimental parameters were optimized to obtain PLGA nanoparticles with proper size and minimized polydispersity index. The particle size, polydispersity, morphology, and stability of nanoparticles were compared. Microfluidic system provided a platform to control over the characteristics of nanoparticles. Using microfluidic system, the obtained particles were more uniform and harmonious in size, more stable, monodisperse and spherical, while particles produced by batch method were non-spherical and polydisperse. The best size and polydispersity index in the microfluidic method was obtained using 2% PLGA and 0.0625% (w/v) polyvinyl alcohol (PVA) solutions, and the flow rate ratio of 10:0.6 for PVA and PLGA solutions. CFD simulation demonstrated the high mixing intensity of about 0.99 at optimum condition in the microfluidic system, which is the possible reason for advantageous performance of this system. Altogether, the results of microfluidic-assisted method were found to be more reproducible, predictable, and controllable than batch method for producing a nanoformulation for delivery of drugs.
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http://dx.doi.org/10.4103/1735-5362.268207DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6827194PMC
October 2019

The correction of ETV6/RUNX1 translocation in acute lymphocytic leukemia cells: a new gene targeting system by homologous recombination mechanism.

J Appl Genet 2020 Feb 10;61(1):67-73. Epub 2019 Oct 10.

Medical Cellular and Molecular Research Center, Golestan University of Medical Sciences, Shastkola road, Falsafi complex, Gorgan, 4934174611, Iran.

Regarding the uncertainty of the exact cause of the acute lymphocytic leukemia (ALL) caused by ETV6-RUNX1t(12;21) translocation, correcting genes of the ETV6 and RUNX1 in ETV6/RUNX1 fusion gene simultaneously on chromosome 12 may be effective in reducing leukemia malignancy. Thus, we designed an homologous recombination (HR) plasmid to target of the ETV6/RUNX1 fusion gene in the REH cell line containing the ETV6-RUNX1t(12;21) translocation. Cells were cultured and transfected by HR plasmid. The presence of the replacement cassette at specific location in the ETV6/RUNX1 fusion gene was verified by PCR and sequencing method. A quantitative gene expression assay was performed to evaluate changes in expression of ETV6, RUNX1, and ETV6/RUNX1 genes following editing. The cell viability was measured by trypan blue staining. The expression of the ETV6 gene was significantly increased in modified cells than unmodified cells by 10.9-fold. In contrast, the expression of the ETV6-RUNX1 fusion gene was significantly decreased in the modified cells compared with unmodified cells by 0.26-fold. The expression of the RUNX1 gene had no significant difference between modified and unmodified cells. The survival rate of edited cells was significantly decreased than unedited cells (p = 013). We designed a gene targeting system based on HR method to correct genes of ETV6 and RUNX1 simultaneously in ETV6/RUNX1 fusion gene on chromosome 12 containing ETV6-RUNX1t(12;21) translocation. The modification of this translocation may lead to reducing effects of the fusion gene's damaging and the dosage compensation related to ETV6 and RUNX1 genes and subsequently reduce the effects of leukemia. This targeting system may open a window for treating leukemia as ex vivo.
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http://dx.doi.org/10.1007/s13353-019-00524-9DOI Listing
February 2020

Design and construction of a recombinant lentiviral vector with specific tropism to human epidermal growth factor-overexpressed cancer cells: Developing a new retargeting system for lentivirus vectors.

J Gene Med 2019 06 20;21(6):e3095. Epub 2019 May 20.

Medical Cellular and Molecular Research Center, Golestan University of Medical Sciences, Gorgan, Iran.

Background: Targeting of specific tissues and cells by viruses is one of the challenges faced by researchers. Lentiviral vectors (LVs) are one of the most promising gene delivery systems in cancer gene therapy. Therefore, we aimed to design a novel lentiviral delivery system that expresses anti- human epidermal growth factor 2 (HER2) designed anykrin repeat protein (DARPin) on the vector envelope to create a pseudotyped lentivirus for targeting HER2-positive cancer cells.

Methods: A helper plasmid producing the viral vector envelope containing anti-HER2 DARPin-G3 was constructed. LV was produced by transfer vector containing green fluorescent protein (GFP) gene and helper plasmids in human embryonic kidney 293 cells. The human breast cancer cell lines SKBR3 (normal and with inhibited endocytosis) (HER2-positive) and MDA-MB-231 (HER2-negative) were transduced by the recombinant viral vector. The GFP-based transduction rate was determined by flow cytometry and fluorescence microscopy.

Results: The anti-HER2 DARPin concentration in DARPin-LVs was significantly higher than the envelope G glycoprotein of the vesicular stomatitis virus-LVs (non-anti-HER2 control) (p < 0.0001). In flow cytometry assays, the percentage of transduction by recombinant LV was significantly higher in SKBR3 cells than in SKBR3 cells with inhibited endocytosis (p = 0.0074) and MDA-MB-231 cells (p = 0.0037). In fluorescence microscopy assays, the percentage of transduction by new LV was significantly higher in SKBR3 cells than in SKBR3 cells with inhibited endocytosis (p = 0.0026) and MDA-MB-231 cells (p = 0.0014).

Conclusions: We constructed a new recombinant LV with a defect in cell entry directly, containing an anti-HER2 DARPin on the vector envelope with specific tropism to HER2 receptor on HER2-positive cancer cells. We assumed that this viral vector transduces cells via an endocytosis-dependent process.
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http://dx.doi.org/10.1002/jgm.3095DOI Listing
June 2019

Clinical Outcomes and Healthcare Resource Utilization for Gastrointestinal Acute Graft-versus-Host Disease after Allogeneic Transplantation for Hematologic Malignancy: A Retrospective US Administrative Claims Database Analysis.

Biol Blood Marrow Transplant 2019 04 6;25(4):834-841. Epub 2019 Jan 6.

Medical College of Wisconsin, Milwaukee, Wisconsin.

Graft-versus-host disease (GVHD) is the leading cause of nonrelapse mortality among patients who receive allogeneic hematopoietic cell transplantation (allo-HCT). In its acute form (aGVHD), GVHD involves the skin, liver, and gastrointestinal (GI) tract, with GI involvement most strongly associated with poor prognosis. This retrospective cohort study used US healthcare claims data for 2008 to 2015 to identify patients who developed GI aGVHD after allo-HCT performed as curative treatment for hematologic malignancy and compared them with patients who did not develop aGVHD in terms of outcomes related to survival, infections, healthcare resource utilization (HRU), and costs. Whereas the patients without aGVHD saw a 66% improvement in 1-year survival between 2009 and 2015, this effect was not observed in patients with GI aGVHD. Compared with patients without evidence of aGVHD, patients with GI aGVHD were 3.9-fold more likely to develop an infection in the year after allo-HCT. Similarly, patients who developed GI aGVHD were 4.3-fold more likely to have an inpatient admission after allo-HCT discharge, and such an admission cost on average 47% more than an admission for patients without aGVHD. Our findings confirm that GI involvement in aGVHD is associated with higher mortality, risk of infection, HRU, and cost compared with absence of aGVHD.
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http://dx.doi.org/10.1016/j.bbmt.2018.12.839DOI Listing
April 2019

Safety and Effectiveness of Vedolizumab in Patients with Steroid-Refractory Gastrointestinal Acute Graft-versus-Host Disease: A Retrospective Record Review.

Biol Blood Marrow Transplant 2019 04 22;25(4):720-727. Epub 2018 Nov 22.

Blood and Marrow Transplant Program, Massachusetts General Hospital, Boston, Massachusetts.

Allogeneic hematopoietic cell transplantation (allo-HCT) can be curative in patients with hematologic malignancies but carries a significant risk of graft-versus-host disease (GVHD). There are no standard treatments for steroid-refractory (SR) gastrointestinal (GI) acute GVHD (aGVHD). This multicenter, international, retrospective medical record review aimed to evaluate the off-label use of vedolizumab, a gut-selective immunomodulator, for treating SR GI aGVHD. Data were collected from patients' medical records; criteria for extraction included no more than 1 allo-HCT and at least 1 dose of vedolizumab as treatment for SR GI aGVHD (ie, stage 1 to 4 GI aGVHD following ≥1 previous treatment regimen(s) containing ≥1 mg/kg methylprednisolone or equivalent). Descriptive analyses of response rate, overall survival (OS), and serious adverse effects (SAEs) were performed. Twenty-nine patients were identified from 7 sites who had received 1 to 10 doses of vedolizumab 300 mg i.v. (median 3 doses) as treatment for SR GI aGVHD. The overall response rate at 6 to 10 weeks after vedolizumab initiation was 64%, and OS at 6 months was 54%. There were 29 SAEs, including 12 infections; 3 SAEs were considered possibly related to vedolizumab, 2 of which were infections. Thirteen SAEs were fatal, 1 of which was possibly vedolizumab-related. There were 8 nonserious infections and 1 serious infection with confirmed GI origin in 8 patients; there was no apparent pattern in the timing of these infections relative to the initiation of vedolizumab treatment. Further data on the efficacy and safety of vedolizumab in this setting from prospective trials are needed.
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http://dx.doi.org/10.1016/j.bbmt.2018.11.013DOI Listing
April 2019

Optimization of de-esterified tragacanth microcapsules by computational fluid dynamic and the Taguchi design with purpose of the cell encapsulation.

Int J Biol Macromol 2017 Dec 14;105(Pt 1):17-26. Epub 2017 Jul 14.

Pharmaceutical Sciences Research Center, School of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, Iran; Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran. Electronic address:

This work presents the development of the new De-Esterified Tragacanth (DET) microcapsules (MCs). Co-flow extrusion method was applied for producing the MCs; the processing parameters were optimized by the Taguchi design to obtain the smallest and the most spherical MCs. Computational Fluid Dynamic (CFD) modeling was accomplished to show the formation of droplets at different airflows, and finally, βTC3 pancreatic cells were encapsulated in the MCs. The optimum MCs had 214.58μm size and 60.75% sphericality. The air pressure and the cross-linking reaction of DET were the most influential parameter in size and the sphericality of MCs, respectively. CFD showed two velocity vortices with rotational flow formed in the chamber, which caused changing the droplet moving direction. The encapsulated cells were proliferated, and cell viability was not reduced during six days. These phenomena make DET MCs a potential candidate for the cell encapsulation.
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http://dx.doi.org/10.1016/j.ijbiomac.2017.06.059DOI Listing
December 2017

A multicenter, retrospective, case-cohort study of the epidemiology and risk factors for Clostridium difficile infection among cord blood transplant recipients.

Transpl Infect Dis 2017 Aug 12;19(4). Epub 2017 Jul 12.

Harvard Medical School, Boston, MA, USA.

Background: Clostridium difficile infection (CDI) is the leading cause of health-care associated infectious diarrhea. The aim of this study was to evaluate the epidemiology and risk factors for CDI in the 100 days following umbilical cord blood transplantation (UCBT) at three Boston hospitals.

Methods: We performed a multicenter, retrospective, case-cohort study of 226 UCBT recipients at Beth Israel Deaconess Medical Center, Massachusetts General Hospital, and Dana Farber/Brigham and Women's Cancer Center from 2003 to 2012. CDI was defined as diarrhea (≥3 unformed bowel movements for at least 2 days) plus a positive stool test for toxinogenic C. difficile and not attributed to any other cause.

Results: Among 226 UCBT recipients, 22 patients (9.7%) developed CDI within the first 100 days of transplant (corresponding to an infection rate of 10.8 cases per 10 000 person-days). The 100-day and 1-year rates were stable across the time period and between institutions. UCBT recipients with CDI were more likely than non-CDI patients to be older, with higher body mass indices, and to have received an antipseudomonal penicillin agent. In a time-dependent case-cohort analysis of the risk factors associated with CDI in the first 100 days after UCBT, bacterial infection after UCBT was the strongest risk factor for CDI (hazard ratio 2.8; 95% confidence interval 1.08-7.24; P=.03), after adjustment for transplant variables including antibiotic exposure.

Conclusion: This study verifies the previously reported risk factors for CDI including older age and antibiotic exposure and identifies a novel association between bacterial infections and risk for CDI.
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http://dx.doi.org/10.1111/tid.12728DOI Listing
August 2017

Preparation of a reproducible long-acting formulation of risperidone-loaded PLGA microspheres using microfluidic method.

Pharm Dev Technol 2017 Sep 8;22(6):836-843. Epub 2016 Sep 8.

b Department of Pharmaceutics, Nano Drug Delivery Research Center, Faculty of Pharmacy, Kermanshah University of Medical Sciences , Kermanshah , Iran.

The aim of the present study is to prepare risperidone-loaded poly lactic-co-glycolic acid (PLGA) microspheres within microfluidic system and to achieve a formulation with uniform size and monotonic and reproducible release profile. In comparison to batch method, T-junction and serpentine chips were utilized and optimizing study was carried out at different processing parameters (e.g. PLGA and surfactant concentration and flow rates ratio of outer to inner phase). The computational fluid dynamic (CFD) modeling was performed, and loading and release study were carried out. CFD simulation indicates that increasing the flow rate of aqueous phase cause to decrease the droplet size, while the change in size of microspheres did not follow a specific pattern in the experimental results. The most uniform microspheres and narrowest standard deviation (66.79 μm ± 3.32) were achieved using T-junction chip, 1% polyvinylalcohol, 1% PLGA and flow rates ratio of 20. The microfluidic-assisted microspheres were more uniform with narrower size distribution. The release of risperidone from microspheres produced by the microfluidic method was more reproducible and closer to zero-order kinetic model. The release profile of formulation with 2:1 drug-to-polymer ratio was the most favorable release, in which 41.85% release could be achieved during 24 days.
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http://dx.doi.org/10.1080/10837450.2016.1221426DOI Listing
September 2017

Systematic review and meta-analysis of third-line salvage therapy with infliximab or cyclosporine in severe ulcerative colitis.

Ann Gastroenterol 2016 Jul-Sep;29(3):341-7. Epub 2016 Apr 7.

Department of Medicine and Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, USA.

Background: In patients with ulcerative colitis who fail corticosteroids and are treated with rescue therapy (e.g. infliximab or cyclosporine) but fail to respond, salvage therapy with infliximab or cyclosporine can be considered. We sought to assess the efficacy and safety of this third-line salvage therapy.

Methods: We performed a meta-analysis of trials published in PubMed up to January 2015 relating to the use of third-line salvage therapy following failure of intravenous corticosteroids and infliximab or cyclosporine. Pooled outcome rates for each salvage strategy and pooled odds ratio comparing the two strategies were calculated using the random effects model. Heterogeneity was assessed by the Q and I(2) statistics.

Results: The search strategy yielded 40 articles of which 4 were eligible for inclusion. Four articles assessed patients who were treated with infliximab after failure of cyclosporine and 2 articles assessed the use of cyclosporine after failure of infliximab. There were 138 patients using infliximab as a third-line salvage therapy and 30 patients using cyclosporine. When comparing these two strategies, there was no significant difference in clinical response (RR 1.03, 95%CI 0.7-1.46 P=0.87), clinical remission (RR 0.69, 95%CI 0.30-1.57 P=0.37), or colectomy at 12 months (RR 1.14, 95%CI 0.79-1.67 P=0.48). Similarly, there was no significant difference in total (RR 1.91, 95% CI0.38-9.64 p=0.43) or serious adverse events (RR 1.18, 95%CI 0.34-4.07 P=0.80).

Conclusion: While third-line salvage therapy may be efficacious in achieving short-term clinical response/remission, there remains a significant risk of colectomy and adverse events.
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http://dx.doi.org/10.20524/aog.2016.0032DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4923821PMC
July 2016

Systematic Analysis and Critical Appraisal of the Quality of the Scientific Evidence and Conflicts of Interest in Practice Guidelines (2005-2013) for Barrett's Esophagus.

Dig Dis Sci 2016 10 15;61(10):2812-2822. Epub 2016 Jun 15.

Department of Medicine and Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, 110 Francis St 8E Gastroenterology, Boston, MA, 02215, USA.

Background: Barrett's esophagus (BE) is a condition that has a small but important risk of progressing to esophageal cancer. To date, no study has assessed the strength of evidence supporting the recommendations for BE. We sought to assess the overall quality of the recommendations and strength of the BE using the AGREE II instrument.

Methods: A PubMed search was performed to identify guidelines published pertaining to BE. Every guideline was reviewed using the AGREE II format to assess the methodological rigor and validity of the guideline. Additionally, guidelines were reviewed for the level of evidence used to support recommendations, conflicts of interest (COI), and differences in recommendations. Statistical analysis was performed using Stata (version 12).

Results: In total, 234 manuscripts were identified of which 8 guidelines published between 2005 and 2013 pertained to BE. Seventy-five percentage (6/8) graded the evidence used to formulate recommendations. Of the 126 recommendations with supporting evidence, 6 % were supported by level A evidence, 49 % level B evidence, and 45 % level C evidence. Using the AGREE II format, the highest overall assessment grade was the BSG BE guideline (6.5 ± 0.6) followed by the AGA (5.5 ± 0.6). The highest rated domains were scope and purpose (mean 77 range 24-96) and clarity of presentation (mean 75), while the lowest rated domains were editorial independence (mean 32 range 0-92) and applicability of the guideline (mean 35 range 7-90). There was significant variability in recommendations regarding who to screen for BE and surveillance intervals. Finally, only 50 % of the guidelines disclosed if COI were present and 75 % (3/4) reported potentially relevant COI.

Conclusions: Majority of the BE guideline fail to meet the AGREE II domains, and most of the recommendations are level B or C quality evidence. Further interventions are necessary to improve the overall quality of the guidelines.
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http://dx.doi.org/10.1007/s10620-016-4222-2DOI Listing
October 2016

The impact of PCR on Clostridium difficile detection and clinical outcomes.

J Med Microbiol 2015 Sep 9;64(9):1082-1086. Epub 2015 Jul 9.

Clinical Research Center, Soroka University Medical Center, Be'er-Sheva, Israel.

PCR has increasingly replaced toxin A and B enzyme immunoassay (EIA) for the testing of Clostridium difficile infection (CDI). This study evaluated the clinical outcomes of CDI and disease epidemiology since the introduction of PCR. Clinical data and outcomes for patients admitted to a tertiary care centre during 2003 to 2012 were extracted using electronic medical records. Outcomes and incidence of disease were compared between types of CDI testing. In total, 15.6% of 108,092 patients admitted were tested for CDI. Among patients tested, 6.1% had positive results. The mean number of tests performed per 1000 admissions by EIA and PCR was 257.4 and 162.6, respectively. A total of 8.2% of PCR tests were positive compared to 5.0% of EIA tests (P < 0.001). The number of tests performed has decreased and the proportion of positive tests increased since PCR introduction. CDI incidence has remained constant. Only albumin (3.09 vs 3.24 g dl(-1), P 0.002) and inflammatory bowel disease (2.6 vs 7.0%, P < 0.001) status differed between the EIA and PCR groups. While hospital mortality did not differ, patients diagnosed by PCR had a shorter median length of stay (10 vs 8 days, P 0.004). Since PCR testing began, less CDI tests have been performed, but the proportion of positive results has increased. The incidence of CDI has remained constant, suggesting no change in disease epidemiology. The length of stay was shorter in the PCR group, reflective of either earlier detection and quicker onset of therapy or detection of less severe disease. Mortality did not change since the introduction of PCR.
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http://dx.doi.org/10.1099/jmm.0.000126DOI Listing
September 2015

Mesalamine, but Not Sulfasalazine, Reduces the Risk of Colorectal Neoplasia in Patients with Inflammatory Bowel Disease: An Agent-specific Systematic Review and Meta-analysis.

Inflamm Bowel Dis 2015 Nov;21(11):2562-9

*Center for Inflammatory Bowel Diseases, Beth Israel Deaconess Medical Center, Boston, Massachusetts; and †Leeds Gastroenterology Institute, St James's University Hospital, Leeds, United Kingdom.

Background: In some studies, 5-aminosalicylates as a class have been associated with protective effects against colorectal cancer in inflammatory bowel disease. In practice, only mesalamine at doses greater than 1.2 g per day is currently widely in this setting. The specific impact of mesalamine at these doses has not has not previously been determined.

Methods: We performed a systematic review and meta-analysis of the effect of mesalamine on risk of colorectal neoplasia (CRN) from prior cohort and case-control studies. Sensitivity analyses for study setting and case definition were performed. A quality assessment was made of all included studies.

Results: Mesalamine was associated with a modest reduction in the odds ratio (OR) of CRN (OR = 0.6, 95% confidence interval, 0.4-0.9, P = 0.04). This effect was only noted in hospital-based studies and only in the reduction of all CRN (not cancers alone). Patients prescribed doses >1.2 g per day had a lower risk of CRN (OR = 0.5, 95% confidence interval, 0.3-0.9, P = 0.02) than lower doses. This effect was also only present in the hospital-based studies. In contrast, there was no reduction in the risk of CRN in patients prescribed sulfasalazine (OR = 0.8, 95% confidence interval, 0.5-1.2, P = 0.3), regardless of study setting.

Conclusions: Mesalamine, particularly at doses >1.2 g per day, produces a modest reduction in the risk of CRN in inflammatory bowel disease patient populations from referral centers. Sulfasalazine does not seem to reduce the risk. No benefit was noted in population-based studies.
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http://dx.doi.org/10.1097/MIB.0000000000000540DOI Listing
November 2015

Socioeconomic Risk Factors for Celiac Disease Burden and Symptoms.

J Clin Gastroenterol 2016 Apr;50(4):307-12

Celiac Center and Department of Gastroenterology, Beth Israel Deaconess Medical Center, Boston, MA.

Background & Aims: Celiac disease (CD) affects approximately 1% of the population and negatively affects aspects of life including physical and social function. The relationship between socioeconomic (SE) factors, symptom severity, and perceived burden of living with CD is not well understood. The objective of this study was to assess the relationships between income, symptoms, and perceived burden of CD.

Methods: In this survey study conducted at a tertiary care center, 773 patients 18 years of age or more with biopsy confirmed CD were eligible to participate. Patients completed a survey with information on SE data, the validated Celiac Symptom Index (CSI), and visual analog scales (VAS) assessing overall health, CD-related health, difficulty in following a gluten-free diet (GFD), and importance of following a GFD.

Results: Three hundred forty one patients completed the survey. Higher income predicted better overall health, better CD related health, and fewer symptoms. In the logistic regression model, low income was associated with greater CD symptoms (odds ratio=6.04, P=0.002). Other factors associated with greater symptoms were younger age, poor overall health state, and more physician visits. Factors associated with increased burden of CD included hospitalizations, more symptoms, poor overall health state, and burden of following a GFD.

Conclusions: Patients with lower incomes have worse CD-related health and greater symptoms. Those with low income had 6 times the odds of greater symptoms compared with those with high income. Our data suggest that income is associated with perceived overall health, CD-related health, and CD symptoms.
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http://dx.doi.org/10.1097/MCG.0000000000000366DOI Listing
April 2016

Patient perception of treatment burden is high in celiac disease compared with other common conditions.

Am J Gastroenterol 2014 Sep 1;109(9):1304-11. Epub 2014 Jul 1.

Celiac Center and Department of Gastroenterology, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.

Objectives: The only treatment for celiac disease (CD) is life-long adherence to a gluten-free diet (GFD). Noncompliance is associated with signs and symptoms of CD, yet long-term adherence rates are poor. It is not known how the burden of the GFD compares with other medical treatments, and there are limited data on the socioeconomic factors influencing treatment adherence. In this study, we compared treatment burden and health state in CD compared with other chronic illnesses and evaluated the relationship between treatment burden and adherence.

Methods: Survey was mailed to participants with CD, gastroesophageal reflux disease (GERD), irritable bowel syndrome, inflammatory bowel disease, hypertension (HTN), diabetes mellitus (DM), congestive heart failure, and end-stage renal disease (ESRD) on dialysis. Surveys included demographic information and visual analog scales measuring treatment burden, importance of treatment, disease-specific health status, and overall health status.

Results: We collected surveys from 341 celiac and 368 non-celiac participants. Celiac participants reported high treatment burden, greater than participants with GERD or HTN and comparable to ESRD. Conversely, patients with CD reported the highest health state of all groups. Factors associated with high treatment burden in CD included poor adherence, concern regarding food cost, eating outside the home, higher income, lack of college education, and time limitations in preparing food. Poor adherence in CD was associated with increased symptoms, income, and low perceived importance of treatment.

Conclusions: Participants with CD have high treatment burden but also excellent overall health status in comparison with other chronic medical conditions. The significant burden of dietary therapy for CD argues for the need for safe adjuvant treatment, as well as interventions designed to lower the perceived burden of the GFD.
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http://dx.doi.org/10.1038/ajg.2014.29DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4159418PMC
September 2014

Systematic analysis underlying the quality of the scientific evidence and conflicts of interest in interventional medicine subspecialty guidelines.

Mayo Clin Proc 2014 Jan;89(1):16-24

Department of Medicine and Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA.

Objective: To determine the validity of guidelines published by interventional medical societies.

Methods: We reviewed the interventional medicine subspecialty society websites of the American Association for Bronchology and Interventional Pulmonology (AABIP), American Society of Diagnostic and Interventional Nephrology (ASDIN), American Society for Gastrointestinal Endoscopy (ASGE), and Society for Cardiovascular Angiography and Interventions (SCAI) as of November 15, 2012, for published interventional guidelines. The study was performed between November 15, 2012, and January 1, 2013. The AABIP did not publish guidelines, so American Thoracic Society and American College of Chest Physicians guidelines were reviewed. All the guidelines were reviewed for graded levels of evidence, methods used to grade the evidence, and disclosures of conflicts of interest (COIs).

Results: Of 153 interventional guidelines evaluated, 4 were duplicates. Forty-six percent of guidelines (69 of 149) graded the quality of evidence using 7 different methods. The ASGE graded 71% of guidelines (46 of 65) compared with 29% (23 of 78) by the SCAI and 0 by the ASDIN (n=4) and the pulmonary societies (n=2). Of the 3425 recommendations reviewed, 11% (n=364) were supported by level A, 42% (n=1432) by level B, and 48% (n=1629) by level C. The mean age of the guidelines was 5.2 years. Additionally, 62% of the guidelines (92 of 149) failed to comment on COIs; when disclosed, 91% of guidelines (52 of 57) reported COIs. In total, 1827 COIs were reported by 45% of the authors (317 of 697), averaging 5.8 COIs per author.

Conclusion: Most of the interventional guidelines failed to grade the evidence. When present, most guidelines used lower-quality evidence. Furthermore, most guidelines failed to disclose COIs. When commented on, numerous COIs were present. Future guidelines should clearly state the quality of evidence, use a standard grading system, be transparent regarding potential biases, and provide frequent updates.
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http://dx.doi.org/10.1016/j.mayocp.2013.09.013DOI Listing
January 2014

Systematic analysis underlying the quality of the scientific evidence and conflicts of interest in gastroenterology practice guidelines.

Am J Gastroenterol 2013 Nov;108(11):1686-93

Department of Medicine and Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.

Objectives: The practice guidelines published by the American Gastroenterological Association (AGA) and the American College of Gastroenterology (ACG) are used to establish standards of care and improve patient outcomes. We examined the guidelines for quality of evidence, methods of grading evidence, and conflicts of interest (COIs).

Methods: All 81 (AGA and ACG) guidelines available online on 26 July 2012 were reviewed for the presence of grading of evidence and COIs. In total, 570 recommendations were evaluated for level of evidence and methods used to grade the evidence. The data were evaluated in aggregate and by society.

Results: Only 31% (n=25) of the guidelines graded the levels of evidence. A total of 12 systems were used to grade the quality of evidence in these 25 guidelines. Of the 570 recommendations reviewed, only 29% (n=165) were supported by the highest quality of evidence, level A; 37% (n=210) level B, 29% (n=165) level C, and 5% (n=30) level D. Since 2007, 87% (n=13/15) of the ACG guidelines graded the evidence compared with only 33% of the AGA guidelines (n=4/12). Furthermore, 70% (n=57/81) of the guidelines failed to disclose any information regarding COIs. Of the 24 articles commenting on COIs, 67% reported COIs.

Conclusions: Although the majority of the gastroenterology guidelines fail to grade the quality of evidence, more recent ACG guidelines grade majority of their recommendations. When the evidence is graded, most of the supporting evidence is based on lower-quality evidence. In addition, most of the guidelines fail to comment on COIs, and when disclosed, numerous COIs were present. This study highlights the critical need to revise the guideline development process. Future guidelines should clearly state the quality of evidence for their recommendations, utilize a standard grading system, and be transparent regarding all COIs.
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http://dx.doi.org/10.1038/ajg.2013.150DOI Listing
November 2013

Prevalence and lifetime risk of endoscopy-related complications among patients with inflammatory bowel disease.

Clin Gastroenterol Hepatol 2013 Oct 10;11(10):1288-93. Epub 2013 May 10.

Department of Internal Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts. Electronic address:

Background & Aims: Few studies have analyzed the safety of endoscopy in patients with inflammatory bowel disease (IBD). We aimed to determine the prevalence of procedure-related complications among these patients, compared with the general population, and estimate the lifetime risk of colonoscopy-related complications.

Methods: We collected data on complications in 685 patients with IBD and 17,000 patients without IBD (controls) using an automated system to track all emergency department visits to the Beth Israel Deaconess Medical Center within 14 days of an endoscopic procedure, from March 1, 2007, to November 30, 2007. We reviewed charts of all IBD patients to determine health care use (telephone calls or visits to a gastroenterologist or primary care physician and visits to other emergency departments or hospitals) after endoscopy. The lifetime risk of procedure-related complications was estimated using a Markov Monte Carlo model.

Results: Rates of complications were 1.17% among patients with IBD and 0.96% among controls (P = .55). The chart review showed that 3.8% of the IBD cohort received medical care within 14 days of the endoscopic procedure. Based on a Markov Monte Carlo simulation model, the lifetime risk of complications after a surveillance colonoscopy protocol was 12.7% among patients with IBD and 2.0% in the general population undergoing screening colonoscopy (P < .001).

Conclusions: Although the risk of adverse events after each endoscopic procedure was similar for patients with IBD and the general population, IBD patients have an increased lifetime risk of complications after colonoscopies. A higher percentage of patients with IBD also seek medical care after endoscopic procedures than controls.
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http://dx.doi.org/10.1016/j.cgh.2013.04.047DOI Listing
October 2013

Systematic review and meta-analysis on the effects of thiopurines on birth outcomes from female and male patients with inflammatory bowel disease.

Inflamm Bowel Dis 2013 Jan;19(1):15-22

Department of Internal Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA.

Background: Inflammatory bowel disease (IBD) affects people during their prime reproductive years. The thiopurines (6-mercaptopurine and azathioprine), commonly used for induction and maintenance of remission, are U.S. Food and Drug Administration (FDA) pregnancy category D, raising concern for fetal risk. We performed a systematic review and meta-analysis to evaluate the effects of thiopurine exposure during pregnancy or at the time of conception on three measures of fetal risk in women and men with IBD.

Methods: A systematic search of PubMed and Web of Science using a combination of Mesh and text terms was performed to identify studies reporting birth outcomes from IBD women and men exposed to thiopurines within 3 months of conception and/or during pregnancy. A meta-analysis was performed using the random effects model to pool estimates and report odds ratio (OR) for three outcomes in women: low birth weight (LBW), preterm birth, and congenital abnormalities and one in men: congenital abnormalities.

Results: In women with IBD exposed to thiopurines, the pooled ORs for LBW, preterm birth, and congenital abnormalities were 1.01 (95% confidence interval [CI] 0.96, 1.06), 1.67 (95% CI 1.26, 2.20), and 1.45 (95% CI 0.99, 2.13), respectively. In men, the pooled OR for congenital abnormality was 1.87 (95% CI 0.67, 5.25).

Conclusions: Thiopurine exposure in women with IBD was not associated with LBW or congenital abnormalities, but was associated with preterm birth. Exposure in men at the time of conception was not associated with congenital abnormalities.
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http://dx.doi.org/10.1002/ibd.22948DOI Listing
January 2013

The association of primary open-angle glaucoma with mortality: a meta-analysis of observational studies.

Arch Ophthalmol 2009 Feb;127(2):204-10

Harvard University School of Public Health, Boston, Massachusetts, USA.

Objective: To conduct a meta-analysis to estimate the relationship between primary open-angle glaucoma (POAG) and mortality.

Methods: A systematic search of the PubMed, Embase, and Web of Science databases yielded 9 cohort studies with relative risk (RR) estimates for all-cause mortality. The studies were critically reviewed by an expert in the field. The data were extracted and analyzed in a pooled analysis by the random-effects model. Meta-regression to assess for heterogeneity by several covariates and subgroup analysis on cardiovascular mortality were performed.

Results: A significant risk was not detected in the final pooled analysis (RR, 1.13; 95% confidence interval [CI], 0.97-1.31) for all-cause mortality. A meta-regression across mean follow-up time, age, and sex was not significant. A meta-regression across diabetes status in 3 of the 9 studies did not demonstrate significant results (P = .94). Subgroup analysis on cardiovascular mortality from 4 of the 9 studies was marginally significant (RR, 1.20; 95% CI, 1.00-1.43; P = .05), but insignificant after removal of a study in which POAG was ascertained by self and proxy report (RR, 1.12; 95% CI, 0.87-1.46).

Conclusion: This meta-analysis does not demonstrate an association between POAG and all-cause or cardiovascular mortality.
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http://dx.doi.org/10.1001/archophthalmol.2008.571DOI Listing
February 2009

Diversity arrays technology (DArT) for high-throughput profiling of the hexaploid wheat genome.

Theor Appl Genet 2006 Nov 11;113(8):1409-20. Epub 2006 Oct 11.

Triticarte P/L, 1 Wilf Crane Crescent, Yarralumla, Canberra, ACT, 2600, Australia.

Despite a substantial investment in the development of panels of single nucleotide polymorphism (SNP) markers, the simple sequence repeat (SSR) technology with a limited multiplexing capability remains a standard, even for applications requiring whole-genome information. Diversity arrays technology (DArT) types hundreds to thousands of genomic loci in parallel, as previously demonstrated in a number diploid plant species. Here we show that DArT performs similarly well for the hexaploid genome of bread wheat (Triticum aestivum L.). The methodology previously used to generate DArT fingerprints of barley also generated a large number of high-quality markers in wheat (99.8% allele-calling concordance and approximately 95% call rate). The genetic relationships among bread wheat cultivars revealed by DArT coincided with knowledge generated with other methods, and even closely related cultivars could be distinguished. To verify the Mendelian behaviour of DArT markers, we typed a set of 90 Cranbrook x Halberd doubled haploid lines for which a framework (FW) map comprising a total of 339 SSR, restriction fragment length polymorphism (RFLP) and amplified fragment length polymorphism (AFLP) markers was available. We added an equal number of DArT markers to this data set and also incorporated 71 sequence tagged microsatellite (STM) markers. A comparison of logarithm of the odds (LOD) scores, call rates and the degree of genome coverage indicated that the quality and information content of the DArT data set was comparable to that of the combined SSR/RFLP/AFLP data set of the FW map.
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http://dx.doi.org/10.1007/s00122-006-0365-4DOI Listing
November 2006