Grant Barber

All Publications

• Editorial: treat-to-target in ulcerative colitis clinical management-a small price to pay? Alimentary pharmacology & therapeutics Barber, G. E., Gubatan, J. 2023; 57 (5): 569-570

  View details for DOI 10.1111/apt.17298

  View details for PubMedID 36786463

• Paternal Medications in Inflammatory Bowel Disease and Male Fertility and Reproductive Outcomes: A Systematic Review and Meta-Analysis. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association Gubatan, J., Barber, G. E., Nielsen, O. H., Juhl, C. B., Maxwell, C., Eisenberg, M. L., Streett, S. E. 2022

  Abstract

  Studies evaluating reproductive outcomes among male patients with inflammatory bowel disease (IBD) are limited. We evaluated use of IBD medications and association with semen parameters, a proxy of male fertility, and adverse pregnancy outcomes [early pregnancy loss (EPL), preterm birth (PB), congenital malformations (CM)].We searched Medline, Embase, Scopus, and Web of Science (PROSPERO CRD42020197098) from inception to April 2022 for studies reporting semen parameters and adverse pregnancy outcomes among male patients exposed to biologics, thiopurine, or methotrexate. Standardized mean difference, prevalence, and odds ratios of outcomes were pooled and analysed using a random effects model.Ten studies reporting semen parameters (268 IBD patients) and 16 studies reporting adverse pregnancy outcomes (over 25,000 IBD patients) were included. Biologic, thiopurine, or methotrexate use were not associated with decreased sperm count, motility, or abnormal morphology compared to non-exposed patients. The prevalence of adverse pregnancy outcomes with paternal biologic (5%), thiopurine (6%), or methotrexate (6%) exposure was comparable to non-exposed patients (5%). Biologic use was not associated with risk of EPL (OR 1.26, I2= 0%, P=0.12), PB (OR 1.10, I2= 0%, P=0.17), or CM (OR 1.03, I2=0%, P=0.69). Thiopurine use was not associated with risk of EPL (OR 1.31, I2= 19%, P=0.17), PB (OR 1.05, I2= 0%, P=0.20), or CM (OR 1.07, I2=7%, P=0.34). Methotrexate use was not associated with risk of PB (OR 1.06, I2= 0%, P=0.62) or CM (OR 1.03, I2=0%, P=0.81).Biologic, thiopurine, or methotrexate use among male patients with IBD are not associated with impairments in fertility or with increased odds of adverse pregnancy outcomes.Biologic therapy, congenital malformations, early pregnancy loss, father, inflammatory bowel disease, male, pregnancy outcomes, preterm birth, reproductive health.

  View details for DOI 10.1016/j.cgh.2022.07.008

  View details for PubMedID 35870769

• Paternal Biologic and Thiopurine Exposure in Inflammatory Bowel Disease and Association With Adverse Pregnancy Outcomes and Semen Parameters: A Systematic Review and Meta-Analysis Gubatan, J., Barber, G., Nielsen, O., Juhl, C., Maxwell, C., Eisenberg, M., Streett, S. LIPPINCOTT WILLIAMS & WILKINS. 2021: S353

  View details for Web of Science ID 000717526101240

• Thiopurine Monotherapy Is Effective in Maintenance of Mild-Moderate Inflammatory Bowel Disease. Digestive diseases and sciences Barber, G. E., Hendler, S., Choe, M., Keyashian, K., Lechner, S., Limketkai, B. N., Limsui, D. 2021

  Abstract

  BACKGROUND: Crohn's disease (CD) and ulcerative colitis (UC) are complex, inflammatory bowel diseases (IBD) with debilitating complications. While severe IBD typically requires biologic agents, the optimal therapy for mild-moderate IBD is less clear.AIMS: To assess the efficacy of thiopurine monotherapy for maintenance of mild-moderate IBD and clinical variables associated with treatment outcome.METHODS: This retrospective study included adults with mild-moderate IBD who were started on thiopurines without biologic therapy. The primary outcome was therapy failure, defined by disease progression based on clinical, endoscopic, and radiologic criteria. Clinical variables were extracted at time of thiopurine initiation. Univariable and multivariable Cox proportional hazards models were used to examine the independent contribution of the clinical variables on treatment response.RESULTS: From 230 CD patients, 64 (72%) were free of treatment failure with mean follow-up of 3.3years. In our multivariable model, thiopurine failure was associated with concomitant systemic steroid administration (aHR 2.43, p=0.001), whereas protective factors included concomitant oral 5-aminosalicylic acid (5-ASA) therapy (aHR 0.54, p=0.02) and non-fistulizing, non-stricturing disease (aHR 0.57, p=0.047). From 173 UC patients, 50 (71%) were free from treatment failure with mean follow-up of 3.3years. On multivariable analysis, concomitant oral steroids were associated with thiopurine failure (aHR 2.71, p=0.001). Only 13 (4%) discontinued thiopurines from adverse effects.CONCLUSIONS: In mild-moderate uncomplicated IBD, thiopurine monotherapy was associated with longitudinal maintenance of remission and may represent a lower-cost, convenient, and effective alternative to biologics. Multiple clinical variables were predictive of treatment response.

  View details for DOI 10.1007/s10620-021-06947-x

  View details for PubMedID 33755823

• Cytomegalovirus infection is associated with worse outcomes in inflammatory bowel disease hospitalizations nationwide. International journal of colorectal disease Hendler, S. A., Barber, G. E., Okafor, P. N., Chang, M. S., Limsui, D., Limketkai, B. N. 2020

  Abstract

  BACKGROUND: Cytomegalovirus (CMV) infection may complicate ulcerative colitis (UC) or Crohn's disease (CD) hospitalizations. Studies examining this relationship are often single-center examining short time periods.AIMS: To quantify the prevalence of CMV and its impact on outcomes among UC and CD hospitalizations over time using nationwide administrative databases.METHODS: The National Inpatient Sample and Nationwide Readmissions Database were analyzed to calculate CMV prevalence per 1000 UC and CD hospitalizations between 1998 and 2014. Univariable and multivariable logistic and linear regression were used to assess CMV's association with outcomes. Separate analyses examined effects from the introduction of anti-TNF therapy in UC in 2005, CD anatomic extent, and Clostridioides difficile infection.RESULTS: Among UC, from 1998 to 2014, the prevalence of CMV infection rose from 1.4 to 6.3 per 1000 UC hospitalizations (p<0.001), although this increase was not statistically significant for the years 2006 to 2014 (p=0.07). Among CD, prevalence rose from 0.3 to 1.8 per 1000 CD hospitalizations (p<0.001) from 1998 to 2014. CMV was independently associated with increased inpatient mortality (UC: odds ratio (OR) 2.3, 95% confidence interval (CI) 1.2-4.5; CD: OR 4.6, CI 1.5-13.7), colectomy in UC (OR 2.5, CI 1.9-3.3), and higher length of stay and costs.CONCLUSION: CMV infection's prevalence among UC and CD hospitalizations is rising over time, but may have slowed after 2005 in UC. CMV is independently associated with increased inpatient mortality, length of stay, and hospital charges in UC and CD and with colectomy in UC.

  View details for DOI 10.1007/s00384-020-03536-8

  View details for PubMedID 32124046

• Rising Incidence of Intestinal Infections in Inflammatory Bowel Disease: A Nationwide Analysis INFLAMMATORY BOWEL DISEASES Barber, G. E., Hendler, S., Okafor, P., Limsui, D., Limketkai, B. N. 2018; 24 (8): 1849–56

  View details for DOI 10.1093/ibd/izy086

  View details for Web of Science ID 000449181900025

• Rising Incidence of Intestinal Infections in Inflammatory Bowel Disease: A Nationwide Analysis. Inflammatory bowel diseases Barber, G. E., Hendler, S. n., Okafor, P. n., Limsui, D. n., Limketkai, B. N. 2018

  Abstract

  Intestinal infections are common in patients with inflammatory bowel disease (IBD) and may mimic IBD flares. In this study, we estimate the changing incidence of intestinal infections among IBD hospitalizations and assess the impact of intestinal infections on key hospitalization metrics.The National Inpatient Sample (NIS) was analyzed for hospitalizations from IBD between 1998 and 2014. Intestinal infections were identified using ICD-9-CM codes, and incidence for each infection was calculated for Crohn's disease (CD) and ulcerative colitis (UC). Linear and logistic regression analyses were used to assess the effects of intestinal infections on hospitalization duration, charges, and mortality.There were 4,030,620 hospitalizations for IBD between 1998 and 2014. The annual incidence of intestinal infections rose from 26.2 to 70.6 infections per 1000 IBD hospitalizations (Ptrend < 0.01). A main driver of this rising incidence was Clostridium difficile infections, which increased from 7.8 to 32.1 per 1000 CD hospitalizations and from 23.0 to 84.7 per 1000 UC hospitalizations (Ptrend < 0.01). The incidence of other intestinal infections increased from 10.2 to 15.3 per 1000 CD hospitalizations and 16.5 to 25.3 per 1000 UC hospitalizations. Intestinal infections and particularly C. difficile infections were associated with longer hospitalizations, greater hospital charges, and greater all-cause mortality.The incidence of intestinal infections among hospitalized IBD patients has increased over the past 15 years, primarily driven by C. difficile infections. Intestinal infections are associated with length of stay, hospital charges, and all-cause mortality. More aggressive measures for prevention of C. difficile infections are needed. 10.1093/ibd/izy086_video1izy086.video15779257979001.

  View details for PubMedID 29722832

• A Comprehensive Study of Costs Associated With Recurrent Clostridium difficile Infection. Infection control and hospital epidemiology Rodrigues, R., Barber, G. E., Ananthakrishnan, A. N. 2017; 38 (2): 196-202

  Abstract

  BACKGROUND Clostridium difficile infection (CDI) is the most common healthcare-associated infection and is associated with considerable morbidity. Recurrent CDI is a key contributing factor to this morbidity. Despite an estimated 83,000 recurrences annually in the United States, there are few accurate estimates of costs associated with recurrent CDI. OBJECTIVE We performed this study (1) to identify the health consequences of recurrent CDI including need for repeat hospitalization, intensive care unit (ICU) stay, and surgery; (2) to determine costs associated with recurrent CDI and identify determinants of such costs; and (3) to compare the outcomes and costs of recurrent CDI to those who develop reinfection. METHODS We identified all patients with confirmed recurrent CDI between January to December 2013 at a single referral center. Healthcare burden associated with recurrence including diagnostic testing, pharmacologic treatment, and inpatient and outpatient healthcare visits were identified in the 12 months following the first recurrence. Total healthcare costs were calculated, and the predictors of high healthcare utilization were identified. RESULTS Our study population included 98 patients with recurrent CDI. The median interval between the initial infection and recurrence was 37 days. The mean age of the cohort was 67 years, two-thirds were women (62%), and the mean Charlson index was 8.6. During the year following the first recurrence of CDI, each patient underwent a mean of 4.4 stool C. difficile toxin tests and received a mean of 2.5 prescriptions for oral vancomycin (range, 0-6). Most patients (84%) with recurrence had a CDI-related hospitalization, and 6% underwent colectomy. The mean total CDI-associated cost was $34,104 per patient, with hospitalization costs accounting for 68%, surgery 20%, and drug treatment 8% of this cost, respectively. Extrapolating to the United States overall, we estimate an annual cost of $2.8 billion related to recurrent CDI. CONCLUSION Recurrent CDI is associated with considerable morbidity and cost. Infect Control Hosp Epidemiol 2017;38:196-202.

  View details for DOI 10.1017/ice.2016.246

  View details for PubMedID 27817758

• Genetic Markers Predict Primary Non-Response and Durable Response To Anti-TNF Biologic Therapies in Crohn's Disease. The American journal of gastroenterology Barber, G. E., Yajnik, V., Khalili, H., Giallourakis, C., Garber, J., Xavier, R., Ananthakrishnan, A. N. 2016; 111 (12): 1816-1822

  Abstract

  One-fifth of patients with Crohn's disease (CD) are primary non-responders to anti-tumor necrosis factor (anti-TNF) therapy, and an estimated 10-15% will fail therapy annually. Little is known about the genetics of response to anti-TNF therapy. The aim of our study was to identify genetic factors associated with primary non-response (PNR) and loss of response to anti-TNFs in CD.From a prospective registry, we characterized the response of 427 CD patients to their first anti-TNF therapy. Patients were designated as achieving primary response, durable response, and non-durable response based on clinical, endoscopic, and radiologic criteria. Genotyping was performed on the Illumina Immunochip. Separate genetic scores based on presence of predictive genetic alleles were calculated for PNR and durable response and performance of clinical and genetics models were compared.From 359 patients, 36 were adjudged to have PNR (10%), 200 had durable response, and 74 had non-durable response. PNRs had longer disease duration and were more likely to be smokers. Fifteen risk alleles were associated with PNR. Patients with PNR had a significantly higher genetic risk score (GRS) (P =8 × 10-12). A combined clinical-genetic model more accurately predicted PNR when compared with a clinical only model (0.93 vs. 0.70, P <0.001). Sixteen distinct single nucleotide polymorphisms predicted durable response with a higher GRS (P =7 × 10-13). The GRSs for PNR and durable response were not mutually correlated, suggesting distinct mechanisms.Genetic risk alleles can predict primary non-response and durable response to anti-TNF therapy in CD.

  View details for DOI 10.1038/ajg.2016.408

  View details for PubMedID 27596696

  View details for PubMedCentralID PMC5143156

• Identification of Recurrent Clostridium difficile Infection Using Administrative Codes: Accuracy and Implications for Surveillance. Infection control and hospital epidemiology Wen, J., Barber, G. E., Ananthakrishnan, A. N. 2015; 36 (8): 893-8

  Abstract

  To develop an algorithm using administrative codes, laboratory data, and medication data to identify recurrent Clostridium difficile infection (CDI) and to examine the sensitivity, specificity, positive and negative predictive values, and performance of this algorithm.We identified all patients with 2 or more International Classification of Diseases, Ninth Edition, Clinical Modification (ICD-9-CM) codes for CDI (008.45) from January 1 through December 31, 2013. Information on number of diagnosis codes, stool toxin assays (enzyme immunoassay or polymerase chain reaction), and unique prescriptions for metronidazole and vancomycin was identified. Logistic regression was used to identify independent predictors of recurrent CDI and a predictive model was developed.A total of 591 patients with at least 2 ICD-9 codes for CDI were included (median age, 66 years). The derivation cohort consisted of 157 patients among whom 43 (27%) had recurrent CDI. Presence of 3 or more ICD-9 codes for CDI (odds ratio, 2.49), 2 or more stool tests (odds ratio, 2.88), and 2 or more prescriptions for vancomycin (odds ratio, 5.87) were independently associated with confirmed recurrent CDI. A classifier incorporating 2 or more prescriptions for vancomycin and either 2 or more stool tests or 3 or more ICD-9-CM codes had a positive predictive value of 41% and negative predictive value of 90%. The area under the receiver operating characteristic curve for this combined classifier was modest (0.69).Identification of recurrent episodes of CDI in administrative data poses challenges. Accurate assessment of burden requires individual case review to confirm diagnosis.

  View details for DOI 10.1017/ice.2015.102

  View details for PubMedID 25924718

• Mitochondrial ADCK3 Employs an Atypical Protein Kinase-like Fold to Enable Coenzyme Q Biosynthesis MOLECULAR CELL Stefely, J. A., Reidenbach, A. G., Ulbrich, A., Oruganty, K., Floyd, B. J., Jochem, A., Saunders, J. M., Johnson, I. E., Minogue, C. E., Wrobel, R. L., Barber, G. E., Lee, D., Li, S., Kannan, N., Coon, J. J., Bingman, C. A., Pagliarini, D. J. 2015; 57 (1): 83–94

  Abstract

  The ancient UbiB protein kinase-like family is involved in isoprenoid lipid biosynthesis and is implicated in human diseases, but demonstration of UbiB kinase activity has remained elusive for unknown reasons. Here, we quantitatively define UbiB-specific sequence motifs and reveal their positions within the crystal structure of a UbiB protein, ADCK3. We find that multiple UbiB-specific features are poised to inhibit protein kinase activity, including an N-terminal domain that occupies the typical substrate binding pocket and a unique A-rich loop that limits ATP binding by establishing an unusual selectivity for ADP. A single alanine-to-glycine mutation of this loop flips this coenzyme selectivity and enables autophosphorylation but inhibits coenzyme Q biosynthesis in vivo, demonstrating functional relevance for this unique feature. Our work provides mechanistic insight into UbiB enzyme activity and establishes a molecular foundation for further investigation of how UbiB family proteins affect diseases and diverse biological pathways.

  View details for DOI 10.1016/j.molcel.2014.11.002

  View details for Web of Science ID 000347711100008

  View details for PubMedID 25498144

  View details for PubMedCentralID PMC4289473