Elevated cord levels of ustekinumab following its use in the treatment of Crohn's disease in pregnancy.

Ustekinumab (USK) was used in the treatment of two pregnant patients with Crohn's disease. It was given in the third trimester and restarted postnatally for both women. One woman remained on USK and in remission throughout pregnancy. The second woman, took a treatment break, flared, and then had remission induced with reintroduction of USK. Both women delivered healthy term infants. The interval from last dose to birth was 11 and 8 weeks respectively. Interestingly, USK levels in cord blood was observed in higher concentrations than in the maternal serum taken in third trimester. While no adverse effect in infants has been observed, clinicians should remain aware of fetal transfer when using USK in pregnancy. An evaluation of risk and benefit may favour continuing USK in pregnancy in patients with refractory disease.

Higher Ustekinumab Levels in Maintenance Therapy are Associated with Greater Mucosal Healing and Mucosal Response in Crohn's Disease: An Experience of 2 IBD Centers.

BACKGROUND: Ustekinumab (UST), a human monoclonal antibody that binds the p40 subunit of interleukin 12 (IL-12) and IL-23, is licensed for induction and maintenance therapy of moderate to severe inflammatory bowel disease (IBD). To date, there is limited data published on any potential association between ustekinumab serum trough levels and mucosal healing in order to guide treatment strategies and appropriate dosing. AIM: This study aims to identify a relationship between maintenance ustekinumab serum trough levels and mucosal healing and/or response in patients with Crohn's disease in an observational cohort study. METHODS: Ustekinumab serum trough levels and antibody titres were analyzed in patients on maintenance drug using an ELISA drug-tolerant assay. Mucosal response (MR) was defined as ≥50% reduction in fecal calprotectin level (FC) and/or ≥50% reduction in the Simple Endoscopic Score for Crohn's Disease (SES-CD score). Mucosal healing (MH) was defined as FC ≤150 µg/mL and/or global SES-CD score ≤5. Median trough levels were analyzed using the Kruskal-Wallis test, and logistic regression was used to determine sensitivity and specificity of levels predicting mucosal response. RESULTS: Forty-seven patients on maintenance ustekinumab for Crohn's disease were included in this study. The majority were female (66%), with a median age of 40 years (21-78 years). The majority of patients were biologic-experienced (89.4%, n = 42). Patients with histologically confirmed Crohn's disease represented 100% (n = 47) of the cohort. Over one-third of patients (n = 18, 38.3%) were on higher than standard dosing of 90 mg every 8 weeks. Patients with mucosal healing (n = 30) had significantly higher mean serum ustekinumab levels (5.7 µg/mL, SD 6.4) compared with those with no response (1.1 µg/mL, SD 0.52; n = 7, P < .0001). A serum ustekinumab trough level greater than 2.3 µg/mL was associated with MH, with a sensitivity of 100% and specificity of 90.6% (likelihood ratio 10.7). Similarly, for patients with MR (n = 40), we observed a higher mean serum ustekinumab trough level (5.1 µg/mL, SD 6.1) compared with those with no response (1.1 µg/mL, SD 0.52; n = 7, P < .0001). Furthermore, a serum ustekinumab trough level greater than 2.3 µg/mL was associated with a 10-fold increased likelihood of mucosal response vs mucosal nonresponse (sensitivity 100%, specificity 90.5%, likelihood ratio 10.5). CONCLUSION: This study demonstrates that higher ustekinumab serum trough levels are associated with a greater likelihood of achieving mucosal healing and mucosal response in patients with Crohn's disease regardless of prior biologic exposure. Further prospective studies are required to correlate target maintenance trough levels and the optimal time to dose-escalate in order to improve patient outcomes.

Gender equality in academic gastroenterology: a review of gastroenterology literature over four decades.

BACKGROUND: Historically males have dominated the physician ranks, although in recent years, there has been an increase in the proportion of female doctors to redress this imbalance. With such attention being paid to gender equality in society, this study aimed to characterise the changing prevalence of female authorship of peer-reviewed published research with in the field of gastroenterology. AIMS: In order to quantitatively assess the growth of female gastroenterologists, we decided to examine the changing face of gender equality within the field of academic gastroenterology from 1971 to 2010. METHODS: All research published in the January and July issues of Gastroenterology from 1971 to 2010 was reviewed. The gender of the first author and last author (considered the senior author) of each study was recorded. Research was subsequently categorised by type: basic science research, clinical trials, and epidemiologic research. Data was analysed in 5-year time periods. RESULTS: Author gender could be identified from a total of 865 abstracts from 80 journal issues. In total, there were 120 (13.8%) female first authors and 91 (10.5%) female senior authors. Female first authorship has tripled since 1995, from 11% (1991-1995) to 32% (2006-2010). Female senior authorship has also tripled since 2000, from 7% (1996-2000) to 24% (2006-2010). DISCUSSION: Results demonstrated that there has been a significant increase in the prevalence of female authorship of published research in Gastroenterology since 1995. The increasing prevalence of females within the field of academic gastroenterology can therefore be extrapolated to demonstrate the growing numbers of female gastroenterologists in the entire field including clinical and academic gastroenterology.

The optimal management of anti-drug antibodies to infliximab and identification of anti-drug antibody values for clinical outcomes in patients with inflammatory bowel disease.

PURPOSE: Secondary loss of response (LOR) to infliximab (IFX) commonly occurs. One cause is the development of anti-drug antibodies (ADAs). Evidence regarding the optimal management of ADAs is lacking. We aim to identify the best practice of management of ADAs to IFX to avoid discontinuation of therapy and to determine specific ADA cut-off values to determine pre-specified clinical outcomes. METHODS: This is a 3-year study of patients receiving IFX who developed ADAs > 8µg/ml. We reviewed the management strategies and subsequent outcomes in patients who developed ADAs. RESULTS: A total of 132 patients are included. Baseline characteristics include 54% male patients and mean age of 39.4 years. Fifty-two percent (n = 69) of patients discontinued IFX following the development of ADAs, 33.3% (n = 44) sited as secondary to LOR. Both an increase in IFX and adjustments to combination therapy were associated with lower rates of discontinuation of IFX vs no intervention (p value < 0.001, p value < 0.001). An increase in IFX resulted in a significant difference in ADAs/IFX trough levels pre- and post-intervention (p value < 0.001, p value = 0.032). ROC curve analysis yielded significant cut-off values for ADAs and treatment failure (ADA >16µg/ml, AUC 0.642, p value 0.003), steroid use (ADA >19 µg/ml, AUC 0.61, p value 0.048) development of infusion reactions (ADA> 37 µg/ml, AUC 0.68, p value 0.045) and switch to another biologic (ADA >45 µg/ml, AUC 0.739, p value <0.001). CONCLUSION: Both escalation of IFX and combination therapy resulted in lower rates of LOR. ROC curve analysis identified significant cut-off values for ADA trough levels and important clinical outcomes.

A novel value-based scoring system for endoscopic ultrasound-guided drainage of pancreatic fluid collections: a single-centre comparative study of plastic and lumen-apposing metal stents (NOVA study).

OBJECTIVE: Healthcare resources are finite. Value in healthcare can be defined as patient health outcomes achieved per monetary unit spent. Attempts have been made to quantify the value of luminal endoscopy, but there is little in the medical literature describing the value of the complex therapeutic endoscopic activity. This study aimed to characterise the value of endoscopic ultrasound (EUS)-guided drainage of pancreatic fluid collections (PFCs) with either plastic or lumen-apposing metal stents (LAMSs). METHODS: This is a single-centre, retrospective-prospective comparative study of 39 patients, who underwent EUS-guided PFC drainage between 2009 and 2018. Procedure value was calculated using the formula Q/(T/C), where Q is the quality of procedure adjusted for complications, T procedure duration and C is the complexity adjustment. Quality and complexity were estimated on a 1-4 Likert scale based on the American Society for Gastrointestinal Endoscopy criteria. Time (in minutes) was recorded from the patient entering and leaving the procedure room. Endoscopy time calculated from procedure time was considered a surrogate marker of cost as individual components of procedure cost were not itemized. RESULTS: Of 39 identified patients who underwent EUS-guided PFC drainage, 11 received double pigtail plastic stents (DPPSs) and 28 received LAMSs. The two groups were comparable in age, gender and aetiology. Nearly 40% of the LAMS interventions were considered high value but only 11% of the plastic stent interventions achieved the same. The difference predominantly was due to a higher rate of complications and longer procedure time. CONCLUSION: In this single-centre study, EUS-guided PFC drainage using LAMS was found to be a higher value procedure compared to the use of DPPS.

Irish data on the safety and efficacy of vedolizumab in the treatment of inflammatory bowel disease.

SUMMARY: This study reviews the safety and efficacy of treatment with vedolizumab for patients with inflammatory bowel disease across 9 Irish hospitals. It generates valuable and timely real-world data on treatment outcomes to add to the existing evidence base. Our population represents a refractory cohort with most patients previously exposed to at least one anti-TNFa agent and expressing an inflammatory phenotype. Results are reassuringly similar to larger international studies with additional insights into potential predictors of treatment response. This study further supports the safety and efficacy of vedolizumab in the treatment of inflammatory bowel disease. Key SummaryVedolizumab has growing real world data on its safety and efficacy in the treatment of IBD. Data on predictors of response are lacking. Studies such as VARSITY require new real-world data to help identify the place VDZ will occupy in the treatment algorithm for IBDThis study provides national Irish data on the safety and efficacy of VDZ in the treatment of IBD. It gives insight into various predictors of response for both UC and CD. It strengthens the available body of evidence on the use of VDZ and helps us determine its position on the treatment algorithm.

Assessment of the value of gastroenterologists' activity in the outpatient setting: applying the "Moneyball" approach to clinical care.

BACKGROUND: With the emergence of alternative payment systems replacing the traditional funding models, the value of physician activity is scrutinized more closely. Attempts have been made to quantify the value of endoscopists' activity; there is little in the medical literature describing gastroenterologists' value in the outpatient setting. AIMS: To characterize the value of clinical activity of gastroenterologists in the outpatient setting. METHODS: The value of clinical activity of ten gastroenterologists in an academic medical center was estimated. Value was defined as Q (quality of clinical care) divided by TA (duration of outpatient visit adjusted for complexity level); TA served as a surrogate measure of the cost of the clinician's services. Medical records of each patient's clinical visit were reviewed and graded independently by three staff gastroenterologists; each reviewer was blinded to the identity of the physician and to other reviewers' scores. RESULTS: Over consecutive weeks, the clinical records of 307 patients who were seen by ten gastroenterologists were reviewed and graded for quality (Q) and complexity (C); the duration of each visit (T) was recorded. Each physician saw a mean of 31 patients; mean physician value varied from 0.28 to 0.87. More senior physicians demonstrated higher levels of value. CONCLUSION: Measurement of the value of clinical activity represents an important component of gastroenterologists' performance. There was a threefold variation among physician levels of value with more experienced clinicians demonstrating higher value levels. Further studies will be required to more clearly define valid metrics for physician value.

Golimumab effectiveness and safety in clinical practice for moderately active ulcerative colitis.

BACKGROUND AND AIMS: Golimumab (GLB) is an antitumour necrosis factor-α (anti-TNF) therapy that has shown efficacy as induction and maintenance therapy for ulcerative colitis (UC). We aimed to describe the outcome of GLB therapy for UC in a real-world clinical practice. PATIENTS AND METHODS: Consecutive patients receiving GLB for UC in six Irish Academic Medical Centres were identified. The primary study endpoint was the 6-month corticosteroid-free remission rate. The secondary endpoints included the 3-month clinical response, time free of GLB discontinuation and adverse events. RESULTS: Seventy-two patients were identified [57% men; median (range) age of 41.4 years (20.3-76.8); disease duration 6.6 years (0-29.9); follow-up 8.7 months (0.4-39.2)]. Sixty-four percent of patients were anti-TNF naive. The 3-month clinical response and the 6-month corticosteroid-free remission rates were 55 and 39%, respectively. Forty-four percent of patients discontinued GLB during the follow-up, median (95% confidence interval) time to GLB discontinuation 18.7 months (9.2-28.1). A C-reactive protein more than 5 mg/l at baseline was associated with failure to achieve 6-month corticosteroid-free remission and a shorter time to GLB discontinuation, odds ratio 0.2 (0.1-0.7), P=0.008, and hazard ratio (95% confidence interval) 2.8 (1.3-5.7), P=0.007, respectively. Adverse events occurred in 7% of patients (n=5), all of which were minor and self-limiting. CONCLUSION: These real-world clinical data suggest that GLB is an effective and safe therapy for a UC cohort with significant previous anti-TNF exposure. An elevated baseline C-reactive protein, likely reflective of increased inflammatory burden, is associated with a reduced likelihood of a successful outcome of GLB therapy.

Measuring the value of endoscopic retrograde cholangiopancreatography activity: an opportunity to stratify endoscopists on the basis of their value.

INTRODUCTION: As finite healthcare resources come under pressure, the value of physician activity is assuming increasing importance. The value in healthcare can be defined as patient health outcomes achieved per monetary unit spent. Even though some attempts have been made to quantify the value of clinician activity, there is little in the medical literature describing the importance of endoscopists' activity. This study aimed to characterize the value of endoscopic retrograde cholangiopancreatography (ERCP) performance of five gastroenterologists. PATIENTS AND METHODS: We carried out a retrospective-prospective cohort study using the databases of patients undergoing ERCP between September 2014 and March 2017. We collected data from 1070 patients who underwent ERCP comparing value among the ERCPists at index ERCP. Procedure value was calculated using the formula Q/(T/C), where Q is the quality of procedure, T is the duration of procedure and C is the adjusted for complexity level. Quality and complexity were derived on a 1-4 Likert scale on the basis of American Society for Gastrointestinal Endoscopy criteria; time was recorded (in min) from intubation to extubation. Endoscopist time calculated from procedure time was considered a surrogate marker of cost as individual components of procedure cost were not itemized. RESULTS: In total, 590 procedures were analysed: 465 retrospectively over 24 months and 125 prospectively over 6 months. There was a 32% variation in the value of endoscopist activity in a more substantial retrospective cohort, with an even more considerable 73% variation in a smaller prospective arm. CONCLUSION: In an analysis of greater than 1000 ERCPs by a small cohort of experienced ERCPists, there was a wide variation in the value of endoscopist activity. Although the precision of estimating procedural costs needs further refinement, these findings show the ability to stratify ERCPists on the basis of the value their activity. As healthcare costs are scrutinized more closely, such value measurements are likely to become more relevant.

Overbooking in Endoscopy: Ensure No-One is Left Behind!

With the growing pressure on physicians to maximize efficiency and enhance the value of clinical practice, overbooking endoscopy schedules appears to hold promise, if implemented strategically, to enhance patient access for endoscopy procedures. Overbooking is a practice that has been routinely utilized by the airline industry to offset losses incurred by passengers not showing for flights, and there is evidence emerging in the medical literature that a similar approach can be utilized in health care. In the context of endoscopy practice, a key aspect of implementing overbooking successfully is the ability to precisely and accurately predict which patients will have a high likelihood of not attending for their procedure, thereby allowing their slots to be double booked while minimizing the likelihood of overburdening the practice with excessive workload. Despite the potential efficiencies that can be realized with overbooking in health care, it remains important not to neglect the needs of those patients who predictably and consistently fail to attend for health-care appointments.

The Inappropriate Prescription of Oral Proton Pump Inhibitors in the Hospital Setting: A Prospective Cross-Sectional Study.

UNLABELLED: Proton pump inhibitors (PPIs) are used to treat upper gastrointestinal tract disorders. Their efficacy and perceived safety have led to widespread prescription. This is not without effect, in terms of adverse events and resource utilization. AIM: To prospectively assess oral PPI prescription in hospitalized patients. METHODS: PPI prescription in consecutive hospitalized patients was assessed. Indication and dose were assessed by patient interview and medical record review. Comparisons with current published prescribing guidelines were made. RESULTS: Four hundred and forty-seven patients were included. 57.5 % were prescribed PPIs. 26.8 % prescriptions were for inappropriate or unclear indications. 68.4 % were on higher doses than guidelines recommended, of which 41.6 % could have undergone dose reduction, and 26.5 % discontinued. In a multivariate analysis, age, gender, and length of stay had no association with PPI prescription. Although aspirin use was appropriately associated with PPI prescription (RR: 1.8, 95 % CI 1.127-3.69; p < 0.05), the PPI was often given at higher than recommended doses (p < 0.001). This may reflect older age and multiple risk factors in this subset. Surgical patients commenced more PPIs and at higher dosages (p < 0.001). Omeprazole and lansoprazole were most often inappropriately prescribed (p < 0.01, p < 0.001, respectively). CONCLUSION: Inappropriate PPI therapy is still a problem in hospitals, though it appears to be at a lower level compared with previous studies. Awareness of evidence-based guidelines and targeted medicine reconciliation strategies are essential for cost-effective and safe use of these medications.

No association between Centers for Medicare and Medicaid services payments and volume of Medicare beneficiaries or per-capita health care costs for each state.

The Centers for Medicare and Medicaid Services recently published data on Medicare payments to physicians for 2012. We investigated regional variations in payments to gastroenterologists and evaluated whether payments correlated with the number of Medicare patients in each state. We found that the mean payment per gastroenterologist in each state ranged from $35,293 in Minnesota to $175,028 in Mississippi. Adjusted per-physician payments ranged from $11 per patient in Hawaii to $62 per patient in Washington, DC. There was no correlation between the mean per-physician payment and the mean number of Medicare patients per physician (r = 0.09), there also was no correlation between the mean per-physician payment and the overall mean per-capita health care costs for each state (r = -0.22). There was a 5.6-fold difference between the states with the lowest and highest adjusted Medicare payments to gastroenterologists. Therefore, the Centers for Medicare and Medicaid Services payments do not appear to be associated with the volume of Medicare beneficiaries or overall per-capita health care costs for each state.

Pricing practices of gastroenterologists in New York.

There is growing awareness of the price disparities for equivalent services in healthcare. We aimed to characterize regional variations in fees charged by gastroenterologists in Manhattan, NY. All private practice gastroenterologists in Manhattan were contacted and asked what they charge fee-paying patients for initial consultations for nonspecific gastrointestinal symptoms. Cost information was obtained from 89 offices, and practices were classified on the basis of location in Manhattan. We observed significant regional variation; gastroenterologists on the Upper East Side (1.20-fold the overall mean) charged more than twice as those on the Upper West Side (0.58-fold the mean) and 50% more than gastroenterologists in South Manhattan (0.76-fold the mean). The coefficient of variation was 46%; the most expensive gastroenterologist charged 14-fold more than the least expensive. We provide evidence for significant regional variation in prices for medical services. Future studies are needed to characterize regional price variations in other aspects of healthcare.