Head-to-Head: Budesonide vs Fluticasone for Eosinophilic Esophagitis

Posted on July 31, 2019 by gutsandgrowth

A recent double-blind, double-dummy study (ES Dellon et al. Gastroenterol 2019; 157: 65-73) found similar efficacy between budesonide and fluticasone for newly-diagnosed eosinophilic esophagitis. They had hypothesized that an oral viscous budesonide would be more effective due to increased esophageal contact time.

Methods: The authors compared an oral viscous budesonide OVB) at 1 mg BID (n=56) to fluticasone (swallowed) MDI dosed at 880 mcg BID (n=55). Patients aged 16-80 years, with mean of 37 years.

Baseline characteristics:

~95% in both groups with dysphagia
~75% with any atopic condition
~50% with dilatation required at baseline

Key findings:

Similar drop in eosinophil count: 73 (OVB) and 77 (MDI) eos/hpf at baseline to 15 and 21 respectively
Histologic response (<15 eos/hpf) rates of 71% (OVB) and 64% (MDI).
Response to <5 eos/hpf occurred in 61% OVB and 49% MDI; response to <1 eos/hpf was noted in 41% and 35% respectively
Symptom scores (DSQ) responded similarly as well
Similar degree of candidiasis 12% for OVB and 16% for MDI

In the associated editorial, the authors speculate that one reason for similar efficacy was the detailed instructions given for patients taking the MDI.

My take: This study supports both topical steroid therapies; practical issues like cost and insurance coverage could be influential in selecting the specific treatment for an individual patient.

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From AGA twitter feed

Bariatric Surgery Survival – 5 Countries, 500,000 Participants

Posted on July 30, 2019 by gutsandgrowth

A recent population-based cohort study (JH Kauppila et al. Gastroenterol 2019; 157: 19-27) examined the effects of bariatric surgery on survival from Nordic countries between 1980-2012.

Link: Effects of Obesity Surgery on Overall and Disease-Specific Mortality in a 5-Country Population-Based Study

Among 505,258 obese individuals, 49,977 had bariatric surgery.

Key findings:

Overall mortality rates were lower in the surgery group during the first 14 years but higher after 15 years (HR 1.20 with CI 1.02-1.42). Thus, overall, obese patients who underwent bariatric surgery had longer survival times than obese patients who did not have surgery. Both groups had higher mortality than the general population
The improved survival compared to those without surgery was related to decreased mortality from cardiovascular mortality, diabetes and cancer. However mortality due to suicide was increased.
Limitations: lack of detailed data including BMI, smoking and alcohol consumption

Graphical abstract (available online)

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Red Meat for Dietary Cynics

Posted on July 29, 2019 by gutsandgrowth

A recent randomized study (L Albenberg et al. Gastroenterol 2019; 157: 128-36) examined whether a diet low in red or processed meats could reduce rates of Crohn’s disease (CD) flares.

Methods: Adults with CD were recruited into the FACES (Food and Crohn’s Disease Exacerbation Study) trial from 2013 to 2015. Participants were recruited from an internet-based cohort (n=15,600). Eligible participants (consumed red meat at least once a week & in remission) were randomly assigned to high meat, n=118 (minimum of 2 servings per week) or low meat, n=96 (no more than 1 serving per month). Outcomes were based on changes in sCDAI scores or need for treatment (new medication or surgery)

Key findings:

Any relapse occurred in 62% of participants in the high meat group compared to 42% in the low meat group. This was not statistically significant.
At week 20, 18 participants in each arm had a stool calprotectin with the high meat group having a higher median: 74.5 mcg/g compared to 36.0 mcg/g (P=.13)
The high meat group did consume at least 2 servings per week in 98.5% of observed weeks compared to 18.8% of the low meat group.

Limitations:

Small number of diet participants
Study was not blinded and only a subset included more objective markers of response
Whether complete avoidance of red meat/processed meats would be more effective is unclear
In those in remission at baseline, it could take longer for the benefits of a dietary intervention to become evident

My take: Limiting consumption of red and processed meats (particularly if meat is not lean) has been shown to have cardiovascular benefits. While this study does not show a statistically-significant improvement in relapse rates in this cohort with Crohn’s disease, there are still strong arguments that a diet with increased fruits/vegetables and less red/processed meats would be beneficial.

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Disclaimer: These blog posts are for educational purposes only. Specific dosing of medications/diets (along with potential adverse effects) should be confirmed by prescribing physician/nutritionist. This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition.

Sagrada Familia, Barcelona

FDA Warning on Tofacitinib

Posted on July 27, 2019 by gutsandgrowth

From FDA: 7-26-19 FDA approves Boxed Warning about increased risk of blood clots and death with higher dose of arthritis and ulcerative colitis medicine tofacitinib (Xeljanz, Xeljanz XR)

An excerpt:

The U.S. Food and Drug Administration has approved new warnings about an increased risk of blood clots and of death with the 10 mg twice daily dose of tofacitinib (Xeljanz, Xeljanz XR), which is used in patients with ulcerative colitis…

Health care professionals should discontinue tofacitinib and promptly evaluate patients with symptoms of thrombosis. Counsel patients about the risks and advise them to seek medical attention immediately if they experience any unusual symptoms, including those of thrombosis listed above. Reserve tofacitinib to treat ulcerative colitis for patients who have failed or do not tolerate tumor necrosis factor (TNF) blockers. Avoid tofacitinib in patients who may have a higher risk of thrombosis. When treating ulcerative colitis, use tofacitinib at the lowest effective dose and limit the use of the 10 mg twice daily dosage to the shortest duration needed

19 cases of blood clots in the lung out of 3,884 patient-years of follow-up in patients who received tofacitinib 10 mg twice daily, compared to 3 cases out of 3,982 patient-years in patients who received TNF blockers

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University of Virginia

“Sub-10-minute High-quality Diagnostic Colonoscopy”

Posted on July 26, 2019 by gutsandgrowth

Like the last two days, this post addresses “high quality” colonoscopy…

A recent report (M Thomson et al. JPGN 2019: 69: 6-12) describes quicker pediatric colonoscopy times than previously reported and with 100% rate of ileal intubation.

In this report, there were 181 colonoscopies.

Time of colonoscopy:

The authors emphasize the fact that their mean time to the terminal ileum was 9.8 minutes. Their good technical skill is probably related in part to experience: all 6 endoscopists had more than 10 years of experience (mean 19 years) and more than a thousand prior colonoscopies each.

Ileal Intubation Rate:

The 100% ileal intubation rate similarly indicates good technical skill. It may indicate that their patient population was healthier as ileal structuring (which can prevent ileal intubation) can be noted in patients with Crohn’s disease.

Low Diagnostic Yield:

In my view, the study reports a low diagnostic yield. They report 33% had abnormal histology (when excluding patients with IBD followup examinations)
38% of their patients had colonoscopy due to abdominal pain. They reported a yield in this group of only 11.6% though this includes 4 patients with “TI lymphoid hyperplasia.” Is this an abnormal finding?

My take: This study shows that with good technical skill colonoscopy can be done quickly with ileal intubation times averaging 10 minutes and with ileal intubation rates close to 100%. In my view, another quality metric is diagnostic yield and their yield is lower than has been reported in most pediatric studies.

Related references:

K Siau et al. JPGN 2019; 69: 18-23. This study describes “Direct Observation of Procedural Skills” (DOPS). Among 29 trainees, 81% of DOPS were rate competent after 125-140 procedures.
MT Barakat et al. JPGN 2019; 69: 24-31. This study noted that the vast majority of pediatric GI centers (>90%) were performing less than 25 ERCPs annually and that >70% “believe their institution’s current arrangement for performing pediatric therapeutic endoscopy is inadequate.”

Quality Metrics in Pediatric Colonoscopy

Posted on July 25, 2019 by gutsandgrowth

Continuing the theme from yesterday’s post…

Because of similar research in our group, I was interested in a recent study looking at pediatric colonoscopy quality indicators: CS Pasquarella et al.. JPGN 2019; 68: 648-54. (Editorial: CG Sauer, CM Walsh. JPGN 2019; 607-08.)

The authors analyzed 391 colonoscopies.

Key findings:

Ileal intubation rate of 91% (which is similar to our rate)
Ileal intubation rate was greater in their endoscopy suite where assistance was readily available.
Time for procedure: 34 minutes with staff alone compared to 42 minutes with a fellow trainee participant

To this point, we have not collected data on procedure duration at our institution –though 34 minutes seemed longer than I expected.

The authors also comment on cecal intubation. I find this statistic to be less useful in pediatrics than adult medicine. Reaching the cecum is important in cancer screening whereas reaching the ileum is important in identifying cases of inflammatory bowel disease. The former is the main focus in adult gastroenterology and the latter is the main focus in pediatric gastroenterology.

My take: The editorial notes that “endoscopic providers and users can only know whether high-quality care is being delivered if it is being measured.” I do think ileal intubation is important but other measures include good prep, low complication rate, appropriate patient selection (eg. good indication), and careful followup. Our work in this area will be presented at our upcoming NASPGHAN meeting–stay tuned.

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Sagrad Familia, Barcelona

Colonoscopy and Isolated Abdominal Pain = Low Value Care

Posted on July 24, 2019 by gutsandgrowth

A recent study (HK Singh, LC Ee. JPGN 2019; 68: 214-7) reviewed a single center’s colonoscopy data (n=652) from 2011-15 with a focus on patients who underwent this procedure for abdominal pain.

Key findings:

Only 15 patients had isolated abdominal pain as an indication. In total 68 patients had abdominal pain as an indication but the majority had other ‘red flags’ such as rectal bleeding, family history of IBD or polyposis, weight loss, anemia, food allergy, or altered bowel habits
None of these 15 patients with isolated abdominal pain had organic disease
Among 36 patients with a measured fecal calprotectin and abdominal pain, all with elevated levels had positive histologic findings.
The ileal intubation rate/biopsy rate was 92.4%

I was particularly interested in this study because our group has reviewed our clinical experience in a large cohort undergoing outpatient colonoscopy (findings will be presented this fall). Our group has a similar ileal intubation rate and a low rate of organic disease in those with isolated abdominal pain.

My take: More efforts are needed to carefully select pediatric patients undergoing endoscopy to minimize low value procedures.

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Georgia Aquarium

Depression Screening for Pediatric Patients with IBD

Posted on July 23, 2019 by gutsandgrowth

Recently, we had a morning conference to review depression screening for pediatric patients with IBD. This lecture was led by Chelly Dykes, MD. Many of these slides were adapted from resources developed by the (ImproveCareNow) ICN Psychosocial Professionals group.

We have started depression screening with a subset of our patients and soon will start screening all children 13 years and older. When this is working well, younger ages may be targeted as well.

Some of the key points:

Depression/anxiety are common, particularly in patients with inflammatory bowel disease
National rates of suicide have been increasing
Asking about suicide does not increase the risk of suicidality
We are fortunate to work closely with two psychologists, Bonney Reed-Knight and Jessica Buzenski

Some of the slides are listed below.

Is There Renal Toxicity with Mesalamine Therapy for IBD?

Posted on July 22, 2019 by gutsandgrowth

A recent study (V Jairath et al. AP&T 2019; https://doi.org/10.1111/apt.15408) provides evidence that 5-aminosalicylic acid therapy for IBD does NOT increase the risk of nephrotoxicity. This paper’s findings run counter to more than thirty years of teaching on this medication.

Full Free Link: No increased risk of nephrotoxicity associated with 5‐aminosalicylic acid in IBD: a population‐based cohort and nested case‐control study

Abstract (bold highlighted by blog author):

Background

There is conflicting evidence about nephrotoxicity risk associated with 5‐aminosalicylates for treatment of IBD.

Methods

Retrospective cohort and nested case‐control study, using the Health Improvement Network primary care database linked to hospital discharge coding for patients in England, 1996‐2017. Nephrotoxicity risk analysis was a first recorded renal impairment diagnosis adjusted for key variables and was assessed between 2008 and 2017.

Results

A total of 35 601 patients with prevalent UC or CD were included. The proportion of patients prescribed 5‐aminosalicylates fell from 83% in 1996‐1999 to 71% in 2012‐2015 for UC patients and 64% to 45% for CD patients. Thirty per cent of patients had prolonged 5‐aminosalicylate use. Between 2008 and 2017, the incident rate of nephrotoxicity was similar and stable for UC (12.6/1000 person‐years) and CD (10.9/1000 person‐years) patients. Multivariate analysis showed no evidence for association between current prescription of 5‐aminosalicylate and nephrotoxicity in UC or CD patients, comparing ≤ 30 days prescription prior to index vs 31‐≤180 days. However, active disease, disease duration, concomitant cardiovascular disease or diabetes and nephrotoxic drug use were independently associated with development of nephrotoxicity in UC and CD.

Conclusions

Despite the paucity of evidence for their benefit, 5‐aminosalicylates were prescribed to approximately half of CD patients (30% prolonged therapy). Nephrotoxicity was rare in this patient cohort, and was not associated with 5‐aminosalicylate use, but rather with disease status, comorbidity and use of nephrotoxic drugs.

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