Category Archives: Uncategorized

William Meyers

Posted on by

Yesterday I attended the Inaugural William Meyers Lecture and intended for this post to be a summary of that.  Sadly, he passed away last night.

Billy, a partner in our GI group, had been fighting brain cancer for the past year. This lecture was established to honor him. Jose Garza gave a lecture which highlighted the important work of the neurogastroenterology service, established in large measure by Billy.

Also, Billy served on numerous hospital committees.  Much of his efforts were ‘behind the scenes’ and usually the type of work that many of us seek to avoid.  In addition to working on these hospital committees, Billy remained a busy clinician.  In the past year, I’ve had the opportunity to interact with many of his patients and families.  Uniformly I have heard how compassionate and patient he was, even with the most complex situations.  In the 22 years that I had the opportunity to work with Billy, I cannot seem to recall him ever being flustered.  He was a truly wonderful person, physician, and mentor..   I will miss his kindness and friendship.

 

 

 

Capsaicin for Cannaboid Hyperemesis Syndrome

Posted on by

Capsaicin is the stuff in chili peppers that makes your mouth feel hot. But it also has some medical purposes. It’s a key ingredient in creams and patches that has been used for pain relief (e.g. joint, muscle, headaches).

From our recent hospital PNT meeting –information on using Capsaicin for Cannaboid Hyperemesis Syndrome (CHS).

What is cannabinoid hyperemesis syndrome (CHS)?

  • Clinical syndrome in which marijuana users develop nausea, cyclic vomiting, and abdominal pain that improves with a hot water bath or cannabis cessation
  • Often refractory to standard treatment for nausea/vomiting
  • No laboratory or diagnostic tests for CHS

Capsaicin Mechanism for CHS

  • Transient receptor potential vanilloid subtype 1 (TRPV1) receptor is expressed in the brain, along enteric and vagal nerves, and on cutaneous receptors in the skin
  • Chronic cannabis use results in inactivation of TRPV1 receptor leading to  nausea & emesis
  • Nociceptive heat, such as topical capsaicin, acts as a TRPV1 agonist restoring gastric motility
  • Activation of TRPV1 receptor results in potent anti-emetic effects
  • Capsaicin exposure results in subsequent desensitization of the sensory axons and inhibition of pain transmission initiation.

Topical Capsaicin

  • Product: Capsaicin cream 0.025% (Generic)
  • Dosing: Apply thin film to affected area not more than 3 to 4 times/day
  • Benefits:
    • Less adverse effects than unconventional antiemetics (e.g., haloperidol)
    • Cost-effective
  • Adverse effects: “burning sensation” on skin
  • Average wholesale price: $10 per 60 gram tube

Supporting literature

  • Graham J, et al.
    • Case series in which capsaicin was successfully used to treat CHS in two pediatric patients presenting to the emergency department (ED).
    • In a 16 yo & 20 yo, each with two ED visits, on the 2nd visit: due to history of cannabis use, CHS became working diagnosis, patients agreed to try capsaicin cream (0.025%, 1 mm-thick coating) applied to the abdomen. Thirty minutes after capsaicin application, patients pain decreased to a 3 out of 10 and her nausea resolved

References:

  1. Moon AM, Buckley SA, Mark NM. Successful treatment of cannabinoid hyperemesis syndrome with topical capsaicin. ACG Case Rep J. 2018 Jan 3;5:e3.
  2. Graham J, Barberio M, Wang GS. Capsaicin cream for treatment of cannabinoid hyperemesis syndrome in adolescents: A case series. 2017 Dec;140(6): e20163795.

My take: Capsaicin use for CHS is supported by case reports.

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.

From Barcelona chocolate museum –everything is chocolate

Aprepitant for CVS

Posted on by

Last year at NASPGHAN meeting (NASPGHAN Highlights and Tweets), there was data presented on aprepitant for cyclic vomiting syndrome (CVS).  This came up at a recent hospital PNT meeting as well.

  • Aprepitant (Emend) is an anti-emetic that works by blocking the NK1 receptor.
  • It has FDA approval for prevention of nausea and vomiting in moderate and highly emetogenic chemotherapy (adults and pediatrics) and prevention of post-operative nausea and vomiting (adult only).

Supporting Data for use of Aprepitant

An abstract published in 2006 reported on the use of aprepitant in 11 children (3-16 years)2.   Patients were refractory to/had poor response to pizotifen (not available in US – serotonin and histamine antagonist), propranol, and ondansetron.  Aprepitant was dosed at 80 mg/m2 up to twice weekly in combination with ondansetron.  Nine out of 11 patients had reduction in cycle frequency, duration of vomiting episodes and intensity of vomiting.  Three patients achieved complete cycle abolishment.

Cristoferi et al retrospectively reviewed 41 patients (age range 4-16.5 years, median 8 years) treated acutely or prophylactically with aprepitant.3  The primary outcome was decrease in frequency and intensity of CVS episodes.  The follow up period was 18-60 months.  The majority of patients failed cyproheptadine/pizotiphen, ondansetron, and amitriptyline as prophylactic medications.

Dosing regimens utilized in Cristoferi paper:

Prophylactic regimen (oral):

  • < 40 kg, 40 mg twice/week = $220/week (average wholesale price)
  • >40 kg to < 60 kg, 80 mg twice/week = $408/week
  • > 60 kg, 125 mg twice/week = $612/week

Acute regimen (oral):

  • >20 kg, 125 mg x 1 followed by 80 mg on day 2 and day 3 = $714
  • 15-<20 kg, 80 mg x 3 days = $612
  • < 15 kg, 80 mg x 1 followed by 40 mg on day 2 and day 3 = $424

Response rates:

  • With the prophylactic regimen, the authors reported a complete response in 3/16 (19%) and a partial response 10/16 (62%) [partial response was considered if there was ≥50% decrease in CVS episode frequency and intensity].
  • With the acute regimen, the authors reported 19/25 (76%) with a complete response and 3/25 (12%) with a partial response.

My take: Aprepitant appears promising as an agent for children who fail first-line therapies like periactin, tricyclic antidepressants, and ondansetron.

References

  1. Bhandari S and Venkatesan T.  Novel treatments for cyclic vomiting syndrome:  beyond ondansetron and amitriptyline.  Curr Treat Options Gastro 2016;14:495-506.
  2. Russell RK, et al. NK1 receptor antagonism ameliorates nausea and emesis in typical and atypical variants of treatment refractory cyclical vomiting syndrome.  J Pediatr Gastroenterol Nutr 2006;42:E13.
  3. Cristoferi F, et al. Efficacy of the neurokin-1 receptor antagonist aprepitant in children with cyclical vomiting syndrome.  Aliment Pharmacol Ther 2014;40:309-17.

Related blog posts:

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.

Highest Reported Prevalence Rates for Eosinophilic Esophagits

Posted on by

A recent retrospective study (J Robson et al. Clin Gastroenterol Hepatol 2019; 17: 107-14) utilized a pathology database encompassing the vast majority of Utah pediatric cases to determine the incidence and prevalence of eosinophilic esophagitis (EoE) from 2011 to 2016.

The authors determined cases of EoE by looking for symptomatic children with isolated esophageal eosinophilia (more that 14 eos/hpf) in the absence of other comorbid conditions.

Key findings:

  • 1060 children met the criteria for a new diagnosis of EoE
  • Average annual incidence of EoE was 24 per 100,000 children; this is nearly double the previously reported rate 12.8 per 100,000 from Hamilton County, Ohio in 2003.
  • Prevalence of EoE was 118 per 100,000 children

The authors speculate on several factors that produced this increased incidence rate –all related to EoE risk factors:

  • Predominant non-Hispanic White population
  • High rates of atopy
  • Increased capture rate of their database
  • Also, the authors did NOT exclude PPI-responsive esophageal eosinophilia (which is a subtype of EoE and not a different disease

The authors note that “there is reason to believe that this [high incidence rate] is a conservative estimate:”

  • ~2% of pathology reports had 10-14 eos/hpf.  Further review of these cases would likely have identified some which have exceeded the >14 threshold
  • Some pediatric EoE cases are diagnosed by adult gastroenterologists who did not use the pathology databases

My take: This study shows high rates of EoE but comes as no surprise.  And, there are likely a large number of individuals with mild EoE which has not been diagnosed.  In my experience, families and physicians often overlook altered eating habits as related solely to behavior.  Useful questions to uncover dysphagia include the following: how long does it take your child to eat? does your child have to drink a lot of liquids when eating? does food get stuck frequently?

Related blog posts:

 

Antidepressants for Patients with IBD and Their (Beneficial) Affect on Bowel Disease Activity

Posted on by

A recent population-based cohort study (MS Kristensen et al. Inflamm Bowel Dis 2019; 25: 886-93) indicates that antidepressants are likely to be beneficial for patients with inflammatory bowel disease and could lower disease activity in addition to improving mood.

This study population, n=42,890, with prospectively collected data comprised all patients in the Danish National Patient Registry from 2000-2017 with ICD diagnoses of ulcerative colitis (UC, 69.5%) or Crohn’s disease (CD, 30.5%).  Outcome measures included markers of disease relapse:

  • hospitalizations with IBD as primary diagnosis
  • surgery with IBD as primary operation code
  • step-up medications with corticosteroids or anti-TNF treatment

Key findings:

  • After adjusting for confounders, lower incidence rate of disease activity was found among antidepressant users than nonusers.
    • For CD, the incidence rate ratio was 0.75 (CI 0.68-0.82).
    • For UC, the incidence rate ratio was 0.90 (CI 0.84-0.95).
    • For CD patients without prior use of antidepressants before diagnosis of CD, there was markedly lower incidence rate ratio of 0.51 (CI 0.43-0.62).
  • 28% of the study population redeemed at least 1 prescription for an antidepressant at some point.  This is similar to a Finnish study in which antidepressant use in IBD was 28% compared to 19% in general population

The authors note that anti-depressants may affect the level of pro-inflammatory cytokines which are involved in the pathogenesis of IBD.  This study did not assess potential adverse effects of using anti-depressants.

My take: This study is intriguing and suggests that antidepressants may improve the disease course in IBD. Whether this is related to more favorable brain-gut interaction or whether this is related to drug effects on inflammatory agents is unclear.

Related blog post: Psychosocial Problems in Adolescents with IBD

Park Guell -Fantastic Park in Barcelona (need to buy a pass to get to some parts)

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.

 

Large Study Shows FMT Efficacy/Safety in Children

Posted on by

Clinical Gastroenterol Hepatol 2019. In press: Efficacy of Fecal Microbiota Transplantation for Clostridium difficile Infection in Children Thanks to Ben Gold for this reference.

Abstract

Background & Aims

Fecal microbiota transplantation (FMT) is commonly used to treat Clostridium difficile infection (CDI). CDI is an increasing cause of diarrheal illness in pediatric patients, but the effects of FMT have not been well studied in children. We performed a multi-center retrospective cohort study of pediatric and young adult patients to evaluate the efficacy, safety, and factors associated with a successful FMT for the treatment of CDI.

Methods

We performed a retrospective study of 372 patients, 11 months to 23 years old, who underwent FMTs at 18 pediatric centers, from February 1, 2004 to February 28, 2017; 2-month outcome data were available from 335 patients. Successful FMT was defined as no recurrence of CDI in the 2 months following FMT. We performed stepwise logistic regression to identify factors associated with successful FMT.

Results

Of 335 patients who underwent FMT and were followed for 2 months or more, 271 (81%) had a successful outcome following a single FMT and 86.6% had a successful outcome following a first or repeated FMT. Patients who received FMT with fresh donor stool (odds ratio [OR], 2.66; 95% CI, 1.39–5.08), underwent FMT via colonoscopy (OR, 2.41; 95% CI, 1.26–4.61), did not have a feeding tube (OR, 2.08; 95% CI, 1.05–4.11), or had 1 less episode of CDI before FMT (OR, 1.20; 95% CI, 1.04–1.39) had increased odds for successful FMT. Seventeen patients (4.7%) had a severe adverse event during the 3-month follow-up period, including 10 hospitalizations.

Conclusion

Based on the findings from a large multi-center retrospective cohort, FMT is effective and safe for the treatment of CDI in children and young adults. Further studies are required to optimize the timing and method of FMT for pediatric patients—factors associated with success differ from those of adult patients.

Related blog posts:

Park Guell, Barcelona

Vedolizumab vs Adalimumab for Infliximab Failure in Ulcerative Colitis –Which is Better?

Posted on by

A recent retrospective study (A Favale et al. Comparative Efficacy of Vedolizumab and Adalimumab in Ulcerative Colitis Patients Previously Treated With Infliximab Inflammatory Bowel Diseases, izz057, https://doi.org/10.1093/ibd/izz057 Published: 01 April 2019) suggests that vedolizumab is more effective for ulcerative colitis with secondary infliximab failure.

Here’s the abstract:

Background

Adalimumab (ADA) and vedolizumab (VDZ) have shown efficacy in moderate to severe ulcerative colitis (UC) patients who failed infliximab (IFX). Although, a comparative efficacy evaluation of ADA and VDZ in this clinical setting is currently missing.

Aim

The aim of this study is to compare the efficacy of ADA and VDZ in patients affected by UC who failed IFX.

Methods

Clinical records of UC patients from 8 Italian IBD referral centers who failed IFX and were candidates to receive either ADA or VDZ were retrospectively reviewed. The primary end point was therapeutic failure at week 52. Secondary end points included therapy discontinuation at weeks 8, 24 and 52, the discontinuation-free survival, and safety.

Results

One hundred sixty-one UC patients, 15 (9.2%) primary, 83 (51.6%) secondary IFX failures, and 63 (39.2%) IFX intolerants were included. Sixty-four (40%) patients received ADA and 97 (60%) VDZ as second line therapy. At week 52, 37.5% and 28.9% of patients on ADA and VDZ, respectively, had therapeutic failure (P = 0.302). However, the failure rate was significantly higher in the ADA group as compared with VDZ group among IFX secondary failures (48.0% ADA vs 22.4%VDZ, P = 0.035). The therapy discontinuation-free survival was significantly higher in the group of IFX secondary failures who received VDZ as compared with ADA at both the univariate (P = 0.007) and multivariate survival analysis (OR 2.79; 95% CI, 1.23–6.34; P = 0.014). No difference in the failure and biologic discontinuation-free survival was observed in the IFX primary failure and intolerant subgroups.

Conclusion

Vedolizumab might be the therapy of choice in those UC patients who showed secondary failure to IFX.

Link to video abstract (2 min):  Comparative Efficacy of Vedolizumab and Adalimumab in Ulcerative Colitis Patients Previously Treated With Infliximab

 

Outcomes and Risk Factors in Cystic Fibrosis Liver Disease

Posted on by

A recent retrospective study (P-Y Boelle et al. Hepatology 2019; 69: 1648-56, associated editorial 1379-81) examines a large cohort of 3,328 patients with cystic fibrosis and pancreatic insufficiency (born after 1985) who were followed into a longitudinal “French CF Modifier Gene Study.”

Background from editorial:

  • Cystic fibrosis liver disease (CFLD) has been thought to occur mainly before puberty with ~40% of patients developing biochemical or ultrasonographic signs of liver involvement by age 12 years.
  • Registry studies have shown slow progression of liver disease with the development of cirrhosis and portal hypertension in 5-10% of patients.  Due to difficulty identifying those at high risk for disease progression and the long time course, it has been impractical to complete definitive clinical trials to establish whether any therapies alter the natural history.
  • Ursodeoxycholic acid (UDCA) is the only current treatment available for CFLD; UDCA has been shown to have beneficial effects on biochemistries and liver stiffness, but effects on survival or need for transplantation are unknown.
  • Concerns have been raised about the potential for toxic UDCA metabolites (eg. lithocholic acid) in part based on unfavorable results of high-dose UDCA with primary sclerosing cholangitis

Key findings of this current study:

  • The incidence of CFLD increased “by approximately 1% every year, reaching 32.2% by age 25”
  • The incidence of severe CFLD increased “only after age 5, reaching 10% by age 30.”
  • Risk factors for CFLD and severe CFLD: male sex, CFTR F508del homozygosity, and history of meconium ileus.
  • Earlier introduction of UDCA (over the last 20 years) “did not change the incidence of severe CFLD.”

My take: This study confirms a previous study showing that CFLD occurs also in adulthood (Koh C et al. Hepatology 2017; 66:591-601) and adds further doubt about whether UDCA is beneficial.

Related article: AJ Freeman et al. “A Multidisciplinary Approach to Pretransplant and Posttransplant Management of Cystic Fibrosis-Associated Liver Disease” Liver Transplantation 2019; 25: 640-57.

Related blog posts:

Peonie in Sandy Springs