Marijuana Use in Adolescents/Young Adults with Inflammatory Bowel Disease

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A recent study (EJ Hoffenberg et al. J Pediatr 2018; 199: 99-105) examined the use of marijuana in 13-23 year age group with inflammatory bowel disease (IBD) at the Children’s Hospital for Colorado.

This relatively small study (n=99 — 62 with Crohn’s, 27 with ulcerative colitis, 10 with indeterminate colitis) found the following:

  • Marijuana use was endorsed by 32 (32%) and that 9 used daily or almost-daily.
  • Users were 10.7 times more likely to perceive low risk of harm (P<.001)
  • 17 of 30 stated a medical reason for use (16 with physical pain)
  • The most common route of use was smoking (83%)

Limitations:

  • 80% of participants had inactive or mild disease
  • There was no control (non-IBD) group to compare frequency of marijuana use
  • Study performed in state with legalized recreational marijuana

My take: We know very little about how marijuana impacts IBD course and whether it is safe.  This study indicates frequent use of marijuana in the 13-23 year age group.  Thus, it is an issue that needs to be examined further.

Related blog posts:

Three Sisters, Peaks near Canmore, Alberta

Parasitology in 2018: Should we still be ordering O&P times three?

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A terrific review article (S Mohapatra et al. Am J Gastroenterol 2018; 113: 805-18) provides a great deal of information about gastrointestinal parasites. Thanks to Ben Gold for this reference (& don’t forget to vote for NASPGHAN president).

Generally, the authors dispute the usefulness of testing for ova and parasites (O&P) with three separate specimens.  While classic training has noted the intermittent shedding of parasites and the suboptimal sensitivity of O&P, the authors note that a recent study showed a detection of 91% of parasites in the first stool sample.  In addition, newer PCR based assays are more appropriate in many clinical situations due to their improved sensitivity.

The authors first review the protozoa, which are single-celled, motile, free-living organisms, in depth & summarized in Table 1; these include the following:

  • Amoeba: Entamoeba histolytica (E histolytica),
  • Dientamoeba fragilis
  • Blastocystis hominis
  • Coccidia: Cryptosporidium, Cystiospora, Cyclospora
  • Ciliates: Balantidium coli
  • Flagellates: Giardia lamblia
  • Microsporidiosis
  • Trypanosoma cruzi

Next, they review the helminths in depth and in Table 2, which are large, multicellular organisms that can be seen with the naked eye and include the following:

  • Ascariasis: A lumbridcoides
  • Capillariasis
  • Diphyllobothriasis
  • Enterobiasis: E vermicularis
  • Hookworm disease: A dudenale, N amercanus
  • Hymenolepiasis
  • Strongyloides: S stercoralis
  • Schistosomiasis
  • Taeniasis
  • Trichinellosis
  • Trichuriasis
  • Groups of helminths: trematodes (eg. Schistosomes), cestodes (tapeworms eg. Taenia), and nematodes (roundworms eg. Ascariasis, hookworm, pinworms, and whipworms).

Key points:

  • For E histolytica, ELISA fecal antigen test is superior to O&P as is the PCR assay.  If the diagnosis of E histolytica is being considered in the setting of ulcerative colitis, the authors note that this infection must be excluded before the initiation of corticosteroid therapy since steroids can lead to hyperinfection and could be fatal.  Also, the so-called “flask shaped” ulcers seen with this infection refers to the microscopic appearance of the ulcer into the submucosa. Most infections (>90%) remain asymptomatic.
  • Blastocystis “is the most common parasite identified in stool samples in the US” though the pathogenicity remains controversial and is often self-limited.
  • D fragilis “as a pathogen is controversial…[but] recent studies on patients infected only with D fragilis have found an association with diarrhea, abdominal pain, nausea, weight loss, anorexia, and flatus which resolve after eradication.”
  • Giardiasis is “the most common intestinal parasitic disease affecting humans in the US.” PCR/molecular methods are highly sensitive (>90%) and specific (nearly 100%)
  • Enterobius vermicularis (pinworms). The “CDC does not recommend stool examination for O&P since the yield is low.” The diagnostic test is the “Scotch test” in which tape is left overnight in the perianal region and then examined for captured eggs.

Author Recommendations:

  • “Restrict stool examination [for parasites] to patients with persistent diarrheal illness with a duration greater than 7 days.”  Do not check O&P in hospitalized patients more than 3 days into their hospitalization.
  • The most  common parasitic infections, Giardia and Cryptosporidium, are best diagnosed with a stool immunoassay (EIA) rather than O&P.  For E histolytica EIA is recommended over O&P.
  • In those who are persistently symptomatic and with travel history with likely parasite exposure, stool O&P with wet mount/AFB stain/special stains for detection of rare parasites still is worthwhile.  In those without exposure history and with persistent diarrhea (after exclusion of Giardia and Cryptosporidium), consider non-infectious causes of diarrhea.
  • We discourage repeating the O&P due to the “very low incremental yield of second and third samples”

My take: This article makes a strong argument that “O&P times three” represents an outdated approach in the diagnosis of parasitic diseases in the US.

Related blog posts:

Near the top of Old Rag Mountain, Shenandoah Natl Park

 

 

 

Exercise and Income/Race/Gender in U.S.

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Thanks again to Ben Gold for another good read: S Armstrong et al. JAMA Pediatr 2018; 172(8): 732-40.

This study provides a great deal of information on the physical activity of adolescents and young adults (age group 12-29) from 2007-2016 using NHANES data from 9472 participants.  The relationship of physical activity compared with income, race and gender is explored.

Background:

  • The current recommendation is for adolescents to engage in a minimum of 60 minutes of moderate to vigorous activity per day.  At age 20, adult guidelines recommend 150 minutes of moderate activity, 75 minutes of vigorous activity  or an equivalent combination of moderate and vigorous activity per week.
  • In previous studies, one-third of adults do not meet the recommended amount of physical activity

Key findings:

  • Percentage of individuals reporting any moderate or vigorous activity: 87.9% for age 12-17 y, 72.6% for age 18-24 y, and 70.7% for age 25-29 y.
  • Mean time for moderate or vigorous activity: For males: 71.1 min or age 12-17 y, 64.3 min for age 18-24 y, and 50.3 min for age 25-29 y. For females: 56.0 min or age 12-17 y, 44.9 min for age 18-24 y, and 39.2 min for age 25-29 y.
  • Younger age, white race, and higher income were associated with greater physical activity.  The breakdown on the specifics are listed in the five Tables.

The limitations of this study include that the data are cross-sectional and do not prove causality.  In addition, the data are self-reported and some groups may over- or under-report activity.

My take: This study shows that a lot of young individuals are not physically-active whihc increases the risk of some chronic diseases.  Examining the groups that have higher and lower physical activity may help understand ways towards improvement.

During a recent trip to Charlottesville, I came across this article. Someone is identifying dog poops with Nicholas Cage’s face –to highlight the problem?  Funny stuff.

Food Additives and Child Health

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For the next several days, this blog is going to highlight articles that Ben Gold (one of my partners at GI Care for Kids) has recently sent me.  For what it is worth, I am not sure that Ben Gold actually sleeps.  He seems tireless.  He shares articles with lots of individuals in our group on a wide range of subjects.  In addition to his loaded clinic schedule, he is busy giving lectures, engaged in NASPGHAN committees, provides guidance for our research projects, participates in hospital meetings, and is active with family pursuits (super-proud Dad).

Ben is also in the running to be the next NASPGHAN president & I think he is very well-suited for this role.  He has  been a Division Chief with a distinguished career both at the CDC and Emory, and has been in a busy private practice. Between these roles, he has acquired practical knowledge with regard to negotiating with hospitals, universities, insurers and industry. This combined academic-private practice experience would benefit NASPGHAN and its members, particularly at a time when the roles of physicians and hospitals are changing so rapidly.

A recent AAP policy statement and technical report (Trasande L, Shaffer RM, Sathyanarayana; Pediatrics 2018; 142 (2): e20181408 & technical report: Pediatrics 2018; 142 (2): e20181410) highlights child health concerns and food additives.

Food additives include the following:

  • Direct additives: colorings, flavorings, and chemicals added during processing. This policy statement notes that there are 10,000 direct food additives which are allowed in the U.S.
  • Indirect additives: food contact materials including adhesives, plastics, paper which can contaminate food as part of packaging and distribution
  • Other contaminants like pesticides are not addressed in this policy statement

Key points:

  • Regulation and oversight of many food additives is inadequate.  This is due to key problems with the Federal Food, Drug, and Cosmetic Act.  Current requirements allow for a “generally recognized as safe” (GRAS) designation. The GRAS process was intended to used in limited situations, but “has become the process by which virtually all new food additives enter the market.”
  • Yet the FDA does not have adequate authority to acquire data on chemicals and data about health effects of food additives on infants and children are limited or absent.
  • Furthermore, FDA regulation does not regularly consider issues of cumulative dosing and synergistic effects of food additives.

Specific examples:

  • Bisphenols, which are used in the lining of metal cans, could result in disruption of  endocrine pathways
  • Phthalates, which are used in adhesives, lubricants, and plasticizers during the manufacturing process, can also  in disruption of  endocrine pathways
  • Perfluoroalkyl chemicals (PFCs), which are used in grease-proof paper and packaging, may result in obsesogenic activity, decreased birth weight, and disruption of endocrine pathways
  • Nitrates and nitrites, which are added as preservatives and color enhancer especially with meats, may contribute to carcinogenicity and thyroid hormone disruption
  • Artificial food colors may be associated with exacerbation of attention-deficit/hyperactivity disorder symptoms

Conflict of interest with GRAS evaluations:

  • Among GRAS evaluations, 22.4% were made by an employee of manufacturer, 13.3% were made by a consulting firm selected by manufacturer, and 64.3% were made by an expert panel selected by manufacturer or manufacturer’s consulting firm

Given the potential safety concerns of numerous additives, the policy statement makes the following recommendations for pediatricians:

  • Prioritize consumption of fresh or frozen fruits and vegetables
  • Avoid processed meats, especially during pregnancy
  • Avoid microwaving food or beverages
  • Avoid placing plastics in dishwasher
  • Recycling labeling often offers clues to the type of plastic with concern for the following codes: 3 often indicating phthalates, 6 for styrene, and 7 for bisphenols –unless labeled as “biobased” or “greenware.”

The policy statement encourages further regulatory steps for government/FDA as well.

My take: These articles sound the alarm that food additives may be making us sick.  This area is ripe for further investigations.

Bow River, Banff

 

How Often Is Surgical Treatment for Biliary Atresia Delayed Beyond 60 Days?

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It is recognized that there is often a delay in the diagnosis of biliary atresia (BA).  A recent study (MR Townsend et al. J Pediatr 2018; 199: 237-42) indicates that hepatoportoenterostomy (HPE) or Kasai procedure is performed in only 37.7% of patients with BA prior to 60 days of age. The data was obtained from the Agency for Healthcare Research and Quality’s Healthcare Cost and Utilization Project (HCUP) Nationwide Inpatient Sample files from 2000-2011.

  • Risk factors for delayed HPE: This study of 1243 patients with BA found that those with delayed HPE were more often uninsured–all self-pay patients had HPE after 60 days, more often black (aOR 4.22), and less likely at a teaching hospital (aOR 0.27).
  • Delayed HPE was associated with increased adverse perioperative outcomes and increased cost.

My take: We have a long way to go if we are going to consistently identify and treat BA in a timely manner.

Related blog posts:

Chronic Fatigue and Irritable Bowel Syndrome -10 years after Giardia Infection!

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A recent study (S Litleskare et al. Clin Gastroenterol Hepatol 2018; 16: 1064-72) involved prospective follow-up of 1252 laboratory-confirmed cases of giardiasis from a 2004 outbreak in Norway.

Key findings:

  • Prevalence of irritable bowel syndrome (IBS) was 43% 10 years after the outbreak among 576 exposed individuals compared with 14% among 685 controls. Thus, the odds ration of developing IBS was 4.74 following Giardia exposure.
  • Chronic fatigue at 10 years was higher as well, reported in 26% in the exposed group compared with 11% in the control group.
  • The authors note that the change in IBS between 6 years and 10 years following the infection was 40% and 43% respectively and the change in chronic fatigue was 31% at 6 years and 26% at 10 years.

My take: Don’t get Giardia!! It may cause chronic fatigue and IBS 10 years after acquisition of an infection.  This study reinforces other studies which have shown that numerous enteric pathogens can increase the risk of IBS.  These other studies reported lower rates of IBS following infections, between 7-36%.

Moraine Lake, Banff

Reslizumab (recombinant anti-IL-5) for Eosinophilic Esophagitis

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Reslizumab, a monoclonal recombinant antibody to interleukin-5 did not receive FDA approval for eosinophilic esophagitis.  However, a recent report (J Markowitz et al. Journal of Pediatric Gastroenterology and Nutrition: June 2018 – Volume 66 – Issue 6 – p 893–897)  describes the outcomes of patients who entered the randomized control trial and continued to receive subsequently via open label extension (OLE, n=6) or through compassionate use (CU, n=4. This study provides data over 9 years of treatment.

Key findings:

  • Median eosinophil count dropped from 35 to 3
  • No serious adverse events were noted
  • Clinical features improved.  For example, dysphagia dropped from 42% to 0% and vomiting dropped from 67% to 17%

My take: Though this is a small study, it shows that in selected patients disruption of the inflammatory pathways can result in significant clinical improvement.

Pics from Ameila Island and thereabouts -Not sure whose dog  (not ours)

Ethics Test for Neonatal Care Providers

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An interesting study ( CL Cummings et al. J Pediatr 2018; 199: 57-64) examined performance levels on a reliable ethics knowledge questionnaire (TEK-Neo). They found that  out of 36 questions:

  • Medical students answered 25.9 correctly
  • Neonatal nurses/practitioners answered 27.7 correctly
  • Neonatal attendings answered 28.8 correctly
  • Neonatal fellows answered 29.8 correctly
  • Clinical ethicists answered 33.0 correctly

While the overall take-home from this study is that the TEK-Neo provides a reliable gauge of neonatal ethic knowledge, I was more interested in some of the specific questions.  Here are three true-or-false questions:

  • #20. “Medically provided fluids and nutrition constitute a medical intervention that may be withheld or withdrawn for the same reasons that justify the medical withholding of other medical treatments.”
  • #21. “Parents of a critically ill 3-day old infant in the NICU born at 26 weeks on noninvasive positive pressure ventilation decline reintubation in the setting of respiratory failure and new grade 3 IVH B/L. Their informed decision to refuse further life-sustaining medical treatment ought to be respected.”
  • #24. “A 14 day-old full-term boy has sustained severe anoxia perinatally and has severe hypoxic-ischemic encephalopathy confirmed on continuous electroencephalogram by persistently low -voltage isoelectric activity. He is unresponsive to his environment. In this situation, the patient’s enteral nutrition (administered via oral gavage tube) may be ethically withdrawn.”

Though the correct answer to these three questions is true, my experience is that parents rarely are interested in withholding or withdrawing care in these type of scenarios.

 

Is it really necessary to check for Cytomegalovirus in Children with Inflammatory Bowel Disease?

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A recent retrospective study (W El-Matary et al. JPGN 2018; 67: 221-24) examined the practice of looking for Cytomegalovirus (CMV) in children with a flareup of their inflammatory bowel disease (IBD) which is currently recommended by expert consensus (JPGN 2018; 67: 292-310 –recommendation #3).

Key findings:

  • “Four of 61 patients encounters (6.6%) with UC/IBD-U, two with corticosteroid refractory disease, had positive biopsies for CMV by PCR but negative H&E and IHC.  They responded to escalated medical therapy, without needing anti-viral therapy.”
  • All children who had colectomy during the study did not have CMV detected in colonic mucosa.

The authors note that the rationale for looking for CMV is derived mainly from adult populations.  Since age is a known risk factor for CMV reactivation, the risk of CMV causing refractory IBD in children is less.

My take (borrowed in part from authors): “The low frequency of CMV in our study challenges current guidelines that recommend assessment for CMV in all pediatric patients with acute severe UC refractory to corticosteroids.”  This issue would be another that would benefit by collecting the experience of a large cohort (eg. ICN).

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Patient T-shirt

Disclaimer: These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) should be confirmed by prescribing physician.  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.