CHOP QI: Anemia in IBD Pathway

Posted on April 6, 2019 by gutsandgrowth

A recent article in Gastroenterology & Enoscopy News, “QI Pathway Improves Anemia Management in Pediatric IBD” (also presented at NASPGHAN 2018 -abstract 7, J Breton et al), discusses anemia and provides a link to CHOP QI Pathway for Anemia

This link contains useful information regarding treatment options and links to recommendations on management. This algorithm suggests using intravenous iron for anemia in all IBD patients with active disease as well as using intravenous iron for those with moderate to severe anemia. The rationale for parenteral iron in those with active disease is due to two factors:

to overcome the block to intestinal iron absorption induced by hepcidin in the setting of inflammation (making oral iron less effective in active IBD regardless of disease location)
due to data showing that oral iron may aggravate intestinal inflammation by altering the gut microbiome and increasing intestinal permeability

My take: The CHOP initiative provides some clear cut recommendations.for anemia in IBD. Parenteral iron is more efficacious in improving anemia; however, the effects of parenteral iron on the microbiome and other potential risks (eg. increased sepsis) are not clear. In my view, more information about outcomes and costs are needed to determine the optimal approach.

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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.

How Do Home Infusions Stack Up?

Posted on April 5, 2019 by gutsandgrowth

One of the advantages of infusions in the office (or hospital) compared to home infusions and home injections is close communication by those giving the infusion with the physician. In addition, with each infusion, in these settings offers an opportunity to review the patient’s progress and adjust the patients orders. A recent study (Fenster M, et al. Clin Gastroenterol Hepatol. 2019;10.1016/cgh.2019.03.030.) indicates that these advantages may make infusions more successful than infusions given at home.

A summary is offered by Healio Gastroenterology: Home biologic infusions in IBD suffer from lack of monitoring

Researchers conducted a matched retrospective cohort study of patients treated with infliximab or vedolizumab with home infusion (n = 69) compared with hospital infusion at a large, tertiary care IBD center. The primary endpoint was a composite of adverse outcomes, including stopping biologic therapy, IBD-related emergency department visit or IBD-related hospitalization.

“Patients on home infusion were more likely to experience adverse outcomes compared with control patients (43.5% vs. 21.7%; P = .006), and they also had a shorter time to adverse outcomes than patients who got hospital infusions.”
“Patients with home infusions trended toward stopping therapy within 1 year (20.3% vs. 8.7%; P = .053) and stopping therapy within the complete follow-up window (27.5% vs. 15.9%; P = .099) compared with controls.”
Patients with home infusions had “more emergency department visits (30.4% vs. 7.2%, P < .001), they did not have significantly more hospitalizations (17.4% vs. 11.6%).”

The authors noted that the “increase in adverse events might have been related to a reduced level of monitoring observed in home infusion patients. In the year following home infusion initiation or matching, patients who persisted on home infusions had significantly fewer IBD clinic visits (1.23 vs. 1.75; P = .018) compared with controls.”

My take (borrowed from a previous post): In my experience, office-based infusions can be provided safely and in a cost-effective manner. While the convenience and potential cost-savings of home-based infusion are desirable, before implementing broadly, issues regarding communication, safety protocols, and documentation to allow modifications in therapy need to be proactively addressed. These issues could affect a patient’s long-term response to biologic therapy.

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Which is Safer and More Effective –Miralax (PEG 3350) or Lactulose?

Posted on April 4, 2019 by gutsandgrowth

A recent randomized multicenter study (D Jarzebicka et al. JPGN 2019; 68: 318-24) compared polyethylene glycol 3350 (PEG, aka Miralax) and lactulose for functional constipation in a cohort of 102 patients (12 weeks of treatment and 4 weeks of follow-up).

Dosing:

PEG 3350 dosing divided into 2 doses:
- <8 kg: 5 g/day
- 8-12 kg: 10 g/day
- 12-20 kg: 15 g/day
- >20 kg: 20 g/day
Lactulose was given as 1 mL/kg twice a day

A “good clinical outcome” was considered if there were three or more stools per week and an improvement in stool consistency of at least 2 types in the Bristol scale.

Key findings:

At week 12, a good clinical outcome was noted in 98% of PEG group compared with 90% in the lactulose group
PEG group had increased defecations relative to lactulose: 7.9 vs. 5.7, less stool retention: 7% vs 10%, and fewer hard stools 7% vs 13%
Side effects, mainly abdominal pain and bloating, were reported more frequently with lactulose than with PEG: 23 vs 15, P=0.02)

My take: This study showed that PEG 3350 was more effective and had fewer side effects than lactulose for constipation in children between 6 months of age and 6 years.

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Which Symptom is Best for Indicating Reflux in Infants?

Posted on April 3, 2019 by gutsandgrowth

A recent study (CR Collins et al. J Pediatr 2019; 206; 240-7) showed that symptoms alone are not able to predict the degree/presence of reflux in infants.

Methods: The authors recruited ‘symptomatic’ infants with median 41 weeks postmenstrual age (median 29 weeks at birth) and employed a combination of 24-hour pH-impedance to determine acid reflux index (ARI) and subsequently used provocative esophageal infusions (with air, water then apple juice) to assess manometry and symptoms. In total, they analyzed 2635 separate esophageal stimula in 74 infants.

The authors considered ARI <3% as normal, 3-7% as indeterminate ARI, and >7% as abnormal ARI.

Symptoms that they recorded included arching, irritability, cough, gag, sneeze, gasp, bradycardia, desaturation, throat clearing, startle, grimace, grunting, mouthing, and yawning.

Key findings:

“The presence of physical symptoms (ARI <3: 80%; ARI 3-7: 77%; ARI >7: 81%; P=0.4), cardiorespiratory symptoms (ARI <3: 27%; ARI 3-7: 40%; ARI >7: 26%; P=0.4),or sensory symptoms (ARI <3: 26%; ARI 3-7: 22%; ARI >7: 35%; P=0.3) were also not significantly different by ARI groups”
All infants had a normal symptom index (SI) for acid, nonacid, or total reflex.
Accepted metrics, SI, SSI, and SAP, had higher association with nonacid events compared with acid events.
Cardiorespiratory symptoms are more likely to be elicited by esophageal infusions with both water and apple juice than air. “Symptoms are indicators of esophageal dysmotility and maladaptive aerodigestive protective mechanisms.”
The authors in their discussion state that “GERD severity plays no role in the generation of symptoms.”

My take: All infants with and without reflux have a lot of “symptoms.” Nonacid reflux is much more likely to provoke symptoms in this population than acid reflux reinforcing the idea that acid suppression is likely ineffective and potentially harmful. “The findings of this study challenge the rationale for instituting anti-GERD therapies in neonates based on either symptoms alone or the existing acid-reflux indices or pH-impedance metrics.”

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Link to article cited below from The Onion: Dog Feels Like He Always Has To Be ‘On’ Around Family Thanks to Jennifer for this reference.

What I Like About ESPGHAN Familial Adenomatous Polyposis Position Paper

Posted on April 2, 2019 by gutsandgrowth

Management of Familial Adenomatous Polyposis in Children and Adolescents: A Position Paper from the ESPGHAN Polyposis Working Group: Link: JPGN 2019; 68 (3): 442-441

Unlike some working groups, the working group for ESPGAN Polyposis did not equivocate in making clear cut recommendations, especially for recommendations #6a and #6b, for Familial Adenomatous Polyposis (FAP) in children.

SOME OF THE RECOMMENDATIONS
Recommendation 1: Predictive genetic testing should be offered to at-risk children at the age of 12 to 14 years. Families should receive genetic counselling before and at the time of testing. Children who are symptomatic with rectal bleeding should undergo earlier testing. (weak recommendation, low-quality evidence, consensus agreement 100%)
Recommendation 3: In those confirmed to have FAP on predictive genetic testing, and those considered at risk where genetic testing is not possible, colonic surveillance should commence age 12 to 14 years. Once adenomas have been identified, intervals between surveillance colonoscopy should be individualized depending on colonic phenotype every 1 to 3 years. Rectal bleeding or mucous discharge should lead to a colonoscopy at any age. (weak recommendation, low-quality evidence, consensus agreement 100%)
Recommendation 4: Colectomy is necessary to prevent CRC in adulthood. Decision on the timing for colectomy should be determined by polyp burden and characteristics of colonic adenomas in the context of social, personal, and educational factors. IRA or IPAA have their merits and disadvantages and many factors impact on the choice of surgery. The choice should be based on patient phenotype (rectal and colonic burden) and genotype, at the discretion of the surgeon. (weak recommendation, low-quality evidence, consensus agreement 100%)
Recommendation 5: Despite the presence of gastric polyps in children, and the
later risk of duodenal polyposis and ampullary cancer in adult practice, there is no justification to commence routine UGI surveillance until the age of 25 years.
(weak recommendation, low-quality evidence, consensus agreement 90%)
Recommendation 6a: Routine screening for HPB [Hepatoblastoma] in patients with FAP is not recommended. In children found to have HPB, there is no evidence that routine genetic testing or endoscopic screening for FAP is required.
(weak recommendation, low-quality evidence, consensus agreement 100%)
Recommendation 6b: Children with bilateral and multiple CHRPE [congenital hypertrophy of retinal pigment epithelium] lesions should
undergo colonoscopy at age 12 to 14 years. If CHRPE lesions are single or unilateral in the absence of relevant family history, further evaluation should not be required. (weak recommendation, low-quality evidence, consensus agreement 100%)
Recommendation 6c: The vast majority of desmoids tumours are sporadic; children identified to have a DT have approximately 10% risk of FAP. If the kindred is known to have FAP and the child has a desmoid, it should be presumed the child has FAP. In a child presenting with a DT, testing the DT for a b-catenin /CTNNB1 mutation is recommended. If a b-catenin /CTNNB1 mutation is found, this indicates sporadic desmoid and further investigations for FAP are not required. If b-catenin /CTNNB1 mutation is not found, the patient should be investigated for FAP. (weak recommendation, low-quality evidence, consensus agreement 100%)
Recommendation 7: There is no role for the use of chemoprevention agents in
children with FAP. (strong recommendation; moderate-quality evidence, 100%
consensus)

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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.

Time to Revise ImproveCareNow Micronutrient Recommendations

Posted on April 1, 2019 by gutsandgrowth

With ImproveCareNow, there have been efforts to minimize variation in care. As such, there have been suggestions to monitor labs like vitamin D, vitamin B12, and folate routinely. I have voiced concern that some of this testing is unnecessary. For vitamin B12, deficiency in pediatrics is rare; at risk populations include those with extensive small bowel resections, gastric resections or strict vegan diet.

A recent article (J Fritz et al. Inflamm Bowel Dis 2019; 25: 445-59) which is a systematic review of micronutrients in pediatric inflammatory bowel disease provides further support for the approach of less testing.

Key points:

A total of 39 studies were included in the final review (2903 subjects, 1115 controls)
Iron deficiency and vitamin D deficiency are common in pediatric patients with IBD
Vitamin B12 and folate deficiency are rare
Zinc deficiency is uncommon but increased in patients with Crohn’s disease compared to healthy controls.
The authors recommend routine (at least yearly) testing for iron, vitamin D and zinc and that there is “insufficient evidence to support routine screening for other micronutrient deficiencies.”

My take: Except in patients with surgical resections and in those with unusual diets (eg. vegan), routinely checking vitamin B12, folate and most other micronutrients is unnecessary & low value care.

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Vitamin B12:

Methylmalonic Acid as a Biomarker of Vitamin B12 deficiency
What I didn’t know about Vitamin B12 deficiency and Crohn’s disease (consider Vitamin B12 deficiency if ileal resection >20-30 cm)
Risk of Vitamin B12 Deficiency with Persistent PPI Usage
Are we missing Vitamin B12? | gutsandgrowth
N2U -Part 2: Poor Growth and Short Bowel Syndrome | gutsandgrowth

Vitamin D:

Iron:

Psychosis with ADHD Treatments

Posted on March 31, 2019 by gutsandgrowth

While I do not prescribe treatments for ADHD, a recent study (LV Moran et al. NEJM 380: 1128-38) was interesting, indicating that amphetamine use was associated with a greater risk of new-onset psychosis than methylphenidate.

Key points:

Amphetamine is used for ADHD treatment in the U.S. but rarely in other developed countries. It releases dopamine four times as much as methylphenidate. “The changes in neurotransmission observed in primary psychosis are more consistent with those induced by amphetamine than methylphenidate”
Using data from two commercial insurance databases, the authors compared 221,846 patients receiving either amphetamine or methylphenidate. There were 343 episodes of new onset psychosis (defined by diagnosis code and prescription for antipsychotic).
The risk of psychosis was 0.10% (n=106) in the methylphenidate group compared to 0.21% (n=237) in the amphetamine group. Overall, 1 in 660 patients had new onset psychosis with a greater risk in the patients receiving amphetamine.

My take: Only a prospective study can eliminate confounding variables and determine conclusively whether amphetamine is more likely to increase the risk of psychosis; that said, this study indicates a potential for more risk with amphetamine compared to methylphenidate.

AGA Recommendations for Management of Functional Symptoms in Patients with Inflammatory Bowel Disease

Posted on March 30, 2019 by gutsandgrowth

Full text: AGA Clinical Practice Update on Functional Gastrointestinal Symptoms in Patients With Inflammatory Bowel Disease: Expert Review (JF Columbel et al. Clin Gastroenterol Hepatol 2019; 17: 380-90).

My take: Overall, this article presents a concise review of a tricky problem and appropiriate management. The algorithm, tables and figures are useful.

Best practice advice 1: A stepwise approach to rule-out ongoing inflammatory activity should be followed in IBD patients with persistent GI symptoms (measurement of fecal calprotectin, endoscopy with biopsy, cross-sectional imaging).

In the report, the authors note that endoscopy and cross-sectional imaging are not needed in all patients; mainly in patients with a suspected flare based on presentation, calprotectin, and blood work.

Best practice advice 2: In those patients with indeterminate fecal calprotectin levels and mild symptoms, clinicians may consider serial calprotectin monitoring to facilitate anticipatory management.

Best practice advice 3: Anatomic abnormalities or structural complications should be considered in patients with obstructive symptoms including abdominal distention, pain, nausea and vomiting, obstipation or constipation.

Best practice advice 4: Alternative pathophysiologic mechanisms should be considered and evaluated (small intestinal bacterial overgrowth, bile acid diarrhea, carbohydrate intolerance, chronic pancreatitis) based on predominant symptom patterns.

Best practice advice 5: A low FODMAP diet may be offered for management of functional GI symptoms in IBD with careful attention to nutritional adequacy.

Best practice advice 6: Psychological therapies (cognitive behavioural therapy, hypnotherapy, mindfulness therapy) should be considered in IBD patients with functional symptoms.

Best practice advice 7: Osmotic and stimulant laxative should be offered to IBD patients with chronic constipation.

Best practice advice 8: Hypomotility agents or bile-acid sequestrants may be used for chronic diarrhea in quiescent IBD.

Best practice advice 9: Antispasmodics, neuropathic-directed agents, and anti-depressants should be used for functional pain in IBD while use of opiates should be avoided.

Best practice advice 10: Probiotics may be considered for treatment of functional symptoms in IBD.

Best practice advice 11: Pelvic floor therapy should be offered to IBD patients with evidence of an underlying defecatory disorder.

Best practice advice 12: Until further evidence is available, fecal microbiota transplant should not be offered for treatment of functional GI symptoms in IBD.

Best practice advice 13: Physical exercise should be encourage in IBD patients with functional GI symptoms.

Best practice advice 14: Until further evidence is available, complementary and alternative therapies should not be routinely offered for functional symptoms in IBD.

Monticello

Origins of Hygiene Hypothesis

Posted on March 29, 2019 by gutsandgrowth

A recent NY Times article explains the background of the ‘hygiene hypothesis’ and how it has held up remarkably well as a likely factor in the rising number of allergic and immune-mediated diseases.

Link: Your Environment is Cleaner. Your Immune System Has Never Been So Unprepared

An excerpt:

The British Journal of Homeopathy, volume 29, published in 1872, included a startlingly prescient observation: “Hay fever is said to be an aristocratic disease, and there can be no doubt that, if it is not almost wholly confined to the upper classes of society, it is rarely, if ever, met with but among the educated.”..

In November 1989, another highly influential paper was published on the subject of hay fever. The paper was short, less than two pages, in BMJ, titled “Hay Fever, Hygiene, and Household Size.”

The author looked at the prevalence of hay fever among 17,414 children born in March 1958. Of 16 variables the scientist explored, he described as “most striking” an association between the likelihood that a child would get hay fever allergy and the number of his or her siblings.

It was an inverse relationship, meaning the more siblings the child had, the less likely it was that he or she would get the allergy…The paper hypothesized that “allergic diseases were prevented by infection in early childhood, transmitted by unhygienic contact with older siblings, or acquired prenatally from a mother infected by contact with her older children…

[To avoid disease] we started washing our hands and took care to avoid certain foods that experience showed could be dangerous or deadly…Particularly in the wealthier areas of the world, we purified our water, and developed plumbing and waste treatment plants; we isolated and killed bacteria and other germs…

What does the immune system do when it’s not properly trained?

It can overreact. It becomes aggrieved by things like dust mites or pollen. It develops what we called allergies, chronic immune system attacks — inflammation — in a way that is counterproductive, irritating, even dangerous.

The percentage of children in the United States with a food allergy rose 50 percent between 1997–1999 and 2009–2011, according to the Centers for Disease Control and Prevention…

There are related trends in inflammatory bowel disease, lupus, rheumatic conditions and, in particular, celiac disease. The last results from the immune’s system overreacting to gluten..

And even doctors have been wrong….They have vastly overprescribed antibiotics. These may be a huge boon to an immune system faced with an otherwise deadly infection. But when used without good reason, the drugs can wipe out healthy microbes in our gut.

My take: With the increasing frequency of many diseases, there has to be environmental influences since our population genetic makeup does not change rapidly. Thus factors like infections, microbiome and exposure to antibiotics are likely important in the changing epidemiology.

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Mortality After Feeding Tube Placement in Children with Neurologic Impairment

Posted on March 28, 2019 by gutsandgrowth

A population-based study (KE Nelson et al. Pediatrics 2019; 143: e20182863) used an administrative data based from Ontario, Canada to examine the mortality rates among children with a diagnosis of neurologic impairment who underwent either gastrostomy placement or gastrojejunal placement between 1993-2015.

Key findings:

Two-year survival after feeding tube placement was 87.4% and 5-year survival was 75.8%
Unplanned hospital days, emergency room visits and outpatient visits were not significantly different after tube placement compared to pre-tube placement.

The authors interpret their findings as showing a high mortality which is likely due to medical fragility as there was “stability of health care use before and after the procedure.”

In the associated commentary (by KJ Lee and TE Corden, e20183623) the authors note the placement of a Gtube often took place after an increase in health care in the weeks prior. They recommended engaging in shared-decision making regarding Gtube placement prior to crisis.

My take: There have been a number of studies, particularly in adults, that have shown that Gtubes may not prolong survival in many conditions. However, they have been shown to improve nutritional status, simplify care, and improve quality of life.

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