Predicting Remission in Pediatric Ulcerative Colitis

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Trying to offer realistic information to families on the long-term success of infliximab (Remicade) for pediatric ulcerative colitis has been difficult due to a limited amount of data.  In addition, many studies have a number of limitations which can make it difficult to extrapolate to a less-selected population (According to the study which you would never qualify for …).

A recent post hoc analysis (Clin Gastroenterol Hepatol 2013; 11: 1460-65) from 51 children (age 6-17 years) provides some insight into this issue.  The authors used data collected prospectively during the T72 clinical trial (Clin Gastroenterol Hepatol; 10: 391-99 -reviewed in blog post: Infliximab for children with Ulcerative Colitis | gutsandgrowth).

Results:

  • Week 8 PUCAI scores best predicted which patients would be in steroid-free remission after 1 year of treatment: 9 of 17 (53%) with scores <10 points were in sustained remission compare with 4 of 20 (25%) with scores ≥10.
  • Week 8 PUCAI outperformed mucosal healing in predicting remission.

Key points:

  • PUCAI may have outperformed mucosal healing because the latter can lag behind clinical response.  Furthermore, mucosal healing is more subjective with less interobserver reliability.
  • In patients with known inflammatory bowel disease, endoscopic assessment remains important in several situations: condition or reason for symptoms is in question (eg. exclude irritable bowel symptoms or medication-induced symptoms), acute severe colitis not responding to 3-day treatment with intravenous steroids to exclude superinfection, and to assess mucosa before major treatment changes “such as when starting or stopping biologics and before referral for colectomy.”

Related blog posts:

Safety Net Hospitals -Left in the Lurch

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A recent perspective piece highlights a new threat to safety-net hospitals (NEJM 2013; 369: 1675-77).

Safety-net hospitals are often referred to as Medicaid Disproportionate Share Hospitals (DSHs).  “Only 2% of acute care hospitals nationwide are safety-net facilities, but they provide 20% of uncompensated care to the uninsured.”  Currently, Medicaid allocates $11.5 billion to support these hospitals.  However, this money is provided to the states and many states including Georgia and Ohio spread these payments broadly rather than targeting these DSHs.

The newest threat:  “Because the Affordable Care Act (ACA) was expected to dramatically expand insurance coverage, safety-net hospitals were expected to need less DSH money…the ACA reduced Medicaid DSH funding by $1.8 billion between fiscal years 2014 and 2020.”  And, “because many states that won’t expand Medicaid currently receive large DSH payments, their safety hospitals will be hit hard when the DSH cuts kick in.”

There are several proposals that the Centers for Medicare and Medicaid Services (CMS) are reviewing to try to address this problem.  However, the authors note that it is unlikely that Congress will restore DSH funding to previous levels.

Bottomline: “If the state governments that refused to expand Medicaid also refuse to rethink their approach to allocating DSH funds, there will be little money left to sustain their safety-net hospitals.”

Related blog post:

Life in the balance (book) | gutsandgrowth

Probiotics for Colic

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Another study has shown the potential for probiotics to help colicy infants.  In an editorial, Carlos Lifschitz sums up the paper (The Journal of Pediatrics Volume 163, Issue 5 , Pages 1250-1252, November 2013); here is an excerpt (link from Kipp Ellsworth twitter feed —goo.gl/b3iMFu):

For reasons that are not clear, human infants are born with a well-developed capacity to cry.1 …Unexplained and severe crying affects 3%-28% of breastfed or formula-fed (otherwise-healthy) young infants.2 Although excessive, inconsolable crying and colic are considered to be a benign, self-resolving problem, they can be very distressing and lead to marital conflict and parental exhaustion.3 Infantile colic is defined as paroxysmal, excessive, inconsolable crying without an identifiable cause in an otherwise-healthy infant occurring in the first 3 months of life and lasting a minimum of 3 hours per day, 3 days per week, for 3 weeks…

Enter probiotics. Lactobacillus reuteri DSM 17 938 at a dose of 108 colony-forming units per day in breastfed infants improved symptoms of infantile colic,19 a finding that was further corroborated.20 Despite evidence that altering the microbiota may result in reduced crying, the physiopathology still remains unclear…

In this issue of The Journal, Pärtty et al22 attempt to prevent excessive crying in former premature infants….To determine whether excessive crying is preventable by manipulation of intestinal microbiota, 94 preterm infants, some breast- and formula-fed, with gestational ages ranging from 32 to 36 weeks and birth weights >1500 g, were randomized in the first 3 days of life in a double-blind study to receive for the following 2 months either a mixture of galacto-oligosaccharide and polydextrose (prebiotic group), Lactobacillus rhamnosus GG (probiotic group), or placebo…Follow-up consultations were conducted by the same study nurse at the age of 1, 2, 4, 6, and 12 months…

Significantly less frequent crying was observed in both the pre- and probiotic groups compared with the placebo group (19% vs 19% vs 47%, respectively; P = .02). At 1 month of age, the infants’ fecal microbiota were investigated. The proportion ofLactobacillus-Lactococcus-Enterococcus group to total bacterial count and the proportion of Clostridium histolyticum group to total bacterial count was greater in excessive criers than in contented infants in all 3 study groups (pre-, probiotics, and placebo). The authors concluded that early pre- and probiotic supplementation may alleviate symptoms associated with crying and fussing in preterm infants.

Although in the study the following associations did not reach statistical significance, they are of interest for future investigation: contented infants were more often exclusively breast-fed during the first 2 months (42% vs 22%, respectively, P= .09) and their mothers had received perinatal antibiotics less often (22% vs 41%, respectively, P = .07) than criers… Contrary to this hypothesis, however, is the finding that persistent criers were more often born by vaginal delivery as opposed to cesarean delivery (81% vs 63%, P = .07) than contented babies. This finding is surprising because birth by cesarean delivery and, therefore, lack of exposure to the microbiota of the vaginal canal and perineum, has been associated with abnormal development of intestinal microbiota and several diseases.

Related blog posts:

In a video, Dr. Sanjay Gupta and Dr. John Bachman say ‘we don’t know why babies have colic, but it will end and is not the parent’s fault:’ ow.ly/q4IsW 

Disclaimer: These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) and specific medical interventions should be confirmed by prescribing physician.  Application of the information in a particular situation remains the professional responsibility of the practitioner.

Additional references:

  • -Pediatrics 2010; 126: e526.  Double-blind randomized placebo-controlled trial of Lactobacillus reuteri.
  • -J Pediatr 2009; 155:823. Increased calprotectin in colicy infants. n=36. editorial pg 772.
  • -J Pediatr 2009; 154: 514-20. Colic and reflux. (Orenstein et al), & 475 (editorial -Putnam). PPIs (lansoprazole) do not help colicy Sx in infants c GERD. n=162. Increased resp infections in pts on PPIs. 44% response in Rx & control group.
  • -J Pediatr 2008; 152: 801. Probiotic helped reduce colic sx in 30 preterm infants, Lactobacillus reuteri
  • -Pediatrics 2007; 119; e124. Probiotics reduced colic in breastfed babies more than simethicone. n=83, lactobacillus reuteri, 10-8th power per day. Decreased crying 18 minutes per day at 1 week compared to simethicone & by 94 minutes/day at 4 weeks (95% response vs 7% of simethicone)
  • -Pediatrics 2005; 116: e709. Low-allergen maternal diet was helpful.
  • -Hochman JA, Simms C: “The role of small bowel bacterial overgrowth in infantile colic“J Pediatr 2005; 147: 410-411 (Letter to Editor).
  • -Arch Pediatr Adol Med 2002; 1183 &1172. lack of sequelae on maternal mental health.
  • -Arch Pediatr Adol Med 2002; 156: 1123-1128. colic 24% of infants, breastfeeding did not help.
  • -Pediatrics 2002; 109: 797-805. carbohydrate malabsorption with breath testing in colicy infants, n=30. 2 hour fasting period.

Sweetened Beverages -A Big Problem for Little Kids

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Many times we may look at a study and think that the results could easily have been anticipated.  Yet, there are many examples when our assumptions are flat-out wrong.

A recent study (Pediatrics 2013; 132: 413-20 -thanks to Jeff Lewis for this reference) helps solidify what we think we already knew, namely that sugar-sweetened beverages (SSB) contribute to weight gain in young children.  This study showed that 2-5 year-olds, followed in the Early Childhood Longitudinal Survey–Birth Cohort (n=9600), who had more frequent SSB consumption had higher BMI z scores by age four (P < .05) than infrequent/nondrinkers of SSB.  This study, for the first time, shows this effect in this younger population.

Related blog posts:

Trends in Clostridium difficile Infection

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Many recent reports have provided conflicting data with regard to Clostridium difficile infection (CDI) epidemiology.  Some of the newest data needs to be interpreted with caution due to the adoption of PCR technology.  Previously, CDI was difficult to culture and identify.  The problem now is proving causation when C diff is identified.

J Pediatr 2013; 163: 699-705.  This study, using an administrative database, analyzed 33,095 first pediatric hospitalizations for malignancy from 43 pediatric hospitals between 1999 and 2011.  A total of 1736 admissions with CDI were identified; 380 were considered hospital-acquired.  The authors noted an apparent decrease in CDI incidence between 2006-2010.  Exposure to chemotherapy, proton pump inhibitors and certain antibiotics were independent risk factors for hospital-acquired CDI.

JPGN 2013; 57: 487-88. New-onset patients with IBD cases were retrospectively reviewed from 2010-2012.  10 cases (8.1%) of 124 were positive for CDI within the first two months of diagnosis.  Only 42% of the total 290 new IBD cases had documented testing for CDI.  The prevalence of CDI without obvious preceding antibiotic exposure was 2.4%.

JPGN 2013; 57: 293-97. Between 2006-2012, stool samples were prospectively obtained from children with IBD (UC, n=76, Crohn, n=69) and controls with other noninflammatory GI conditions (n=51).

Key points:

  • The prevalence of positive PCR results were 11.6% in patients with Crohn disease, 18.4% in patients with UC, and 11.8% in controls.  No significant difference.
  • CDI as identified by PCR may be an incidental finding.
  • Only test diarrheal stools.  Testing for cure is not recommended.
  • Asymptomatic colonization with C diff is frequent in patients with and without IBD

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“Poo in You” Video

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New “Poo in You” education video for constipation / encopresis available through YouTube channel: http://www.youtube.com/NASPGHANencopresis

I took a look at this 5 minute video and it explains why kids soil and the basics of treatment; in addition, there is a “wah-wah-wah” sound effect at 2:29 in video when soiling occurs.  Probably worth including this link on an after visit summary:

Related blog posts:

Constipation Guidelines:

Rett Reference

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JPGN 2013; 57: 451-60.  “Assessment and Management of Nutrition and Growth in Rett Syndrome”

  • This references expert recommendations from an international multidisciplinary panel.  “The level of evidence for the statements was low.”
  • “A body mass index of approximately the 25% can be considered a reasonable target in clinical practice.  Gastrostomy is indicated for extremely poor growth, if there is risk of aspiratrion and if feeding times are prolonged.”
  • There was no consensus with regard to fundoplication.  It should be used with “caution in those with significant air swallowing.”

Related previous post:

GI & Nutrition Problems in Rett Syndrome | gutsandgrowth

PPIs -another reference for EoE

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“The outcome of patients with oesophageal eosinophilic infiltration after an eight-week trial of a proton pump inhibitor”

  1. G. Vazquez-Elizondo1,
  2. S. Ngamruengphong1,
  3. M. Khrisna2,
  4. K. R. DeVault1,
  5. N. J. Talley1,
  6. S. R. Achem1,*

Article first published online: 5 OCT 2013

DOI: 10.1111/apt.12513

Link to article: bit.ly/18bA3SS (from John Pohl’s twitter feed)

Methods: Sixty consecutive symptomatic patients with documented oesophageal eosinophilia received open-label omeprazole 20 mg orally twice daily before meals for 8 weeks.  Mean age 48.7 years (18-79).

Results: Clinical improvement occurred in 43 (71.6%), endoscopic signs were reduced in 34 (61.8%) and normalised in 12 (21.8%), and histologically, 34 (56.6%) improved, while 15 (25%) obtained complete resolution. Overall, 22 patients (36.7%) obtained both complete clinical and histological remission

Additional related blog entries:

Casting a Wide Net: Whole-Exome Sequencing

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A recent study shows that whole-exome sequencing can be used to diagnose genetic defects in patients with a range of phenotypes (NEJM 2013; 369: 1502-11).

In this study, the first 250 patients who had whole-exome sequencing performed at Baylor College of Medicine were studied.  80% had neurological problems and all had undergone previous extensive evaluation.

Results:

  • The authors identified “86 mutated alleles that were highly likely to be causative in 62 patients (25%)”
  • 83% of the autosomal dominant mutant alleles (n=33) and 40% of the X-linked mutant alleles (n=9) occurred de novo.
  • In four patients, the authors identified multiple causative genes.  This may lead to a paradigm shift from Occam’s razor towards more cases of “multiple hits.”
  • The authors speculate that the yield of this type of testing will improve as databases grow since many mutations at this time are of uncertain clinical significance

Bottomline: While this approach was used mainly in individuals with unexplained neurological problems, the use of whole-exome sequencing has broad potential.  In GI/Liver, the uses could include unexplained diarrheal disorders, metabolic/cholestatic liver disease, failure to thrive, inflammatory bowel disease, and many other conditions.

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