More Frequent Foreign Body Ingestions

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A recent retrospective study (D Orsagh-Yentis) Pediatrics 2019; 143: pii:320181988) examined children <6 years of age (n=759,054) and presentation to an emergency department in the U.S. for a foreign body ingestion (FBI) from 1995-2015. This study was reviewed at our recent national meeting by David Brumbaugh -related blog post: #NASPGHAN19 Postgraduate Course (Part 1) (Slides below).

Key findings:

  • FBI rates increased from 9.5 to 18 per 10,000 during the 20 year study period
  • Coins accounted for 61.7% of FBI
  • Most children (89.7%) were able to be discharged after their suspected ingestion
  • Battery ingestion represented 0.14% of all ingestions in 1995  to 8.4% in 2015

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Hidden Costs of Medical Schools

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From NY Times: ‘I Have a Ph.D. in Not Having Money’

An excerpt:

Medical school is expensive for everyone. But for low-income students, the hidden costs can be prohibitive…

American medical schools are the training grounds for a white-collar, high-income industry, but they select their students from predominantly high-income, and typically white, households…Between 1988 and 2017, more than three-quarters of American medical school students came from affluent households…

Students from low-income families who choose to apply to medical school find the path lined with financial obstacles. The application phase entails MCAT registration ($315) and preparation, application fees ($170 for the first school and $40 for each additional one), travel and attire for interviews (on average more than $200 per school). After enrollment, students are expected to purchase equipment and study aids. Each year brings new certification tests, with registration fees running upward of $600.

Aspiring doctors know that tuition is costly; the median educational debt held by medical school graduates in 2018 was $200,000, up 4 percent from the previous year. But less advertised are all the hidden costs of a medical education.

Gastrostomy Tube Placement in Extremely Low Birthweight Infants

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A recent analysis (MG Warren et al J Pediatr 2019; 214: 41-6) examined gastrostomy tube (GT) placement among 4569 extremely low birthweight (ELBW) infants (birth wt <1000 gm) who were enrolled in the National Instittue of Child Health and Human Development Neonatal Research Network (25 centers).

Key findings:

  • 333 (7.3%) underwent GT placement; 76% had GT placed postdischarge from NICU
  • Among patients with GT placement, 56% had weight <10th percentile, 61% had neurodevelopmental impairment (NDI), and 55% had chronic breathing problems
  • At last follow-up, 32% of infants who required GT placement were taking full oral feeds.
  • Rates of fundoplication varied widely between centers, ranging from 0% to 6.4% among the centers.

In the discussion, the authors note the well-recognized associations between feeding difficulties and language delays in ELBW infants.  In addition, “behavioral and emotional problems have …been described in children with feeding problems.”

The authors also state, without evidence, that the high rate of GT placement after discharge suggests that “a large proportion of ELBW infants were first discharged from the NICU orally feeding but could not maintain these skills.”  Alternative explanations include the following:

  • Many infants were sent home with NG (nasogastric) supplementation and after not making progress with oral feedings, elective GT placement was done when the infant was a more suitable candidate (eg. improved respiratory status, better nourished, etc.)
  • Problems with oral feeding became apparent after discharge including poor growth and aspiration.  In fact, the authors note that “orormotor dysfunction and avoidant feeding behaviors at 3 and 12 months corrected age” were nearly twice as likely in infants born <34 weeks
  • While this study did not fully capture data regarding home NG feedings, 14% of patients sent home with NG feedings eventually received a GT

My take: This study indicates that 7% of ELBW infants undergo GT placement and that about one-third out-grow the need for GT supplementation after ~2 years.

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Transnasal Endoscopy in Unsedated Children to Monitor Eosinophilic Esophagitis

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A recent retrospective study (N Nguyen et al. Clin Gastroenterol Hepatol 2019; 17: 2455-2462) describe the feasibility of unsedated transnasal endoscopy (TNE) for monitoring eosinophilic esophagitis (EoE) in children (n=190, subject ages 3-22 years).

TNE was facilitated by distraction with either video google or virtual reality (starting 2016).  NPO time was 2 hours before the TNE.

Key points:

  • Over 294 TNEs were completed from 300 attempts (98% success)
  • Cost of TNE was halved: $4393 compared to $9444 for EGD (does not count pathology costs)
  • Adverse events: 8 (2.7%) with vomiting, 9 (3.1%) spit up, 11 (3.7%) with epistaxis
  • By 2017, TNE accounted for 31.8% of upper endoscopies in 2017

The authors recommend that TNE be offered starting at age 5 years in those without a known stricture.

My take: I am looking forward to less invasive/less costly ways of monitoring treatment response in EoE.  I think TNE can lower costs –though I am a little surprised that the cost of TNE in their institution was still more than $4000.  In our outpatient endoscopy center, costs for an upper endoscopy/biopsy with anesthesia are typically about one-third the cost of an EGD in their study and about three-fourths the cost of a study TNE.

Related study: A Krigel et al. Clin Gastroenterol Hepatol 2019; 17: 2489-96. This study showed increasing use of anesthesia assistance (AA) for colonoscopy in adults from 16.7% in 2006 to 58.1% in 2015. This data was derived from the Premier Perspective database with more than 4.6 million patients who had an outpatient colonoscopy. AA was associated with a median increase in cost of $182 for patients with commercial insurance.

Related blog post: Waiting for the String Test for EoE

 

Celiac Disease: “”80 percent of success is just showing up”

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“80 percent of success is just showing up” —Woody Allen

Reading a recent (brief) study (BA Blansky et al. Clin Gastroenterol Hepatol 2019; 17: 2503-4) reminded me of the quote from Woody Allen.  This study of children with Celiac disease (CD) demonstrates a high rate of children who were lost to follow-up at a leading Children’s hospital.

Key findings:

  • From a randomly selected retrospective cohort (2010-2014) with 241 eligible subjects, one-fourth of children were lost to follow-up within a year of diagnosis. 22 (9%) had NO GI visits after their diagnostic procedure.
  • Risk factors for loss of follow-up: sibling with CD (HR 1.90), Medicaid insurance (HR 2.19), and older age at diagnosis; those with adherence had median age at diagnosis of 8.7 years compared with 11.4 years for those lost to follow-up.
  • Median time to tissue transglutaminase (TTG) IgA normalization was 17 months.  Of 141 who had recommended follow-up, 25% had elevated TTG IgA at last GI visit.

My take: These numbers should not be surprising to most clinicians.  If clinicians want to improve follow-up and outcomes, then families will need more nudging; EMRs can be configured to help in this task.

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Easy Advice for Pediatric Hepatologists: PSC Surveillance Recommendations

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A recent clinical practice update (CL Bowlus et al. Clin Gastroenterol Hepatol 2019; 17: 2416-22) makes several recommendations on surveillance for hepatobiliary cancers in patients with primary sclerosing cholangitis (PSC).

Full Text Link: AGA Clinical Practice Update on Surveillance for Hepatobiliary Cancers in Patients With Primary Sclerosing Cholangitis: Expert Review

I will highlight the most important recommendation for pediatric hepatologists:

  • Best practice advice 6: Surveillance for cholangiocarcinoma should not be performed in PSC patients with small-duct PSCs or those younger than age 20.

In the text, the authors note that “in pediatric PSC patients, cholangiocarcinoma is very rare, with only 8 of 781 (1%) …developing cholangiocarcinoma” (MR Deneau et al. Hepatology 2017; 66: 518-27)

Here are the other recommendations:

  • Best practice advice 1  Surveillance for cholangiocarcinoma and gallbladder cancer should be considered in all adult patients with PSC regardless of disease stage, especially in the first year after diagnosis and in patients with ulcerative colitis and those diagnosed at an older age.
  • Best practice advice 2 Surveillance for cholangiocarcinoma and gallbladder cancer should include imaging by ultrasound, computed tomography, or magnetic resonance imaging, with or without serum carbohydrate antigen 19-9, every 6 to 12 months
  • Best practice advice 3  Endoscopic retrograde cholangiopancreatography with brush cytology should not be used routinely for surveillance of cholangiocarcinomas in PSC.
  • Best practice advice 4  Cholangiocarcinomas should be investigated by endoscopic retrograde cholangiopancreatography with brush cytology with or without fluorescence in situ hybridization analysis and/or cholangioscopy in PSC patients with worsening clinical symptoms, worsening cholestasis, or a dominant stricture.
  • Best practice advice 5  Fine-needle aspiration of perihilar biliary strictures should be used with caution in PSC patients considered to be liver transplant candidates because of concerns for tumor seeding if the lesion is a cholangiocarcinoma.
  • Best practice advice 7 The decision to perform a cholecystectomy in PSC patients with a gallbladder polyp should be based on the size and growth of the polyp, as well as the clinical status of the patient, with the knowledge of the increased risk of gallbladder cancer in polyps greater than 8 mm.
  • Best practice advice 8  Surveillance for hepatocellular carcinoma in PSC patients with cirrhosis should include ultrasound, computed tomography, or magnetic resonance imaging, with or without α-fetoprotein every 6 months.

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From The Onion

 

20-Year Follow-up of Statins in Children

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A recent study (IK Luirink et al. NEJM 2019; 381: 1547-56) examined the effects of statin therapy in children with familial hypercholesterolemia (FH) who were followed for 20 years. At baseline, the median age was 13 years in the treated cohort and in their sibling control group.  184 of 214 (86%) of patients with FH were seen in follow-up and 77 of 95 (81%) of siblings.

Key findings:

  • The mean LDL cholesterol had decreased from 237 to 161 mg/dL
  • LDL target of <100 mg/dL was achieved in 37 patients (20%)
  • Mean progression of carotid intima-media thickness over the entire follow-up period was 0.0056 mm/year in patients with FH and 0.0057 mm/year in sibling controls
  • The cumulative incidence of cardiovascular events and death from cardiovascular causes at age 39 years was lower in the treated group compared to  their affected parents: 1% vs. 26% and 0% vs. 7% respectively

Discussion:

“This makes a strong case for not only ‘the lower the better’ but also for ‘the younger the better” as atherosclerotic disease is determined not only by the LDL level but also by cumulative exposure.

My take: This study provides convincing data that statin therapy prolongs health and life in patients with familial hypercholesterolemia.

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IBD Updates December 2019

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SR Gupta et al. JPGN 2019; 69: 544-50.  This article reports on preliminary experience in 54 children who received external (non-hospital) infliximab infusions. The average age was 17.6 years. The authors noted no serious safety concerns.  Prior to arranging these infusions, the authors insisted on the following:

  • Infusion services had to guarantee pediatric trained nurses with PALS certification
  • Emergency medications had to be available
  • A plan for emergency communication was arranged
  • Postinfusion communication would occur with each infusion

BN Limketkai et al. Inflamm Bowel Dis 2019; 25: 1828-37.  This study, using Truven Health MarketScan database (2007-16) reviewed proactive or reactive mucosal monitoring after biologic initiation in IBD.  Early (< 6 months) proactive monitoring (88% endoscopy-based) was performed in 11% (n=2195/19,899) of patients with Crohn’s and 12.8% (925/7247) of patients with ulcerative colitis.

  • “Early proactive monitoring was associated with a reduction in disease-related complications for CD (aHR 0.90) and UC (aHR 0.87) and predominantly driven by a reduction in corticosteroid use.”
  • Another interesting finding was that ~40% of patients had biologic therapy initiated without assessment of mucosal disease activity within 6 months.
  • The authors state that disease monitoring is typically more useful in CD than UC because with the latter, cessation of bleeding and diarrhea appear to be adequate surrogates.
  • This study was not able to assess whether a biomarker like fecal calprotectin would be suitable due to its low utilization.

RZ Cohen, BT Schoen, S Kugathasan, CG Sauer. JPGN 2019; 69: 551-6. In this chart review, the authors identified anti-drug antibodies (ADA) in 24.8% (n=58) of patients undergoing therapeutic drug monitoring (n=234) with both infliximab and adalimumab.  54% of this group had antibody suppression with dose optimization. Of note, 37 patients had detectable ADA at time of initial drug monitoring. Dose optimization was 10 mg/kg every 4 weeks with infliximab or 40 mg weekly with adalimumab. Patients who were switched to a second anti-TNF agent (n=23) were not more likely to develop ADA to the second agent (small sample size). Also, the authors caution that in the five patients with ADA levels (>10 U/mL), dose optimization failed and patients required a therapeutic switch. My take: This study provides some useful information about the frequency of ADA.  My view is that the actual drug level is more critical than the presence of ADA; though, the presence of high ADA often precludes the ability to deliver a therapeutic drug level.

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More Details on Drug-Resistant E coli Transmitted by Fecal Microbiota Transplant

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In June 2019, the FDA delivered a warning about the potential danger of transmitting drug-resistant E coli with fecal microbiota tranplantaion (FMT).  (FDA Warning for FMT)

A report on this issue has now been published: Z DeFilipp et al. NEJM 381: 2043-50, editorial M Blaser pgs 264-6.

The authors describe two patients, a 69 year-old with cirrhosis and a 73 year-old sp stem cell transplantation, who developed bacteremia due to transmission of a drug-resistant (extended-spectrum beta-lactamase [ESBL]) E coli following FMT which was delivered by oral capsules. The latter patient died from sepsis. The two patients had a genomicly-identical strain isolated that was also found in the donated aliquot.

In the commentary, a couple of important points:

  • “Up to now, the complications have been infrequent [from FMT], and for recurrent C difficile infection, the benefits of FMT clearly outweigh the risks; however, as the use of FMT is broadened and more compromised patients are treated, complications may be more frequently observed.”
  • “In the short term, improved and uniform screening of FMT material is needed to reduce the risks.”

My take: Both of these patients who became developed bacteremia were at risk for more severe infections.  However, we need to remain aware that severe complications can and do occur with FMT.  In context, though, there are risks of severe complications from routine use of antibiotics as well.

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