Budesonide Looks Better for Eosinophilic Esophagitis

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A recent retrospective study (JM Fable et al. JPGN 2018; 66: 26-32) found that patients with eosinophilic esophagitis (EoE) who were treated with oral viscous budesonide (OVB) had more favorable outcomes than those treated with fluticasone propionate (FP).  This single center study included 68 pediatric patients (mean age 10.6 years) with 20 receiving FP and 48 OVB.

Dosing in study:

  • FP 110 mcg/actuation 2 puffs twice a day if 1-10 years, and 220 mcg/actuation 2 puffs twice a day if >10 years
  • OVB: 0.5 mg twice a day if 1-10 years, and 1 mg twice a day if >10 years
  • The authors noted that Duocal (which contains cornstarch and coconut oil) was a suitable alternative to Splenda.  They note that Neocate Nutra is effective too (limited by cost/coverage) as is pasteurized honey and maple syrup.

Key findings:

  • Histologic response (<15 eos/hpf) was noted in 75% (36/48) of OVB group and 40% (8/20) of FP group
  • Mean post-treatment peak eos/hpf was 12 ± 16 in OVB group and 20 ± 29 in the FP group (P=0.002)
  • Histologic remission (<5 eos/hpf) was noted in 54% OVB group and 35% FP group
  • In OVB-treated patients, those without asthma were more likely to achieve a histologic response (P=0.031)

Since this is a retrospective study, there are several potential limitations, including possible selection bias.  In addition, higher doses of topical agents have been shown to have higher response rates.

My take: Budesonide is probably better than fluticasone for EoE and its high first-pass metabolism indicates that it is probably safer as well.

Related blog posts:

What Happens Four Years After Fecal Microbiota Transplantation?

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A recent study (J Jalanka et al. AP&T 2018; 47: 371-9-thanks to Ben Gold for this reference) provide long-term data of fecal microbiota transplantation (FMT).

In this study of 84 adult patients who were treated for C difficile infection, 45 who had received FMT and 39 treated with antibiotics, the authors determined the frequency of adverse sequelae at 3.8 years using a retrospective questionnaire.

Key findings:

  • There were no difference in the development of severe diseases between FMT recipients and control patients (eg. IBD, cancer, autoimmune diseases, allergy, and neurological diseases)
  • There were no differences in weight gain
  • FMT patients reported faster improvements in bowel habits and reported that their mental health improved after treatment
  • FMT patients had fewer symptoms of functional gastrointestinal disorders than the control (antibiotic) patients

The authors note that FMT is frequently recommended based on three recurrences of C difficile infection and that their study would support using FMT earlier as a treatment option.

My take: Though a small study, these data suggest that FMT is effective and without long-term consequences.

High-resolution Esophageal Manometry for Rumination Syndrome.

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Briefly noted: While in most cases, rumination syndrome does not require manometry for diagnosis, in cases of uncertainty, it can be helpful.  A recent retrospective study (FR Grunder, A Aspirot, C Faure. JPGN 2017; 65: 627-32) highlights the utility of high-resolution esophageal manometry (HREM) in the diagnosis of rumination syndrome using 15 patients with rumination and 15 control patients.

Background: The sensitivity of HREM can be lower in a clinical setting as many “subjects with rumination are often able to tolerate the test meal during the manometry study with minimal or no symptoms.”

HREM also helps determine whether rumination is primary, secondary or if there is supragastric belch-associated rumination.

  • Primary rumination indicates that abdominal pressure increases before the retrograde flow
  • Secondary rumination indicates that abdominal pressure increases after a reflux event
  • Supragastric belch-associated rumination indicates an association of air inflow (detected with combined impedance) in the esophagus immediately followed by a rumination event

Key finding from this study:

  • HREM had a sensitivity and specificity of 80% and 100% respectively to confirm the diagnosis of rumination.  “the association of a clinical rumination episode with a rise in gastric pressure >30 mmHg seems to be specific for the diagnosis of rumination syndrome in children.”

My take: Manometry is usually not needed for the diagnosis of rumination syndrome but does help explain the pathophysiology.

Bright Angel Trail, Grand Canyon

 

 

 

Increasing Cost/Use of Biologic Therapies for Inflammatory Bowel Disease

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As noted in a previous blog post (Changes in the Use of IBD Biologic Therapy), there has been an increased use of biologic therapy early in the course of patient’s with inflammatory bowel disease (IBD). Another retrospective study (H Yu et al AP&T 2018; 47: 364-70 -thanks to Ben Gold for this reference) examines the market share and costs of biologic therapy for IBD using the Truven Marketscan Commercial Claims and Encounters database (2007-2015).  This database consists of out-patient and in-patient pharmaceutical claims of approximately 40-50 million privately insured patients each year from patients from all 50 states (U.S.).

Key findings:

  • Among 415,405 patients with IBD (188,842 with Crohn’s, 195,183 with ulcerative colitis, 31,380 with indeterminate IBD), the proportion using biologics increased over the 9-year period (2007-2015); overall, the market share increase was from 7.1% (2007) to 20.5% (2015).
  • There were 28,797 pediatric patients with IBD (17,296 with Crohn’s, 9368 with ulcerative colitis, and 2133 with indeterminate colitis). The overall market share in pediatric patients was the highest, increasing from 19.1% to 45.9%.
  • For all patients with Crohn’s disease (CD) the proportion receiving biologic therapy increased from 21.8% to 43.8%.  For patients with ulcerative colitis (UC), the proportion increased from 5.1% to 16.2%.
  • Per-member per-year (PMPY) costs increased. “The average biologic-taking patient accounted for $25,275 PMPY in 2007 and $36,051 PMPY in 2015.”  This was similar in the pediatric population, going from $23,616 PMPY in 2007 to $41,109 PMPY in 2015.
  • The share of costs of medicines: the costs of biologics as a share of the total increased from 72.9% in 2007 to 85.7% in 2015. 95% of the pharmacy costs in children with IBD are attributed to biologics.

My take: This trend of increasing use of biologics and their associated costs is going to continue due to their effectiveness. While there are direct costs related to these medications, the net cost is unclear as they can prevent hospitalizations and surgeries. In addition, by helping to spare corticosteroids and increasing response rates, biologic therapies improve quality of life, minimize opportunity loss, and optimize long-term health outcomes.

Bright Angel Trail, Grand Canyon

 

Unbound Bilirubin and Prematurity

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A recent prospective study (SB Amin, H Wang. J Pediatr 2018; 192: 47-52) indicates that premature infants have lower bilirubin binding affinity which could place them at risk for neurological complications.

Background: Very high levels of unconjugated bilirubin can lead to bilirubin-induced neurotoxicity/kenricterus.  There is increased susceptibility in newborns, particularly premature infants.  Unbound bilirubin (not bound to protein) can cross blood-brain barrier.  However, unbound bilirubin, rather than total serum bilirubin, is a better predictor of abnormal neurological outcomes.

Key findings:

  • Among 166 infants, peak unbound bilirubin significant correlated with bilirubin-albumin binding affinity (Ka) (r=-0.44, P=.001)
  • Gestational age was a significant modifier for the association between Ka and peak unbound bilirubin.
  • Peak unbound bilirubin was primarily associated with a decrease in binding affinity in infants ≤30 weeks gestational age

Implications of study: “Phototherapy as a sole intervention may be insufficient in preventing or reducing bilirubin-induced neurotoxicity”

My take: If there is low bilirubin binding affinity, among premature infants ≤30 weeks gestational age, some neurologic toxicity could occur even with bilirubin levels that have been considered safe previously.

Related blog posts:

Bright Angel Trail, Grand Canyon

Legalized Cannabis Associated with Increased Vomiting and Dependency But What About Alcohol?

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In politics, one hears a lot of “What about?”  If a problem is identified, many times a politician will try to divert the focus and/or justify a contentious issue to a related issue with a “what about” question. In medicine, when we see problems with marijuana, one could ask, ‘What about alcohol?’

A recent retrospective study (M Al-Shammari et al. Clin Gastroenterol Hepatol 2017; 15: 1876-81) found an increase in cannabis dependency unspecified (CDU) (ICD code) coinciding with the legalization of marijuana. Thanks to Seth Marcus for pointing out this study.

Key finding:

  • “We observed an increasing trend of CDU or an aggregate of CDU and persistent vomiting…the legalization of marijuana significantly increased the incidence rate during the legalization period (by 17.9%)…compared to the prelegalization period.

Related article: Aaron Carroll Alcohol or Marijuana? A Pediatrician Faces the Question

An excerpt:

The immediate answer, of course, is “neither.” …

The easy answer is to demonize marijuana. It’s illegal, after all. Moreover, its potential downsides are well known. Scans show that marijuana use is associated with potential changes in the brain. It’s associated with increases in the risk of psychosis. It may be associated with changes in lung function or long-term cancer risk, even though a growing body of evidence says that seems unlikely. It can harm memory, it’s associated with lower academic achievement, and its use is linked to less success later in life.

But these are all associations, not known causal pathways…

When I’m debating my answer, I think about health as well…Binge drinking accounted for about half of the more than 80,000 alcohol-related deaths in the United States in 2010, according to a 2012 report by the Centers for Disease Control and Prevention. The economic costs associated with excessive alcohol consumption in the United States were estimated to be about $225 billion. Binge drinking, defined as four or more drinks for women and five or more drinks for men on a single occasion, isn’t rare either. More than 17 percent of all people in the United States are binge drinkers, and more than 28 percent of people age 18 to 24…

Marijuana, on the other hand, kills almost no one…

I think about which is more dangerous when driving. A 2013 case-control study found that marijuana use increased the odds of being in a fatal crash by 83 percent. But adding alcohol to drug use increased the odds of a fatal crash by more than 2,200 percent. A more recent study found that, after controlling for various factors, a detectable amount of THC, the active ingredient in pot, in the blood did not increase the risk of accidents at all. Having a blood alcohol level of at least 0.05 percent, though, increased the odds of being in a crash by 575 percent…

 In 1995 alone, college students reported more than 460,000 alcohol-related incidents of violence in the United States… On the other hand, a 2014 study looking at marijuana use and intimate partner violence in the first nine years of marriage found that those who used marijuana had lower rates of such violence…

[Thus]  if I’m forced to make a choice, the answer is “marijuana.”

My take: While the cited study shows a correlation between cannaboid legalization with both CDU and increased vomiting, the commentary by Dr. Carroll helps provide context to the risks of marijuana use.  From a safety standpoint, the risks posed by alcohol appear much greater.

Related blog posts:

Bright Angel Trail, Grand Canyon

Medication Manager Apps

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From Cincinnati Children’s Staff Bulletin: A review of medication manager apps

My take: I have not tried the apps below.  I do think ‘old school’ products like weekly pill boxes can be very useful.

An excerpt:

For some families, medication apps can help them establish a routine of taking medication at the same time each day. For others, the app acts as a reminder every once in a while when the family has a really busy day and may have forgotten otherwise.

Possible Features
 MyMedScheduleMobile Mango Health Medication Manager
 MedCoach Medication Reminder MediSafe Meds & Pill Reminder
Alerts you to take meds  X X X
Prescription refill reminders  X
Connect with pharmacy to refill prescriptions  X  X
Track progress  X  X
Create medication schedules  X  X
Create list of medications for doctor  X  X
Synchronizes with other family members  X
Drug interaction warnings  X
Gives points and rewards  X
FREE  X  X  X  X

 

“Is There a Downside to Going Gluten-Free if You’re Healthy?” Yes

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From NY Times: Is There a Downside to Going Gluten-Free if You’re Healthy?

Yes. This short commentary explains a lot of reasons why going gluten-free is not a great idea for healthy individuals.

  1. Often, a gluten-free diet incorporates more fat, more sugar, more salt and less fiber –all bad for your health.  A gluten-free diet can increase the risk of weight gain, type 2 diabetes, and cardiovascular disease.
  2. A gluten-free diet may make definitive testing for celiac disease inaccurate after more than a few weeks.
  3. “While much has been written in books and online sources about the purported benefits of avoiding gluten, such as weight loss, cognitive well-being and overall wellness, these claims are not supported by evidence….Though some patients with irritable bowel syndrome, or I.B.S., may see symptoms improve after cutting out gluten-containing foods, research suggests it’s likely to be a result of something other than gluten.”

My take (borrowed): “There’s no reason for someone who feels well to start a gluten-free diet to promote wellness,” said Dr. Benjamin Lebwohl, director of clinical research at the Celiac Disease Center at Columbia University. “It is not an intrinsically wellness-promoting diet.”

Related blog posts:

 

Overweight Children (like Adults) Are Prone to Underestimate Their Body Size

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Reference: Steinsbekk Silje, Klöckner Christian A., Fildes Alison, Kristoffersen Pernille, Rognsås Stine L., and Wichstrøm Lars. Body Size Estimation from Early to Middle Childhood: Stability of Underestimation, BMI, and Gender Effects. Front. Psychol., 21 November 2017. DOI: 10.3389/fpsyg.2017.02038

This recent study examined how children perceive their own body size.  Given the prevalence of overweight/obesity, an accurate understanding of body size is needed if one is going to try to work on this issue.

An excerpt of a summary from Brinkwire: Overweight children more likely to underestimate their body size

The study is based on data from the Norwegian research project Tidlig Trygg i Trondheim, a longitudinal population-based study that looks at the risk and protective factors contributing to children’s psychological and social health…

The children were shown seven pictures of girls and boys with known body mass index and asked which picture looked the most like them. The researchers then calculated the difference in BMI between the figure identified by the children and the children’s own BMI based on measured height and weight…

Generally, the researchers found that children more often underestimated than overestimated the size of their body, although the majority made accurate estimates…

“We also found that the higher the children’s BMI, the more they underestimated their size over time,” Steinsbekk says.

The largest children thus underestimated their body size the most and showed an increased degree of underestimation over time (that is, from 6 to 8 and from 8 to 10 years old).

My take: Given the prevalence of overweight/obese children, this has skewed our perception of what a normal weight should be.

Related blog post: Can parents not know if their child is overweight?

Bright Angel Trail, Grand Canyon

Ketchup Packet Ingestion–Crohn’s Disease Mimic

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In the category of –“I have not seen that before”…

Link: NY Daily News Women diagnosed with Crohn’s disease actually had ketchup packet in her intestines for six years (Thanks to my son for pointing out this story)

An excerpt:

A woman believed she was suffering from Crohn’s disease for six years until doctors performed surgery and discovered a ketchup packet in the lining of her intestine.

The 41-year-old patient had symptoms consistent with the serious bowel disease — including acute abdominal pain and bloating lasting up to three days — but she did not respond to the standard treatments.

Case study reference: Visagan R, et al. BMJ Case Rep 2013. doi:10.1136/bcr-2013-009603

Related blog post: Add it to the list