The Story Behind a 30 Year Esophagitis Study

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A recent retrospective study ( SS Baker et al. JPGN 2015; 61: 538-40) reported on changes in esophagitis over a 30 year period at one center.  While the authors focus on the fluctuating percentage of esophagitis noted during three periods, in my opinion, they miss the opportunity to discuss more relevant findings.

Specifically, the authors note the following:

  • From 1980-88 (n=186 over 8 years) that 26.9% had esophagitis and 4.8% had >15 eos/hpf.  Normal pathology in the esophagus was noted in 73.1%.
  • From 2000-2002 (n=321 over 2 years), 41.2% had esophagitis and 8.5% had >15 eos/hpf.  Normal pathology in the esophagus was noted in 58.8%.
  • In the most recent period, 2011, (n=675 over 1 year), 31%* had esophagitis and 12.7% had >15 eos/hpf.  Normal pathology in the esophagus was noted in 69%.     *erroneously reported as 33%

What is baffling to me are the following:

  • Why the authors assert that there has been a fluctuating prevalence.  In absolute terms, the increase in cases is marked, though one can argue that in earlier periods there may have been many undiagnosed cases.
  • Why the authors do not comment on the tremendous increase in the use of endoscopy in their discussion.  In the first period, they were averaging ~23/year, the second period ~95/year and in the most recent period, they performed 675 in one year.

My take: This study shows that esophageal eosinophilia has been present for a long time and that identification of cases has increased considerably over 32 years.  In addition, the use of endoscopy has increased markedly, yet the yield of abnormal findings remains similar.

Briefly noted: C Menard-Katcher et al. JPGN 2015; 61: 541-46.  This retrospective study of 22 children showed that 55% had esophageal strictures identified by esophagram but not endoscopy.

Related blog posts:

Bamboo

Eosinophilic Esophagitis Review -NEJM

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Good review:  Glenn T. Furuta, M.D., and David A. Katzka, M.D. N Engl J Med 2015; 373:1640-1648

A couple pointers from this review:

  • Estimated prevalence of eosinophilic esophagitis (EoE) 0.4% in Western countries.  Symptoms are often underestimated due to patient ‘accommodation’ which includes eating slowly/carefully, drinking a lot of liquids and avoiding items more prone to become lodged (meats, pills, breads)
  • Pathogenesis: “Birth by cesarean section, premature delivery, antibiotic exposure during infancy, food allergy, lack of breast-feeding, and living in an area of lower population density have all been associated with eosinophilic esophagitis.”
  • Impaired barrier function and enhanced the activity play a role in pathogenesis
  • Food allergy is a non-IgE-mediated process.  Omalizumab, an anti-IgE biologic, is ineffective in EoE and EoE can develop in IgE-null mice
  • Male predominance (3:1) suggests that there is a genetic component.
Esophagus with ringed appearance, furrowing, and loss of vascular markings

Esophagus with ringed appearance, furrowing, and loss of vascular markings

Another useful reference on Eosinophilic Gastritis in Children: Am J Gastroenterol 2014; 109; 1277-85.  This article provides data on clinical and histologic remission with eosinophilic gastritis (>70 eos/hpf), n=30 children.  “Response to dietary restriction was high” (82% clinical, 78% histologic response) Thanks to Seth Marcus for this reference.

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NY Times: End the Gun Epidemic in America

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Full link: End the Gun Epidemic in America.  This editorial published on A1 in the Dec. 5 edition of The New York Times. It is the first time an editorial has appeared on the front page since 1920.

An excerpt:

It is a moral outrage and a national disgrace that civilians can legally purchase weapons designed specifically to kill people with brutal speed and efficiency. These are weapons of war, barely modified and deliberately marketed as tools of macho vigilantism and even insurrection. America’s elected leaders offer prayers for gun victims and then, callously and without fear of consequence, reject the most basic restrictions on weapons of mass killing, as they did on Thursday. They distract us with arguments about the word terrorism. Let’s be clear: These spree killings are all, in their own ways, acts of terrorism.

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Antibiotics and Growth in India

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A recent study (Rogawski ET, et al. J Pediatr 2015; 167: 1096-102) examined a prospective observational cohort of 497 children in India (from “semi-urban slums”).  The authors found that early exposure to antibiotics were not associated with increased or decreased growth.

“There are several potential explanations for the lack of a growth-promoting effect.  Most of the previous studies showing increased weight gain or risk of obesity associated with antibiotics were conducted in high-income countries with Western diets.”

My take: This was a negative study on antibiotics and obesity.  This suggests that the effects of antibiotics with regard to weight gain may be limited and/or modified by diet.

Also noted: Wakamoto H, et al. J Pediatr 2015; 167: 1136-42.  This study showed that Krebs von den Lungen-6 (KL-6) which is abundant on type II alveolar pneumoctyes and respiratory epithelial cells is a fairly good serum biomarker for chronic aspiration in this study of children with severe motor and intellectual disabilities.  Figure 1 shows the distribution of KL-6 among the 37 with aspiration and the 29 without aspiration.  The median in the former was 344 vs 207 in the later, though there was overlapping results.

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Sandy Springs

Sandy Springs

“New Math on Drug Cost-Effectiveness”

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Competing commentaries on rising drug prices:

  • Bach PB. “New Math on Drug Cost-Effectiveness” NEJM 2015; 373: 1797-99
  • Chin WW. “A Delicate Balance –Pharmaceutical Innovation and Access” NEJM 2015; 373: 199-1801)

Dr. Bach’s commentary focuses on the exorbitant costs of many medications.  His key points:

  • “The rate of introduction of new and expensive drugs has accelerated; the pace of conversion to generics is slowing; the prices of many generics are rising; and expensive drugs are now being introduced for conditions that affect millions of people rather than thousands.”
  • “Drug prices are increasing more rapidly than their benefits.”

Dr. Chin counters that there have been more than 500 new medications that have been approved in the United States since 2000.

  • “The United States relies on competitive markets to set prices and encourage innovation —a system that, as I see it, is working well.”
  • “The…hepatitis C medications, with cure rates above 90% are a good case study: within a year, competing medications entered the market, driving down prices by about half.”
  • “Any centralized government-purchasing model would probably result in drastically limited choices for physicians and patients.”

Another “must-read” on this topic comes from Ezekiel Emmanuel & the NY Times: I Am Paying for Your Expensive Medicine  Here’s an excerpt:

In July, the Food and Drug Administration approved the first of two new PCSK9 inhibitors that lower the bad type of cholesterol, LDL. Studiessuggest that they can reduce it by up to 60 percent, … and reduce it up to 36 percent more than statins… However, there are no definitive data on how much these drugs actually reduce heart attacks, strokes and deaths from heart disease…the retail price for a prescription would be more than $14,000 per patient per year. The price is particularly steep given that these drugs may need to be taken for the rest of the patients’ lives. How much patients pay directly would depend on their insurance plan….even if the price came down to about $11,000 per patient per year, and only 1.1 million of the roughly 23 million middle-age Americans with high cholesterol actually took these drugs, the bill would be so high that for a typical insurance plan, “annual insurance premiums would increase by $124 for every person” in the insurance plan…

As the PCSK9 story is making clear, the drug cost debate is now beginning to focus on two questions that are currently unresolved: First, how do we determine value so the perspectives of all Americans are considered? Second, how do we implement and enforce that determination of value?…

Many people hope that the drug industry will self-regulate, using value-based pricing of its new drugs. But if past experience is any indication of future behavior, self-regulation may be a pipe dream. 

My take: I don’t agree with Dr. Chin that our system has the right balance at this time, though he is right that too much interference could slow innovation.  In my view, recent high-profile excesses by pharmaceutical companies have strengthened the argument for more government intervention.

Morning in Sandy Springs

Morning in Sandy Springs

 

Dietary Diversity in Infants

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A recent study (Woo JG et al. J Pediatr 2015; 167: 969-74) indicates that breastfed infants in a US cohort had lower dietary diversity at 6-12 months of age than a cohort from Shanghai and Mexico City.

The diversity of consumed foods helps ensure intake of all necessary macro- and micronutrients.  One indicator, the “minimum dietary diversity” (MDD) developed by the World Health Organization has been used.  Infants meeting MDD standards between 6-23 months are less likely to experience stunting.

Key findings:

  • “Only 28% of Cincinnati [US cohort] infants fed >50% human milk achieved MDD between 6 and 12 months.”
  • Across all cohorts, dietary diversity increased from 31% at 6 months of age to 92% at 12 months of age.
  • Shanghai infants had the highest diversification, “largely accounted for by significant consumption of eggs”

This study shows that some of previous recommendations, prior to 2008, to avoid foods like eggs and peanuts to lessen atopic disease/food allergies may have affected introduction of a more diverse diet.  Newer data has shown that earlier introduction of foods lessens the likelihood of food allergies.

The associated editorial (pg 952-53) notes that despite the ‘breast is best’ philosophy, that “if this principle is taken to extreme and introduction of nutrient dense complementary foods is delayed well past 6 months of age, the extensively breastfed older infant is at risk for suboptimal intakes of multiple micronutrients, anemia, growth faltering, and other poor health outcomes.”

From recent painting class (it's an improvement from stick figure drawing)

From recent painting class (it’s an improvement from stick figure drawing)

“I’ve Got the Best Doctor”

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In numerous conversations, I have had heard from friends and family that “I’ve Got the Best Doctor.”  For everyone who thinks that, here’s a good read by Ezekiel Emanuel in NY Times:

“Are Good Doctors Bad for Your Health?”

Here’s an excerpt:

One of the more surprising — and genuinely scary — research papers published recently appeared in JAMA Internal Medicine. It examined 10 years of data involving tens of thousands of hospital admissions. It found that patients with acute, life-threatening cardiac conditions didbetter when the senior cardiologists were out of town. And this was at the best hospitals in the United States, our academic teaching hospitals. As the article concludes, high-risk patients with heart failure and cardiac arrest, hospitalized in teaching hospitals, had lower 30-day mortality when cardiologists were away from the hospital attending national cardiology meetings. And the differences were not trivial — mortality decreased by about a third for some patients when those top doctors were away…

One possible explanation is that while senior cardiologists are great researchers, the junior physicians — recently out of training — may actually be more adept clinically. Another potential explanation suggested by the data is that senior cardiologists try more interventions…

One thing patients can do is ask four simple questions when doctors are proposing an intervention, whether an X-ray, genetic test or surgery. First, what difference will it make? Will the test results change our approach to treatment? Second, how much improvement in terms of prolongation of life, reduction in risk of a heart attack or other problem is the treatment actually going to make? Third, how likely and severe are the side effects? And fourth, is the hospital a teaching hospital?

My take: Perhaps some of the differences in outcome are related to severity of illness that more experienced physicians may manage.  Nevertheless, it is clear that the reputation of the physician does not correlate well with clinical outcomes.

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Improving Outlook in Neonatal Nutrition (Part 2)

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Besides arguing for more aggressive and earlier use of intravenous protein, Dr. Adamkin noted that newer lipid emulsions (eg. SMOFlipid) are likely to be helpful due to the concentrations of docosahexaenoic acid (DHA) and arachidonic acid (ARA).  DHA and AA are the two main long chain polyunsaturated fatty acids (LCPUFAs) and are integral to the structural membranes of cells in the central nervous system and retina.

Slow Evolution of Lipid Emulsions

Slow Evolution of Lipid Emulsions

Decreasing Incidence of Growth Failure with More Aggressive Nutrtion

Decreasing Incidence of Growth Failure with More Aggressive Nutrition –average daily protein intake in most recent cohort during 1st 5 days is 3 g/kg/day (much higher than in previous years

At U of L, they have developed a quick card to calculate glucose infusion rate based on dextrose and fluid volume (mL/kg/day)

At U of L, they have developed a quick card to calculate glucose infusion rate based on dextrose and fluid volume (mL/kg/day)

Other points:

  • SGA infants have low lioprotein lipase –>higher triglycerides
  • Slow lipid infusion associated with better tolerance
  • Insulin may be needed if not able to provide a glucose infusion rate of at least 4 mg/kg/min; otherwise, he recommends avoiding insulin.
  • Dr. Adamkin recommended adding carnitine after 4 weeks of TPN
  • During transition to enteral feeding, in order to continue with 3.5-4 g/kg/day of amino acids, many infants will need a stock solution of IVFs with supplemental amino acids to supplement enteral feeds

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Improving Outlook in Neonatal Nutrition (Part 1)

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I recently had the opportunity to hear a terrific lecture by David Adamkin (University of Louisville) on neonatal nutrition.  Unlike previous lectures that I’ve highlighted on this blog (Neonatal Nutrition Lecture -What We Know Right Now …) which focused on enteral nutrition and breastmilk.  This lecture focused on providing early parenteral nutrition to prevent postnatal growth failure.

"Father" of TPN was Stanley Dudrick (1968)

“Father” of TPN was Stanley Dudrick (1968)

Introduction of TPN dramatically improved survival for many infants.  In disorders like gastroschisis, TPN increased survival from ~10% to 90%.

Extreme premature infants have minimal energy reserves

Extreme premature infants have minimal energy reserves

At 24-28 weeks gestational age, fetuses are ‘bathed in amino acids’ and extreme premature infants need early amino acids.  At University of Louisville, the neonatologists try to deliver ~3 gm/kg/day of amino acids in 1st 1-2 days in order to match intrauterine growth and prevent growth failure. Half of postnatal weight loss is water; other half is related to proteolysis.  To facilitate TPN at all hours, they use a stock solution (4% amino acids at 60 mL/kg/day delivers 2.4 mg/kg/day of protein; 80 mL/kg/day delivers 3.2 mg/kg/day of protein.

Return to Birth Weight Time is Correlated with Growth Failure

Return to Birth Weight Time is Correlated with Growth Failure.  Extreme prematurity has been correlated with slower return to birth weight

Screen Shot 2015-11-11 at 10.59.04 PM

Lack of correlation between BUN and Protein Intake

Lack of correlation between BUN and Protein Intake

BUN increases with any protein intake but not affected by protein intake -issue has to do renal fxn, comorbidity.  Smaller & sicker have higher BUN.

Key points:

  • The more premature, then the longer it takes to return birth weight and more growth failure
  • Poor growth related to neurodevelopment outcomes
  • With higher protein intake, there is better glucose tolerance; protein intake helps with glucose tolerance & lowers chance of hyperkalemia

More tomorrow…

Henoch-Schonlein Purpura and Neurologic Manifestations

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Briefly noted:

Stefek B, et al. J Pediatr 2015; 167: 1152-4.  This study reports on an 8-year-old with Henoch-Schonlein purpura (HSP) who developed posterior reversible encephalopathy syndrome (PRES).  The authors state that neurologic manifestations develop in 2-8% of patients with HSP; of these patients, 20% suffer long-term effects.

Also, in commentary to my post on Thursday, one blog follower pointed out that the Fred Hollows Foundation is another charitable organization dedicated to restoring eyesight and has been doing this for a long time.

Atlanta Botanical Gardens

Atlanta Botanical Gardens