The Rise of Eosinophilic GI Diseases –Not Likely Connected to Helicobacter Pylori

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A recent prospective case-control study (J Molina-Infante et al. Am J Gastroenterol 2018; 113: 972-9 -thanks to Ben Gold for this reference) examined the potential connection between Helicobacter pylori and eosinophilic GI diseases.  They examined 808 individuals (404 cases of eosinophilic esophagitis [EoE], 404 controls). Key findings:

  • H pylori prevalence was not different between cases and controls (37% vs. 40%, odds ratio 0.97).  The authors conclude that H pylori which has declined in prevalence globally is not inversely associated with EoE as had been suggested in some previous reports

In an associated editorial, (pg 941-4), the authors note that there has been a dramatic increase in atopic diseases over the past 30 years.  One hypothesis has suggested that these epidemiologic changes are related to a changing microbiome.  This in turn may be related to frequent antibiotic usage.  An example of the proliferation of antibiotics: “20-25% of Swedish adults receive an antibiotic prescription annually.”

While H pylori may be a biomarker associated with poor hygiene/less antimicrobial exposure, it does not appear to be directly related to EoE.  The authors indicate that until we have a better understanding, “in the meantime attention to healthier diets and minimizing antibiotic exposure may optimize public health in terms of atopic disease risk.”

My take: Since our genetics do not change quickly, the dramatic changes in disease frequency of conditions like EoE and Crohn’s disease must be influenced by environmental exposures.  How to lower the risk of these conditions remains uncertain.

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Gastric Residual Volumes in Premature Infants

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Briefly noted: B Singh et al. J Pediatr 2018; 200: 79-83.  In this study of 87 infants witth birth weights 1500-2000, avoiding routine assessment of gastric residual volumes before feeding advancement did not shorten the time to reach full feeds.  However, checking these residuals provided no clear advantages and have some potential disadvantages:

  • Time-consuming to check and may inaccurate depending on size/location of orogastric/nasogastric tube
  • Discarding gastric contents results in loss of gastric enzymes and acid

The authors note that prior studies have shown that gastric residuals are “unreliable predictors of feeding intolerance” studies have had discrepancies with regard to whether they are predictive of necrotizing enterocolitis.

Related blog post: When to Check Gastric Residuals in Preterm Infants

“Transparency Hasn’t Stopped Drug Companies From Corrupting Medical Research”

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NY Times Commentary by Marcia Angell: Transparency Hasn’t Stopped Drug Companies From Corrupting Medical Research

Dr. Angell, a former editor of the New England Journal of Medicine examines the recent outrage regarding Dr. José Baselga who resigned from his position as chief medical officer at Memorial Sloan Kettering Cancer Center after “ProPublica and The New York Times revealed that he’d received millions of dollars from drug and device companies … Most of his outside income was not disclosed to the journals in which he published, in violation of their requirements.”  Dr. Baselga has had a huge impact in cancer research; his work led to the discovery of Herceptin, a widely used treatment for breast cancer.

  • She argues that disclosure alone is not sufficient to prevent pharmaceutical companies from corrupting research:
  • “Drug company involvement biases research in ways that are not always obvious, often by suppressing negative results. A review of 74 clinical trials of antidepressants, for example, found that 37 of 38 positive studies — that is, studies that showed that a drug was effective — were published. But 33 of 36 negative studies were either not published or published in a form that conveyed a positive outcome.”
  • “Bias can also be introduced through the design of a clinical trial. For example, the sponsor’s drug may be compared with another drug administered at a dose so low that the sponsor’s drug looks more powerful.”
  • “Disclosure is better than no disclosure, but it does not eliminate the conflict of interest. It’s simply a way of … leaving it to readers to decide whether the research was biased. But most people — even doctors and science reporters — aren’t really equipped to make those judgments, particularly when data are suppressed.”
  • She argues that drug companies should have “no control over the design, interpretation and publication of trial results” and that “doctors should not accept gifts from drug companies, even small ones, and they should pay for their own meetings and continuing education, as is standard in other professions.”

My take (borrowed from author): “we should not let drug companies buy the hearts and minds of researchers. The cost of this is high, and not just in drug prices. It means both doctors and patients believe prescription drugs are better and safer than they really are.”

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Anemia in Pediatric Inflammatory Bowel Disease

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A recent retrospective study (G Aljomah et al. JPGN 2018; 67: 351-5) provides some useful information about anemia in the pediatric inflammatory bowel disease (IBD) population. This study included 153 patients, though the diagnostic tests varied considerably; for example, only 42 patients had a serum transferrin receptor (sTR) assay available at followup.

Key points:

  • 67.3% of patients had anemia at diagnosis.  38.5% had anemia of chronic disease (ACD) and the remainder had either iron deficiency anemia (IDA) or IDA in combination with ACD.
  • 20.5% had anemia at followup approximately 1 year after diagnosis. 5.1% with ACD alone and 15.4% had IDA or IDA in combination with ACD.
  • In a subset of patients with more complete data, it was shown that anemia was much more common in patients with Crohn’s disease: 91.2% at diagnosis and 27.3% at followup compared with patients with ulcerative colitis with 40.0% at diagnosis and 7.7% at followup.

The authors used the sTR index (sTR/log ferritin index) to determine if ACD was present.  “This index can differentiate IDA from ACD; however, it cannot separate IDA from the combination of IDA/ACD.  IDA or IDA/ACD were considered to be present if the sTR index was greater than 1.03. An sTR index of <1.03 was taken to be indicative of the presence of ACD.”

Briefly noted: MR Serpico et al. JPGN 2018; 67: 341-5.  This retrospective study  examined the use of allopurinol to optimize thiopurine levels.  32 of 52 patients remained on the combination for 1 year.  In this group, median alanine transaminase decreased to 19 from 77 (P<0.001) and median 6-TG levels increased to 322 from 166 (P<0.001). In addition, steroid-free remission rates improved to 82% (23 of 28).  About 40% of the initial cohort of 52 patients were switched to antitumor necrosis factor therapy.

My take: The initial study shows that anemia is frequent in pediatric IBD, especially at diagnosis (67%).  Even at followup, 20% of patients had ongoing anemia.

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Does PPI Use Increase Pneumonias in Otherwise Healthy Infants?

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A recent study (M-L Blank, et al. JPGN 2018; 67: 335-40) showed that proton pump inhibitors (PPIs) do not appear to increase the risk of pneumonia in otherwise healthy infants.

This study used a cohort of 21,991 patients (2005-2012) in New Zealand and examined the use of a PPI (omeprazole, lansoprazole, or pantoprazole) and its association with lower respiratory tract infections (566 validated cases) and 65 cases of radiography-confirmed community acquired pneumonia (CAP).  For each LRTI and each CAP, there were 10 matched controls.

Key findings:

  • Neither current nor recent use of a PPI was associated with an increased risk of CAP or LRTI resulting in hospitalization or death.
  • The matched odds ratio for CAP with current or past use of PPI was 0.88 and for all LRTI cases the matched odds ratio was 1.13.

My take: This study indicates that PPIs are unlikely to contribute to respiratory infections in otherwise healthy infants.  The larger question is how many of these infants really should be receiving PPIs and what other adverse consequences that may occur.

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Does Gastrostomy Tube Prolong Life in Rett Syndrome?

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A recent study (K Wong et al. J Pediatr 2018; 200: 188-95) examined a longitudinal cohort of 323 females in the Australian Rett Syndrome Study.

Key findings:

  • 30.3% of the cohort underwent gastrostomy placement
  • BMI was greater in individuals with gastrostomy placement
  • Median age of gastrostomy placement was 9 years
  • The all-cause mortality rate was greater in those who had gastrostomy placement compared with those who had not (hazard ratio 4.07, CI 1.96-8.45)
  • Survival: 66.1% of the entire cohort was alive at 20 years of age (median survival was 33 years). The survival was 87.3% in those without a gastrostomy.
  • Placement of a gastrostomy tube was not associated with fewer hospitalizations or improvement in parental physical or mental health

While the mortality was higher in those who received a gastrostomy tube, the study’s nonrandomized design does not allow definitive assessment of whether a gastrostomy tube is detrimental to long-term survival.  Children who received gastrostomy tube may have had additional comorbidities.

My take: In adult medicine, it is generally accepted that Gtube placement does not prolong life (Clin Gastro & Hep 2007; 5: 1372).  This study indicates that a Gtube may not improve longevity in many pediatric disorders as well.

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Clinical Evaluation Not Sensitive for Aspiration

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A recent retrospective study (in press): abstract link: Presenting Signs and Symptoms do not Predict Aspiration Risk in Children DR Duncan et al. J Pediatr 2018;  https://doi.org/10.1016/j.jpeds.2018.05.030

From Boston Children’s Hospital Notes (9/12/18):

  • More than 80 percent of aspiration was silent
  • Rosen, Duncan and colleagues also found that observed feedings, even by very skilled clinicians, are not sensitive enough to diagnose aspiration in children because of the high rates of silent aspiration. Based on statistical analyses, the degree of agreement between observed feeding and the VFSS was poor for the diagnosis of aspiration.
  • Almost a third of the patients experienced symptoms during or after meals, which may help explain why physicians frequently misdiagnose oropharyngeal dysphagia with aspiration as gastroesophageal reflux disease (GERD).

Full abstract:

Objectives

To determine if any presenting symptoms are associated with aspiration risk, and to evaluate the reliability of clinical feeding evaluation (CFE) in diagnosing aspiration compared with videofluoroscopic swallow study (VFSS).

Study design

We retrospectively reviewed records of children under 2 years of age who had evaluation for oropharyngeal dysphagia by CFE and VFSS at Boston Children’s Hospital and compared presenting symptoms, symptom timing, and CFE and VFSS results. We investigated the relationship between symptom presence and aspiration using the Fisher exact test and stepwise logistic regression with adjustment for comorbidities. CFE and VFSS results were compared using the McNemar test. Intervals from CFE to VFSS were compared using the Student ttest.

Results

A total of 412 subjects with mean (±SD) age 8.9 ± 6.9 months were evaluated. No symptom, including timing relative to meals, predicted aspiration on VFSS. This lack of association between symptoms and VFSS results persisted even in the adjusted multivariate model. The sensitivity of CFE for predicting aspiration by VFSS was 44%. Patients with a reassuring CFE waited 28.2 ± 8.5 days longer for confirmatory VFSS compared with those with a concerning CFE (P < .05).

Conclusions

Presenting symptoms are varied in patients with aspiration and cannot be relied upon to determine which patients have aspiration on VFSS. The CFE does not have the sensitivity to consistently diagnose aspiration so a VFSS should be performed in persistently symptomatic patients.

My take: This study provides more data indicating that clinical evaluations are not reliable in children less than 2 years of age to exclude formal swallow study evaluations and that some symptoms attributed to reflux are in fact due to aspiration.

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