Headlines and Shorts for IBD and IBS

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“Higher Levels of Knowledge Reduce Health Care Costs in Patients with Inflammatory Bowel Disease.” Inflamm Bowel Dis 2015; 21: 615-22.  This retrospective observational cohort study asked 91 patients to complete a questionnaire about their knowledge on the disease after 1 year of follow-up. The authors noted an association between higher levels of knowledge and lower health care costs. While their are many limitations to this study, it is hard to argue with the conclusion that better education is worthwhile; it may also improve outcome and costs.

“Surgery and Postoperative Recurrence in Children with Crohn Disease.” Hansen LF et al. JPGN 2015; 60: 347-51. In a retrospective study dating back to 1978, the authors noted a high recurrence of surgery in children (n=115) with Crohn disease (CD).  More than 1 bowel resection was needed in 39%. The use of biologics occurred late in the study and its potential effect on lowering recurrent resection is unclear in this study. Related post:  More Lessons in TNF Therapy (Part 1) | gutsandgrowth

“Risk of Drug-Induced Liver Injury from Tumor Necrosis Factor Antagonists.” Bjornsson ES, et al. Clin Gastroenterol Hepatol 2015; 13: 602-08.  9 cases of DILI associated with infliximab (1 in 120 patients), 1 case (of 270) with adalimumab, and 1 case (of 430) associated with etanercept. 8 of 11 patients who were tested for ANA were positive. DILI was treated with steroids in 5 patients. 8 patients went on to receive a different anti-TNF without recurrent liver dysfunction. Related blog posts:

“The Prevalence of Intestinal Parasites is Not Greater Among Individuals with Irritable Bowel Syndrome: A Population-based Case-control Study” Clin Gastroenterol Hepatol 2015; 13: 507-13. Related post: Does it make sense to look for parasites in RAP …

Gastritis –Not Due to Helicobacter pylori

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A gastroenterologist identifying gastritis or an ulcer due to Helicobacter pylori is akin to an emergency room doctor treating a nursemaid’s elbow.  In both cases, identifying the cause allows for effective treatment and families are typically quite grateful. But what about the cases of Helicobacter-negative gastritis.  This is less straightforward.

A recent study (Genta RM, Sonnenberg A. Aliment Pharmacol Ther 2015; 41: 218-26 thanks to Ben Gold for this reference) provides some helpful data.  From a pathology national database, the authors reviewed 895,323 patient records from individuals with gastric biopsies (2008-2014).

Key findings:

  • 10.6% had Hp-gastritis. The prevalence of Hp-gastritis declined mildly from 11.2% in 2008 to 9.9% in 2014.
  • 1.5% had Hp-negative gastritis.  The prevalence of Hp-negative gastritis declined from 2.1% in 2008 to 1.1% in 2014.
  • In patients with Hp-negative gastritis who underwent a repeat endoscopy, on average 18 months after index biopsy, 7.4% had detectable Helicobacter pylori.  Thus, a small number of Hp-negative gastritis may represent a missed infection.
  • The authors note that only 3.5% of Hp-negative gastritis was associated with inflammatory bowel disease (IBD).

It is well-recognized that there are many limitations with analyzing databases.

Take-home message: Given the limited amount of information about Hp-negative gastritis, this study is helpful by indicating that only a small fraction represent a missed case of H pylori and a smaller fraction have coexistent IBD.  With improvements in microbiology, perhaps more clarity will emerge to determine what Hp-negative gastritis is rather than what it isn’t.

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No Effect of Proton Pump Inhibitors and Irritability on Crying in Infants

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While the title of this blog will come as no surprise to most pediatric gastroenterologists, many parents would be surprised that a systemic review of randomized controlled trials (RCTs) showed` that proton pump inhibitors (PPI) are ineffective for crying infants (J Pediatr 2015; 166: 767-70).

In this review, only five trials (with 430 infants) met the prespecified inclusion criteria.  While some trials showed a decrease in crying/irritability form baseline to the end of the intervention, a similar effect was evident in the control group.  The authors found that one trial reported a higher risk of lower respiratory tract infections in the PPI group and note that “administration of PPIs is not without risk.”

Take-home message: “the limited data available suggest that PPIs are not effective for the management of crying/irritability in infants.”

Another PPI citation: Rosen R et al. J Pediatr 2015; 166: 917-23.  In this study, the authors prospectively showed that PPI use was associated with differences in gastric, lung, and oropharyngeal microflora (n=116 children with 59 receiving PPIs)

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Behavioral Economics and Insurance Exchanges

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A recent commentary (NEJM 2015; 372: 695-98) explains how information provided on healthcare exchanges influences choices on coverage and what types of modifications could help improve these decisions.

Current plans are categorized as Bronze, Silver and Gold based on monthly premiums and out-of-pocket expenses (Related link: Understanding Plans on Healthcare.gov).  Gold plans are characterized by higher monthly premiums and lower out-of-pocket expenses.  However, the authors sampled a group of people.  They found that plans that are labeled as “gold” were preferred by the majority whether the plans had higher monthly premiums and lower out-of-pocket expenses or the reverse (low monthly premiums and higher out-of-pocket expenses).  Rather than using “gold,'” “silver,” or “bronze,” their recommendation would be to provide more practical information by providing estimates of annual costs with best-case and worst-case scenarios.

On many exchanges, the plans are listed by order of lowest monthly premiums to highest monthly premiums.  “When people make choices, they often settle for options at the top of a menu…for example, all else being equal, politicians listed at the top of ballots receive more votes than those whose names appear lower on the list.” Also, using monthly premium differences rather than weekly premium differences also influences choices. Thus, even the innocuous design of a website, could adversely influence the selection of the best plan for a given participant.

Bottomline: If the affordable care act and health exchanges are not eliminated, improving the presentation of information could help many participants get the health coverage that actually meets their needs.

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An Apple a Day …

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According to research, published in JAMA Internal Medicine (April 1st edition –done for fun and “is very tongue in cheek”) an apple a day does not “keep the doctor away.”

Here’s an excerpt from USA Today summary:

At first glance, data on 8,728 U.S. adults looked like it might uphold the saying: The 9% who ate at least one small apple daily were less likely to visit doctors several times a year….They adjusted their statistics to account for ways other than apple-eating that “apple eaters might be very different from everyone else,” Davis says. For example, they found apple lovers were less likely to smoke, were more educated and were less likely to be white than the 91% of the population eating less than an apple a day.

After adjusting for those factors, they found daily apple-eaters were just as likely as otherwise similar individuals to go to doctors…Other studies have found numerous possible health benefits associated with apple consumption, including weight loss, reduced cancer risk and improved cardiovascular health.

Empathy vs. Sympathy

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A short animated video from Brene Brown/Katy Davis (thanks to Kayla Lewis for this link) helps explain the difference between empathy and sympthany.  Here’s the link: Short Video on Empathy (the animation is not that great but the message is important)

Key points:

  • Empathy brings people to together and sympathy often drives people apart.
  • Empathy never begins with “at least” …it wasn’t worse
  • Sometimes empathy means saying ‘I don’t know what to say but I’m glad you told me.’

Harrison Ford defines Sympathy in 42 – YouTube.  In the movie “42,” Harrison Ford’s character describes sympathy as being derived from the Greek word to suffer together.  In many cases, sympathy can be difficult to distinguish from pity; this is one reason why empathy can be much more helpful.

Unrelated (but interesting): Comic Version Graphic Points Need for Discussions DNR

Here’s one frame:

From Annal of Intern Medicine Twitter Feed

From Annal of Int Med Twitter Feed

Vaccine Proven Effective for Hepatitis E

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An important advance in Hepatology -more data showing efficacy of a Hepatitis E vaccine (N Engl J Med 2015; 372:914-922).

Here’s the abstract:

BACKGROUND

Hepatitis E virus (HEV) is a leading cause of acute hepatitis. The long-term efficacy of a hepatitis E vaccine needs to be determined. 

METHODS

In an initial efficacy study, we randomly assigned healthy adults 16 to 65 years of age to receive three doses of either a hepatitis E vaccine (vaccine group; 56,302 participants) or a hepatitis B vaccine (control group; 56,302 participants). The vaccines were administered at 0, 1, and 6 months, and the participants were followed for 19 months. In this extended follow-up study, the treatment assignments of all participants remained double-blinded, and follow-up assessments of efficacy, immunogenicity, and safety were continued for up to 4.5 years. 

RESULTS

During the 4.5-year study period, 60 cases of hepatitis E were identified; 7 cases were confirmed in the vaccine group (0.3 cases per 10,000 person-years), and 53 cases in the control group (2.1 cases per 10,000 person-years), representing a vaccine efficacy of 86.8% (95% confidence interval, 71 to 94) in the modified intention-to-treat analysis. Of the participants who were assessed for immunogenicity and were seronegative at baseline, 87% of those who received three doses of the hepatitis E vaccine maintained antibodies against HEV for at least 4.5 years; HEV antibody titers developed in 9% in the control group. The rate of adverse events was similar in the two groups.

CONCLUSIONS

Immunization with this hepatitis E vaccine induced antibodies against HEV and provided protection against hepatitis E for up to 4.5 years. (Funded by the Chinese Ministry of Science and Technology and others; ClinicalTrials.gov number, NCT01014845.)

Related blog post:

Briefly noted:

Experience with molecular adsorbent recirculating system (MARS). Lexmond WS, et al. Liver Transpl 2015; 21: 369-80. Editorial 277-78. n=20 over 10 years. From the editorial: “Although MARS therapy has been available for more than a decade, there have been no randomized controlled trials of its use in children…the time has come to get the data necessary to prove whether MARS has utility or not.” Related blog post: Living on MARS | gutsandgrowth

“Unrecognized Chronic Hepatitis C Virus Infection Among Baby Boomers in the Emergency Department.” Hepatology 2015; 61: 776-82. 102 of 1529 individuals were confirmed to have HCV infection. Interestingly, only 54% were successfully contacted by phone and of these only 21 had attended their initial visit with a liver specialist. Related blog post: Wiping out Hepatitis C | gutsandgrowth

From NY Times Twitter Feed (screenshot)

From NY Times Twitter Feed (screenshot)

Unrelated story/link (from NY Times): FDA Slow to Act on Diet Supplement Dangers

 

UTI in Infancy–New Risk Factor for Chronic Abdominal Pain?

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A recent study (Rosen JM, et al. JPGN 2015; 60: 214-16) identifies a history of a urinary tract infection (UTI) in infancy as a risk factor for development of chronic abdominal pain.

The authors identified 57 patients with a history of UTI during the first year of life and compared them to 58 sibling controls.  Mean age of UTI was 4.8 months and mean time since UTI was 9.3 years.

Key finding:

  • Chronic abdominal pain was noted in 10 (17.5%) of patients with prior UTI compared with 2 (3.4%) of controls (P=0.02)

The authors state that this is the first study showing an infection outside the GI tract could increase the risk of chronic abdominal pain.  It is not clear to me if the UTI would truly be a sensitizing factor or whether other factors like the administration of antibiotics could play a role.

Bottomline: While this is a small study and the incidence of chronic abdominal pain was fairly low in both groups, it suggests that a history of a UTI may be a risk factor for recurrent abdominal pain; a bigger study is needed to validate these findings.

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From Twitter

Trending on Twitter -CampWeeKanEatIt Shoutout

Mongerson -Phase II Data Available in NEJM

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Previously, this blog noted that a phase II study showed that Mongerson, an oral SMAD7 antisense oligonucleotide, had promising data for moderate-to-severe Crohn’s: An Oral Oligonucleotide in the Crohn’s Treatment Pipeline …

The study has now been been published: NEJM 2015; 372: 1104-13.  Among patients who received 40 mg and 160 mg of mongerson, remission (CDAI <150) at 15 days was achieved in 55% and 65% respectively compared to 12% for 10 mg dose and 10% for placebo group.

The associated editorial (pg 1166-67) notes that only 18% of the patients with elevated C-reactive protein and randomized to the 40 mg and 160 mg doses normalized these levels at the end of the treatment period.  Thus, further trials will need to look more closely at objective biomarkers.

Unrelated but interesting -from John Pohl & Bryan Vartabedian’s twitter feeds:  “Food Babe” Exposed as a Fraud

How Likely is Celiac Disease if My TTG Test Is Only a Little Bit Abnormal?

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A terrific celiac serology study (Gidrewicz D, et al.Am J Gastroenterol 2015; -advanced online publication doi: 10.1038/ajg.2015.87) helps answer questions about the utility of serology in making diagnostic decisions. (Thanks to corresponding author J Decker Butzner for sharing reference.)

Using consecutive samples in a laboratory database with 17,505 patients, the authors retrospectively examined the performance of the tissue transglutaminase (TTG), endomysial antibody (EMA) tests and the ESPGHAN celiac guidelines for nonbiopsy diagnosis of celiac disease.  Among this large cohort, 775 with positive TTG and 574 with a negative TTG were biopsied.

Key findings:

  • If the TTG >10-fold the upper limit of normal (ULN) along with a positive EMA and symptoms were present, 98.2% had biopsies consistent with celiac disease.
  • If the TTG was 3-10-fold-ULN along with positive EMA, then 75.7% had biopsies consistent with celiac disease.  The histology of celiac disease (CD) was present in only 40% of the TTG 3-10-fold ULN if EMA was negative.
  • If the TTG was 1-3-fold-ULN along with positive EMA, 52.2% had CD-positive histology, whereas CD-positive histology was evident in only 13.3% of TTG 1-3-ULN if EMA was negative.
  • IgA deficiency is common in CD (“1in 60 vs 1 in 700” in general population)

Implications & Take-home points:

  • The researchers note that the positive predictive value of TTG drops when the prevalence of CD in the testing population is lower.  Thus, in their population and most clinical practice where the prevalence is below 35-40%, the PPV of the TTG-based tests drops to <80%.
  • While TTG-based tests have high specificity, there are multiple medical conditions that can cause a false positive (additional reference below), including autoimmune diseases like diabetes mellitus, inflammatory bowel diseases as well as infections, and liver disorders.
  • Asymptomatic patients with low TTG titers and negative EMA may benefit from following celiac serology rather than proceeding immediately to intestinal biopsy.
  • Using ESPGHAN nonbiopsy criteria (symptomatic child, TTG ≥10 ULN, positive EMA, positive HLA typing), there were four patients whose initial biopsies were not consistent with CD.  Thus these criteria identified 98.2% accurately who did not need an intestinal biopsy.  One of these four developed CD subsequently.  To achieve 100% PPV for non biopsy, the authors note that one would need an EMA titer ≥1:80.
  • Study limitations: retrospective study, lack of standardization between TTG assays

Bottomline: EMA improves the PPV of TTG testing, especially when low titer elevations are noted.  TTG alone is a highly sensitive test “with a 99.4% negative predictive value” in this study.

Related study: “Serum Anti-Tissue Transglutaminase Antibodies Detected during Febrile Illness May Not be Produced by the Intestinal Mucosa” J Pediatr 2015; 166: 761-3.  This case report describes two children with abnormal TTG (one more than 20-fold ULN)) both were EMA-negative. No mucosal anti-TTG was identified using two immunoassays.

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