“Aging Elephant in the Room”

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Happy New Year!

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“Adults are just obsolete children” –Theodor Seuss Geisel

So, begins an interesting commentary (B Kinnear. JAMA pediatrics 2015; 169: 1081-2 -thanks to Ben Gold for this reference).

This editorial discusses a growing problem of patients older than 21 years of age seeking care in pediatric institutions.  Currently, ~15,000 admissions occur annually in the U.S..  At the author’s institution (Cincinnati Children’s), the average daily hospital census was 15.7 patients between 2012-2014.  In fact, at Cincinnati, which has an adult care hospital across the street, they have developed a team to care for these patients: “the Hospital Medicine Adult Care team.” In addition, they have established protocols to recognize and initiate treatment on problems like acute coronary syndrome, pulmonary embolism, and acute stroke.

The author argues that age should not be the only factor determining which institution would offer the best care.  Some cognitively impaired adults with cerebral palsy may be better-suited at a pediatric facility and some obese teenagers with type 2 diabetes and hypertension may fit better at an adult care hospital.

Common barriers to transitioning to adult care hospitals:

  • Lack of adult health care professional knowledge and comfort by adult health care physicians
  • Poor communication between pediatric and adult care providers
  • Families fear of leaving established care settings

These adults in pediatric care settings do have increased length of stays and greater odds of mortality than adolescents, even when adjusting for  the increased number of chronic conditions.  Thus, it is not entirely clear that outcomes will be improved by retaining this vulnerable population at pediatric institutions.  Much of this question will be determined by the institutional resources available for their care.

My take: I worry that keeping adults (patients >21 years) in pediatric institutions is a mistake.  There are increasing numbers of vulnerable patients and their needs should be addressed by adult care providers.

Isle of Palms, SC

Isle of Palms, SC

My Favorite Posts 2015

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I want to thank all of those who have provided input to this blog this year.  Best wishes to all for a happy and healthy 2016.

Here’s my list of favorite posts in the past year:

On being a doctor:

Nutrition posts:

Gastroenterology posts:

IBD posts:

Liver posts:

Screen Shot 2015-12-09 at 8.21.20 PM

Popular Posts 2015

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Today and tomorrow I am posting the most popular posts and my personal favorite posts from 2015.  I am labeling the most popular posts as those posts that had the highest number of visits in the past year.

Most popular posts:

Shem Creek, SC

Shem Creek, SC

‘Don’t Believe Our Study’

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The message I inferred from a recent study (CA Siegel et al. Clin Gastroenterol Hepatol 2015; 13: 2233-40) was to disregard their results which generally showed a lack of benefit of combination therapy (aka “concomitant immunomodulator” or dual therapy) compared with anti-tumor necrosis factor (anti-TNF) monotherapy for Crohn’s disease.

Specifically, the authors state the following in their discussion:

Although our results challenge the clinical importance of combination therapy in this specific scenario, it is hard to ignore the preponderance of data to date relating to the pharmacokinetics of anti-TNF medications that support the approach of combination therapy over monotherapy.

Here’s the background for this study.  The authors performed a meta-analysis of placebo-controlled trials (n=1601 subjects) to examine the question of whether continued use of immunomodulators (IMs) would be of benefit in patients who had failed monotherapy with IMs (“IM-experienced”).  The authors note that the SONIC study showed that combination therapy (infliximab and azathioprine) was more beneficial in patients who were IM-naive than monotherapy.  This meta-analysis included data from 3 anti-TNF agents: infliximab, adalimumab, and certolizumab.

Key findings:

  • Combination therapy was no more effective than monotherapy in inducing 6-month remission (odds ratio 1.02) or in maintaining a response (OR 1.53).
  • In subgroup analysis, there was a statistically-significant protective effect of baseline IM exposure versus no baseline IM exposure among those treated with infliximab.
  • Generally, combination therapy was not associated with any change in adverse reactions; however, combination therapy with infliximab had lower adverse events, which was driven by infusion reactions.

My take: This study indicates that combination therapy is likely helpful in IM-experienced patients who are starting infliximab and possibly not effective with the other anti-TNF agents.  The authors emphasize the need for well-designed, prospective, randomized, placebo-controlled trial for a definitive answer.  Until then, don’t believe their study.

Of interest: Recently I became aware of a college scholarship opportunity for young adults with IBD: Abbvie Scholarship Program.

Related blog posts:

Clever Marketing or Truth in Advertising?

Clever Marketing or Truth in Advertising?

Yosemite National Park

Yosemite National Park

Should Teenagers with Severe NAFLD Undergo Bariatric Surgery?

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A recent commentary (Stavra A. Xanthakos and Jeffrey B. Schwimmer. Nat Rev Gastroenterol Hepatol. 2015 Jun; 12(6): 316–318.) discusses the role of bariatric surgery for teenagers with severe nonalcoholic fatty liver disease (NAFLD).  Full text Link: On a knife-edge—weight-loss surgery for NAFLD in adolescents.

Here’s an excerpt:

Abstract: A new position statement from Europe endorses expert-based recommendations to consider bariatric surgery as a treatment for severe NAFLD in severely obese adolescents. This article discusses the problem of severe paediatric obesity, its relationship with NAFLD, and the knowledge and needs regarding bariatric surgery in adolescents… it is critical that adolescents with NAFLD undergoing bariatric surgery be evaluated and managed in bariatric surgery centres with appropriate paediatric multidisciplinary expertise and a commitment to rigorously phenotype NAFLD histology at baseline and to follow outcomes prospectively as long as possible. These procedures can be particularly challenging in adolescents, who are prone to relocate in adulthood and thus might not return for follow-up. High quality prospective multicentre studies with low attrition rates, such as the Teen Longitudinal Assessment of Bariatric Surgery (USA) and the Adolescent Morbid Obesity Study (Sweden) have begun to provide short to intermediate term (1–2 year) outcomes after adolescent bariatric surgery, but do not include prospectively collected data on histological liver outcomes to support evidence-based recommendations regarding NASH as a specific indication for bariatric surgery. However, given the benefits that are emerging for type 2 diabetes and sleep apnoea, (which are comorbid conditions often associated with NASH), we concur with previously published expert guidelines that conclude that bariatric surgery is not contraindicated in a non-cirrhotic patient with NAFLD who otherwise meets appropriate medical and psychosocial criteria for bariatric surgery.2 The adolescent and family should, however, be counselled that a positive outcome with respect to NAFLD is, as yet, not a foregone conclusion.

Related blog posts:

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Should Patients with IBS be Screened for Celiac Disease?

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Despite widespread expert opinion that those with irritable bowel syndrome (IBS) should be screened for celiac disease, whether it is a good idea is not settled.  A recent study (RS Choung et al. Clin Gastroenterol Hepatol 2015; 13: 1937-43) showed that celiac disease has a low prevalence in US patients (mean age 61 yrs in this cohort) with IBS.

Here’s an excerpt of a summary of this report from the AGA Blog: “Should all Patients with IBS be Screened for Celiac Disease?”

Rok Seon Choung et al investigated whether subjects with positive results from serologic tests for celiac disease are frequently diagnosed with IBS or other functional gastrointestinal disorders (FGIDs).

They sent self-report bowel disease questionnaires to 7217 residents of Olmsted County, Minnesota, to collect data on symptoms compatible with functional GI disorders, including IBS, collecting data on symptoms compatible with functional GI disorders, including IBS. These symptom data were linked to surveys of undiagnosed celiac disease conducted among more than 47,000 individuals from the same region, based on results of tests for immunoglobulin A tissue transglutaminase and then endomysial antibody.

Among the 3202 subjects who completed the questionnaires and had their serum sample analyzed, 13.6% had IBS and 55.2% had some gastrointestinal symptoms.

The prevalence of celiac disease, based on serologic markers, was 1.0%. However, whereas 3% of patients with celiac disease met the criteria for IBS, 14% of patients without celiac disease met the criteria for IBS.

Abdominal pain, constipation, weight loss, and dyspepsia were the most frequent symptoms reported by subjects who tested positive for celiac disease, but none of the gastrointestinal symptoms or disorders were significantly associated with results of serologic test for celiac disease.

My take: This study along with others show that celiac disease is infrequent in patients with IBS.  Since the symptoms of celiac disease overlap with IBS, I doubt this study will dissuade practitioners from screening for celiac despite the low yield.

Also, this fall I posted several blogs on GMOs.  An interesting article (from Vox/Grist) on this subject explains how GMOs are a lot like pornography: It’s practically impossible to define “GMOs”

Leaving Work

Atlanta Sky

Early Study Shows That Relamorelin Impoves Constipation and Transit Time

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An early study shows that Relamorelin relieves constipation & accelerates colonic transit in a placebo-controlled, randomized trial.  Abstract follows.

Relamorelin Relieves Constipation and Accelerates Colonic Transit in a Phase 2, Placebo-Controlled, Randomized Trial A Acosta et. Clin Gastroenterol Hepatol; December 2015Volume 13, Issue 13, Pages 2312–2319.e1. DOI: http://dx.doi.org/10.1016/j.cgh.2015.04.184

Abstract:

Background & Aims

Ghrelin receptors are located in the colon. Relamorelin is a pentapeptide selective agonist of ghrelin receptor 1a with gastric effects, but its effects in the colon are not known. We aimed to evaluate the effects of relamorelin on bowel movements (BMs) and gastrointestinal and colonic transit (CT) in patients with chronic constipation.

Methods

We performed a study of 48 female patients with chronic constipation who fulfilled the Rome III criteria and had 4 or fewer spontaneous BMs (SBMs)/wk. In a randomized (1:1), double-blind, parallel-group, placebo-controlled trial, the effects of relamorelin (100 μg/d, given subcutaneously) were tested during 14 days after a 14-day baseline, single-blind phase in which patients were given placebo at 2 Mayo Clinic sites. The participants’ mean age was 40.6 ± 1.5 y, with a mean body mass index of 25.7 ± 0.6 kg/m2, with 1.7 ± 0.1 SBM/wk, and a mean stool consistency of 1.2 ± 0.1 on the Bristol scale during this baseline period. The effect of treatment on transit was measured in 24 participants with colonic transit of less than 2.4 (geometric center at 24 h) during the baseline period. Gastric emptying, small-bowel transit, and CT were measured during the last 2 days that patients received relamorelin or placebo. Bowel function was determined from daily diaries kept by patients from days 1 through 28. Study end points were time to first BM, SBMs/wk, complete SBMs/wk, stool form, and ease of stool passage. Effects of relamorelin were assessed by analysis of covariance.

Results

Compared with placebo, relamorelin accelerated gastric emptying half-time (P = .027), small-bowel transit (P = .051), and CT at 32 hours (P = .040) and 48 hours (P = .017). Relamorelin increased the number of SBMs (P < .001) and accelerated the time to first BM after the first dose was given (P = .004) compared with placebo, but did not affect stool form. Adverse events associated with relamorelin included increased appetite, fatigue, and headache.

Conclusions

Relamorelin acts in the colon to significantly reduce symptoms of constipation and accelerate CT in patients with chronic constipation, compared with placebo. ClinicalTrial.Gov registration number: NCT01781104.

Lights at Life University

Lights at Life University

More on Staying Up All Night

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In September, this blog (Does Staying Up All Night Affect Surgery the Next Day …) noted a recent study indicating that adverse surgical outcomes with elective daytime procedures were similar irrespective of whether the surgeon had operated overnight.  Some of the letters to the editor on this study were of interest.  In one, the authors note that sleep deprivation was associated with a lower adenomatous polyp detection rate on colonoscopy but was not associated with major complications like death or perforation (M Benson et al. Am J Gastroenterol 2014; 109; 1133-7).  Thus, the letter contends that there are likely to be subtle effects of sleep deprivation on physician performance that could require more sensitive quality metrics.

Another letter notes that extended work was associated with an increased risk of motor vehicle accidents by interns.  The monthly risk increased 16.2% for every extended work shift (LK Barger et al. NEJM 2005; 352: 125-34).  Thus, sleep deprivation could represent a hazard for the physician themselves as well as their patients.

My take: I’m sorry I didn’t quite follow this post. (I was on-call last night.)

Lights at Life University

Lights at Life University

Hepatitis C Cure: Too Late for Many

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Before the recent vast improvements in hepatitis C virus (HCV) treatment, there had been a number of studies predicting a huge increase in HCV-related mortality due to hepatocellular carcinoma (HCC) and cirrhosis.

Despite the optimism that have come with the new treatments, the most recent data (LA Beste, et al. Gastroenterol 2015; 149: 1471-82) continue to predict a huge and increasing burden of chronic liver disease due to HCV.

The authors used a national retrospective cohort of Veteran Affairs (VA) patients with cirrhosis (n=129,998) or HCC (n=21,326) from 2001-13.  They identified an increasing proportion of cirrhosis and HCC during that timeframe.

Key findings:

  • From 2001 to 2013, cirrhosis prevalence nearly doubled (664 –>1058 per 100,000 enrollees) driven by HCV and nonalcoholic fatty liver disease; deaths due to cirrhosis also increased from 83 to 126 per 100,000 patient years
  • From 2001 to 2013, HCC incidence increased 2.5-fold from 17 to 45 per 100,000 patient-years and HCC mortality tripled from 13 to 37 per 100,000 patient-years.  HCC incidence was driven overwhelmingly by HCV.
  • Based on current trends, cirrhosis prevalence will peak in 2021 according to the authors, though they acknowledge that patients from the VA may not be representative of the population at large and that the study has inherent weaknesses due to computerized data collection in this retrospective study.

My take: Despite dramatic improvements in HCV treatment, sadly, it is still going to get a lot worse with regard to disease burden & mortality from HCV before it will improve.

Briefly noted: F Negro. Gastroenterol 2015; 149: 1345-60.  “Extrahepatic morbidity and mortality of chronic hepatitis C”  This review article discusses diabetes, cardiovascular manifestations of HCV, fatigue, cognitive impairment, mixed cryoglobulinemia, and non-hodgkin lymphoma.

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Chattanooga Aquarium

Chattanooga Aquarium

Exome Sequencing in VEO-IBD: More Data

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With more widespread use of whole-exome sequencing (WES), the ability to study the genetic basis for rare disorders like very early onset inflammatory bowel disease (VEO-IBD) has improved considerably. A recent study (JR Kelsen et al. Gastroenterol 2015; 149: 1415-24) analyzed 125 patients (3 weeks to 4 years of age) and compared with pediatric IBD patients (n=45), adult-onset Crohn’s (n=20), and healthy controls (n=145). Link to abstract and online material. (Link includes full-text as well).

The authors focused their study on 400 genes/regions associated with primary immunodeficiency.

Key finding:

  • “Our analysis showed novel and rare variants within these genes that could contribute to the development of VEO-IBD, including rare heterozygous missense variants in IL10RA and previously unidentified variants in MSH5 and CD19.”

In their discussion, the authors elaborate on these findings. In addition, in Table 3, the authors elaborate on potential immunologic studies for these children.

Take home message: The authors recommend “a more complete immunologic evaluation be performed in patients with VEO-IBD.”  Ultimately, understanding the complex genetics will lead to more individualized and successful treatments.

Related blog posts:

Lights at Life University

Lights at Life University