What is Driving Racial Disparities in Access to Living Donor Liver Transplants

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Recent articles highlight a huge gap in the availability of living donor liver transplants (LDLTs) when examined based on racial/ethnic background.

  • YR Nobel et al. Liver Transpl 2015; 21: 904-13.
  • A Doyle et al. Liver Transpl 2015; 21: 897-903.

What is the reason for this inequality?

The first study examined UNOS data from 2002-2014 among adult liver transplant recipients.  Of 35,401 recipients, 2171 (6.1%) received a LDLT.

Key findings:

  • Cholestatic liver disease: When compared with white patients, the odds ratios of receiving LDLT were 0.35 for African American, 0.58 for Hispanic, and 0.11 for Asian.
  • Noncholestatic liver disease: When compared with white patients, the odds ratios of receiving LDLT were 0.53 for African American, 0.78 for Hispanic, and 0.45 for Asian.
  • LDLT recipients were more likely to have private insurance

The second study did not look at racial/ethnic background but instead focused on other recipient factors.  Using a retrospective cohort of 491 consecutive patients, they determined that all of the following resulted in a lower likelihood of LDLT:

  • Single — OR 0.34
  • Divorced –OR 0.53
  • Immigrant — OR 0.38
  • Low income quintile — OR 0.44

Together these studies allow speculation on why there is such a disparity.

  • Financial costs, including lost wages, could preclude those with lower socioeconomic status from being available as donors
  • Distrust of donation system and/or fear of surgery

Bottomline: Racial/ethnic differences and financial resources are associated with significant access inequality to living donor liver transplantation.

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Cascade Canyon, Grand Tetons

Cascade Canyon, Grand Tetons

 

Low FODMAPs Diet in Pediatric Irritable Bowel

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A low FODMAPs diet has been associated with clinical improvement in adults with irritable bowel syndrome and “gluten sensitivity” (see links below).  Now, there is more data that this diet can be effective in the pediatric population (Chumpitazi BP, et al. Aliment Pharm Ther DOI: 10.1111/apt.13286. Article first published online: 24 JUN 2015 -Thanks to KT Park for this reference).  In addition, this small study (n=33) tries to correlate changes in symptoms with changes in the gut microbiome. Interestingly, the dietary trials were only 48 hours.

From the methods: Following a 7-day baseline period, “we employed a randomised, double-blind, crossover study design. Subjects received either a low FODMAP or typical American childhood diet (TACD) for 48 h. After 48 h on the first assigned diet, they returned to their habitual diet for 5 days. Following this 5-day washout period, they were crossed over to the other intervention diet for 48 h.”

Here is the abstract and a link to the full text: Randomised clinical trial: gut microbiome biomarkers are associated with clinical response to a low FODMAP diet in children with the irritable bowel syndrome

Abstract:

Background

A low fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAP) diet can ameliorate symptoms in adult irritable bowel syndrome (IBS) within 48 h.

Aim

To determine the efficacy of a low FODMAP diet in childhood IBS and whether gut microbial composition and/or metabolic capacity are associated with its efficacy.

Methods

In a double-blind, crossover trial, children with Rome III IBS completed a 1-week baseline period. They then were randomised to a low FODMAP diet or typical American childhood diet (TACD), followed by a 5-day washout period before crossing over to the other diet. GI symptoms were assessed with abdominal pain frequency being the primary outcome. Baseline gut microbial composition (16S rRNA sequencing) and metabolic capacity (PICRUSt) were determined. Metagenomic biomarker discovery (LEfSe) compared Responders (≥50% decrease in abdominal pain frequency on low FODMAP diet only) vs. Nonresponders (no improvement during either intervention).

Results

Thirty-three children completed the study. Less abdominal pain occurred during the low FODMAP diet vs. TACD [1.1 ± 0.2 (SEM) episodes/day vs. 1.7 ± 0.4, P < 0.05]. Compared to baseline (1.4 ± 0.2), children had fewer daily abdominal pain episodes during the low FODMAP diet (P < 0.01) but more episodes during the TACD (P < 0.01). Responders were enriched at baseline in taxa with known greater saccharolytic metabolic capacity (e.g. Bacteroides, Ruminococcaceae, Faecalibacterium prausnitzii) and three Kyoto Encyclopedia of Genes and Genomes orthologues, of which two relate to carbohydrate metabolism.

Conclusions

In childhood IBS, a low FODMAP diet decreases abdominal pain frequency. Gut microbiome biomarkers may be associated with low FODMAP diet efficacy.

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Baseball Broadcast with a Sense of Humor

Baseball Broadcast with a Sense of Humor

Selective Data Mining: Reflux and Bronchopulmonary Dysplasia

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With some studies, the abstract may suggest a more compelling result than is truly evident.  That’s how I feel about a recent report (Nobile S, et al. J Pediatr 2015; 167: 279-85).

Here’s the conclusion (verbatim) from the abstract: “The increased number of (and sensitivity for) pH-only events among infants with BPD may be explained by several factors, including lower milk intake, impaired esophageal motility, and a peculiar autonomic nervous system response pattern.”

To me, it sounds like this prospective study of pH-multichannel intraluminal impedance (pH-MII) of 46 infants born ≤32 weeks gestation (12 with bronchopulmonary dysplasia (BPD) and 34 without BPD) must have identified something important linking gastroesophageal reflux disease (GERD) and BPD.  But, the real findings, in my view, are that this is a negative study. Period.

Here are the results reported in the abstract:

  • “Infants with BPD…had increased numbers of pH-only events (median number 21 v 9) and a higher symptom symptom sensitivity index for pH-only events (9% vs. 4.9%)”
  • They also state: “the number and characteristics of acid, weakly acid, nonacid and gas gastroesophageal reflux events, acid exposure, esophageal clearance, and recorded symptoms did not significantly differ between the 2 groups.”

Here’s a little more data –not in the abstract:

  • The P value for the difference in pH-only events was .360
  • The authors could just have easily pointed out (in the abstract) that infants without BPD had increased acid exposure: 40.5 min compared with 27.0 min (P = .599)

What should have been in the abstract conclusion? Perhaps, the first line of their discussion: “Infants with BPD did not have significantly higher GER features compared with infants without BPD as measured by esophageal pH-MII monitoring, except for higher occurrence of pH-only events and higher SSI for pH-only events.”

The authors try to explain the differences in the BPD patients by highlighting some of the potential mechanisms of reflux and/or autonomic dysfunction.  I think the limitations of this study deserve careful scrutiny.  This was a small study with only 12 BPD infants.  There was a significant selection bias -only ‘symptomatic’ infants were included.  Some of the factors affecting BPD directly could have an indirect effect on reflux (eg. caffeine).

The authors make one other point: “we believe pharmacologic treatment for GER should be initiated only after the demonstration of pathologic pH-MII monitoring to avoid unnecessary drug therapy, adverse events, and costs.”

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Grand Prismatic Spring, Yellowstone

Grand Prismatic Spring, Yellowstone

“Negative Externality,” Splitting Checks, and Feeding Psychology

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If you have a great psychology book that you recommend, please let me know.  As frequent readers of this blog know, I am fascinated with psychology experiments.

In a recent blog from fivethirtyeight.com, the author tackles the question of whether people eat more when they know they are splitting a dinner check. Does it Make Sense to Split The Check at a Restaurant?

Here’s an excerpt:

In 2004, a study in The Economic Journal, a publication of the Royal Economic Society, …the researchers told four groups of diners (always three men and three women) to split the bill equally among them. They told another four groups to pay for what they had ordered. Lastly, they told two lucky groups that they would get their meals for free…

Those who were getting a free meal spent the most … Those who were splitting the bill spent less, and those who were paying individually spent the least…

Any time you make a decision that affects someone else without considering how it might affect that person, whether positively or negatively, you create an externality — it’s basically a fancy way of saying “indirect effect.” There are positive externalities (e.g. when you decide to get a flu shot, other people benefit) and negative externalities (e.g. when you decide to fart, other people suffer).

The unscrupulous diner’s dilemma reveals how negative externalities — and even the mere threat of negative externalities — affect our behavior. Participants in the bill-splitting experiment expected the others to order more, so they tried to maximize what they could get out of the situation by ordering more themselves.

Bottomline: It is fascinating to me how something as simple as splitting a bill may encourage someone to order a lot more.

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Near Fairy Falls, YW

How the Trans-Pacific Partnership Could Affect Health Outcomes

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Generally, trade agreements are not something I scrutinize and typically have little to do with the medical field.  Recently, I was surprised to learn that the Trans-Pacific Partnership (TPP) has language in its intellectual property chapter that could impact the lives of millions (A Kapczynski. NEJM 2015; 373: 201-3).  The background for this story is that pharmaceutical companies want to have patent protection for their medications for as long as possible.  This has a substantial impact on pricing.  “For example, patents increase the annual cost of antiretroviral therapy from around $100 per person to $10,000 per person.”

Some countries, like India, have undermined patent protections.  “India allows patents on new drugs but not on new uses of old drugs or new forms of known drugs that do not increase therapeutic efficacy.”  Other countries have been following India’s lead.  Even in the U.S., there are efforts to decrease data exclusivity, which prevents regulatory agencies like the FDA from registering a generic version of a drug.

“President Barack Obama’s fiscal year 2016 budget proposes rolling back the data exclusivity period for biologic drugs in the United States to 7 years from 12 years, yielding a projected savings of more than $4 billion over the next decade. In the TPP negotiations, however, the United States is proposing a 12-year term of exclusivity.”

Other potential concerns include both the elimination of a provision to use “competitive market-derived prices” and the potential for promoting foreign companies to sue TPP countries for millions of dollars in damages due to loss of profits.

Currently there are escalating drug prices, both with innovative new medications and well-established treatments. Even lifesaving cures are being rationed in the United States.  While the TPP has not been finalized, there are provisions that could limit the United States  from regulating “critical aspects of health policy for years to come.”

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Cascade Canyon, Grand Tetons

Cascade Canyon, Grand Tetons

 

 

Stress and IBD Flareups

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Over the years, I’ve had several experiences in which some patients had flareups of their inflammatory bowel disease (IBD) in relation to specific stresses (eg. going to away camp).  This was not just stomach pain but instead bloody diarrhea.  While this is very infrequent, I’ve come to believe that there may be some individuals who develop IBD flareups in response to stress. A recent study (Targownik LE, et al. AJG 2015; 110, 1001-1012 | doi:10.1038/ajg.2015.147) suggests that most of the time when individuals report a flareup in response to stress, that there is not objective evidence of increased inflammation.

The Relationship Among Perceived Stress, Symptoms, and Inflammation in Persons With Inflammatory Bowel Disease

From Abstract:

METHODS:

Participants were recruited from a population-based registry of individuals with known IBD. Symptomatic disease activity was assessed using validated clinical indices: the Manitoba IBD Index (MIBDI) and Harvey Bradshaw Index (HBI) for Crohn’s disease (CD), and Powell Tuck Index (PTI) for ulcerative colitis (UC). Perceived stress was measured using Cohen’s Perceived Stress Scale (CPSS). Intestinal inflammation was determined through measurement of fecal calprotectin (FCAL), with a level exceeding 250 μg/g indicating significant inflammation. Logistic regressions were used to evaluate the association between intestinal inflammation, perceived stress, and disease activity.

RESULTS:

Of the 478 participants with completed surveys and stool samples, perceived stress was associated with symptomatic activity (MIBDI) for both CD and UC (1.07 per 1-point increase on the CPSS, 95% confidence interval (CI) 1.03–1.10 and 1.03–1.11, respectively). There was no significant association between perceived stress and intestinal inflammation for either CD or UC. Active symptoms (MIBDI ≤3) were associated with intestinal inflammation in UC (odds ratio (OR) 3.94, 95% CI 1.65–9.43), but not in CD (OR 0.98, 95% CI 0.51–1.88).

CONCLUSIONS:

Symptomatic disease activity was unrelated to intestinal inflammation in CD and only weakly associated in UC. Although there was a strong relationship between perceived stress and gastrointestinal symptoms, perceived stress was unrelated to concurrent intestinal inflammation. Longitudinal investigation is required to determine the directionality of the relationship between perceived stress, inflammation, and symptoms in IBD.

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For worried hikers in Yellowstone

For worried (“stressed”) hikers in Yellowstone

Magnetic Placement of NJ Feeding Tubes

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From ASPEN twitter feed: Placement of a Magnetic Small Bowel Feeding Tube at the Bedside

Abstract

Background: Current methods of achieving postpyloric enteral access for feeding are fraught with difficulties, which can markedly delay enteral feeding and cause complications. Bedside tube placement has a low success rate, often requires several radiographs to confirm position, and delays feeding by many hours. Although postpyloric enteral tubes can reliably be placed in interventional radiology (IR), this involves greater resource utilization, delays, cost, and inconvenience. We assessed the utility of bedside enteral tube placement using a magnetic feeding tube (Syncro-BlueTube; Syncro Medical Innovations, Macon, GA, USA) as a means to facilitate initial tube placement. Methods: We recorded the time to insertion, location of tube, success rate, and need for radiographs in a series of patients given magnetic feeding tubes (n = 46) inserted by our hospitalist service over an 8-month interval. Results: Of the 46 attempted magnetic tube placements, 76% were successfully placed in the postpyloric position, 13% were in the stomach, and 11% could not be placed. In 83% of the magnetic tubes, only 1 radiograph was needed for confirmation. The median time to placement was 12 minutes (range, 4–120 minutes). Conclusion: The use of a magnetic feeding tube can increase the success rate of bedside postpyloric placement, decrease the time to successful placement, and decrease the need for supplemental radiographs and IR

Roadside Elk, Grand Tetons

Roadside Elk, Grand Tetons

Stick with the (intestinal) rehab program?

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More data on the progress of treatment of short bowel syndrome (SBS) programs:

  • Avitzur J, et al. JPGN 2015; 61: 18-23

In this study, the researchers from Toronto and the Group for Improvement of Intestinal Function and Treatment (GIFT) retrospectively examine 84 patients over 3 time periods: 1999-2002, 2003-2005, and 2006-2009.

Key points:

  • Across those time periods, the authors find fewer SBS patients that needed to be listed for transplantation despite similar baseline characteristics.  In addition, many more patients in the late period were removed from the transplant waiting list due to clinical improvement.
  • Another important finding was a drop in mortality (15% vs >60%) and a shift from previous causes like liver failure and sepsis to death from other comorbid conditions.
  • “Since 2009, we have performed only 1 IT [intestinal transplant].”  They note this is a worldwide trend with ~50% reduction in pediatric IT since 2008.
  • Even with ultrashort bowel (small bowel length <30 cm), there are reports that “50% of these patients achieved PN independence within 2 years.”  As such, this is a declining indication for IT listing. In this study, ultrashort bowel was the reason for listing in 11% in the last period compared 21% in the first time period.

Why is this happening?

The authors credit the intestinal rehab program (IRP) for this impact along with specific management changes including new lipid emulsions/lipid minimization to reduce IFALD, use of ethanol locks to reduce bloodstream infections, and bowel reconstructive procedures (e.g. STEP).

Briefly noted: Merras-Salmio L, Pakarinen MP. JPGN 2015; 61: 24-9. This second retrospective study (n=48) from Finland reinforces the view of improvements in cholestasis  and prognosis from 1988-2014.  Similar strategies, as noted above, were implemented in SBS management protocols.

Bottomline: The outlook has improved for SBS.  While this is good news, at the same time, there will be less pediatric gastroenterologists with extensive intestinal transplantation experience.

In Wyoming often there are stretches of nearly deserted highways

In Wyoming often there are stretches of nearly deserted highways

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Impact of Kasai Portoenterostomy on Liver Transplantation

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Briefly noted: JS Neto, et al. Liver Transpl 2015; 21: 922-7.

This retrospective cohort study of 347 biliary atresia patients who underwent liver transplantation )LT) (1995-2013) divided patients into eraly Kasai failures (K-EF) (27%), late Kasai failures (K-LF) (33%), and no Kasai portenterostomy (No-K) (40%). K-EF was defined by patients who underwent LT before 12 months of age.

Key findings:

  • After adjustment of confounding factors, the K-LF group had an 84% less probability of dying and 55% less chance to undergo retransplantation.
  • Having a K-EF did not have an effect on patient or graft survival compared to No-K.
  • Both the K-LF and K-EF had more post-LT biliary complications.

Bottomline: This retrospective study suggests that if a Kasai portoenterostomy helps postpone LT then this results in improved outcomes; whereas if it is ineffective, it does not impact survival compared to those who did not undergo a Kasai.

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From Cascade Canyon, Grand Tetons

From Cascade Canyon, Grand Tetons

Looking Twice for Eosinophilic Esophagitis

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Not only do you have to take a lot of esophageal biopsies, now you may need to call your pathologist to make sure you do not miss a case of eosinophilic esophagitis (EoE), especially if there are mildly increased eosinophils.  At least, that’s the message I inferred from a recent study (Rothenberg ME, et al. JPGN 2015; 61: 65-8).

In this study, the researchers identified 477 biopsies from 429 patients with EoE; 316 were from “PPI confirmed patients.”

Key finding: Of the 477 biopsies, 106 had a peak count of between 1 and 14 eos/hpf cited in the pathology report.  However, 23/106 (22% with 1-14 eos/hpf) had ≥15 esos/hpf after a second review.

Overall, 5% of the 477 biopsies were mischaracterized as not meeting the threshold of ≥15 esos/hpf prior to review.  Given this frequency at a major medical center and frequent referral center for EoE, my suspicion is that the yield of a 2nd look would be at least as high in most other centers.

Take-home point: Look twice for EoE if eosinophil count is between 1/hpf and 14/hpf. Maybe some new diagnoses are being missed and maybe some of your EoE patients in histologic remission really aren’t.

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Grand Tetons from Jenny Lake

Grand Tetons from Jenny Lake