Should Younger Transplant Patients Receive Better Organs?

Posted on October 23, 2015 by gutsandgrowth

Many physicians are unhappy with the current liver transplantation allocation system. A recent article (A Cucchetti et al. Liver Transl 2015; 21: 1241-49, editorial LB Vanwagner, AI Skaro. Liver Transpl 2015; 21: 1235-37) suggests that there should be adjustments to consider age in liver organ allocation. While this issue is not new, the article does suggest the idea of “age-mapping” which is a different twist on this subject.

The editorial notes that the current MELD system as been a poor predictor of post transplant outcomes and “does little to promote utility in organ allocation.” Because age is not a factor in MELD, “there is a subsequent loss of equity in the current system because younger recipients receive fewer opportunities to achieve a full lifespan compared with older recipients.” However, age matching is prohibited by discrimination laws.

“Age mapping differs from age matching.” With age mapping, all candidates would have an “equal chance of getting a liver” but the probability of receiving a ‘better organ’ (donor ≤35 years) would be more likely for younger recipients.

My take: The scarcity of organ availability compounded with the possible decline in organ quality leads to these discussions. Who really can balance unfair against unfortunate?

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Should All Pediatric Patients with Crohn’s Disease Continue Combination Therapy?

Posted on October 22, 2015 by gutsandgrowth

Among patients/families who are not in denial about their inflammatory bowel disease, especially Crohn’s disease, an important discussion is the use of combination therapy. This has been discussed on this blog before (see some links below). More data on this subject has been published and again favors the use of combination therapy (V Grossi, T Lerer, et al. Clin Gastroenterol Hepatol 2015; 13: 1748-56).

This study collected data from 2002-2014 on 502 children who participated in a prospective multicenter study. This data was derived from an observational registry rather than a randomized trial, but likely reflects real-world experience with regard to newly diagnosed patients. The authors excluded those with prior biologic therapy and prior resectional surgery.

KEY FINDINGS:

Children receiving combination immunomodulator (IM) treatment were more likely to have durable infliximab therapy at 1 year, 3 years, and 5 years.
Greater length of concomitant IMs was associated with better durability.
For patients who had IM > 6 months after starting infliximab (n=194), durability was 0.70 at 5 years compared with 0.55 for patients with IM <6 months (n=144), and 0.48 for those who did not receive IMs (n=135).
In boys, methotrexate appeared to be superior to thiopurines (P<.01): 0.98 at 5 yrs compared with 0.58. However, there were 60 males receiving methotrexate. In the study, only 21 females received methotrexate which limited any conclusions.

Among patients who stopped IFX, the reasons included loss of response (n=61, 43%), hypersensitivity reaction (n=41, 29%), elective (n=25, 18%), lost to f/u (n=5, 3%), and other causes (10, 7%).

The “right” dose of methotrexate as a combination agent remains unclear. There was a wide range of dosing schedules in this study. It is worth observing that the COMMIT study in adults found no significant difference in adults who received methotrexate in addition to infliximab compared with those receiving infliximab monotherapy.

Take-home message: In this large pediatric observational study, the use of immunomodulators increased the likely durability of infliximab. Given prior conflicting data (particularly with regard to methotrexate), even more studies are needed to determine exactly how useful combination therapy is and when monotherapy will suffice. From my viewpoint, I worry much more about loss of efficacy to infliximab than I worry about medication adverse effects. As such, I will continue to inform families that combination therapy appears to improve infliximab durability.

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Mount Washburn, Yellowstone

Doctor Scorecards: Affecting Care (but not in the way you think)

Posted on October 21, 2015 by gutsandgrowth

A recent perspective article (L Rosenbaum. NEJM 2015; 373: 1385-8) explains how the use of physician scorecards are negatively affecting patients and the pitfalls in their interpretation. Her article describes a situation, that is ‘not uncommon,’ in which a higher risk cardiology patient will not have a surgical consult for a few days because most surgeons “wouldn’t touch our patient with a 10-foot pole.” In several states, the increase reports of cardiac surgery outcomes has resulted in surgeons avoiding the sickest patients. The author notes that transparency/public reporting needs to be balanced against the potential harms. Other key points:

The public reporting thus far has been deeply flawed, based on insurance claims that are “notoriously inaccurate.” The reports have poor reliability, in part, due to too few surgeries to make accurate conclusions.
The public reports amount to “fear mongering” rather than the “professed commitment to protecting patients.”
“The key question, then, is less about transparency with regard to quality than it is about what constitutes quality in the first place.”
“The irony in hailing the scorecard as a victory for transparency is that its purported objectivity obscures its methodologic limitations.”

My take: While you are looking a surgeon’s scorecard, keep in mind, he/she may decide to not operate on you when he/she looks at your scorecard (of illness). Related blog posts:

What Functional MRI Finds with Anorexia

Posted on October 20, 2015 by gutsandgrowth

In yesterday’s post, functional MRI showed how rapidly anti-TNF agents can improve pain response in patients with Crohn’s disease. A more complete description of this study is available from the AGA Blog: This is Your Brain on Anti-TNF Therapy. This link also includes access to a video abstract discussion with the author.

Another intriguing use of this technology provides insight into why Anorexia is difficult to treat. The study was summarized in the NY Times:

Anorexia May Be Habit, Not Willpower Here’s an excerpt:

The study’s findings may help explain why the eating disorder, which has the highest mortality rate of any mental illness, is so stubbornly difficult to treat. But they also add to increasing evidence that the brain circuits involved in habitual behavior play a role in disorders where people persist in making self-destructive choices no matter the consequences, like cocaine addiction or compulsive gambling…

The researchers used a brain scanning technique to look at brain activity in 21 women with anorexia and 21 healthy women while they made decisions about what foods to eat…

As expected, both the anorexic and the healthy women showed activation in an area known as the ventral striatum, part of the brain’s reward center. But the anorexic women showed more activity in the dorsal striatum, an area involved with habitual behavior, suggesting that rather than weighing the pros and cons of the foods in question, they were acting automatically based on past learning…

My take: This study shows an association between food selection and differences in brain activity between women with anorexia and in controls. These changes do not prove a causal association but provide an important piece of information about what might be going wrong.

Atlanta Botanical Garden, Bruce Munro Exhibit

Anti-TNF Therapy: Rapid Reduction in Pain in Crohn’s Disease

Posted on October 19, 2015 by gutsandgrowth

A pretty cool use of technology provides strong evidence that decreased pain perception in the brain of patient’s with Crohn’s disease (CD) occurs well before anti-inflammatory effects like mucosal healing (A Hess et al. Gastroenterol 2015; 149: 864-66). In this study, the authors prospectively identified 4 patients with CD and performed functional MRI on day -1, day 1, and day 27. Key findings:

In three patients, who responded with a decrease in Harvey-Bradshaw Index by ≥2 points 14 weeks after anti-TNF initiation, the pain signal induced by either finger tapping or compression (see cover below) was markedly improved 1 day after anti-TNF initiation.
In the CD non responder, there was only slight reduction in signals at 24 hours and no improvement from baseline at day 27.

My take: This study explains why so many patients with severe symptoms can be managed quickly as outpatients. The effects of anti-TNF therapy on pain occur within 24 hrs! Pretty cool.

Final Tweets from #NASPGHAN15

Posted on October 18, 2015 by gutsandgrowth

From debate regarding importance of mucosal healing:

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ER Evaluations of Visits Related to Inflammatory Bowel Disease

Posted on October 17, 2015 by gutsandgrowth

A short communication (C Pant et al. JPGN 2015; 61: 282-84, ed 267-8) provides some insight into what is happening in the ER when patient with inflammatory bowel disease are evaluated.

The authors analyzed a national database, the Healthcare Cost and Utilizationa Porject Nationwide Emergency Department Sample (NEDS), from 2006-2010.

Key findings:

ED visits for children 5-19 years of age increased from 14,527 (2006) –>18,193 (2010)
Frequency of computerized tomography (CT) imaging increased 80.43% (P<0.01) for Crohn’s disease and 59.26% (P<0.01) for ulcerative colitis
Overall rate of hospital admissions decreased by 14.32% (P<0.01)

The associated editorial by Jennifer Dotson and Michael Kappelman explain the limitations of relying on data that are derived mainly for billing rather than research and comment on the “alarming increase” in CT usage due to the risk of radiation exposure and the potential alternatives (eg. ultrasound, MRE). With regard to limitations, they likely included inaccurate and incomplete entries. In addition, the database included 950 hospitals, but may have under-sampled large freestanding children’s hospitals. This could skew the data. Finally, the data uses “visit-level” data rather than “patient-level” data; thus, one ‘cannot distinguish between a single patient who is seen on three separate visits or three unique patients.’

My take: There has been increasing use of ER visits and CT scanning for pediatric patients with IBD. One of my colleagues in town (Cary Sauer) has a humorous slide of a CT scanner as the entrance door to the ER. The message from this study indicates that we should be working on changing practice by working with our ER colleagues along with radiologists to minimize CT scans in favor of more gently imaging.

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Atlanta Botanical Gardens, Bruce Munro exhibit

Working While Sick: Red Badge of Courage or Scarlet Letter?

Posted on October 16, 2015 by gutsandgrowth

With the respiratory virus season fast approaching, a recent study and editorial (J Szymczak et al. JAMA Pediatr 2105; 169: 815-21, editorial 809-10 -thanks to Ben Gold) are worth a look; they focus attention on the practice of working while sick. In the study, the researchers use an anonymous survey of more than 900 physicians and advance practice clinicians working at a large children’s hospital. 83% reported working sick at least 1 time in the past year and 9% reported working while sick at least 5 times. The authors note “some ambiguity persists around what constitutes being too sick to work, and a perception exists that sick leave is impractical.” Most of the respondents understood that their illness could have an adverse effect on patients, but 97% did not want to let colleagues down and 94% did not want to create staffing shortages.

The editorial makes several more points:

Healthcare workers “will likely continue to come to work when mildly ill, especially when they identify their role as being essential for care and unique within the institution.”
“Working while sick was regarded as a badge of courage, and ill physicians who stayed home were regarded as slackers.”
The editorial argues for more clarity and/or use of key symptoms: conjunctivitis, vomiting, bloody diarrhea, fever >38.5, >2 episodes of watery diarrhea, or jaundice
“For many respiratory viruses, individuals are most contagious before they are highly symptomatic, so staying home after symptoms develop may not be effective or practical.”
For influenza, the CDC has recommended that employees “not return to work until 24 hours after they are fever free or 7 days, whichever is longer, with longer periods of time off for HCWs returning to work in a setting of high-risk individuals.” However, with this approach, “staffing shortages would become critical.”

My take: These articles suggest a need for a culture change that supports paid sick leave that is adequate and non-punitive. At the current time, adequate backup is often lacking. Also, these articles serve as a reminder: it is a good idea to get your flu shot!

Portopulmonary Hypertension -A Little More Data

Posted on October 15, 2015 by gutsandgrowth

A recent study (E Echocahrd-Dugelay et al. JPGN 2015; 61: 346-54, editorial 268-9) provides a little more data on the rare condition of portopulmonary hypertension (POPH). Untreated POPH can lead to right-sided heart failure and death; a prompt diagnosis improves the chance for responding to treatment.

In brief, the authors reviewed their experience with 14 patients that were diagnosed with POPH between 1983-2009. The authors also reviewed the literature for a total of 98 patients.

Findings:

0.5% of children with portal hypertension had POPH
0.9% of children with end-stage liver disease awaiting liver transplantation had POPH
Congenital portosystemic shunts (CPSS) appeared to be a risk factor for POPH and were noted in 3 of their 14 cases as well as 22 of 98 cases overall.
In treated patients (n=42), five-year survival was noted to be 80%. Treatment included vasodilator therapy, closure of CPSS, or liver transplantation.
Hepatopulmonary syndrome (with hypoxemia) may precede POPH; this was reported in 6 of the 98 patients in this report

Dr. Ronald Sokol’s commentary noted that guidelines for timing/frequency of pulse oximetry testing and formal echocardiographic screening are needed but “challenging given the present body of evidence.” He recommends screening all pediatric liver transplantation candidates who have cirrhosis and portal hypertension with pulse oximetry and echocardiography as well as those with clinical features of POPH (eg. syncope, shortness of breath, dyspnea). For other patient populations, it remains unclear.

Bottomline (from the authors): “Detection of POPH at an early stage requires systematic screening at regular intervals by echocardiography in children with all causes of portal hypertension.” Unanswered questions:

how much portal hypertension is needed to merit screening?
how often should screening take place?

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NY Times: “Should We Bank Our Own Stool?”

Posted on October 14, 2015 by gutsandgrowth

A provocative article poses the question: Should we bank our own stool?

Here’s an excerpt:

The scientific term for this is “autologous fecal transplant.” In theory, it could work like a system reboot disk works for your computer. You’d freeze your feces, which are roughly half microbes, and when your microbiome became corrupted or was depleted with antimicrobials, you could “reinstall” it from a backup copy.

That damage from antibiotics may not be trivial. Studies have linked antibiotic use early in life with a modestly increased risk of asthma,inflammatory bowel disease, obesity and rheumatoid arthritis. These are associations, of course; they don’t prove that antibiotics cause disease…

Almost 60 years later, the “fecal transplant” is a cutting-edge treatment for the pathogen Clostridium difficile, a bug that kills 29,000 yearly and infects nearly half a million…

Memorial Sloan Kettering Cancer Center in New York has also started a proactive stool-banking study. Most of the subjects are patients with leukemia. Before stem cell transplants, patients receive antibiotics andchemotherapy, often wiping out their microbiota…

OpenBiome…started a pilot self-banking program called “PersonalBiome.” One complication: If he stores your stool, you can generally withdraw it only to treat C. difficile, not for preventive “reconstitution.” That’s because stool is regulated as a drug and not, as with embryos or blood, a tissue, which makes its use more complex.

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