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About gutsandgrowth

I am a pediatric gastroenterologist at GI Care for Kids (previously called CCDHC) in Atlanta, Georgia. The goal of my blog is to share some of my reading in my field more broadly. In addition, I wanted to provide my voice to a wide range of topics that often have inaccurate or incomplete information. Before starting this blog in 2011, I would tear out articles from journals and/or keep notes in a palm pilot. This blog helps provide an updated source of information that is easy to access and search, along with links to useful multimedia sources. I was born and raised in Chattanooga. After graduating from the University of Virginia, I attended Baylor College of Medicine. I completed residency and fellowship training at the University of Cincinnati at the Children’s Hospital Medical Center. I received funding from the National Institutes of Health for molecular biology research of the gastrointestinal tract. During my fellowship, I had the opportunity to work with some of the most amazing pediatric gastroenterologists and mentors. Some of these individuals included Mitchell Cohen, William Balistreri, James Heubi, Jorge Bezerra, Colin Rudolph, John Bucuvalas, and Michael Farrell. I am grateful for their teaching and their friendship. During my training with their help, I received a nationwide award for the best research by a GI fellow. I have authored numerous publications/presentations including original research, case reports, review articles, and textbook chapters on various pediatric gastrointestinal problems. In addition, I have been recognized by Atlanta Magazine as a "Top Doctor" in my field multiple times. Currently, I am the vice chair of the section of nutrition for the Georgia Chapter of the American Academy of Pediatrics. In addition, I am an adjunct Associate Clinical Professor of Pediatrics at Emory University School of Medicine. Other society memberships have included the North American Society for Pediatric Gastroenterology Hepatology and Nutrition (NASPGHAN), American Academy of Pediatrics, the Food Allergy Network, the American Gastroenterology Association, the American Association for the Study of Liver Diseases, and the Crohn’s and Colitis Foundation. As part of a national pediatric GI organization called NASPGHAN (and its affiliated website GIKids), I have helped develop educational materials on a wide-range of gastrointestinal and liver diseases which are used across the country. Also, I have been an invited speaker for national campaigns to improve the evaluation and treatment of gastroesophageal reflux disease, celiac disease, eosinophilic esophagitis, hepatitis C, and inflammatory bowel disease (IBD). Some information on these topics has been posted at my work website, www.gicareforkids.com, which has links to multiple other useful resources. I am fortunate to work at GI Care For Kids. Our group has 17 terrific physicians with a wide range of subspecialization, including liver diseases, feeding disorders, eosinophilic diseases, inflammatory bowel disease, cystic fibrosis, DiGeorge/22q, celiac disease, and motility disorders. Many of our physicians are recognized nationally for their achievements. Our group of physicians have worked closely together for many years. None of the physicians in our group have ever left to join other groups. I have also worked with the same nurse (Bernadette) since I moved to Atlanta in 1997. For many families, more practical matters about our office include the following: – 14 office/satellite locations – physicians who speak Spanish – cutting edge research – on-site nutritionists – on-site psychology support for abdominal pain and feeding disorders – participation in ImproveCareNow to better the outcomes for children with inflammatory bowel disease – office endoscopy suite (lower costs and easier scheduling) – office infusion center (lower costs and easier for families) – easy access to nursing advice (each physician has at least one nurse) I am married and have two sons (both adults). I like to read, walk/hike, bike, swim, and play tennis with my free time. I do not have any financial relationships with pharmaceutical companies or other financial relationships to disclose. I have helped enroll patients in industry-sponsored research studies.

Predicting long-term response with calprotectin levels

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This blog has been a fan of calprotectin levels (see related posts below) as both a screening test for inflammatory bowel disease and as a marker of disease activity.  Now more data is available indicating that calprotectin levels, much like endoscopic mucosal healing, after induction therapy correlates with long-term response (Inflamm Bowel Dis 2012; 18: 2011-17).

This retrospective study (2005-2010) examined 60 patients with IBD with elevated baseline calprotectin levels.  34 patients had Crohn’s disease (CD) and 26 had ulcerative colitis (UC).  42 patients received infliximab therapy and 18 patients received adalimumab.  After induction therapy, therapy was discontinued in primary non responders or continued as scheduled maintenance therapy for at least one year if not relapsing.

The average age at induction for CD patients was 30 and the corresponding age at diagnosis was 21.  For UC patients, the average age at induction was 29 and the corresponding age at diagnosis was 26.

Median calprotectin level at baseline was 810 μg/g (n=60).  After induction, the median value dropped to 97 μg/g (n=60) and at 1 year the value dropped to 27 μg/g (n=25).  The calprotectin level normalized in 31 patients after induction.  At 12 months, the sustained remission was present in 84% (26/31).  In contrast, only 38% (11/29) who had elevated levels after induction were in remission at 12 months.

Related blog entries:

Bystander effect –Genovese syndrome

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Genovese syndrome is more commonly called the “bystander effect” (NEJM 2013; 368: 8-9).

“Genovese syndrome” was coined after the brutal stabbing of Catherine Genovese in Queens, NY on March 13, 1964.  What was astonishing was that ~38 people either observed the attacks or heard the victim’s pleas for help and did nothing.  This prompted a large amount of psychological research.  The central factor identified as the reason for the bystander effect was the diffusion of responsibility.

Awareness of the bystander effect is increasingly important in medicine where large teams often are involved in the care of complex patients.  Sometimes it is difficult even to answer “Who is my doctor?”

When many doctors are involved in the care of a patient, it is easy for a passive approach to patient care to develop.  How can this be reversed?

  • Bystanders are far more likely to intervene when they are friends with one another.  Thus, encouraging collegial interactions is important.
  • Understanding that oral communication, even briefly, with the primary care team is crucial.  Written communication is useful for documentation, but important information should be relayed directly.
  • An initiative by the U.S. Agency for Healthcare Research and Quality, TeamSTEPPS (Team Strategies and Tools to Enhance Performance and Patient Safety) may be helpful in improving. team-based skills (TeamSTEPPS Home)

Related Links:

Augmentin Hepatotoxicity

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Augmentin (amoxicillin-clavulanic acid) hepatotoxicity is common, anywhere from 1 in 1000 prescriptions to 1 in 78,000 prescriptions.  Despite its frequent use in pediatrics, there is limited data on augmentin hepatotoxicity in this population.  A recent study adds some information (JPGN 2012; 55: 663-67).

As part of a prospective observational study involving 8 Spanish hospitals from 2008 to 2011, 11 patients, ages 1 to 11 years, with augmentin hepatotoxicity were identified.  Drug-induced hepatotoxicity was suspected in the presence of augmentin therapy if ALT was >2 time ULN, conjugated bilirubin was >2 times ULN, or if other liver biochemistries (AST/GGT or bilirubin) were >2 times ULN.  Causality criteria relied on the Council for International Organizations of Medical Sciences (CIOMS) scale.

According to CIOMS scale, 3 cases were highly probable for augmentin hepatotoxicity, 3 cases were probable, and 5 cases were possible.  In this study, the patient’s details and labs are given in Table 1.  Most cases were mild.  The most common symptom was vomiting. Only one had a bilirubin >1 mg/dL.  Two had very high ALT values (one 52 times normal). Viral serology (measured at least 2 determinations) and autoimmune titers were negative in all patients.

Resolution of the hepatotoxicity occurred over a 4 to 16 week period.  No cases required a biopsy.  The authors note that many more cases of milder disease likely go undetected.

Related blog entry:

Reference:

  • -Curr Drug Saf 2010; 5: 212-22.  Antibiotic-induced liver toxicity –clinical features/causality.
  • -JPGN 2008; 47: 395-405.  Drug-related hepatotoxicity/liver failure
  • -J Pediatr 2000; 136: 121.  Augmentin & cholestasis. 1.7 cases per 10,000 prescriptions.

Linaclotide –not for kids

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Linaclotide has been approved for adults (≥18 years) with chronic constipation and constipation-predominat irritable bowel syndrome (IBS-C) (Gastroenterol & Hepatol 2012; 8: 653-60).

Linaclotide is a 14-amino acid peptide that stimulates guanylyl cyclase C (GCC) receptors.  It mimics the endogenous peptides guanylin (15 amino acids) and uroguanylin (16 amino acids) which activate GCC through a cascade which activates CFTR to increase luminal levels of bicarbonate, chloride and water.  This in turn improves gastrointestinal transit.

There were several trials undertaken to assess the efficacy of linaclotide in IBS-C:

  • 47 patients (36 women) with IBS-C were treated with linaclotide (100 μg or 1000 μg) or placebo –5 day study. The 1000 μg dose significantly decreased colonic transit time compared with placebo.  No serious adverse events were reported.
  • 420 patients were enrolled in a 12-week, randomized, double-blind, placebo-controlled, dose-ranging study.  The population was 92% female, 80% caucasian with a mean age of 44 years.  337 patients completed the study.  There were improvements in the number of complete spontaneous bowel movements (CSBMs) per week and in abdominal pain.  Additional results:
  1. With 300 μg dose, there were 3.93 CSBMs/week, with150 μg dose 2.79 CSBMs/week compared with 1.47 for placebo.
  2. With 300 μg dose, there was -0.90 in pain score, with 150 μg dose -0.71 compared with -0.49 for placebo.  Overall, abdominal pain improved in 31.1-38.7% of linaclotide-treated patients compared with 22.7% of placebo-treated patients.

For chronic constipation, four trials (n=42, n=310, n=630, and n=642) have shown increased CSBMs/week.  On average, a dose of 290-300 μg dose resulted in 1.8-2.7 CSBMs/week, a dose of 145-150 μg dose resulted in 1.6-2.0 CSBMs/week compared with 0.5-0.6 CSBMs/week for placebo.  Changes in stool frequency were also reflected in quality of life scores.  When linaclotide was stopped, patients reverted to similar stooling rates as placebo-treated patients but no rebound effects were noted.

Prior to approval of linaclotide, lubiprostone (Amitiza) had been the only FDA-approved medication for IBS-C.  For chronic constipation, polyethylene glycol is another approved treatment.

Related blog entries:

More frequent pediatric IBD

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Using a national cohort of prospective and retrospective data on pediatric inflammatory bowel diagnosis, (PIBD) a recent report indicates a rising incidence of PIBD in Scotland (Inflamm Bowel Dis 2012; 18: 999-1005).

Key findings:

  • Between 2003-2008, 436 patients were diagnosed with PIBD; this equates to 7.82/100,000; Crohn’s was 4.75 and UC 2.06 per 100,000 respectively
  • Between 1990-1995, 260 patients were diagnosed with PIBD; this equates to 4.45/100,000; Crohn’s was 2.86 and UC 1.59 per 100,000 respectively
  • Mean age of diagnosis in more recent cohort was younger: 12.7 years compared with 11.9 years

Currently, a data-base coordinated in a single center along with collaboration with regional networks enables the capture of all new IBD diagnosis (since 1999).  Prior cohort was determined by “exhaustive examination” of previous IBD records.

Increased complexity or improper coding?

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Not surprisingly, the adoption of electronic health records (EHR) has been associated with higher charges, especially in the emergency room setting (NEJM 2012; 367: 2465-67).  The question remains whether this increased complexity that is being billed is justified or simply due to “gaming” the system with electronic technology.

A specific example has been the increase in the highest level 5 codes used in emergency department (ED) visits, from 27% to 48% of Medicare charges (2001 to 2010).

While “gaming” may be part of the answer, more of the answer lies in the increasing complexity of patient conditions and more complex therapeutic options.  Specifically, the increase in higher coding has been associated with the following:

  • Marked increased use in new diagnostic technology. Overuse of technology is ill defined and failure to diagnose carries a much heavier penalty for physicians.
  • Increased numbers of patients without medical homes.  This increases the need for more diagnostic certainty.
  • Reduced hospital capacity.  Patients may be boarding in ED for quite some time before eventual admission or discharge.

Although the reasons stated explain how there may be more justification for higher complexity, it is well-recognized that EHRs facilitate billing by presenting check-boxes to more easily satisfy coding requirements.  This helps eliminate undercoding.  One of the drawbacks, though, with EHRs has been elaborate documentation at the expense of more direct patient contact.

Take home message:

The current system of coding is flawed.  While the complexity of care has increased, it remains difficult to identify the true value of the care provided. When most incentives reward increased testing and increased documentation which are easy to quantify, this is what will happen.

Running out of options

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A series of articles on natalizumab were published which give practical advice for this drug which clinicians often turn to when ‘running out of options’ (Gastroenterol Hepatol 2012; 8: 4-17).

Slides from these articles should be available soon (not online on 1/2/13):

http://www.clinicaladvances.com/index.php/our_publications/gastro_hep-issue/gh_november_2012/

According to an algorithm on page 7, in patients with moderate-severe Crohn’s disease who have failed conventional therapies and anti-TNF drugs (or unable to tolerate), the next step is to obtain anti-JCV (John Cunningham Virus) antibody status.  Patients who test negative are ‘Okay to treat with natalizumab’ due to very low risk of progressive multifocal leukoencephalopathy (PML).  Repeated testing at least once a year is then recommended.

For patients who test positive for anti-JCV at any time point, natalizumab can be considered if no other treatment options are available, but the risk of PML is much greater. Previous blog entries (below) have discussed this in greater detail and have provided additional references:

Another article published the experience in 36 Mayo clinic patients between April 2008-September 2010 (Inflamm Bowel Dis 2012; 18: 2203-08).  Consecutive patients who received natalizumab were prospectively followed.  Of the 36 treated with natalizumab, 30 agreed to participate in the study.  23 patients had failed two anti-TNF agents and 7 had failed one anti-TNF agent.  Median age was 35 years.

Results:

  • 14 (46%) had a complete clinical response, 12 had a partial response, and four had no response.  Cumulative probability of a complete response within 1 year was 56%.
  • Time to response: 10% after 1st dose, 50% of patients had complete response after 4th dose
  • Adverse events were common –though this rarely caused drug cessation. Common events included headache and infections (listed in Table 4 of article).  Some infections prompted holding natalizumab for up to 8 weeks.
  • 11 stopped natalizumab due to lack of improvement.

Critical drug shortages in U.S.

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While the U.S. spends a lot of money on health care, there is little incentive to produce older drugs with small profit margins.  In addition to the financial aspects, there are many other factors involved including the following:  limited number of manufacturers, increased worldwide demand, aging production plants, shortages of materials, stockpiling, and regulatory demands. This is resulting in detrimental outcomes (NEJM 2012; 367: 2461-63).

A specific example is the shortage of mechlorethamine (nitrogen mustard).  Since the 1960s it has been part of a MOPP regimen for Hodgkin’s lymphoma.  For pediatric patients, a modification of this regimen, the Stanford V regimen, has had good success rates for Hodgkin’s lymphoma.

Due to the shortage of mechlorethamine, cyclophosphamide has been substituted into the regimen.  While this substitution was thought to be equally efficacious, a group of investigators from St. Jude/Univ Tennessee, Dana-Farber/Boston Children’s, and Lucile Packard Children’s/Stanford have found that this substitution has resulted in a much lower 2-year event-free survival: 75% with new regimen compared with 88% with previous regimen.  This is despite the fact that patients receiving the newer regimen did not have a more unfavorable treatment profile.

Patients who relapsed had salvage therapy with stem-cell transplantation.  The long-term outcome of the newer regimen group, nevertheless, appears substantially worsened.

This example is not isolated.  Other cancer-drug shortages have included cytarabine, daunorubicin, and methotrexate.  While some of these shortages have been resolved quickly, the frequency of these shortages as well as drugs used for multiple other diseases is alarming.  When physicians and pateints are faced with the prospect of receiving inferior care due to drug shortage, this is extremely “hard to swallow.”

The burden of being a physician

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The following link comments on a study regarding the high rate of physician burnout:

The Widespread Problem of Doctor Burnout – NYTimes.com

Among my physician friends, the topic of emotional fatigue comes up infrequently.  While there are different difficulties for every type of job, I think if you are not a physician it is hard to understand the emotional toll of the job.  If you care about what you do, it is hard to disassociate from the obvious suffering that some patients endure.  In addition, in many cases the decisions that we help families reach often have unexpected outcomes.

Though some physicians may not struggle with these issues, the link above indicates that this problem is pervasive.

If you have a practical solution, let me know.  Happy New Year.

Related blog (more upbeat):

“It is never boring to be a physician” | gutsandgrowth