When A Disease Turns Out to Be Fictitious -The Sad Story on Sphincter of Oddi Dysfxn

Posted on by

When parents make up diseases in their children, the consequences can be dire.  What happens when doctors find out that a disease that they have been treating probably doesn’t exist?

  • Cotton PD et al. “Effect of endoscopic sphincterotomy for suspected sphincter of Oddi dysfunction on pain-related disability following cholecystectomy: the EPISOD randomized clinical trial” JAMA 2014; 311: 2101-2109.

A detailed analysis of this study (Gastroenterol 2015; 148: 440-44) and the author’s reply provides some insight into that questions and helps place this study and its results into context.

Key points from the Gastroenterology Selected Summary:

Background:

  • “Sphincter of Oddi dysfunction (SOD) is the term used to describe an episodic abdominal pain syndrome, typically occurring in young to middle-aged women in the setting of prior cholecystectomy…SOD remains a diagnosis of exclusion.”

Design:

  • “The investigators conducted a double-blind, sham-controlled, randomized trial at 7 US tertiary centers, enrolling 214 adult post-cholecystectomy patients with debilitating abdominal pain due to suspected biliary SOD (predominantly type III).” Sham patients underwent ERCP, manometry, and pancreatic duct stenting.
  • Patients were randomized 2:1 to sphincterotomy or sham; those randomized to sphincterotomy and subsequently shown to have a hypertensive pancreatic sphincter were then re-randomized (1:1) to have biliary or combined biliary/pancreatic sphincterotomies.

Results:

  • “Most patients in both study groups experienced considerable reduction in their pain disability scores…the proportion meeting the trial’s 1-year primary endpoint was higher among those treated with sham compared with sphincter ablation (37% vs. 23%, P=.01)”
  • “The manometry findings did not predict treatment success.”  There were no other useful predictors of success identified (eg. elevated liver enzymes, prior stone at cholecystectomy)
  • Adverse effects from procedures included 26 cases of acute pancreatitis (2 severe) and 2 perforations.

Discussion:

  • “The results of this trial are fascinating…the authors, many of whom had dedicated entire careers to the management of these patients using the very procedure they have now conclusively shown to be futile, may be understandably disheartened by the results.”
  • Numerous limitations of the study are noted.  In particular, “the 1-year time frame of the trial is likely to have been too short to capture the deleterious impact of prophylactic pancreatic duct stenting, which…has been associated with interval induction of pancreatic ductal abnormalities mimicking chronic pancreatitis.”
  • “It is our view that the authors’ data…provide an unambiguous mandate for imposing an immediate moratorium on subjecting this group of patients to ERCP.“

Dr. Cotton’s reply:

  • “It may be premature to discard the whole concept of sphincter dysfunction as a cause of pain.”
  • He indicates that “gallbladder dyskinesia” is another related question and was the reason for surgery in half of EPISOD subjects.
  • The results of the study “clearly show the need for equally stringent studies to answer the many remaining questions.”

For those who read this much of this post:  I wanted to let you know that yesterday’s online post on early peanut introduction was updated with recommendations from the associated editorial.

Related blog posts:

Another headline from Freaknomics Website follows. Of course I probably should think twice about poking fun at typos given the volume of them on this blog.

Screen Shot 2015-02-22 at 9.33.13 AM

The Peanut Story -From NEJM Blog

Posted on by

If you listen to any news source over the last day, there is a buzz about a new study regarding early peanut exposure in the prevention of peanut allergy.  A link to a blog that summarizes the study and the associated editorial:  NEJM Blog -Peanut Consumption in Infants For those who prefer a 1 minute video summary: Here’s a brief excerpt: The Learning Early About Peanut Allergy (LEAP) study, now published in NEJM, was a randomized, open-label, single-center study designed to compare two strategies to prevent peanut allergy: consumption or avoidance of peanuts. The trial enrolled children 4-11 months of age who were thought to be at high risk for developing a peanut allergy based on a history of severe eczema or egg allergy.  Participants were given a skin prick test to evaluate for sensitivity to peanut.  Children with a negative skin prick result (meaning no measureable skin wheal) or moderately positive (1-4mm wheal) were included in the study; children with a highly positive result (wheal >4mm) were excluded.  Infants were then stratified based on their skin prick test results. 530 infants in the skin prick test negative group and 98 infants in the skin prick test positive group were randomly assigned to either consume 6g of peanut protein per week or to avoid peanuts.  The primary outcome was the proportion of participants with a peanut allergy at age 5, determined by response to an oral peanut protein challenge. The results were impressive:  in the negative skin prick test group, the prevalence of peanut allergy at age 5 was 13.7% in the avoidance group versus 1.9% in the consumption group (P<0.001).  In the positive skin prick test group, 35.3% of those who avoided peanuts were allergic as compared with 10.6% of the consumption group (P=0.004).

This study (NEJM 2015; 372: 803-13) showed that the early introduction of peanuts (median age 7.8 months) significantly decreased the frequency of the development of peanut allergy among children at high risk for this allergy.  These results will result in changes in practice recommendations.  It is noted that approximately 10% of children who had a wheal of more than 4 mm develop after skin-prick testing were excluded.  The associated editorial (pages 875-77) by Rebecca Gruchalla and Hugh Sampson recommends a cautious approach: “any infant between 4 months and 8 months of age believed to be at risk for peanut allergy should undergo skin-prick testing for peanut. If the results are negative, the child should be started on a diet that includes 2 g of peanut protein three times a week for at least three years.” For those with mild positivity, “the child should undergo a food challenge…by a physician who has experience performing a food challenge.”

Marketing to Doctors -Informative Satire

Posted on by

One of my colleagues recently shared a youtube link that I recommend highly to anyone who is concerned about the relationship between pharmaceutical companies and physicians.  As with any good piece of satire, it is both funny and thought-provoking.  As one would question the impartiality of politicians who receive funds from constituents with a specific agenda, likewise patients may question whether physicians are unduly influenced by their relationship with pharmaceutical companies.

For those too busy to enjoy the entire ~17 minutes, watch the last three minutes:

 

Taking One ‘Bite’ At A Time -For Celiac Diagnosis

Posted on by

A small study (reference from KT Park’s Twitter feed –Gastrointestinal Endoscopy DOI: http://dx.doi.org/10.1016/j.gie.2014.10.024) suggests that taking a single biopsy per pass rather than two biopsies per pass results in better quality specimens:

Link: Endoscopic Biopsy Technique in the Diagnosis of Celiac Disease

Here are the results and conclusion of the abstract:

Results

Patients (N = 86) were enrolled, 47% with known celiac disease, 36% with suspected celiac disease, and 17% with an unknown celiac disease status. Well-oriented biopsy specimens were noted in 66% of patients with the single-biopsy technique and 42% of patients with the double-biopsy technique (P < .01). Analysis of matched pairs showed improved orientation with the single-biopsy technique (odds ratio 3.1; 95% confidence interval, 1.5-7.1; P < .01). This persisted in subgroup analysis of patients with known celiac disease (P = .02), villous atrophy (P = .02), and a final diagnosis of celiac disease (P < .01).

Conclusion

The single-biopsy technique improves the yield of well-oriented duodenal biopsy specimens. Endoscopists should consider taking only 1 biopsy specimen per pass of the forceps in patients undergoing biopsies of the duodenal mucosa.

Related blog posts:

I'm the one on the right

I’m the one on the right

Lost Decade from Smoking

Posted on by

A recent study (NEJM 2015; 372; 631-40) showed that smoking is more deadly than previously estimated.  Key points:

  • Deaths per year due to smoking: a new analysis suggests the true figure may be closer to 575,000.  That equates to 1 death in every 5 in the United States.
  • Smoking is thought to shorten life expectancy by more than one decade!
  • The 21 causes of death that have been officially blamed on smoking accounted for only 83% of the actual deaths among smokers

Here’s a link to a summary of the article:  Cigarette Smoking is Even More Deadly Than You Thought (from LA Times)

Related blog post:

From NPR: Enormous Ice Formations at Niagara Falls:

From NPR

From NPR

Accelerated Infliximab Dosing in Acute Severe Ulcerative Colitis -plus one link

Posted on by

A small retrospective study (n=50) suggests that more rapid induction with infliximab may improve response and lower colectomy rate in acute severe ulcerative colitis (UC).

Link: Accelerated Infliximab in Acute UC

Here’s the abstract:

Background & Aims

Administration of infliximab to patients with acute severe ulcerative colitis (ASUC) (rescue therapy) can reduce the rate of early colectomy (within 12 months), but long-term rates of colectomy are the same as those of the pre-biologic era for these patients. The half-life of infliximab is shorter in patients with ASUC than in patients with non-severe UC, so more frequent dosing might be required to produce a therapeutic effect.

Methods

We performed a retrospective analysis of 50 hospitalized patients who received infliximab for steroid-refractory ASUC at a single academic center from September 2005 through 2013. In 2011 an accelerated dosing strategy for infliximab was introduced; we compared outcomes of standard and accelerated dosing regimens. One group of patients (n = 35) were placed on a standard dosing regimen for infliximab and then given the drug at 0, 2, and 6 weeks and then every 8 weeks thereafter. A second group (n = 15) were placed on an accelerated regimen and received 3 induction doses of infliximab within a median period of 24 days. Rates of colectomy were compared between the groups during induction and follow-up periods.

Results

There were no differences between groups in median baseline levels of C-reactive protein, albumin, or hemoglobin. The rate of colectomy during induction therapy was significantly lower with the accelerated regimen (6.7%, 1 of 15) than with the standard regimen (40%, 14 of 35) (Fisher exact test, P = .039). The standard regimen was associated with shorter time to colectomy (log-rank test, P = .042). Among patients who completed induction therapy, subsequent need for colectomy was similar between the groups during the follow-up period. Multivariate analysis showed that factors independently associated with successful induction therapy were level of albumin (g/L) when the treatment began (P = .003) and the accelerated dosing regimen (P = .03).

Conclusions

In patients with ASUC, an accelerated infliximab induction strategy reduces the need for early colectomy. An intensified infliximab dosing strategy in response to clinical or laboratory signs of breakthrough inflammation merits consideration in prospective studies.

One other link: IBD and College: Do the two play nicely (from Jeremy Adler and UofM) -describes college transition issues for our IBD patients.  Probably the most important piece of advice: “Take your medicine.”  Many really good kids decide to see what happens off therapy, often to their detriment.

How Effective are the Treatments for Functional Abdominal Pain?

Posted on by

According to a recent systematic review (Korterink JJ et al. J Pediatr 2015; 166: 424-31), “there is no evidence to support routine use of any pharmacologic therapy” for pediatric functional abdominal pain (FAP).  How many pediatric gastroenterologists want to discuss this conclusion with their patients?

How did the authors reach their conclusion?

Design: The authors screened 557 articles and ultimately identified only four articles with a total of 6 studies met inclusion criteria which included the following:

  • systemic review or randomized control trial
  • children 4-18 years
  • diagnosis of FAP established with well-defined criteria
  • intervention was compared to placebo or alternative treatment

Results: All of the studies were reviewed –each received an overall quality rating by the authors as “very low.” The particular treatments included amitriptyline, peppermint oil, famotidine, miralax, tegaserod, and cyprohepatadine.  The study with the most patients had only 90 patients and the longest treatment period was 4 weeks.

In the discussion, the authors make several key points:

  • there is a lack of adequately powered, high-quality, placebo-controlled drug trials in children with FAP
  • weak evidence was found in support of peppermint oil, cyproheptadine, and laxatives at reducing pain; amitriptyline and famotidine had weak evidence supporting some improvement in global symptoms or quality of life.
  • problems with the studies: small sample sizes, poorly reported side effects, lack of follow-up, risk of bias
  • “several nonpharmacologic therapies (e.g.. hypnotherapy and cognitive behavioral therapy) have shown their efficacy in treating children with” FAP…with success rates up to 85%.  Moreover, these therapies are not hampered by severe side effects.”

Bottomline: Our office-based psychologist may be more helpful for our patients than all the medications combined.

Related posts:

How to Reduce Suffering

Posted on by

A recent NY Times article (yesterday) discussed ways to reduce patient suffering and improve physician/hospital evaluations: Doctors Strive to Do Less Harm

  • Minimize waking patients up at night.  Eliminate waking patients up for vital signs and blood draws.
  • Reduce waiting times.
  • Spend more time listening.

Related blog posts:

 

 

Increased Narcotic Usage in Pediatric Patients with IBD

Posted on by

A summary from the AGA Journals Blog of a recent article highlights the increased use of chronic narcotics, not related to surgery, in pediatric patients with IBD.

Here’s a link:  Chronic Use of Narcotics in Children with IBD and here’s an excerpt:

Jessie P. Buckley et al used data from a large insurance claims database, collected from 2010 through 2011, to compare the prescription narcotic use among children (younger than 18 years old) with and without IBD who were not undergoing surgery. Buckley et al also searched for factors associated with narcotic treatment of pediatric patients with IBD.

Of 4344 children with IBD during the study period, 63% had Crohn’s disease, and 37% had ulcerative colitis.

Buckley et al found that 5.6% among children with IBD vs 2.3% in the general population received chronic narcotic therapy. Associations between IBD and narcotic use revealed a particularly high burden among children with concomitant anxiety or depression.

Cover of Clinical Gastroenterology & Hepatology

Cover of Clinical Gastroenterology & Hepatology –The pills look cool but wrong age depicted