Head-to-Head: Capsule Endoscopy versus Colonoscopy

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A recent study shows how useful capsule endoscopy (CE) can be in diagnosing Crohn disease (Clin Gastroenterol Hepatol 2014; 12: 609-15).  Congratulations to one of my partners, Dr. Stan Cohen, who is one of the authors.

This prospective study examined 80 patients with signs and/or symptoms of small-bowel Crohn disease (age, 10-65 years) who underwent CE, small-bowel follow-through (SBFT), and colonoscopy.

Presenting suggestive features included the following:

  • Diarrhea >6 weeks but less than 3 years
  • Abdominal pain >6 weeks but less than 3 years
  • Extraintestinal IBD manifestations: pyoderma gangrenosum, erythema nodosum, perianal disease, arthritis, aphthous stomatitis, and uveitis
  • Along with abnormal laboratory/clinical finding:
  1. positive inflammatory marker: sedimentation rate, C-reactive protein, calprotectin/lactoferrin
  2. unexplained iron deficiency
  3. hypoalbuminemia
  4. positive IBD serology (eg. anti-Saccharomyces cerevisiae antibodies)
  5. or other clinical findings: recurrent fevers, GI bleeding, growth failure, abnormal radiologic study

Results:

  • CE/colonoscopy in combination detected 107 of 110 inflammatory lesions (97.3%)
  • SBFT/colonoscopy detected 63 lesions (57.3%)
  • “The diagnostic yield of CE compared with colonoscopy was not different.”
  • Of the 80 patients with suspected Crohn disease, 25 (31.3%) had the diagnosis confirmed. 9 patients had diagnostic findings on at least 2 of the 3 modalities.  11 were diagnosed with CE alone and 5 by colonoscopy alone.

The authors conclude that colonoscopy remains the initial diagnostic test of choice.  However, “CE is safe and can establish the diagnosis of Crohn’s disease in patients when ileocolonoscopy results are negative or the terminal ileum cannot be evaluated.”

Take-home message: in patients with symptoms suggestive of Crohn disease, a negative colonoscopy is not sufficient to exclude the disease.  Other modalities like CE or MRE may be needed.

Related post:

Pediatric Capsule Endoscopy Experience

It is Hard to Keep Track…

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of all the new Hepatitis C virus (HCV) studies that are being published.  A recent study shows that the combination of sofusbuvir with either ledipasvir or GS-9669 was effective for HCV genotype 1 infections (Gastroenterol 2014; 146: 736-43).

Two years ago publication of this study would have been met with incredible enthusiasm.  However, now this study, while important, is part of a big trend showing that oral HCV therapies are going to make the treatment of HCV easier, safer, and expensive.  Ledipasvir (LDV) is a NS5A inhibitor and  GS-9669 is a NS5B non-nucleoside inhibitor.

The particulars of this study:  113 patients were enrolled.  All patients received sofusbuvir (400 mg daily).  LDV was dosed at 90 mg daily and GS-9669 at 500 mg daily.  Three of the four treatment arms used ribavirin (RBV) with 1000 mg for those patients <75 kg and 1200 mg for those patients >75 kg.

Four arms:

  1. SOF/LDV/RBV 12 weeks–n=25 treatment-naive (TN)/n=9 null responders (NR)
  2. SOF/GS-9669/RBV 12 weeks –n=25 TN/10 NR
  3. SOF/LDV or SOF/LDV/RBV 12 weeks–n=19 NR with cirrhosis
  4. SOF/LDV/RBV for 6 weeks –n=25 TN (noncirrhotic)

Key Results:

  • Group 1 had SVR12 of 100%, group 2 had SVR 12 of 92%, and group 4 (6 week Rx) had SVR12 of 68%.
  • Among cirrhotic NR, SVR12 was achieved in 9 (100%) of those with triple therapy (SOF/LDV/RBV) and 7 (70%) of those with SOF/LDV dual therapy.

Take home message: Oral direct-acting agents in combination are effective in all groups of patients affected by HCV, included those with cirrhosis and prior null responders.

An editorial (Clin Gastroenterol Hepatol 2014; 12: 533-36) titled “The End of Hepatitis C” indicates that “interferon-free treatment is likely to become the new standard of care within the next 12-18 months.”  However, the potential price tag for treating 3.2 million infected individuals in the U.S. would be about $270 billion in drug costs alone.

A related NEJM article: (link) “Curing Chronic Hepatitis C –The Arc of a Medical Triumph.”  And another study, (link) Sapphire II, showed the effectiveness of other oral agents for HCV.  This study examined ombitasvir, ritonavir, and dasabuvir in 394 patients.

More HCV study results will be reviewed later this week on this blog.

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Withdrawing Immunosuppression with Autoimmune Hepatitis

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A recent retrospective study indicates that withdrawal of immunosuppression in autoimmune hepatitis (AIH) can be successful in carefully selected children (J Pediatr 2014; 164: 714-19).

A cohort of 56 children with AIH were followed for a median of 5.6 years and with a median age of 11 years (62% female).  Demographics noted that cirrhosis was present in 14%, primary sclerosing cholangitis 21%, and AIH type II in 9%.

Key findings:

  • Biochemical remission with immunosuppression was achieved in 76% of all patients at a median of 1.2 years; 23% of these patients experienced a subsequent relapse.
  • Withdrawal of immunosuppression was successful in 14 of 16 of patients with type 1 AIH who had been treated for a median of 2.0 years after diagnosis.
  • When the authors excluded patients with inflammatory bowel disease, they noted that the probability of achieving a sustained immunosuppression-free remission was 42% at 5 years.  Sustained remission was defined as biochemical remission for >1 year, liver biopsy without inflammation, and no relapses.
  • Patients less likely to reach a biochemical remission with immunosuppression included patients with cirrhosis, elevated INR, positive ANCA titer, and patients with coexisting autoimmune disorder.

In their discussion, the authors note that treatment withdrawal is “generally considered more successful after at least 3 years of therapy,” though only 50% of their patients who had therapy withdrawn had been treated that long.  In addition, they state that while coexisting immune disorders often result in more frequent relapses, the one exception in the literature is celiac disease when patients adhere to a strict gluten-free diet.  They also urge all patients diagnosed with AIH to undergo testing for celiac disease and thyroid disease.

Limitations of the study include the following: small numbers of patients, single center (Utah), retrospective design, and cholangiography was not performed uniformly.

Take-home message: In patients doing well with AIH for 2-3 years & with normalized liver histology, it may be possible to withdraw immunosuppression.

Related blog posts:

Disclaimer: These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) and specific medical management interventions should be confirmed by prescribing physician.  Application of the information in a particular situation remains the professional responsibility of the practitioner.

 

How Common is Eosinophilic Esophagitis?

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There have been numerous epidemiologic studies regarding eosinophilic esophagitis.  A recent summary of a recent study (Clin Gastroenterol Hepatol 2014; 12: 589-96) has been posted on the AGA Journals Blog.  Here’s the link to the full summary:  EoE Prevalence AGA Journal Blog

Here’s an excerpt:

Eosinophilic esophagitis (EoE), which was barely recognized 20 years ago, affects at least 150,000 people in the United States, with three-quarters being adults, report Evan Dellon et al. in the April issue of Clinical Gastroenterology and Hepatology.

EoE, also known as allergic esophagitis, is an allergic inflammatory disease characterized by increased numbers eosinophils in the esophagus. Symptoms include difficulty swallowing, food impaction, and heartburn…

They found that despite its relatively recent description, EoE is frequently diagnosed in the US, with an estimated prevalence of 56.7/100,000 persons. The mean age of patients, surprisingly, was 33.5 years; 65% were male, 55.8% had dysphagia, and 52.8% had at least 1 other allergic condition. Prevalence peaked in men 35–39 years old (see figure).

EoE Prevalence by Age

Dellon et al. identified patients based on the International Classification of Diseases (ICD), 9th revision code for EoE (530.13). They state that this prevalence could be an underestimate, because knowledge of the code and recognition of EoE are increasing…

Take home point: This study shows that EoE in adults and in children is much more common in males than females, especially in those with other allergic diseases.  Given the frequency of those with mild symptoms, the prevalence data are likely to be huge underestimates.

Related blog posts:

 

Life and Limb: The Price of Not Vaccinating Children

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A recent article in USA Today focused some light on the issue of vaccine avoidance and its consequences. Two specific examples in the article included the death of an infant to pertusis and healthy boy who lost his arms and legs as a consequence of the measles. In my opinion, the authors and editors of this publication make a mistake by offering up too much credence to the vaccine naysayers presumably to provide a “balanced report.”  Their arguments should have been subjected to further scrutiny.  Here’s the link, decide for yourself:

http://usat.ly/1lEVlOe

Excerpt:

Recent measles outbreaks in New York, California and Texas are examples of what could happen on a larger scale if vaccination rates dropped, says Anne Schuchat, the CDC’s director of immunizations and respiratory diseases. Officials declared measles, which causes itchy rashes and fevers, eradicated in the United States in 2000. Yet this year, the disease is on track to infect three times as many people as in 2009. That’s because in most cases people who have not been vaccinated are getting infected by others traveling into the United States. Then, Schuchat says, the infected spread it in their communities.

The 189 cases of measles in the U.S. last year is small compared with the 530,000 cases the country used to see on average each year in the 20th century. But, the disease — which started to wane when a vaccine was introduced in 1967 — is one of the most contagious in the world and could quickly go from sporadic nuisance to widespread killer.

Measles kills about once in every 1,000 cases. As cases mount, so does the risk. “We really don’t want a child to die from measles, but it’s almost inevitable,” says Schuchat. “Major resurgences of diseases can sneak up on us.”…

Even so, in some states the anti-vaccine movement, aided by religious and philosophical state exemptions, is growing, says Paul Offit, chief of infectious diseases at Children’s Hospital of Philadelphia. He points to states like Idaho, Illinois, Michigan, Oregon and Vermont — where more than 4.5% of kindergartners last year were unvaccinated for non-medical reasons — as examples of potential hot spots. Such states’ rates are four times the national average and illustrate a trend among select groups.

“People assume this will never happen to them until it happens to them,” Offit says. “It’s a shame that’s the way we have to learn the lesson. There’s a human price for that lesson.”

The most vulnerable are infants who may be too young to be vaccinated, children with compromised immune systems and others who may be unable to be vaccinated for medical reasons, scientists say.

Related blog posts:

Quitting Smoking Associated with Better Mental Health

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Given the amount of information about the negative consequences of smoking that is currently available, some might say that you would have to be mentally-ill to start smoking.  The good news is that stopping smoking has been associated with improvements in mental health (BMJ 2014; 348: g1151 dii 10.1136/bmj.g1151 -thanks to Mike Hart for this reference).  Free full-text BMJ article PDF

From Abstract:

Design Systematic review and meta-analysis of observational studies.

Eligibility criteria for selecting studies Longitudinal studies of adults that assessed mental health before smoking cessation and at least six weeks after cessation or baseline in healthy and clinical populations.

Results 26 studies that assessed mental health with questionnaires designed to measure anxiety, depression, mixed anxiety and depression, psychological quality of life, positive affect, and stress were included…. the standardised mean differences (95% confidence intervals) were anxiety −0.37 (95% confidence interval −0.70 to −0.03); depression −0.25 (−0.37 to −0.12); mixed anxiety and depression −0.31 (−0.47 to −0.14); stress −0.27 (−0.40 to −0.13). Both psychological quality of life and positive affect significantly increased between baseline and follow-up in quitters compared with continuing smokers 0.22 (0.09 to 0.36) and 0.40 (0.09 to 0.71), respectively). There was no evidence that the effect size differed between the general population and populations with physical or psychiatric disorders.

Conclusions Smoking cessation is associated with reduced depression, anxiety, and stress and improved positive mood and quality of life compared with continuing to smoke. The effect size seems as large for those with psychiatric disorders as those without. The effect sizes are equal or larger than those of antidepressant treatment for mood and anxiety disorders.

Figure 2 shows the relationship of the individual studies and the mental health outcomes.  In every study except one, there was improvement in those who quit smoking, though many of the studies had confidence limits that indicated that the results did not meet statistical significance.

Bottomline: This study indicates that quitting smoking can improve rather than worsen mental health.

Adenoma Detection Rate: Life or Death Quality Measure

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Many physicians bristle at numerous quality measures due to concerns that they may have little relevance to clinical practice or that they are not representative since they measure only a tiny fraction of their work.  For adult gastroenterologists, adenoma detection rate may become a quality measure that will be more difficult to dismiss (NEJM 2014; 370: 1298-306).

Background: In this study, the authors evaluated 314,872 colonoscopies by 136 gastroenterologists by using data from an integrated health care delivery organization.  They determined associations between adenoma detection rate and the risks of colorectal cancer/cancer-related deaths diagnosed 6 months to 10 years after colonoscopy.  Estimates of attributable risk were adjusted for the demographics of the patients, indications for colonoscopy, and coexisting conditions.

Key Results:

  • The adenoma detection rate varied considerably, from 7.4% to 52.5%.
  • 712 colorectal adenocarcinomas were identified during followup, including 255 advanced-stage cancers.
  • 147 deaths from interval colorectal cancer occurred.
  • Among patients of physicians with adenoma detection rates in the highest quintile, compared with patients of physicians in the lowest quintile, the adjusted hazard ratio for any interval cancer was 0.52; it was 0.43 for advanced-stage interval cancer and 0.38 for fatal interval cancer.
  • For each 1% increase in the adenoma detection rate, there was an associated decrease in the risk of cancer by 3%.

Bottomline: Previous studies have shown that spending longer than 6 minutes on a screening colonoscopy increases detection rates.  This study shows that doing a high quality colonoscopy really does alter the outcome.

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Buyer Beware: Supplement at Your Own Risk

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Although I’m a pretty good swimmer, I am always a little uneasy when I see signs that say “Swim at Your Own Risk.” Perhaps, signs like that should accompany ‘dietary supplements’ since they are unregulated and often pose a significant unknown danger.

A fascinating perspective article discusses the myriad of problems with over-the-counter supplements (NEJM 2014; 370: 1277-80).  The article begins by detailing the cases of severe hepatitis and death due to OxyElite Pro, a supplement marketed for weight loss and muscle building.  This agent was linked to 97 patients, 47 required hospitalizations, 3 resulted in liver transplantation (that’s one way to lose weight!), and one death.  An astute liver-transplant surgeon was the first to suspect this supplement.

Since then “nothing has been done to prevent another supplement from causing organ failure or death.”

Key points:

  • Supplement industry: $32 billion spent in U.S. per year on 85,000 different combinations of vitamins, minerals, botanicals, amino acids, probiotics, and other ingredients
  • Supplements do not require premarketing approval.  “Under the Dietary Supplement Health and Education Act of 1994, anything labeled as a dietary supplement is assumed to be safe until proven otherwise.”
  • More than 500 supplements have already been found to be adulterated with pharmaceuticals like anabolic steroids, unapproved antidepressants, banned weight-loss medications, untested sildenafil analogues, and even methamphetamine analogues.
  • The FDAs ability to monitor these supplements is poor.  The MedWatch (https://www.safetyreporting.hhs.gov) is plagued with underreporting and lack of timeliness.  Local health departments have frequently stumbled upon the problem first.

Some common problems with current supplements include the following:

  1. Arrhythmias with agents like Ephedra, horny goat weed, and oleander
  2. Bleeding with Ginkgo
  3. Cancer with anabolic steroids (hepatoma), Beta-carotene (lung cancer), and Vitamin E (prostate cancer)
  4. Hepatotoxicity with numerous supplements including chaparral, comfrey, fo-ti, gerrymander, and kava
  5. Other problems: stroke, kidney stones, panic attacks, rashes, and mood alterations

The perspective notes that a bill in a Senate committee if passed would require that manufacturers register their products and provide some safety information.  This is unlikely to make any significant change.  The author recommends that “every supplement ingredient should undergo rigorous safety testing before marketing.”

Bottomline: when a patient asks you if “this supplement” is OK, the honest answer is nobody knows.

Related blog post:

Living on MARS

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As anyone who follows this blog knows, I really like good acronyms.  MARS which stands for molecular adsorbents recirculating system is another good one.  Data regarding the use of MARS for acute liver failure (ALF) due to Wilson disease in children has been recently reported (JPGN 2014; 58: 160-64, editorial 140-41).

Background: MARS is a form of dialysis to remove albumin-bound toxins via a specialized membrane. MARS has been studied as a potential bridge to liver transplantation or as a support to try to avoid liver transplantation in some cases.

The present study with only four children is not terribly informative.  However, both the article and the editorial provide references on small randomized controlled trials which concur with the conclusions of the authors that “biological and clinical improvement is demonstrated in the MARS treatment group compared with the standard medical treatment group.”  Yet, recent large multicenter randomized controlled trials are inconclusive with regard to whether MARS improves survival.

Bottomline (from editorial): “MARS does not prevent transplantation, and survival outcome post transplantation is unclear.  There is no robust evidence to justify the financial implications of this intervention in a clinical setting. The present role of MARS remains within the research setting.”

Macrolide Antibiotics and Pyloric Stenosis

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It is well-recognized that infants who receive macrolide antibiotics are at increased risk of pyloric stenosis. A recent study (BMJ 2014;348:g1908) indicates that maternal macrolide intake can also increase the risk of pyloric stenosis in their infants.

Link to article from NASPGHAN twitter feed: http://t.co/CnkbdZoRVf

Conclusions Treatment of young infants with macrolide antibiotics was strongly associated with IHPS and should therefore only be administered if potential treatment benefits outweigh the risk. Maternal use of macrolides during the first two weeks after birth was also associated with an increased risk of IHPS. A possible association was also found with use during late pregnancy.