How Common is Eosinophilic Esophagitis?

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.

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Adenoma Detection Rate: Life or Death Quality Measure

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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How Colonoscopy & Preps are Indicative of Patient Activation and Health Care Decision-Making

I found two recent studies on bowel preps interesting primarily because of how they help us understand problems with utilization and problems with patient motivation.

The first study (Clin Gastroenterol Hepatol 2014; 12: 443-50) utilized a 5% random national sample of Medicare claims data.  The authors determined that among 57,597 Medicare beneficiaries 66 years and older that underwent screening colonoscopy (not therapeutic) 24.8% of these procedures were performed in individuals with a life expectancy <10 years.  Given the nature of the study (eg. relying on administrative data), there were several limitations.  However, the implication of the study is that there are a lot of unnecessary colonoscopies.  That is, screening colonoscopies are intended to interrupt a sequence of adenoma to adenocarcinoma that can take years; even when cancer is present, it can take several years before the onset of clinical symptoms.  Currently, the US Preventive Services Task Force (USPSTF) recommends against routine screening in those aged 75-84, precisely because the benefits of screening may be outweighed by the risks of screening.”  The authors note that “people with multiple comorbidities (and therefore lower life expectancy) are more likely to visit multiple providers, which increases the chances of receiving testing.”

The second study (Clin Gastroenterol Hepatol 2014; 12: 451-57) showed that patients with lower “patient activation” are much more likely to have a poor colonoscopy preparation.  Patient activation is defined as “an individual’s knowledge, skill, and confidence for managing his/her own health and health care.”  The author’s note that the “Patient Activation Measure (PAM) is a validated scale developed…to measure this construct.” This cross-sectional study took place in Chicago between 2008-2010 at either an academic practice or a ‘federally qualified health center.’ Key findings:

  • One-third of patients (n=134/462 adults) had suboptimal quality of bowel preparations. Of these, 15% (n=62) were fair quality and 17% (n=72) were poor quality.
  • After multivariable analysis and adjustments, patient activation (OR 2.12) and diabetes (OR 2.45) were independent predictors of suboptimal bowel preparation quality.
  • Health literacy (a measure of cognitive skill) was not correlated with patient activation (a measure of patient engagement).

Also noted in same journal issue: Clin Gastroenterol Hepatol 2014; 12: 470-77.  “In a supervised setting, nurse endoscopists perform colonoscopies (after a minimum of 100) according to quality and safety standards that are comparable with those of physician endoscopist and can substantially reduce costs.”

Take-home messages:

  1. Poor bowel preparations are common.  In studies of adult patients, split-dose preparations can help.  The associated editorial (pg 458-462) recommends delaying case and considering further oral prep or enemas for patients arriving with stool that is not clear or yellow.
  2. Colonoscopies are performed too frequently in some patients and not frequently enough in others.  Thus, something as simple as a colonoscopy is not so simple.

Related blog posts:

Probiotics For Fatty Liver Disease

Probiotics and alterations in the microbiome are being examined for a range of ailments.  However, as noted in previous blog posts, the current evidence shows only a limited number of disorders where probiotics have been proven effective.  There is more evidence, now, that probiotics may be beneficial for nonalcoholic fatty liver disease (NAFLD).

  • Am J Clin Nutr 2014; 99: 425-6. editorial
  • Am J Clin Nutr 2014; 99: 535-42.

The referenced article examined 52 nondiabetic patients with fatty liver disease in a double-blind, randomized, placebo-controlled trial. Patients were considered to have NAFLD on the basis of an ultrasonography and an alanine aminotransferase value >60 U/L.  Those who received a probiotic were compared with a placebo group and followed for 28 weeks.

In this study, rather than a probiotic, technically, the treatment group received a synbiotic because it contained fructooligosaccharides (FOS) which are non digestible oligosaccharides in addition to a probiotic mixture.  FOS can stimulate the growth of intestinal bacteria.  The probiotic mixture included Lactobacillus case, Lactobacillus rhamnosus, Streptococcus thermopiles, Bificobacterium breve, Lactobacillus, acidophilus, B. longum, and Lactobacillus bulgaricus.

Key findings:

  • There were improvements in ALT values and in baseline mild fibrosis (estimated by Fibroscan).
  • There were decreased levels of circulating TNF-α and decreased nuclear transcription factor κβ in circulating mononuclear leukocytes –both consistent with decreased systemic inflammation

Limitations: 

  1. Study did not include liver histology (biopsy).  In addition, in nearly all subjects, the fibroscans were near normal, both before and after the intervention.  Thus, the reduction in liver stiffness is not clear cut.
  2. Small number of participants.
  3. Short study period.

Bottomline: This study along with several others points towards a potential role for modulating the microbiome to improve NAFLD along with metabolic syndrome more broadly.

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What is Evidence-Based Medicine for Helicobacter Pylori?

Full article (Clin Gastroenterol Hepatol 2014; 12: 177-86): http://ow.ly/sPKbi 

My take on the most important parts of this Helicobacter pylori (HP) article:

  • Success defined: curing HP ≥95% =excellent, curing HP ≥90% =good, acceptable ≥85%, and unsatisfactory <85%.
  • “Because clarithromycin-containing triple therapy and 10-day sequential therapy are now only effective in special populations, they are considered obsolete.”
  • The “preferred choices for Western countries” are the following
  1. 14-day concomitant therapy: PPI, amoxicillin 1 g, clarithromycin 500 mg, metronidazole -all twice daily
  2. 14-day bismuth quadruple therapy: PPI BID, bismuth BID, tetracycline 500 mg QID, metronidazole 500 mg TID
  3. 14-day hybrid sequential-concomitant therapy: 7 days of PPI-amoxicillin 1 g, followed by amoxicillin 1 g, clarithromycin 500 mg, metronidazole 500 mg for 7 days-all BID

Other useful points:

  • Tetracycline is not available in many parts of the world and generally doxycycline is not an adequate substitute for tetracycline.
  • Triple therapies are extremely sensitive to resistance of the third drug (eg. clarithromycin and metronidazole).  The increase in resistance is making these regimens ineffective
  • An online calculator can help predict which therapy to choose: https://hp-therapy.biomed.org/tw/ (need to know local resistance)
  • Poor compliance is the other factor besides resistance that can undermine a well-constructed treatment regimen. Spending ample time educating patients about the need to  take all of their medicines is crucial.
  • Figure 1 on page 178 outlines the recommended treatment approach.  Unfortunately, availability of susceptibility testing has been quite limited.

Take-home message: The authors emphasize using regimens that work locally and using the evidence that we have to choose the best treatments.  However, given the resistance patterns, working on collaborating with laboratories to culture HP for susceptibility/resistance would be worthwhile to increase the likelihood of excellent outcomes.

Related blog links:

Also noted:  full text article online (from Kipp Ellsworth twitter feed): http://goo.gl/dD2ooF “Intestinal Transplantation: An Unexpected Journey”  This is a succinct overview of intestinal transplantation’s progress and potential.

Disclaimer: These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) should be confirmed by prescribing physician.  This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition.

Why an ERCP Study Matters to Pediatric Care

While there are pediatric patients who undergo endoscopic retrograde cholangiopancreatography (ERCP), this is a relatively infrequent occurrence. Nevertheless, a recent study has a couple useful clinical pearls that may have broader application.

  1. Clin Gastroenterol Hepatol 2014; 12: 303-07.
  2. Clin Gastroenterol Hepatol 2014; 12: 308-10 Associated editorial
  3. Gastroenterol 2014; 146: 581-82. Associated summary

Key points/Implications:

  • Aggressive hydration may prevent post-ERCP pancreatitis. In the study, the treatment group received an average of 3290 mL over the 9-hour period compared with 945 mL in the standard infusion group.
  • Implication: The speculation from the study and the editorials is that improved pancreatic perfusion will result in better oxygenation and reduce the likelihood of  pancreatitis. In the 2nd reference, the author states that his practice is to administer “at least 3 L of crystalloid in recovery to young, healthy patients who have undergone high-risk ERCP and an additional 3 to 5 L within the first 12 hospital hours to those admitted with postprocedure pain”
  • The best fluid (for post-ERCP and acute pancreatitis) may be lactated Ringer’s (LR).
  • Implication: The lactate in LR may help reduce pancreatitis by avoiding acidosis which could promote zymogen activation and pancreatic inflammation. A previous small trial (n=40) of acute pancreatitits from any cause showed lesser degrees of systemic inflammatory response with LR in compared with normal saline (Clin Gastroenterol Hepatol 2011; 9: 710-17e1).
  • This study adds aggressive IVFs as another intervention to prevent ERCP.  Rectal indomethacin and prophylactic stent placement (in high-risk patients) are other accepted treatments.

Study details:

This pilot study randomly assigned 39 patients to aggressive hydration and 23 to standard hydration; all patients were inpatients who were not at risk for fluid overload. The aggressive group received 3 mL/kg/h during the procedure, a 20 mL/kg bolus after the procedure, and then continued on 3 mL/kg/hr for 8 hours.  In contrast, the standard group received LR at 1.5 mL/kg/h during and for 8 hours afterwards.

Demographics: The average age was 43 years in the aggressive hydration group and 45 years in the standard group. 78% were hispanic.  The ERCP procedures were mostly “average risk.”  74% had ERCP for choledocholithiasis.  Only 2 subjects needed precut sphinterotomy (3%).

Results:

  • No patients in the aggressive hydration group developed acute pancreatitis compared with 4 (17%) in the standard hydration group
  • Elevated amylase (23% vs. 39%) and epigastric pain (8% vs 22%) were also less frequent in the aggressive hydration group.

Numerous Limitations: This was a small pilot study with an atypical population; thus, the findings are difficult to generalize.  A false-positive (type 1 error) can easily occur due to the small numbers, especially as the standard hydration group had a rate of acute pancreatitis that was about double from previous studies. In addition, this study was not blinded and could have been susceptible to bias.  Furthermore, the authors defined acute pancreatitis differently than in previous studies.  In this study, the authors required enzyme increases 2 or 8 hours after ERCP with new abdominal pain; in previous studies, the definition of acute pancreatitis relied on enzyme increases for at least 24 hours after the ERCP.

Take-home message for those not doing ERCPs: Think about using lactated ringer’s and aggressive hydration in otherwise-well patients who present with acute pancreatitis.

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What and When for ERCP with Gallstone Pancreatitis

A recent case vignette highlights several key points regarding use and timing of ERCP (endoscopic retrograde cholangiopancreatography) for gallstone pancreatitis (NEJM 2014; 370: 150-7). Figure 1 provides a nice illustration of ERCP.

Indications:  Suspected bile-duct stones as the cause of pancreatitis AND one of the following:

  • cholangitis (fever, jaundice, sepsis)
  • persistent biliary obstruction (conjugated bilirubine level >5 mg/dL)
  • clinical deterioration (worsening pain, increasing white cell count, worsening vital signs)
  • stone evident in the common bile duct on imaging

AGA position paper (2007):

  • Urgent ERCP (within 24 hours of admission) was recommended in those with cholangitis
  • Early ERCP (within 72 hours of admission) was recommended if suspicion of persistent bile-duct stones remained high

Patient information/animated videos for pancreatic diseases from the National Pancreas Foundation: http://ow.ly/sF9vb 

Related post:

Indomethacin to prevent post-ERCP pancreatitis | gutsandgrowth

Variation in Practice -The Influence of Money

A recent study highlights the problem of bundling and shows how financial incentives distort care in some gastroenterology practices (Clin Gastroenterol Hepatol 2014; 12: 58-63).

Background: When needed, patients can undergo both colonoscopy and esophagogastroduodenoscopy (EGD) at the same time; when combined, the procedures are considered bundled.  It is more convenient for patients and less costly to do the two procedures during the same sedation.  However, Medicare reimbursement to physicians for bundled procedures is less than the sum of the two procedures when charged separately. This creates an incentive for physicians to unbundle these procedures.

Study design: The authors examined Medicare claims from 2007-2009 in a national, random sample (patients ≥66 years) –part of the Surveillance Epidemiology and End Results Program.

Results:

  • 12,982 had colonoscopy and EGD within 180 days.  ~35% of these were not bundled.  This included 2359 (18%) unbundled procedures which were performed within 30 days of each other.
  • Geographic differences were noted: bundling occurred less often in the Northeast (55%) and most often in the West (68%)

What does this study indicate about bundling (& human nature)?  This study indicates that physicians respond to underlying financial incentives to separate these procedures.  In our pediatric practice, we do not unbundle procedures.  The additional facility costs, use of anesthesia, costs to families from missing work, and convenience are compelling reasons to combine procedures if feasible.  However, this data indicates that unless physicians are paid the same value for each EGD and colonoscopy, there will continue to be many patients who have their procedures scheduled on separate dates.

Bottomline: Medicare and other insurance companies will save money by not paying less for combined procedures.

Another example of financial incentive influencing care with regard to ambulance and EMS care:  How Perverse Incentives Drive Up Health Care Costs / ideastream 

Moving to All Oral Therapy for Hepatitis C

Two more studies show the promise of all oral treatment for Hepatitis C virus:

  • NEJM 2014; 370: 211-21.
  • NEJM 2014; 370: 222-32.

A summary of these articles is available at the following link: http://t.co/Z8jMPKoLGz.

Here is an excerpt:

Hepatitis C treatment isn’t pretty, but the dark days of weekly injections, rough side effects and no guarantee of full recovery from the liver-damaging disease may soon be over, researchers report.

Two studies, both published in the Jan. 16 issue of the New England Journal of Medicine, involved giving various combinations of antiviral pill cocktails to patients with hepatitis C. Some had failed to respond to standard treatments, and some had not received treatment yet. Yet, the cocktails cleared the virus in both studies for between 93 percent and 98 percent of the patients…

The first study, conducted by Johns Hopkins researchers, included 211 men and women with hepatitis C who took two pill-form antiviral medications, daclatasvir and sofosbuvir. The patients were treated at 18 medical centers in the United States and Puerto Rico. They took 60 milligrams of daclatasvir and 400 milligrams of sofosbuvir for either 12 or 24 weeks, with or without a third drug, ribavirin….

98 percent of the 126 previously untreated patients and 98 percent of 41 patients whose infections had not cleared despite treatment with standard hepatitis C therapy, were considered cured. “There was no detectable virus in their blood three months after the treatment stopped,” he noted.

The second study, headed up by researchers at Virginia Mason Medical Center in Seattle, involved more than eight medical centers in the United States and internationally. It included 571 patients with hepatitis C, some of whom had not received treatment previously and others who had previously received standard treatments with interferon injections and ribavirin — an antiviral drug that when given reduces relapses — but had not responded to them.

The participants were randomly assigned to take any of three combinations of antiviral pills — medications called ABT-450, ABT-267, and ABT-333 — for eight, 12 or 24 weeks…

Almost all of the patients (more than 93 percent in both groups) saw the virus cleared from their systems within 24 weeks.

Bottomline: Once daily treatment with a combination of medicines will be an effective and safe cure for more than 90% of individuals with HCV. Whether these agents will be affordable remains in doubt.

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AGA Guidelines for the Use of Thiopurines and Anti-TNF Agents for Crohn’s

The link (from KT Park’s twitter feed): gastrojournal.org/article/S0016-5085(13)01521-7/fulltext …

Some of the key points/recommendations for adults with Crohn’s disease:

  • In clinical practice, CD of moderate severity is defined as disease requiring systemic corticosteroids for symptom control.

For Induction of Remission:

  • We Suggest Against Using Thiopurine Monotherapy to Induce Remission in Patients With Moderately Severe CD (Weak Recommendation, Moderate-Quality Evidence)
  • We Suggest Against Using Methotrexate to Induce Remission in Patients With Moderately Severe CD (Weak Recommendation, Low-Quality Evidence)
  • We Recommend Using Anti–TNF-α Drugs to Induce Remission in Patients With Moderately Severe CD (Strong Recommendation, Moderate-Quality Evidence)
  • We Suggest Using Anti–TNF-α Drugs in Combination With Thiopurines Over Anti–TNF-α Drug Monotherapy to Induce Remission in Patients Who Have Moderately Severe CD (Weak Recommendation, Moderate-Quality Evidence)

Maintenance of Remission:

  • We Recommend Using Thiopurines Over No Immunomodulator Therapy to Maintain a Corticosteroid-Induced Remission in Patients With CD (Strong Recommendation, Moderate-Quality Evidence)
  • We Suggest Using Methotrexate Over No Immunomodulator Therapy to Maintain Corticosteroid-Induced Remission in Patients With CD (Weak Recommendation, Low-Quality Evidence)
  • We Recommend Using Anti–TNF-α Drugs Over No Anti–TNF-α Drugs to Maintain Corticosteroid- or Anti–TNF-α—Induced Remission in Patients With CD (Strong Recommendation, High-Quality Evidence)
  • We Make No Recommendation for or Against the Combination of an Anti–TNF-α Drug and a Thiopurine Versus an Anti–TNF-α Drug Alone to Maintain Remission Induced by a Combination of These Drugs in Patients With CD (No Recommendation, Low-Quality Evidence)

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