Benefits of Gluten-Free Diet for “Asymptomatic” Celiac

Here’s a link to the abstract: gastrojournal.org/article/S0016-

Methods: “We performed a prospective trial of 3031 individuals at risk for celiac disease based on screens for EmA. Of 148 seropositive individuals, 40 fulfilled inclusion criteria and were randomly assigned to groups placed on a GFD or gluten-containing diets.”

Results: “The GFD group also had reduced indigestion (P=.006), reflux (P=.05), and anxiety (P=.025), and better health, based on the visual analog scale (P=.017), than the gluten-containing diet group.”

Take-home message: A gluten free diet improves symptoms (even in “asymptomatic” patients) with celiac disease

Comparing Biologics for Ulcerative Colitis

A recent study has reviewed biologic therapies for ulcerative colitis (Ann Intern Med. 2014;160(10):704-711). Here’s the abstract link: bit.ly/1o5PpRX.

Data Synthesis: ..There were 7 double-blind, placebo-controlled trials that were rated as low risk of bias and showed that all biological agents (adalimumab, golimumab, infliximab, and vedolizumab) resulted in more clinical responses, clinical remissions, and mucosal healings than placebo for induction therapy. The results of network meta-analysis suggested that infliximab is more effective to induce clinical response (odds ratio, 2.36 [95% credible interval, 1.22 to 4.63]) and mucosal healing (odds ratio, 2.02 [95% credible interval, 1.13 to 3.59]) than adalimumab. No other indirect comparison reached statistical significance. For maintenance, 6 double-blind, placebo-controlled trials that were rated high risk of bias showed that all biological agents have greater clinical efficacy than placebo. The occurrence of adverse events was not different between biological agents and placebo.

Limitation: Few trials, no head-to-head comparisons, and inadequate follow-up in maintenance trials.

Conclusion: Biological agents are effective treatments for UC, but head-to-head trials are warranted to establish the best therapeutic option.

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“Do Unto Others”

A recent article from NY Times discusses the topic of advance directives and how physicians are likely to choose a “no code” status for themselves rather than heroic measures if faced with a terminal illness.

Here’s a link:  What doctors would choose and an excerpt:

Young doctors… 88.3 percent would choose a do-not-resuscitate or “no code” status. An allow-me-to-die status, in other words.  “Doctors see a lot,” Dr. Periyakoil told me later that day. Resuscitation attempts are so aggressive — likely to break an older patient’s ribs but unlikely to restore them to their previous state of health or function —that after witnessing several, “you know too much and you’re much more wary,” she said.

Perhaps readers here remember a much-circulated web essay by Dr. Ken Murray, a retired family practitioner, called “How Doctors Die.” He claimed that his fellow physicians largely reject the sort of high-tech care they routinely dispense to their patients.

Take-home message: Physicians frequently provide high-intensity heroic measures to many of their patients which they usually would reject for themselves.  Even in pediatrics, frequently parents demand that “everything be done” when many physicians would advise otherwise.

Is Water The Best Beverage for Dieters? Maybe Not

According to a recent study in Obesity (2014; 22: 1415-21), during the first 12 weeks of a weight loss program water is not as helpful as non-nutritive sweetened drinks (eg. diet soda) when trying to lose weight (Thanks to Jeff Schwimmer for this reference).

The study describes the findings from the 12-week weight loss phase of a 1-year randomized, clinical trial to test the hypothesis that the amount of weight lost (12 weeks) and maintained (9 months) in a behavioral weight management program will be equivalent in participants consuming beverages containing non-nutritive sweetened beverages (NNS) compared to water.

  • Demographics: n=303, mean age ~48 years, 82% female, mean BMI 33
  • Design: “Participants randomized to the NNS beverage group were asked to consume at least 24 fluid ounces of NNS beverage per day and their water consumption was not restricted. An NNS beverage qualified if it had <5 kcal per 8 ounce-serving, was pre-mixed, and contained non-nutritive sweeteners.” Similarly, in the water group, individuals were instructed to consume at least 24 fluid ounces of water per day, and not drink any NNS beverages.
  • Results: “The two treatments were not equivalent with the NNS beverage treatment group losing significantly more weight compared to the water group (5.95 kg versus 4.09 kg; P < 0.0001) after 12 weeks. Participants in the NNS beverage group reported significantly greater reductions in subjective feelings of hunger than those in the water group during 12 weeks.”
  • Conclusion: “These results show that water is not superior to NNS beverages for weight loss during a comprehensive behavioral weight loss program.”

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Infliximab Compared to Adalimumab -Which is Better?

Pharmaceutical companies are not motivated to provide a definitive answer on the title question.  A recent study (Clin Gastroenterol Hepatol 2014; 12: 811-17) states that “head-to-head clinical trials of anti-TNF therapies are unlikely to ever be undertaken because of the extreme cost to conduct such studies and the financial risk that such trials would entail for the manufacturers.”  The two most popular biologics, infliximab (IFX) and adalimumab (ADA), for inflammatory bowel disease have been incredibly successful (Multi-billion dollar biologics | gutsandgrowth).

The current study is “one of the first to directly compare the effectiveness” of IFX and ADA for Crohn’s disease.  The authors retrospectively examined a U.S. Medicare data cohort from 2006-2010 and identified new users with 1459 IFX and 871 ADA patients.  While 94% of Medicare enrollees are >65 years, this study had a range of patient ages due to those who received Medicare due to disability.  In fact, in the ADA group, ~60% were between 30-60 years and in the IFX group, ~44% were in this age group.

Key result:

  • After 26 weeks of treatment, 49% of patients receiving IFX remained on drug compared with 47% of those receiving ADA.
  • Fewer patients with IFX underwent surgery (5.5 vs 6.9 surgeries per 100 person-years) but this did not reach statistical significance.
  • Rates of hospitalization did not differ among the two groups

While persistence is an imperfect measure of effectiveness, the fact that surgeries and hospitalizations were similar indicates that the medications are likely to have similar clinical effectiveness, at least in this population.  Data on mucosal healing, more direct measures of effectiveness, and longer followup certainly would strengthen this conclusion.

My First Take: It is Hard to Save $$$ at a Rolls-Royce Dealership

A recent article looked at a crucial issue –trying to deliver “best care at lower cost” (Inflamm Bowel Dis 2014; 20: 946-51).  “The goal of this report is to answer the primary question: What are implementable strategies and exploratory considerations for cost-efficient anti-TNF use while maintaining the highest quality of IBD care?”

The strategies that are discussed include the following:

  • Reduce costs of avoidable dose intensification of class switching by eliminating episodic anti-TNF use and improving patient education
  • Reduce over-utilization costs by accurately determining indication for escalating anti-TNF use
  • Reduce nondrug infliximab costs through shortened infusion times after initial safety is clearly established

Exploratory considerations:

  • Self-injectable anti-TNFs
  • Combination therapy
  • Monitoring anti-TNF drug levels and autoantibodies
  • Assessing mucosal healing as a clinical endpoint

The authors discuss both the exploratory issues and the strategies.  Some of each could easily increase costs, at least in the short-term, rather than reduce them.  The authors also make note of the development of an infliximab biosimilar (Inflecta) which could be approved in U.S. by 2015.

While the review article is a good read, in my opinion the authors fail to address in a meaningful way the larger context.  The costs for hospital-based care are enormous; pediatric hospitals are like Rolls-Royce dealerships; and by the way, if you have to ask how much it costs, you probably cannot afford it.  With regard to charges/costs, there is little transparency, high variability, and little accountability.  Understanding health care costs and trying to get a good deal is much harder than buying a car.

For IBD care, as an example, the authors make note of the cost of infliximab at one pediatric tertiary care center.  At this institution, “77% of the total health care cost for each infusion encounter” was for non-drug costs.  Given how expensive the drug cost is, the expense for an infusion is very high, but probably similar to many other pediatric hospitals.

If one is interested in reducing the costs of infliximab and other infusions, the first practical step would be to consider infusion outside of a hospital-based setting, such as an infusion center.  In such a setting, the patient safety would still be excellent but the costs would be less.

In Atlanta, there have been some high-profile hospital acquisitions that have increased health care costs (When doctors sell out, hospitals cash in | www.myajc.com).  In many circumstances, when a hospital acquires a physician practice, infusion center, or endoscopy center, the charges and reimbursement increase despite no change in clinical care.  In this way and many others, the current system promotes cost-inefficient care.

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When “All-Natural” Really Isn’t

A recent tweet from David Kessler provided this link, fooddive.com/news/the-case-, regarding all-natural products and recent spate of lawsuits:

Here’s an excerpt from “The case against ‘all-natural’:

But how “natural” is the “natural” label? It might be a bit more misleading than you think. The U.S. Food and Drug Administration admits it doesn’t even have a hard-and-fast definition on what the term means. The agency also doesn’t object to a product being labeled as such, so long as “the food does not contain added color, artificial flavors, or synthetic substances.”

However, some consumers just aren’t buying that “all-natural” claim, and there have already been many notable court cases to prove it. Here’s a roundup of five recent lawsuits forcing food producers to cough up cash and remove labels after products didn’t live up to their farm-to-store promise.

Five recent lawsuits -highlighted in article

  • Kashi
  • Nature Valley
  • PopChips
  • Naked Juice
  • Tropicana Orange Juice

In a related post, ClarkHoward.com discusses how labels are misleading:

Here’s the link: 5 Label Tricks

“Food labels like “organic,” “free range,” “all natural,” and “multigrain” don’t necessarily mean what you think.”  He provides specific advice to avoid buying a misleading product.

“ProCESS” for Improvement or Reason for Caution

“There is no such thing as the world of letters apart from the world of men…The scholar without this vision is a pedant.  He mistakes learning for an end in itself, instead of seeing that it is only a weapon in a wise man’s hands.” (Seth Low, 1890 -quoted in NEJM 2014; 370: 1679).

While sepsis, “the syndrome of dysregulated inflammation that occurs with severe infection,” is not frequent among pediatric gastroenterology patients, it does occur. Pediatric GI patients at risk include patients receiving immunosuppression medications, patients with inflammatory bowel disease, and patients with central lines.  So, it is not simply an academic exercise to understand the efforts to improve sepsis treatment. A recent study and related editorials discuss the role for protocols in treating sepsis, and likely have broader implications [NEJM 2014; 370: 173-76 (editorial-http://nej.md/1hYoAXc ), 1683-93 (article-http://nej.md/1qvKwBc ), 1750-51 (editorial-http://nej.md/1gkt6D2 )].

Overall, sepsis was reported as the 11th leading cause of death in the U.S. in 2010 and was the single most expensive condition treated in hospitals.  Nevertheless, the diagnosis is in part subjective and these statistics rely on insurance claims.

Key points:

  • Policymakers in New York require hospitals to adopt sepsis protocols (“Rory’s regulations”) following the death of a 12 year-old boy who died from unrecognized sepsis.  Other agencies, like the National Quality Forum (NQF), have recommended this as well. The Centers for Medicare and Medicaid is considering whether to adopt the NQF metric.
  • The ProCESS (Protocolized Care for Early Septic Shock) study (31 centers) enrolled 1341 patients (average age 61 years) into 3 randomized separate arms: protocol-based goal-directed therapy bundle, protocol-based standard therapy, and usual care. Conclusion: protocol-based resuscitation did not improve outcomes.
  • Sepsis mandates are not without risks.  Overdiagnosis can lead to unwarranted antibiotics, excessive testing, excessive blood transfusions, diversion of scarce ICU resources, and complications from central line placement.
  • Two more multicenter studies are underway (ARISE and ProMISE) which will further determine the utility of protocoled sepsis care

While the ProCESS trial did not identify improvements in protocol-driven care, most patients (76%) in all three groups received antimicrobials by the time of randomization (mean of ~3 hours).  Thus, early recognition of sepsis with treatment, particularly antibiotics and volume resuscitation, remain critical.  The editorial (pg 1750) imparts some useful advice from Machiavelli: “the physicians say it happens in hectic fever, that in the beginning of the malady it is easy to cure but difficult to detect, but in the course of time, not having been either detected or treated in the beginning, it becomes easy to detect but difficult to cure.”

More Eloquently Stated Concerns Over MOC

Recently, I stated my concerns over the MOC process: After I Passed The Test | gutsandgrowth

The same issues I discussed are articulated more precisely in a recent editorial, titled “Maintenance of Certification: Beauty is in the Eyes of the Beholder:”

Ann Intern Med. Published online 13 May 2014 doi:10.7326/M14-1014

Here’s the link: http://bit.ly/Centor 

AJG Celiac Practice Guidelines 2013 -Useful Link

This full-text link to AJG Practice Guidelines for Celiac Disease 2013 (Am J Gastroenterol 2013; 108:656–676; doi:10.1038/ajg.2013.79) provides 45 evidence-based recommendations for diagnosis and management of celiac disease along with 264 references.  

Table of Contents for Article

Table of Contents for Article

Topics of particular interest

  • Whether to test first-degree relatives.  The article recommends testing in symptomatic individuals and consideration of testing in asymptomatic individuals
  • When to perform genetic testing
  • When to use tests besides tissue transglutaminase antibody (TTG IgA) (mainly in children less than 2 years)
  • Recommends against use of stool or salivary testing
  • How to approach refractory celiac disease
  • The limited circumstances which justify followup endoscopy

Potential Reasons for Genetic Testing:

Potential Reasons for Genetic Testing

Celiac vs. Gluten Sensitivity:

Celiac vs. Gluten Sensitivity

Bottomline: This practice guideline covers most of the issues dealing with celiac and gluten sensitivity –it is a useful reference.

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