Sunday, March 23, 2014

Research Update - Late Winter

Research Update 


Sleep and IBD


There have been a number of articles in the past 12 months related to sleep and IBD.  The theme is consistent – IBD is associated with higher levels of fatigue and poor sleep quality.  The first study looked at two years of IBD patients and determined that active disease is strongly correlated with fatigue.  

Additionally, IBD-related fatigue is correlated with increased psychological stress and decreased quality of sleep.(1)  For those with impaired sleep, there was a two-fold increase in risk for disease relapse in Crohn’s disease (but not ulcerative colitis) (adjusted odds ratio, 2.00; 95% confidence interval, 1.45–2.76).  Interestingly, females were more likely to have sleep disturbances and related issues in both studies.(2)  Doctors may want to include basic sleep questions as part of their diagnostic regime, such as the Pittsburgh Sleep Quality Index (http://www.opapc.com/images/pdfs/PSQI.pdf).

Vitamin D and IBD


Often-discusses is the relationship of Vitamin D and Inflammatory Bowel Disease.  A recent survey looked at Vitamin D studies and found the following:

·         Between 16 and 95% of IBD patients are vitamin D deficient. To appropriately bound this, however, some studies have estimated the global vitamin D deficiency percentage to be 42% in the general population, with much higher numbers I higher latitudes.(3)
·         Low vitamin D was associated with an increased risk in surgery for Crohn’s disease (OR 1.8, 95% CI 1.2–2.5) but not Ulcerative Colitis.
·         Low vitamin D was associated with increased hospitalizations for both Crohn’s (OR 2.1, 95% CI 1.6–2.7) and UC (OR 2.3, 95% CI 1.7–3.1).(4)

While the studies showed correlations between vitamin D deficiency and IBD, they have not shown causation.  Those who are the least healthy may venture out less (less sun exposure) or have worse absorption.  Alternatively, vitamin D deficiency may cause a worsening of symptoms.  Although the causality isn’t know, there are other risks of low vitamin D that warrant supplementation when extremely low (such as cardiac disease and rickets).

Diet, Revisited


We have looked at the role in diet on this blog before, but another review study came to essentially the same conclusions.  The study looked at all of the papers mentioning diet and IBD between 1975 and the present and came to the conclusion that:

                There is little evidence from interventional studies to support specific dietary recommendations.

The study did confirm that enteral nutrition can be helpful in inducing remission, but that as soon as enteral nutrition is stopped the diet factors become irrelevant.  The key takeaway in this study, which is one of the few to stress this with IBD, is that “dietary intake should not be inappropriately restrictive.”(5)

Bottom Line


·         For physicians, asking about sleep issues can assist IBD patients that may be aggravating their symptoms (and general quality of life) identify issues.
·         Low vitamin D may be correlated with IBD.  Extremely low levels should be supplemented as with any deficiency, especially in the winter and in climates at high latitudes.
·         Individual diets and IBD relapse are not well correlated.  While more work is warranted in this area, patients should not unnecessarily restrict diets based on outdated advice.
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1.       Graff, Lesley A., Ian Clara, John R. Walker, Lisa Lix, Rachel Carr, Norine Miller, Linda Rogala, and Charles N. Bernstein. "Changes in fatigue over 2 years are associated with activity of inflammatory bowel disease and psychological factors." Clinical Gastroenterology and Hepatology 11, no. 9 (2013): 1140-1146.
2.       Ananthakrishnan, Ashwin N., Millie D. Long, Christopher F. Martin, Robert S. Sandler, and Michael D. Kappelman. "Sleep Disturbance and Risk of Active Disease in Patients With Crohn's Disease and Ulcerative Colitis." Clinical Gastroenterology and Hepatology 11, no. 8 (2013): 965-971.
3.       Prentice, Ann. "Vitamin D deficiency: a global perspective." Nutrition reviews66, no. s2 (2008): S153-S164.
4.       Ardizzone, Sandro, Andrea Cassinotti, Maurizio Bevilacqua, Mario Clerici, and Gabriele Bianchi Porro. "Vitamin D and inflammatory bowel disease." Vitamins and hormones 86 (2010): 367-377.

5.       E. Richman, J. M. Rhodes.  Evidence-Based Dietary Advice for Patients With Inflammatory Bowel Disease.  Aliment Pharmacol Ther. 2013;38(10):1156-1171.

Sunday, March 16, 2014

Old Crap

Coprolites


Although they sound like a type of sea life, coprolites are fossilized feces.  While they are applicable to many fields (imagine having to look through brontosaurus feces), human coprolites can tell us about our ancestor’s dietary habits, infections, and biome makeup.  Human coprolites have even helps us date the first humans present in North America (though there is valid controversy over the dating).(1,2)

Disease-wise, ancient coprolites have been found to contain most modern parasites, in addition certain bacterial strains.  Clostridium has been identified as early as 1240 CE in fossilized feces.  Evidence of tapeworms, hookworms, mites, lice, and fleas have been identified in coprolites dating back to approximately 4,000 BCE.  Charcot-Leyden Crystals, evidence of diarrhea, were identified in at least one sample of ancient coprolites as well.(3)

Prehistoric coprolites dating from 3500 BCE in the Americas showed a change in diet around that time, shifting from pochote and millet as food crops to cassava, mesquite, maguey, and beans.  Additionally, pollen analysis showed the use of juniper tea, potentially for medicinal reasons.(4)

To-date, coprolites have not been used to identify the prevalence of IBD in earlier societies.  Diseases ranging from tuberculosis to pertussis have been identified, but they were found through the presence of relevant pathogens.(5)  Because there have been no pathogens definitively identified as causing IBD (though previous posts discuss the correlational evidence), this route has not been fruitful.  There is reason, however, to believe that future analysis may yield some information.  Possible avenues for identification include:

·         Mineral analysis.  Based on the likely deficiencies present in IBD, there would be an expected difference in absorption for those with IBD based on other samples from the then-current diet.
·         Pathogen analysis.  Though we haven’t found causal pathogens, correlated pathogen presence may provide indicators of IBD. 
·         Evidence of diarrhea.  Evidence that a coprolite “creator” suffered from diarrhea without corresponding infections being present may be a possible indicator.
·         Protein analysis.  Analyzing the proteins present in coprolites may yield clues as well.(6)  Fecal calprotectin is a protein marker for IBD, and has a possibility of being present in ancient feces.

Unfortunately, little is known about the presence of inflammatory bowel disease through the ages.  Hopefully, coprolites may play a role in the near future in tracing back the history of Crohn’s disease and ulcerative colitis.

Bottom Line


·         Coprolite analysis can provide insight into ancient human dietary intake and the presence of pathogens
·         No published research was found trying to analyze coprolites for markers of IBD, but possible avenues exist for future research.

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1.       Gilbert, M. Thomas P., Dennis L. Jenkins, Anders G√∂therstrom, Nuria Naveran, Juan J. Sanchez, Michael Hofreiter, Philip Francis Thomsen et al. "DNA from pre-Clovis human coprolites in Oregon, North America." Science 320, no. 5877 (2008): 786-789.
2.       Poinar, Hendrik, Stuart Fiedel, Christine E. King, Alison M. Devault, Kirsti Bos, Melanie Kuch, and Regis Debruyne. "Comment on “DNA from pre-Clovis human coprolites in Oregon, North America”." Science 325, no. 5937 (2009): 148-148.
3.       Reinhard, Karl J., and Vaughn M. Bryant Jr. "Coprolite analysis: A biological perspective on archaeology." (1992).
4.       Bryant Jr, Vaughn M. "Prehistoric diet in southwest Texas: the coprolite evidence." American Antiquity (1974): 407-420.
5.       Appelt S, Armougom F, Le Bailly M, Robert C, Drancourt M (2014) Polyphasic Analysis of a Middle Ages Coprolite Microbiota, Belgium. PLoS ONE 9(2): e88376. doi:10.1371/journal.pone.0088376

6.       Newman, Margaret E., Robert M. Yohe II, Howard Ceri, and Mark Q. Sutton. "Immunological protein residue analysis of non-lithic archaeological materials."Journal of Archaeological Science 20, no. 1 (1993): 93-100.

Sunday, March 9, 2014

Short Book Review - Gulp: Adventures on the Alimentary Canal

This blog is about Evidence-based IBD, but this post is a bit different – I generally don’t review books, but Mary Roach’s Gulp. (the period is part of the title, but I’ll drop if for the rest of the post to avoid having my grammar checker go crazy) is unique.  Roach has written about several “taboo” subjects in polite conversation before – namely Bonk (sex) and Stiff (dead people).  Gulp takes readers on a trip through the digestive system in a fascinating way and is highly entertaining reading.

The reason Gulp appeals to Evidence-based IBD is that it gets people who don’t have the disease talking about their digestive health.  While those with IBD feel comfortable discussing the difference between “soft” and “loose” bowel movements and can talk about a colonoscopy without blushing, the general public doesn’t have the same tolerance levels.  Staying out of the public eye has some serious downsides:

1.       It alienates those with IBD and keeps them from being able to discuss an important part of their lives.
2.       It keeps those who are undiagnosed from seeking treatment due to the taboos surrounding the issue.
3.       “Popular” diseases receive more funding.  The more public-facing, the more likely that research dollars will be directed to a particular disease.

Gulp tackles digestive issues head-on, while remaining as sensitive as possible given the topic.  Roach looks at the fringes of the alimentary system, starting with the mouth and ending with the rectum (what did you expect from a book with the subtitle Adventures on the Alimentary Canal?)  Instead of dealing directly with disease, Roach paints interesting vignettes about the different parts of the digestive system.  For instance:

·         The possibility (or impossibility) of being eaten alive and surviving.
·         Exploding intestines from colonoscopies.
·         The viability of fecal transplantation.
·         The potential impact of bowel disease on the death of Elvis.

All of Roach’s chapters use the digestive system as a rough roadmap to tell interesting stories about people (and parts of people).  She brings a critical eye to scientific areas, but has a voice that entertains while educating.  The humor (especially the footnotes) that is present is the equal of any current author, and brings a light hearted bent to a heavy subject.

Of particular note (and the one the tale vignette that stuck with me) was the story of Alexis Bidagan St. Martin.  A 20 year old fur trader injured by a musket shot on Mackinac Island, St. Martin ended up with a hole in his stomach.  The treating doctor, William Beaumont, treated the wounds but left an open fistula in the stomach.  Miraculously, St. Martin survived almost 60 more years.  In the decades following his injury, Beaumont experimented on St. Martin by placing food directly into the stomach, measuring how it digested in-situ (this was, of course, before IRBs and perhaps even "medical ethics"). 

There is no Bottom Line to this post – it is simply a recommendation to read Gulp, to enjoy a lighter view on what is usually covered in a more serious tone (at places like Evidence Based IBD), and to think about how we can all socialize IBD in a more effective way.

Sunday, March 2, 2014

Colonoscopy - Knock 'em Out or Not?

Colonoscopies and Sedation


In the United States, individuals remember the prep much more than the procedure.  This is because, unlike most of Europe and Asia, colonoscopies are done under sedation.  What is sedation, and what are the pros and cons of having a colonoscopy without the sleepy-time option?

First, many individuals don’t understand what it means to be sedated.  Sedation is often confused with general anesthesia – and rightfully so.  The main source of the confusion is that sedation and general anesthesia can be induced by the same drug – one is just a deeper state than the other.  In colonoscopies, drugs like midazolam and Propofol (yes, the same drug that was found in Michael Jackson’s system) are used.  Because sedatives are not analgesics, they are frequently paired with drugs like fentanyl to reduce the pain associated with the procedure.  Basic IV sedation does not require substantial airway management and is generally done using a skilled nurse and does not require an anesthesiologist. 

The level of sedation used varies by practitioner – it can go from mild conscious sedation, where the patient is “awake” but not completely aware to full anesthesia (no responsiveness to even painful stimuli).  Because amnesia is one of the side effects, the patient may not even know how “deep” they were under.  Not remembering a colonoscopy can be a positive thing, but is it necessary?

Anesthesia has become much safer since the days of ether in the operating room.  The rates of death due primarily to anesthesia are now believed to be along the order of 1 in 100,000 (back in 1950 the rate was closer to 1 in 1,000).(1)  With 15 million colonoscopies a year in the US, this would mean an average of 150 deaths per year due to the application of anesthesia, but only if anesthesia didn’t prevent other risks.(2)  Unfortunately, the data shows that anesthesia also increases the risk of splenic rupture and other fun things – this is believed to be due to the sedated patient not being able to communicate when things go wrong.(3,4)
Despite the potential for complications, the primary driver for not using anesthetics isn’t safety, but cost.  A typical Propofol administration can add anywhere between $600 and $1,000 to the cost of a procedure.  When screening colonoscopies are recommended for the masses, this may mean an increased healthcare cost of over $1 Billion per year.(5)  Given finite health resources, the societal question becomes one of the greatest application of funds.

Most patients, when provided the opportunity to have sedation free colonoscopies, are able to tolerate the procedure fairly well.  Only 2.3% of patients rated the pain “moderate” or “severe” when provided a sedation-free procedure.  Most rated it as non-existent or mild.(6)  The population used, however, was the screening colonoscopy population – individuals less likely to need extensive polyp removal or navigation through strictured areas.  A recent study looked specifically at this issues facing IBD patients and found that those with intestinal inflammation required more sedation (and analgesic application) than those without inflammation.  This may suggest a bifurcated approach – using sedation with IBD patients and no sedation for screening colonoscopies.(7)  Or, perhaps, a hybrid approach that allows for patient-directed sedation.(8)

There are other intangible benefits to the non-sedation colonoscopy as well.  These include less time spent with the procedure and the ability to drive oneself home afterward (a major benefit for those of us that are single and have to rely on friends).  These may outweigh the discomfort factor for some individuals.

The use of sedation is largely a personal choice in the US.  Since most health plans will pay for it, there is minimal individual cost.  The small amount of increased risk may be a consideration for some, but the increased pain likely with those suffering from IBD (and increased duration) may counteract that.  Ultimately, it comes down to personal choice.

Bottom Line


·         There is an increased risk of death and complications in sedation colonoscopies, though it is not large.
·         The costs associated with sedation are large for the healthcare system overall, but not for the individual patient.
·         Those with IBD may have more severe and longer pain when having colonoscopies performed than those having a screening colonoscopy.
·         Sedation is an individual choice – it can always be added (as long as an IV has been started) if a patient begins to feel too much pain.

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1.       Lienhart, Andre, Yves Auroy, Francoise Pequignot, Dan Benhamou, Josiane Warszawski, Martine Bovet, and Eric Jougla. "Survey of anesthesia-related mortality in France." Anesthesiology 105, no. 6 (2006): 1087-1097.
2.       Seeff, Laura C., Thomas B. Richards, Jean A. Shapiro, Marion R. Nadel, Diane L. Manninen, Leslie S. Given, Fred B. Dong, Linda D. Winges, and Matthew T. McKenna. "How many endoscopies are performed for colorectal cancer screening? Results from CDC’s survey of endoscopic capacity."Gastroenterology 127, no. 6 (2004): 1670-1677.
3.       Eckardt, Volker F., Gerd Kanzler, Thomas Schmitt, Alexander J. Eckardt, and Gudrun Bernhard. "Complications and adverse effects of colonoscopy with selective sedation." Gastrointestinal endoscopy 49, no. 5 (1999): 560-565.
4.       Cooper, Gregory S., Tzuyung D. Kou, and Douglas K. Rex. "Complications following colonoscopy with anesthesia assistance: a population-based analysis." JAMA Internal Medicine 173, no. 7 (2013): 551-556.
5.       Fleisher, Lee A. "Assessing the Value of “Discretionary” Clinical Care The Case of Anesthesia Services for Endoscopy." JAMA: The Journal of the American Medical Association 307, no. 11 (2012): 1200-1201.
6.       Takahashi, Yuuichi, Hideaki Tanaka, Mitsuyo Kinjo, and Ken Sakumoto. "Sedation-free colonoscopy." Diseases of the colon & rectum 48, no. 4 (2005): 855-859.
7.       Kale, V., C. Dunne, M. Ahmed, S. Lee Chun, G. Cullen, H. Mulcahy, and G. Doherty. "PATIENTS WITH INTESTINAL INFLAMMATION REQUIRE MORE SEDATION DURING COLONOSCOPY." Gut 62, no. Suppl 2 (2013): A9-A10.

8.       Leung, J. W., S. Mann, and F. W. Leung. "Options for screening colonoscopy without sedation: a pilot study in United States veterans." Alimentary pharmacology & therapeutics 26, no. 4 (2007): 627-631.