Sunday, June 23, 2013

Phone Tag


When to Call the Doctor


Having a chronic illness creates complications in deciding when to call the doctor.  Both Ulcerative Colitis and Crohn’s Disease have common symptoms that would send anyone without a chronic illness running for the ER.  To quote the Mayo Clinic’s web page, you should see your doctor if you have diarrhea and:

1.       Your diarrhea persists beyond three days without any sign of improvement
2.       You become dehydrated — as evidenced by excessive thirst, dry mouth or skin, little or no urination, severe weakness, dizziness or lightheadedness, or dark-colored urine
3.       You have severe abdominal or rectal pain
4.       You have bloody or black stools
5.       You have a fever of more than 102 F (39 C) (1)

These are great general guidelines, but they may need modification for those with IBD.  Looking at them in order:

1.       Diarrhea is frequently chronic, and can last extensive periods of time (and can even be the baseline for some folks). 
2.       This one is pretty good.  Dehydration is always a problem, and should result in a call to the doc.
3.       Many folks with structuring have frequent abdominal pain, and rectal pain from bowel movements is common as well. 
4.       Small amounts of bleeding from rectal irritation (“surface blood”) can be the baseline for some with IBD.  Black, tarry stools is generally an upper GI bleed and should result in a call to the doc.
5.       Night sweats are common with IBD and several of the treatments.  Frequent night sweats can make differentiating a serious fever difficult.

From just this one symptom, it’s easy to see why calling the doctor when you have IBD may not be as easy of a decision to make.  Calling five times a week isn’t practical, but there are times when you should absolutely give your doc a call.  A few guidelines:

1.       When your doctor wants you to.  You should discuss with your GI doctor, based on your personal situation, when you should call.  This will vary greatly based on your status (flaring or stable) and your particular manifestations, as well as what medications you are taking.
2.       When there is no proximal cause.  Though we can never definitively attribute a symptom to a single data point (a proximal cause), it does become a factor in when to call.  If you are lactose intolerant and consumed a large milkshake, a little GI upset may be expected.  On the other hand, if you have a poison-ivy like rash appear and haven’t left the house for a week, it may be worth checking in.
3.       When your baseline changes.  Each of us has our own baseline.  “Normal” may mean 5 loose bowel movements a day and fatigue in the afternoon.  If that number increases to 8 a day, it’s time to call the doc. 
4.       When there are immediate threat symptoms.  Bloody tar in the stool, vomiting bile, and sustained fever are all reasons to call the doctor immediately (and if they are not available, its time for a visit to the ER). 
5.       When in doubt.  If you are on the fence about whether or not to call your doctor, err on the side of caution and make the call.  The worst that will happen is you expend a couple minutes of your time in exchange for piece of mind.

Bottom Line


-          Symptoms that would necessitate a call to the doctor for those without IBD may be “normal” for those with Crohn’s and Colitis.
-          When experiencing a new symptom or in doubt about your current state, call your doc.
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Sunday, June 16, 2013

IBD and Fish Oil


Omega-3 Fatty Acids, Crohn's, and Ulcerative Colitis


One of the most touted diet supplements for general good health is Omega-3 fatty acids (n-3 acids).  Generally available in pill form and sold as “fish oil”, they have been presented to the general public as having tremendous health benefits ranging from cardiovascular improvement to lowering the risk of stroke.  They have also been put forth as a part of maintenance regimes for both Crohn’s Disease and Ulcerative Colitis.  This post will look at the evidence of efficacy and safety in taking omega-3 fatty acid supplements as a maintenance treatment for inflammatory bowel disease and won’t address the benefits/risks if any in taking them to treat other conditions.

n-3 acids are polyunsaturated fats found naturally occurring in a variety of foods, with fish having the highest levels.  A single serving of salmon has over 1 gram of n-3 acids, flounder has .5 grams, and shrimp and crabs both have around .25 grams.  Other foods contain n-3 acids also, with eggs topping out the charts at .1 gram per egg.  Diets high in seafood have generally been shown to have positive coronary effects, and n-3 acids are believed to be part of that positive impact (there are other positives to eating certain types of fish also – including having low fat and avoiding other types of food with poor diet profiles).(1)

The mechanism for action in n-3 acids with IBD is the reduction of proinflammation cytokines.  Baseline studies in humans showed that triglycerides were reduced with the intake of n-3 acids in Crohn’s disease patients, along with epidemiological evidence showing a low incidents in Eskimo populations where a fish heavy diet is prevalent (though the studies don’t isolate fish or fish oil).(2,3)  Further, animal studies showed lesion healing commensurate with the intake of n-3 supplements.(4)

The first major study to address fish oil supplements, an enteric-coated capsule was provided to a small sample of Crohn’s patients prospectively in a double-blind, placebo controlled study of 78 patients (39 controls).  The fish oil group showed higher rates of remission, though there were a few individuals that dropped out and the sample size was small.(5)  Similar early studies with Ulcerative Colitis showed no maintenance effect, but did show a small effect in inducing remission.(6)

Unfortunately, the initial study results did not hold up when larger studies were conducted (notably the EPIC studies).  Reviews of the well-designed studies showed no significant result from taking Omega-3 fatty acids with either Ulcerative Colitis or Crohn’s Disease, and found a likelihood of publication bias (not publishing negative results).  While the smaller studies had mixed results, the larger studies showed no statistical impact in taking fish oil for IBD.(7)  There is still some room for experimentation – there may be different dosing or delivery mechanisms with higher efficacy, but they haven’t come out yet in the evidence.

Omega-3 supplements have not been shown to have any major side effects, however two of the minor side effects are of particular interest to those with IBD.  Both diarrhea and upper GI upset are common side effects, and caused drop-outs in several of the studies noted above. 

The lack of efficacy of omega-3 fatty acids in maintaining remission in IBD is disappointing.  That said, there is no reason to stop eating fish as a regular part of your well balanced diet.  Salmon and flounder are excellent sources of lean protein.  I recommend trying cedar plank cooking of both (if you have not tried it, Google “cedar plank salmon”) now that the grilling season is upon us!

Bottom Line

·         Omega-3 fatty acid supplements have no statistically significant effect on IBD remission based on the current research.
·         While the side effects of fish oil supplements are minor, the most common – diarrhea and upper GI upset, can effect quality of life in Crohn’s and UC patients.
·         Eating fish is still recommended as part of a well-balanced diet – skip the supplements, eat the fish.

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2.       Belluzzi, A., C. Brignola, M. Campieri, E. P. Camporesi, P. Gionchetti, F. Rizzello, C. Belloli et al. "Effects of new fish oil derivative on fatty acid phospholipid-membrane pattern in a group of Crohn's disease patients."Digestive diseases and sciences 39, no. 12 (1994): 2589-2594.
3.       Belluzzi, Andrea, Stefano Boschi, Corrado Brignola, Alessandra Munarini, Giulio Cariani, and Federico Miglio. "Polyunsaturated fatty acids and inflammatory bowel disease." The American journal of clinical nutrition 71, no. 1 (2000): 339s-342s.
4.       Vilaseca, J., A. Salas, F. Guarner, R. Rodriguez, M. Martinez, and J. R. Malagelada. "Dietary fish oil reduces progression of chronic inflammatory lesions in a rat model of granulomatous colitis." Gut 31, no. 5 (1990): 539-544.
5.       Belluzzi, Andrea, Corrado Brignola, Massimo Campieri, Angelo Pera, Stefano Boschi, and Mario Miglioli. "Effect of an enteric-coated fish-oil preparation on relapses in Crohn's disease." New England Journal of Medicine 334, no. 24 (1996): 1557-1560.
6.       Hawthorne, A. B., T. K. Daneshmend, C. J. Hawkey, A. Belluzzi, S. J. Everitt, G. K. Holmes, C. Malkinson, M. Z. Shaheen, and J. E. Willars. "Treatment of ulcerative colitis with fish oil supplementation: a prospective 12 month randomised controlled trial." Gut 33, no. 7 (1992): 922-928.
7.       Turner, Dan, Prakesh S. Shah, A. Hillary Steinhart, Stanley Zlotkin, and Anne M. Griffiths. "Maintenance of remission in inflammatory bowel disease using omega3 fatty acids (fish oil): A systematic review and metaanalyses."Inflammatory bowel diseases 17, no. 1 (2011): 336-345.

Sunday, June 9, 2013

Link Spamming and IBD


Scamming the search results


Google is the still the primary search engine most of us use to find useful information on the Web.  Their PageRank algorithm is generally effective – promoting pages that have more links to them, and ordering search results based on the popularity of the results.  Unfortunately, this means that popular pseudoscientific ideas can show up higher in the rankings than legitimate articles and studies on a particular topic.  While this affects all searches for any topic, in this post I’ll look at some of the most common searches related to IBD and examine the top Google results.

Inflammatory Bowel Disease.  This term is probably the most reasonable in terms of results.  The top 10 are all legitimate medical providers (e.g. the Mayo clinic), information aggregators (e.g. Wikipedia), or government sources (the Centers for Disease Control in the US). 

Crohn’s.  The first link is to the Crohn’s and Colitis Foundation of America – the leading advocacy group for those that suffer from IBD.  There are a few links to Wikipedia, WebMD, and other several provider sites, but there is one link that has poor information in the top 10:

Fox News, a bastion of accurate journalism (sarcastic note), has an article titled “Curing Crohn's? Man says he found way to beat incurable disease”.  While the article itself is fairly balanced overall and talks about an individual that went into remission after maintaining a healthy diet and being on 6-MP, the first half implies that the patient got better due to things like “krill oil, garlic, cat’s claw and probiotics”, before providing a medical opinion:

“He got better because of the 6MP,” Kummer told FoxNews.com, “and he took it for a long time. We have an objective measure of him getting better, and he felt good, so he stopped taking it – and he continued to feel good. But, that’s the mechanism of the drug.”
And
Meisel did go off all medications, and although he realizes he fundamentally cannot be ‘cured’ of an incurable disease, he and Kummer can agree he is in remission – for now

The highly suggestive and inaccurate headline (bordering on negligent) makes implications about cures for Crohn’s, despite covering nothing of the sort.

Ulcerative Colitis.   As with Crohn’s disease, searching for UC provides links to solid medical sites and basic information portals.  Fortunately, none of the first-page links appear to be to any questionable cures or charlatan sites.

What happens when we add the word cure (this is an expected term that the newly diagnosed would put in)? 

Crohn’s Cure.  All appears to be similar with the addition of the word cure – the same articles above appear (including the Fox News article), but there is one additional article that looks unusual at first glance at cureforcrohns.co.uk.  The title is a bit frightening, and the summary appears to imply someone claiming to have cured Crohn’s disease with diet.  Going to the site, however, shows a fairly balanced account of one individual that does not claim to have been cured.  The site is from the mother of a 16 year old boy who is in drug-free remission that she attributes to removing lactose from his diet.  While this constitutes no proof whatsoever of the effectiveness of removing lactose (it is a single account, has no experimental value, and there are no secondary details), the site does look at Mycobacterium Avium Paratuberculosis (MAP) as a cause for Crohn’s disease in a relatively objective manner.  MAP is potentially linked to Crohn’s (this will be the subject of a future post),, and there is some correlation between the two found in multiple studies, but it tends to attract followers who overstate the evidence.  (2)

Ulcerative Colitis Cure.  Uh-oh.  The very first link is to an Ayurveda-based “medical” site claiming to have a cure for Ulcerative Colitis in the form of Ulcerin.  The site claims:

Approximately 85% patients, who never had a remission with 5-aminosalicylic acid, 5-ASA, and mesalazine (Brands-Asacol; Mesasal; Pentasa; Salofalk) and steroid therapy, became symptoms free with the addition of these compounds. Many patients were thinking of surgery, because they were advised Colectomy (total removal of large intestines) before my treatment. Many (approx. 85%) patients went in remission. This success gave me lot of satisfaction in my life.

Reading further, however, there is a caveat added:

After treatment only a few patients could be subjected to investigations like colonoscopic or Sigmoidoscopic and Histopathological examination due to the lack of facilities in my center.

The site has questionable links (you need to get a phone call back to make a payment) and the drug they are selling has no efficacy nor even safety (or minimum toxicity) information available.  I’ll take a deeper look at this product and Ayurveda-based medicine in future posts also.  For now, anyone purchasing from this site and taking the medicine is taking quite a risk.  (3)

 I suspected this site has moved to number 1 through manipulation of the Google algorithm, and I was not disappointed.  The site is primarily linked from forums related to Crohn’s disease.  The forums generally consist of a member that has signed up, linked to the site on the available boards with a “Found this miracle cure” posting, then dropped off.  This has all of the hallmarks of a quack attack (where the proprietors of a website create multiple identities claiming to be cured, post a link to a quack medicine they are selling, then disappear).  The remaining sites appear to be valid, as with Crohn’s disease.  

IBD Cure.  The number 4 link on IBD is similar to the above-mentioned questionable links.  Curezone provides a basic overview of IBD (that is fairly well done), but then trails off into irresponsible territory, citing toxins and a water cure.  It goes into colon, kidney, and liver cleansing, containing dangerous methods like the coffee enema, covered previously, as part of the regime. 

A closer look at the site shows that their regime is used to cure everything from fibromyalgia to cancer – any time a site claims to cure disparate diseases that should be considered a clue.   Their cure protocol has no research backing it up (there is no clinical trial where their protocol is evaluated against another or against a control), and several steps have known side effects that are dangerous.  This one looks like it took a slightly different approach to jump up in the rankings – the site itself consists of tons of internal reference links, allowing each page to jump higher in the listings.   Fortunately, the site appears to have been covered by skeptical sources as well: http://quackfiles.blogspot.com/2004/10/quacksites-most-unreliable-health.html

The remaining IBD Cure links seem to be legit (not generated by link spamming) as well.

Summary


Overall, at least compared to other search terms, the prime links associated with IBD, Crohn’s, and Ulcerative Colitis are mostly legit sites.  A few questionable sites snuck in – mostly due to link spamming as noted above, but they are still in the minority.  As a community, we can keep them out by linking to legitimate medical sites, and by doing our homework when we come across them and not taking their results at face value.

Bottom Line


·         Google rankings are fairly robust, but can be manipulated by dedicated individuals.
·         Fortunately, very few of the top 10 sites related to Crohns and UC appear to have been link manipulated.
·         If you want to know why a site is ranked so high, try using the “link:” prefix in Google to find out who linked to it.
·         Simply typing the name of a site followed by “quack” into Google can also lead to interesting debunkings if the content is fraudulent.  As with the site itself, though, the “debunk” site should be providing documented research backing up there assertions.


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Sunday, June 2, 2013

IBD RoadMAP


Mycobacterium avium paratuberculosis (MAP) and IBD


Potentially the most controversial topic with Crohn’s disease – the one that generates the most passionate postings in the message boards – is the role (if any) of mycobacterium avium subspecies paratuberculosis (MAP) in causing or “activating” Crohn’s disease.  Proponents believe that MAP (and by association milk consumption) should be a major research focus, and that by curing MAP infections the underlying Crohn’s disease will be cured.  A good, early debate on the subject can be found in Gut, but there have been developments on both sides since its publication [Note to the publisher of Gut: In the Internet age, calling your debate “Mycobacterium avium subspecies paratuberculosis is a cause of Crohn’s disease” leads to bad search result-based conclusions] (1)

MAP is the known cause of Johne’s disease, a condition that mimics the symptoms of Crohn’s disease.  It affects the small intestines, forming granulomas and causing malnutrition and severe diarrhea.  With limited exceptions, Johne’s disease impacts only ruminants (though many other mammals can be carriers of MAP), with cattle and goats being particularly susceptible (sheep are infected by a different variant).  Transmission is primarily oral (though sexual transmission is possible), with environmental contamination through consumption of manure of infected animals being a primary pathway.(2)  There is evidence of MAP being present in milk, suggesting nursing as a possible secondary transmission pathway, though the presence of environmental MAP on the teats may also be a cause.(3)

While MAP had been found in 1980s in a few isolated case reports of individuals with Crohn’s, a small study of 40 individuals in 1992 provided the basis for most of the current interest.  In the study, Sanderson et al took samples from 103 individuals, 40 with Crohn’s, 40 with no disease, and 23 with UC, and found that there was MAP present in 65% of those with Crohn’s, 12.5% of the controls, and 4.3% of the UC patients, leading them to conclude:

The presence in two thirds of Crohn's disease tissues but in less than 5% of ulcerative colitis tissues is consistent with an aetiological role for Mparatuberculosis in Crohn's disease.(4)

The authors rightfully note the difficulty in culturing MAP and accurately identifying early stage infections. 
Based on their work, there have been multiple follow-on studies looking at the correlation factors.  While individual results have been divergent, the meta-analyses looking across the board showed that there is a significant increase in the incidence of MAP in individuals with Crohn’s disease.  The numbers appear to confirm they are within the same order of magnitude as Sanderson et al.(5,6) 

While Sanderson et al’s conclusion is accurate, it is potentially misleading as well – their results may have been due to sampling factors, due to environmental differences between the patients (e.g. differing diets due to the disease), due to individuals with Crohn’s being unable to fight MAP and ending up as secondary carriers, or to many other unknown factors.  Their study only showed correlation (on a limited sample), not causation, as have the other follow-on studies. 

The above results show a correlation in some trials between MAP infection and Crohn’s disease.  Calling MAP a cause for Crohn’s is very premature, however, based on other research.  One prominent arguments against comes from a meta-analysis looking at long term antibiotic treatments as a way to combat Crohn’s.  Their analysis showed that there was no significant efficacy of the traditional MAP treatments against Crohn’s disease, though they acknowledge the underlying trials were fairly small.(7)  This could mean that MAP is not a causative factor for Crohn’s, or that the drugs are ineffective in treating MAP in intestinal tissue, but it puts a minus in the likelihood column. 

Another negative in the likelihood column comes from the epidemiological evidence.  Crohn’s disease is more prevalent in developed nations with more urbanized environments.  Locations where humans and cattle live in close proximity tend, on average, to have lower incidence and prevalence numbers for Crohn’s. 

While there is some promising evidence of an infectious cause for Crohn’s, calling MAP the cause (or even a contributory factor) is still premature.  It is convenient to cite the great story of H. Pylori causing ulcers as a parallel David v. Goliath story, but there are a substantial number of individuals looking for a potential infections cause for IBD.  That said, MAP has not been completely ruled out as a factor in Crohn’s disease, but there are equally compelling argument for other pathogens.  There is room for additional research on MAP and Crohn’s, but the initial evidence is not so compelling that it warrants a laser-like focus to the exclusion of other potential causes.

Bottom Line

·         MAP is more likely to be prevalent in the intestines of those with Crohn’s disease.
·         Despite a higher prevalence, compelling evidence of a causal relationship has not been established by current research.
·         Some further research (with appropriately tempered enthusiasm) is warranted into a MAP-IBD link.
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3.       Taylor, T. K., C. R. Wilks, and D. S. McQueen. "Isolation of Mycobacterium paratuberculosis from the milk of a cow with Johne's disease." Veterinary Record 109, no. 24 (1981): 532-533.
4.       Sanderson, J. D., M. T. Moss, M. L. Tizard, and J. Hermon-Taylor. "Mycobacterium paratuberculosis DNA in Crohn's disease tissue." Gut 33, no. 7 (1992): 890-896.
5.       Feller, Martin, Karin Huwiler, Roger Stephan, Ekkehardt Altpeter, Aijing Shang, Hansjakob Furrer, Gaby E. Pfyffer, Thomas Jemmi, Andreas Baumgartner, and Matthias Egger. "Mycobacterium avium subspecies paratuberculosis and Crohn's disease: a systematic review and meta-analysis." The Lancet infectious diseases 7, no. 9 (2007): 607.
6.       Abubakar, I., D. Myhill, S. H. Aliyu, and P. R. Hunter. "Detection of Mycobacterium avium subspecies paratuberculosis from patients with Crohn's disease using nucleic acidbased techniques: a systematic review and metaanalysis." Inflammatory bowel diseases 14, no. 3 (2008): 401-410.
7.       Feller, Martin, Karin Huwiler, Alain Schoepfer, Aijing Shang, Hansjakob Furrer, and Matthias Egger. "Long-term antibiotic treatment for Crohn's disease: systematic review and meta-analysis of placebo-controlled trials." Clinical infectious diseases 50, no. 4 (2010): 473-480.