Something New with FMT

Posted on December 9, 2013 by gutsandgrowth

“Resentment is like drinking poison and then hoping it will kill your enemies.” –Nelson Mandela

A brief review on Fecal Microbiota Transplantation (FMT) (Gastroenterol 2013; 145: 946-53) made a few points that I was not familiar with and reiterated many other important aspects.

With regard to preparation of FMT, early data suggests that using water rather than saline may result in better resolution of Clostridium difficile infection (CDI)
Adequate volumes of FMT material are needed, with rates as high as 97% CDI resolution with infusions >500 mL
While preliminary data suggested higher CDI resolution with colonoscopy infusion, a recent randomized controlled trial indicated that duodenal infusion was as effective as colonoscopic administration
Short-term data indicate very low adverse effect rates
While the only accepted role for FMT outside of clinical trials is for CDI, the review examined the potential benefit for inflammatory bowel disease (IBD), irritable bowel syndrome, chronic fatigue syndrome, and metabolic/cardiovascular disorders.
With IBD, there are currently 6 registered trials testing FMT for patients with IBD. Preliminary data have been more evident in small studies with ulcerative colitis.
The rationale for FMT in IBD is that IBD patients have reduced diversity and altered microbial flora. “However, it is not clear whether these differences are a cause or a consequence of the development of IBD.”

Related blog posts:

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.

Did you see this? –Cost of multiple births

Posted on December 8, 2013 by gutsandgrowth

“A good head and a good heart are always a formidable combination.” –Nelson Mandela

A recent study from the American Journal of Obstetrics and Gynecology has found that “the adjusted total health care cost for singletons was around $21,000 per delivery, but the number for twins was $105,000 and over $400,000 for triplets or more.”

“The Centers for Disease Control and Prevention (CDC) shows that in 2010, 3% of all births in the US were multiple deliveries. The twin birth rate was 33.2 per 1,000 live births, and the triplet or higher birth rate was 1.4 per 1,000 live births.”

“The research was based on nearly 440,000 births among US women aged 19-45 from 2005 to 2010… The tally included all medical expenses for the mothers from 27 weeks before birth until 30 days afterward, combined with the medical costs of infant care for the first year.”

Links (with more information):

Buyer Beware: Online Pharmacy Problems

Posted on December 7, 2013 by gutsandgrowth

“It always seems impossible until it’s done.” –Nelson Mandela

From NY Times:

http://well.blogs.nytimes.com

Though technically illegal, millions of Americans buy prescription drugs from overseas pharmacies to save money. But the practice can be a huge gamble.

The National Association of Boards of Pharmacy, a professional group, reviewed over 10,000 Internet drug outlets and found that many sold fake or unapproved drugs. Some that claimed to be Canadian pharmacies actually sold medicines from developing countries where regulations are weak and counterfeit drugs are common.

Roger Bate, a pharmaceutical expert at the American Enterprise Institute, estimates that 2 to 3 percent of online pharmacies are legitimate. When buying Canadian, he said, look for outlets certified by the Canadian International Pharmacy Association, a trade group of Canadian pharmacies, or those certified by PharmacyChecker.com, a free website that verifies that the foreign sites it approves protect consumer information and meet quality standards.

Last year, Mr. Bate and his colleagues published a study analyzing 372 orders of five popular prescription drugs – Lipitor, Celebrex, Viagra, Nexium and Zoloft – that they purchased from 79 domestic and foreign online drug outlets. Products bought from Canadian or other foreign sites certified by C.I.P.A. or PharmacyChecker.com were of high quality. So were products ordered from American sites verified by either the N.A.B.P. or LegitScript.com, a certification agency founded by a former White House aide on drug policy issues.

But that was not the case for sites that were not certified by any of these four groups. Many of the drugs they sold were fakes, including about a quarter of the Viagra samples, which largely appeared to have originated in China.

“You can’t be 100 percent certain with any sites, frankly,” Mr. Bate said. “But you are running a much lower risk if you buy from a credentialed site.”

Fiber Intake and Crohn’s Disease

Posted on December 6, 2013 by gutsandgrowth

There are several lines of evidence that diet can contribute to the development and treatment of Crohn’s disease.

From a treatment standpoint, the most dramatic data has been with the effectiveness of enteral nutrition as a treatment option. In addition other environmental factors like being raised on a farm and use of antibiotics have been shown to alter the risk for Crohn’s disease; the former has been associated with a reduction in risk and the latter with an increased risk.

A new prospective study from 170,776 women followed over 26 years in the Nurses’ Health Study has identified up to a 40% reduction in the risk of Crohn’s disease among the highest fiber intake quintile (24 g/day) in comparison to the lowest intake quintile (12 g/day) (Gastroenterol 2013; 145: 970-77, editorial 925). Link to abstract: http://dx.doi.org/10.1053/j.gastro.2013.07.050 …

Specific findings:

Fruit intake was associated with greatest risk reduction. The median daily intake of fiber from fruit in the highest quintile was 6 g/day which is equivalent to 2 fruits (eg. banana or orange).
Vegetable intake was not associated with protection from Crohn’s disease.
The editorial notes that “reverse causation was addressed by evaluating cumulative exposure and including a 2-4 year lag period.”
However, the women in this study may not be representative and fiber intake could be an epiphenomenon. The women in the highest quintile were also less likely to smoke, use aspirin and have a body mass index <30 kg/m-squared.
Fiber intake did not significantly reduce the risk of ulcerative colitis

Bottomline: the “Institute of Medicine recommends that daily fiber consumption should be 14 g of fiber for every 1000 calories.” Thus, if one were to follow the guidelines by the IOM, all individuals would be consuming enough fiber to potentially reduce their risk of Crohn’s disease by 40%. Other fiber benefits include improve bowel habits, lowered cholesterol levels, weight loss, and lowered diabetes risk.

Reporting Bias: Infections with TNF Inhibitors

Posted on December 5, 2013 by gutsandgrowth

A recent article (Clin Infect Dis 2013; 57: 1318-30 -thanks to Jeff Lewis for this reference) summarized the pediatric literature on infectious complications associated with tumor necrosis factor-α (TNF) inhibitors for both Juvenile Idiopathic Arthritis (JIA) and Inflammatory Bowel Disease (IBD).

In total 33 studies for JIA were included and 39 studies for IBD. Many others were excluded due to overlapping cohorts or lack of sufficient data.

For JIA, the authors identified 296 infliximab (IFX) patients, 2465 etanercept patients, and 242 adalimumab patients. Most infectious were mild and mainly viral etiology. For example, 1016 upper respiratory illnesses with etanercept were reported. However there were a significant number of more serious infections which included lower respiratory infections (n=37), cellulitis/abscess (n=15), histoplasmosis (n=2), and meningitis (n=4). Four patients had infectious fatalities.

Similarly, for IBD, most patients had mild infections. Among 1407 IFX patients and 241 adalimumab (ADA) patients, there were 105 URIs noted. Again, more serious infectious were noted in many. Four fatalities were reported; 1 was due to disseminated CMV, 1 due to bacterial sepsis, and 2 were due to central line infections.

When examining this report, the question of reporting bias cannot be avoided. The various reports that were summarized included 30 prospective studies, 23 retrospective studies, and 19 various reports (case reports, case series, and FDA reports). The composite, in my view, likely overestimates the risk of serious infections. In addition, many of the infections may have been due to concurrent immunosuppressive therapy, but the details for this are lacking.

With regard to microbiology:

5 JIA patients had tuberculosis; there were no tuberculosis cases reported in the IBD cohort
Varicella/zoster was the most frequent viral infection and was frequently severe. In JIA cohort, there were 39 VZV cases (11 severe); among IBD cohort, there were 16 VZV cases (3 severe).

Bottomline: Given the frequent use of anti-TNF agents, better prospective pediatric data are needed. In addition, careful analysis of the data is needed for better attribution; the risk for many of these infections is likely due to concurrent medications like corticosteroids.

Also Noted:

Clin Gastroenterol Hepatol 2013; 11: 826-31. In a prospective cohort of 200 anti-TNF-naive adult patients (100 treated with IFX and 100 with ADA), the effectiveness was similar for IFX and ADA at both 1 and 2 year followup. Improved efficacy was noted when these agents were combined with immunomodulators, though this was statistically significant for IFX. The total patient response was 63.5% at 1 year and 45% at 2 years.

Understanding PEWs & Online Reputation

Posted on December 4, 2013 by gutsandgrowth

Most pediatric gastroenterologists would think that the acronym PEWS referred to “Pediatric Early Warning Score” which is used to identify patient deterioration (Sensitivity of the Pediatric Early Warning Score to Identify Patient …). This PEWS has been an important achievement in patient safety contributing to lower mortality, reduced codes, and shortened intensive care unit stays (Simple Scoring System and Action Algorithm Identifies Children at …).

PEWs acronym also refers to “physician evaluation websites.” These type of scores are growing in importance and may also reflect quality care. As such, a recent article highlights this emerging phenomenon (Am J Gastroenterol 2013; 108: 1676-85 -thanks to Ben Gold for this reference). While physicians are concerned about their reputations, these websites have not been widely embraced. This article makes several points about why physicians may need to reconsider.

Key points:

35 websites met criteria to be included in this study: 18 were dedicated physician evaluation websites, 5 were health information websites, and 12 were general information websites (eg. Angieslist.com, kudzu.com, yelp.com).
Frequent analysis/questions besides demographics/affiliations: punctuality, quality of staff (office/nursing), bedside manner, ability to make correct diagnosis, spent sufficient time, costs
Five sites allow physician feedback and chance to respond to dissatisfied patients: docspot.com, doctorscorecard.com, healthgrades.com, ratemds.com, and your city.md
Multiple charts indicate the huge traffic on these websites. For dedicated PEWs, healthgrades.com has the highest volume at over 5 million unique visitors per month (2011-2012).
Most online evaluations are completed by females (with at least some college education) with a peak age between 45-65 years. Some smaller PEWs attract a younger crowd (eg. Zocdoc.com -4th most visited dedicated PEW).
Most evaluations are positive. “Site administrators…self-reported figures…ranged from 60-75% positive, 4-22% neutral, and 9-21% negative.”

Unique Aspects:

ucomparehealthcare.com (3rd most visited dedicated PEW) allows multiple physician profiles to be analyzed side-by-side.
docspot.com compiles existing reviews from over 15 other websites.
healthgrades.com (most visited dedicated PEW) allows users to rate physicians with a star scale but does not allow free response (avoids libelous comments).
vitals.com -2nd most visited dedicated PEW.
yourcity.md considered most “doctor friendly.” Prior to publicizing negative comments, this site allow doctors the option to respond publicly or privately; afterwards, the negative review can be revised. In addition, per user agreement, a negative claim which cannot be substantiated could result in the anonymous reviewer’s name being revealed to the physician or be removed.

One of my mentors told me that the key to patient care was the the 3 A’s: availability, affability, and ability. PEWs likely can help evaluate the first two A’s. PEWs allow for constructive criticisms but need to evolve to include other measures of physician performance. Ignoring PEWs would be a mistake for physicians –they are here to stay.

Rehabilitation for Short Bowel Syndrome

Posted on December 3, 2013 by gutsandgrowth

As noted in several blog posts, there have been some important advances in the care of short bowel syndrome (SBS)/intestinal failure (IF) patients which have resulted in improved outcomes. A recent review of 28 children with ≤20 cm of small bowel has been published (J Pediatr 2013; 163: 1361-6, editorial 1243) and provides tangible evidence of these changes.

This retrospective study reviewed the charts of these children managed at Omaha’s intestinal rehabilitation program. 7 patients had NEC, 6 intestinal atresia, 6 had gastroschisis, 3 omphalocele, 5 had malrotation, and 1 patient had vascular disease.

Key results:

27 survived (96%)
14 (50%) had at least one lengthening procedure; in this cohort, bowel lengthening was not associated with a greater rate of adaptation than native bowel.
13/27 (48%) achieved parenteral nutrition independence (“nutritional autonomy”) with their native bowel.
Predictors of “successfully rehabilitated” patients: intact colon and ileocecal valve
All patients had improvements in lowering PN requirements, total bilirubin, and growth z-scores.
Serum transaminase levels did not improve in the nonrehabilitated patients

The main medical treatments at IRP include use of agents for control of bacterial overgrowth, reducing gastric acid production, lipid minimization, promotility and antimotility agents (eg. loperamide), and ethanol locks. The editorial comments on the “poor results” for surgical intervention, “particularly among those with ultra-short bowel.” This may be due to ‘marginal motility, ischemia, severe wall thickening, or due to adhesions.’

With regard to ethanol locks, the editorial supports them but states, “the main factor in prevention [of line infections] has been maintaining a consistent and strict protocol for catheter care.”

Previous related blog entries:

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

Posted on December 2, 2013 by gutsandgrowth

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)

Related blog posts:

Cancer Risk Not Increased with Assisted Conception

Posted on December 1, 2013 by gutsandgrowth

Using a UK National registry with 106,013 children, investigators determined that there was no overall risk of cancer among children born after assisted conception during a 17-year study period (NEJM 2013; 369; 1819-27).

Among individual cancers, this cohort had an increased risk of hepatoblastoma and rhadomyosarcoma, though the absolute risk was quite low. The risks for these cancers may be related to chance or indirectly related to parental infertility through mechanisms like low birth weight or imprinting disorders.

How Birth Can Affect Your GI Tract

Posted on November 30, 2013 by gutsandgrowth

A recent review (JPGN 2013; 57: 543-49) provides information about the relationship between neonatal environment and subsequent inflammatory gastrointestinal disease.

While most of the review, focuses on physiology and pathophysiology, the most interesting part is the assertions (with references) in Table 1 which include the following:

Breastfeeding reduces risk of IBD
Cesarean section increases the risk of celiac disease, cow’s milk allergy, and other IgE-mediated food allergies
Many chronic adult diseases have been shown to have origins in neonatal life, particularly cardiovascular disease/metabolic syndrome

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