Methotrexate Abstract: Subcutaneous vs. Oral Administration

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A recent abstract (Link: Gut doi:10.1136/gutjnl-2014-307964) indicates that there may be some advantages with subcutaneous methotrexate compared with oral administration, especially at the onset of treatment.

Here’s the abstract (thanks to KT Park for sharing this abstract on his twitter feed):

Efficacy of oral methotrexate in paediatric Crohn’s disease: a multicentre propensity score study

Background Oral methotrexate (MTX) administration avoids weekly injections, reduces costs and may improve quality of life of patients with Crohn’s disease (CD), especially children. Routes of administration have never been systematically compared in CD. We aimed to compare effectiveness and safety of orally (PO) versus subcutaneously (SC) administered MTX in paediatric CD.

Methods 226 children with CD treated with oral or subcutaneous MTX were included in a multicentre, retrospective 1-year cohort study (62% boys, mean age 13.8±2.8 years, 88% previous thiopurines). 38 (17%) were initially commenced on oral, 98 (43%) started subcutaneous and switched to oral and 90 (40%) were treated with subcutaneous only. Matching and ‘doubly robust’ weighted regression models were based on the propensity score method, controlling for confounding-by-indication bias. 11/23 pretreatment variables were different between the groups, but the propensity score modelling successfully balanced the treatment groups.

Results 76 children (34%) had sustained steroid-free remission with a difference that did not reach significance between the PO and the SC groups (weighted OR=1.72 (95% CI 0.5 to 5.9); p=0.52). There were no differences in need for treatment escalation (p=0.24), elevated liver enzymes (p=0.59) or nausea (p=0.85). Height velocity was lower in the PO group (p=0.006) and time to remission was delayed in the PO group (p=0.036; Fleming (0, 1) test).

Conclusions In this largest paediatric CD cohort to date, SC administered MTX was superior to PO, but only in some of the outcomes and with a modest effect size. Therefore, it may be reasonable to consider switching children in complete remission treated with subcutaneous MTX to the oral route with close monitoring of inflammatory markers and growth.

Related blog posts:

What Better Care Looks Like -Five Examples

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From Harvard Business Review and the New England Journal of Medicine: Five examples of Better Care

  1. Increased transparency with patient feedback at University of Utah
  2. Shared responsibility to coordinate care experience at Mayo Clinic
  3. Teamwork with all members of health care team at Northwestern
  4. Addressing socioeconomic barriers at Contra Costa
  5. Consolidating care in London to specialized centers to improve outcomes and costs (with stroke)

What sets your institution apart from others?

“Show Don’t Tell” –Colonoscopy Prep Instructions

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A recent study, summarized in this link– Gastroenterology and Endoscopy News, indicates that providing an 11 minute video with colonoscopy prep instructions was more effective than written instructions.  Not only were the cleanouts better, but this resulted in better outcomes including higher adenoma detection rate and higher rates of completed colonosocpy.

Here’s an excerpt:

Dr. Bearelly and his colleagues randomized 298 individuals scheduled for screening colonoscopy to receive either the practice’s usual written instructions, or to receive the paper handout plus an instructional video (right). The 11-minute video—burned on a disk —covers the same instructions as the written materials, but in an interactive format that depicts a typical patient asking questions of one of the practice’s doctors.

The quality of bowel preparation between the two groups differed significantly (P=0.0098). Cecal intubation was 96% in the intervention group compared with 89% in the control group, and the adenoma detection rate was 53% and 42% in the two groups, respectively.

Patients in the intervention group had a Boston Bowel Preparation Score (BBPS) of 6.99±1.87, whereas those in the control group had a score of 6.43±2.54, although the difference was not statistically significant. A BBPS of 6, with a minimum of 2 in each segment, was considered adequate.

Take-home message:  Video instructions for colonoscopy are worthwhile.  In pediatrics, variability in cleanout regimens is a limiting factor.

Related blog posts:

PEG vs Lactulose in Hepatic Encephalopathy

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In a study (JAMA Intern Med. Published online September 22, 2014. doi:10.1001/jamainternmed.2014.4746) with 50 participants, PEG was more effective than standard therapy of lactulose for hepatic encephalopathy.  PEG vs Lactulose (HELP study) Abstract.

Here’s an excerpt:

Design, Setting, and Participants  The HELP (Hepatic Encephalopathy: Lactulose vs Polyethylene Glycol 3350-Electrolyte Solution) study is a randomized clinical trial in an academic tertiary hospital of 50 patients with cirrhosis (of 186 screened) admitted for HE.

Interventions  Participants were block randomized to receive treatment with PEG, 4-L dose (n = 25), or standard-of-care lactulose (n = 25) during hospitalization…

Results  Thirteen of 25 patients in the standard therapy arm (52%) had an improvement of 1 or more in HESA score, thus meeting the primary outcome measure, compared with 21 of 23 evaluated patients receiving PEG (91%) (P < .01)… The median time for HE resolution was 2 days for standard therapy and 1 day for PEG (P = .01). Adverse events were uncommon, and none was definitely study related.

Conclusions and Relevance  PEG led to more rapid HE resolution than standard therapy, suggesting that PEG may be superior to standard lactulose therapy in patients with cirrhosis hospitalized for acute HE.

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Looking More Closely at a Persistent Question

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Virtually everyday, families that I care for are trying to ascertain the link between their GI symptoms and the foods in their diet.  Many authoritative recommendations on irritable bowel have concluded that “food allergies (symptoms caused by an immune response) are rarely the culprit in IBS patients. Most IBS patients with food-related symptoms have food sensitivities or intolerances, which are not caused by an immune response.” (From Univ Virginia Irritable Bowel Diet PDF)

Whether the process is a sensitivity or an immune-reaction, many patients are quite sensitive to certain foods and many have had improvement with a low FODMAPs diet.

A much closer look at this problem with confocal laser endomicroscopy (CLE), in a pilot study (Gastroenterol 2014; 147: 1012-20), has shown measurable changes within five minutes of a food challenge that takes place during an endoscopy.  In this study, the researchers examined 36 patients with IBS who had suspected food intolerance and 10 control patients with Barrett’s esophagus.  Then during an endoscopy, the researchers used provoking solutions of cow’s milk, wheat, yeast, or soy.  The subjects had CLE before and after the challenges. To enhance visualization of changes, subjects had fluorescein dye injected intravenously prior to examination of the duodenum.

Results

  • In 22 of 36 patients, the challenges were considered positive.  These patients had mucosal changes including increase in intraepithelial lymphocytes, followed by disruption of the villi tips/shedding of cells, then fluorescein leakage into the lumen.
  • None of the control patients exhibited these changes.
  • 19 of 22 patients with positive challenges had a >50% reduction, after 4-weeks, in symptom score with individualized diet based on inciting antigen.

Bottomline:

This provocative study indicates that subtle mucosal changes can occur in a number of IBS patients in a quick and direct response to food challenges.  Perhaps when we look closer with technologies like CLE we will find more answers as to why certain foods provoke symptoms in adults and children with IBS.

Related blog posts:

Also noted –web-based information on gastroparesis:

“There is No ‘Healthy’ Microbiome”

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While thinking about what you might eat later today and pondering how this may affect your GI tract, perhaps a recent editorial may provide some reassurance.

A recent editorial provides an insightful view regarding a ‘healthy’ microbiome.  Despite all of the publications on this subject (and the numerous posts on this blog), there is not a one-size fits all microbiome.

Here’s the link  “No Healthy Microbiome” and an excerpt:

These microscopic partners help us by digesting our food, training our immune systems and crowding out other harmful microbes that could cause disease. In return, everything from the food we eat to the medicines we take can shape our microbial communities — with important implications for our health. Studies have found that changes in our microbiome accompany medical problems from obesity to diabetes to colon cancer.

As these correlations have unfurled, so has the hope that we might fix these ailments by shunting our bugs toward healthier states. The gigantic probiotics industry certainly wants you to think that, although there is little evidence that swallowing a few billion yogurt-borne bacteria has more than a small impact on the trillions in our guts….

But how can you tell when it needs replacing? A bloom of C. difficile is an obvious problem, but most other communities are not so easily classified. The microbiome is a teeming collection of thousands of species, all constantly competing with one another, negotiating with their host, evolving, changing. While your genome is the same as it was last year, your microbiome has shifted since your last meal or sunrise.

We need to start thinking about it as an ecosystem, like a rain forest or grassland, with all the complexities that entails. And just as the gorillas and leopards of African forests differ from the wolves and moose of American ones, so, too, do microbiomes vary around the world.

Cornering the Generic Markup

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Older generic drugs are not always a bargain these days.  A recent editorial (NEJM 2014; 371: 1859-62) highlights how some of these drugs have seen dramatic increases in prices.

  • Albendazole, an antiparasitic drug, used to cost $5.92 per daily dose. Now $119.58 per daily dose.  The total Medicaid costs for albendazole have increased from less than $100,00 per year in 2008 to more than $7.5 million in 2013.
  • Captopril, a blood pressure medication, increased from 1.4 cents per pill in 2012 to 39.9 cents per pill one year later.
  • Doxycycline, a commonly-used antibiotic, increased from 6.3 cents per pill to $3.36 per pill.

What’s driving these changes?  While these medications are not protected by patents or market exclusivity, some pharmaceutical companies attempt to corner a market and then unilaterally raise the prices.

Bottomline: Businesses that exert near monopolies don’t have to offer any “Black Friday” specials.

AGA Guidelines on Medicines for Irritable Bowel

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New guidelines on the use of medicines for irritable bowel syndrome from Atlanta Gastroenterology Association (AGA) have been published (Gastroenterol 2014; 1146-48, technical review: 1149-72).

Here’s the link: AGA IBS Guidelines.

In brief:

For IBS-C

  • Linaclotide: AGA recommends as better than no drug treatment in adult. This is the only “strong” recommendation with high-quality evidence.
  • Lubiprostone: AGA suggests over no drug treatment.
  • PEG Laxatives: AGA suggests over no drug treatment.

For IBS-D:

  • Rifaximin: AGA suggests over no drug treatment.
  • Alosetron: AGA suggests over no drug treatment.
  • Loperamide: AGA suggests over no drug treatment.

For IBS:

  • Tricyclic antidepressants: AGA suggests over no drug treatment.
  • Selective Serotonin Reuptake Inhibitors: AGA suggests against using for IBS.
  • Antispasmotics: AGA suggests over no drug treatment.

 

Also noted:

Am J Gastroenterol 2014; 109: 1547-61. (Thanks to Ben Gold for this reference.) Meta-analysis of prebiotics/probiotics for IBS.  43 RCTs were eligible for inclusion.  Key finding: IBS symptoms, including pain, bloating and flatulence were improved with RR of 0.79 compared with placebo.  “Probiotics are effective treatments for IBS, although which individual species and strains are the most beneficial remains unclear.”

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Clostridium difficile/Fecal Microbiota Transplantation Video

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I have been a fan of OpenBiome (www.OpenBiome.org).  Their website provides a nice ~3 minute explanation of Clostridium difficile and the rationale for fecal microbiota transplantation (FMT). Here’s the link: C diff FMT video

In addition to this video, their website has a lot of information (for families and clinicians) about how to obtain and use safe, screened stool products. Here’s their background information (from their website):

Why we’re here:

We founded OpenBiome, a nonprofit 501(c)(3) organization, after watching a friend and family member suffer through 18 months of C. difficile and 7 rounds of vancomycin before finally receiving a successful, life-changing Fecal Microbiota Transplantation (FMT). The remarkable efficacy of this treatment and the great lengths required to receive it convinced us that we needed to help expand access. After many discussions with local clinicians and the FDA, we launched OpenBiome in 2012 to make FMT faster and easier for patients and doctors alike.

What we do:

We work with clinicians to make FMT easier, cheaper, safer and more widely available. We do so by providing hospitals with screened, filtered, and frozen material ready for clinical use. This service eliminates the time, staff, protocols, and facilities needed to screen and prepare material from new donors for each treatment. With OpenBiome, all that’s needed to deliver FMT is a doctor and an endoscope.

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Is Drinking Milk Healthy?

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A recent article in the Washington Post (thanks to Ben Enav for forwarding this link) which summarizes a study from Sweden questions the long held assumption that milk is a beneficial dietary element in adults.  In fact, drinking a lot of milk may have detrimental effects.

Here’s an excerpt:

a new study from researchers in Uppsala University in Sweden suggests that consuming more milk could actually be associated with higher mortality and bone fractures in women and higher mortality in men.

The study, published in the British Medical Journal, utilized data from two large, long-term Swedish studies of adult men and women, which asked about their dietary habits — how much and what types of milk and dairy products they consumed…

Recently, Americans — and indeed much of the world — have been coming down from their milk high for some time.

Since the 1970s, milk consumption in the United States has dropped from about 1.5 cups a day to about 0.8 cups a day today….

In children, encouraging milk consumption through the National School Lunch Program often takes the form of sugar-sweetened chocolate milk, which has sugar content similar to soda, points out David Ludwig, a Harvard professor of nutrition.

In a 2013 paper Ludwig co-wrote, he suggested that there is not enough scientific evidence to support federal milk consumption recommendations.

And in fact, he added, there is more evidence that humans — who only recently began consuming milk with the domestication of large animals — don’t need it at all.

“Until very very recently, from an evolutionary perspective, humans would have consumed no milk products at all and would have consumed calcium from other sources,” Ludwig said. “Populations that drink no milk at all have perfectly fine bones.