Single High-Dose Oral Vitamin D Therapy (Stoss) for Children with Inflammatory Bowel Disease

Posted on October 29, 2015 by gutsandgrowth

A retrospective study (D Shepherd et al. JPGN 2015; 61: 411-14) shows that a single high-dose oral vitamin D3 therapy can be effective for 6 months. This study involved treatment of 76 children between 2006-2010.

Stoss vitamin D dosing used in this study:

< 3 yrs 200,000 IU
3-12 yrs 400,000 IU
>12 800,000 IU

Followup levels of Vitamin D (25-OH) and calcium were checked at 1 week, 4 weeks, 3 months and 6 months..

Key finding:

25-OHD >50 nmol/L (=20 ng/mL) was seen in 96.6% at 3 months and 76.4% at 6 months. 63% had a level >75 nmol/L (=30 ng/mL) at 1 month.

Bottomline: Authors noted: “Stoss therapy safely and effectively achieved and maintained a level of 25OHD > 50 nmol/L during 6 months in these children with IBD.”

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Atlanta Botanical Gardens

What is Your Infliximab Adherence Rate?

Posted on October 28, 2015 by gutsandgrowth

I started thinking about this question after a recent study (DS Vitale, et al. JPGN 2015; 61: 408-10) examined adherence at a single pediatric center (2010-2012). Adherence indicated “those who attended >80% of scheduled infusions.” Key findings:

91.4% adherence rate of patients (n=151 with >4 infusions)
Adherent patients (n=138) attended an average of 98% of their infusions. Nonadherent patients attended, on average, 76% of their infusions.
The study provided some preliminary evidence that there was greater acute care use in nonadherent patients.
There were no demographic features that could predict adherence pattern.

My take: One of the key advantages of infusion therapy is improved and documented adherence. Infusions also provide opportunities to assess patient in a scheduled manner. This study shows that subsets of patients with scheduled infusions have suboptimal adherence — another target for quality improvement!

Atlanta Botanical Gardens, Bruce Munro Exhibit

Be Aggressive! Treating Anemia Associated with Inflammatory Bowel Disease

Posted on October 27, 2015 by gutsandgrowth

A number of recent publications have made the point that anemia is a biomarker for severe inflammatory bowel disease and undertreatment affects quality of life. Reading one of the more recent studies (IE Koutroubakis et al. Clin Gastroenterol Hepatol 2015; 13: 1760-66) brought to mind the high school football cheer: Be Aggressive!

This particular retrospective study involved 410 patients (245 with Crohn’s disease, 165 with ulcerative colitis) from 2009-2013. This study is from the same group that published data on a somewhat smaller cohort and showed that IBD treatment alone often will not resolve anemia (Koutroubakis, IE et al. Inflamm Bowel Dis 2015; 21: 1587-93–see previous blog links).

Key findings:

Prevalence of anemia: 37.2% in 2009 and 33.2% in 2013
Anemia was associated with increased hospitalizations (P<.01), clinic visits (P<.001), telephone calls (P<.004), surgeries for IBD (P=.001), and lower quality of life scores (P<.03)

The associated editorial (pgs 1767-69) suggests that IBD-related anemia, if mild (w/in 1 g/L below normal) to treat with oral iron replacement and if moderate-to-severe, then to replace intravenously (using Ganzoni’s formula calculator). In addition, if anemia is not improving, looking for alternative explanations (e.g. vitamin B12 or folate deficiency) is recommended.

Ganzoni Equation: Total Iron Deficit = Weight {kg} x (Target Hb – Actual Hb) {g/l} x 2.4 + Iron stores {mg}. Iron stores: { 500 if W > 35kg } & { 15 mg/kg if W < 35kg }

My take: Anemia is a biomarker for severe disease. While treating the underlying inflammatory bowel disease, don’t forget to make sure the patient’s anemia is addressed.

Related blog posts:

Disclaimer: These blog posts are for educational purposes only. Specific dosing of medications/diets (along with potential adverse effects) should be confirmed by prescribing physician/nutritionist. 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.

Central Park

Biosimilars -Position Statement

Posted on October 26, 2015 by gutsandgrowth

Briefly noted:

“Use of Biosimilars in Paediatric Inflammatory Bowel Disease” Position Statement. JPGN 2015; 61: 503-08. Conclusions:

“IBD Porto group advocates giving high priority to performing paediatric trials with long-term followup to support” the use of biosimilars (97% agreement)
“Treatment of a child with sustained remission on a specific medication should not be switched to a biosimilar until clinical trials in IBD are available to support the safety and efficacy of such a change” (94% agreement)
“Postmarketing surveillance…in children with IBD should be a mandatory requirement.” (100% agreement)

My take: Keep this reference handy. The lower expected costs (>30% reduction) could create pressure to change treatment before the safety/efficacy is proven.

Atlanta Botanical Gardens

NY Times: Frequent Antibiotics May Make Children Fatter

Posted on October 25, 2015 by gutsandgrowth

The topic of antibiotics and obesity has been discussed several times on this blog (see links below). More information on this topic has been published and is summarized by the NY Times: Frequent Antibiotics May Make Children Fatter

Children who regularly use antibiotics gain weight faster than those who have never taken the drugs, according to new research that suggests childhood antibiotics may have a lasting effect on body weight well into adulthood.

The study, published in the International Journal of Obesity, examined the electronic medical records of 163,820 children ages 3 to 18, counting antibiotic prescriptions, body weight and height. The records, which covered pediatric exams from 2001 through 2012, showed that one in five — over 30,000 children — had been prescribed antibiotics seven or more times. By the time those children reached age 15, they weighed, on average, about 3 pounds more than children who had received no antibiotics.

While earlier studies have suggested a link between antibiotics and childhood weight gain, they typically have relied on a mother’s memories of her child’s antibiotic use. The new research is significant because it’s based on documented use of antibiotics in a child’s medical record.

This story was covered by Time: Too many antibiotics may make children heavier

My Take: More evidence that antibiotics could contribute to obesity. Perhaps this will help with antimicrobial stewardship.

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Lack of Survival Benefit With MELD Exception Points in Hepatocellular Carcinoma

Posted on October 24, 2015 by gutsandgrowth

Briefly noted:

Another study also looks at transplant utility by showing the use of MELD exception points for hepatocellular carcinoma provides almost no survival benefit: K Berry, GN Ioannou. Gastroenterol 2015; 149: 669-80, editorial 531-34. The article states that the “survival benefit of patients with HCC was similar to that of patients without HCC who had the same actual MELD score…a much lower mean 5-year survival benefit was achieved by providing liver transplants to patients with HCC (0.12 years/patient) than patients without HCC (1.47 years/patient).”

How is this possible?

When patients are transplanted at lesser illness acuity, it takes longer to achieve a transplant benefit because they can live longer without a transplant. In essence, the survival clock starts ticking much later than the transplant date.

Why this is important (from editorial):

The proportion of patients undergoing liver transplantation for HCC has increased from “4.6% before the introduction of MELD exception to 16.5% currently.” And, “the results, put simply, suggest that allocating donor livers and performing liver transplantation in patients with HCC MELD exception points produces almost no survival benefit.”

My take: Liver allocation policies need to be modified. This study suggests that prioritizing HCC patients does not make much sense.

Atlanta Botanical Garden

Should Younger Transplant Patients Receive Better Organs?

Posted on October 23, 2015 by gutsandgrowth

Many physicians are unhappy with the current liver transplantation allocation system. A recent article (A Cucchetti et al. Liver Transl 2015; 21: 1241-49, editorial LB Vanwagner, AI Skaro. Liver Transpl 2015; 21: 1235-37) suggests that there should be adjustments to consider age in liver organ allocation. While this issue is not new, the article does suggest the idea of “age-mapping” which is a different twist on this subject.

The editorial notes that the current MELD system as been a poor predictor of post transplant outcomes and “does little to promote utility in organ allocation.” Because age is not a factor in MELD, “there is a subsequent loss of equity in the current system because younger recipients receive fewer opportunities to achieve a full lifespan compared with older recipients.” However, age matching is prohibited by discrimination laws.

“Age mapping differs from age matching.” With age mapping, all candidates would have an “equal chance of getting a liver” but the probability of receiving a ‘better organ’ (donor ≤35 years) would be more likely for younger recipients.

My take: The scarcity of organ availability compounded with the possible decline in organ quality leads to these discussions. Who really can balance unfair against unfortunate?

Related blog posts:

Should All Pediatric Patients with Crohn’s Disease Continue Combination Therapy?

Posted on October 22, 2015 by gutsandgrowth

Among patients/families who are not in denial about their inflammatory bowel disease, especially Crohn’s disease, an important discussion is the use of combination therapy. This has been discussed on this blog before (see some links below). More data on this subject has been published and again favors the use of combination therapy (V Grossi, T Lerer, et al. Clin Gastroenterol Hepatol 2015; 13: 1748-56).

This study collected data from 2002-2014 on 502 children who participated in a prospective multicenter study. This data was derived from an observational registry rather than a randomized trial, but likely reflects real-world experience with regard to newly diagnosed patients. The authors excluded those with prior biologic therapy and prior resectional surgery.

KEY FINDINGS:

Children receiving combination immunomodulator (IM) treatment were more likely to have durable infliximab therapy at 1 year, 3 years, and 5 years.
Greater length of concomitant IMs was associated with better durability.
For patients who had IM > 6 months after starting infliximab (n=194), durability was 0.70 at 5 years compared with 0.55 for patients with IM <6 months (n=144), and 0.48 for those who did not receive IMs (n=135).
In boys, methotrexate appeared to be superior to thiopurines (P<.01): 0.98 at 5 yrs compared with 0.58. However, there were 60 males receiving methotrexate. In the study, only 21 females received methotrexate which limited any conclusions.

Among patients who stopped IFX, the reasons included loss of response (n=61, 43%), hypersensitivity reaction (n=41, 29%), elective (n=25, 18%), lost to f/u (n=5, 3%), and other causes (10, 7%).

The “right” dose of methotrexate as a combination agent remains unclear. There was a wide range of dosing schedules in this study. It is worth observing that the COMMIT study in adults found no significant difference in adults who received methotrexate in addition to infliximab compared with those receiving infliximab monotherapy.

Take-home message: In this large pediatric observational study, the use of immunomodulators increased the likely durability of infliximab. Given prior conflicting data (particularly with regard to methotrexate), even more studies are needed to determine exactly how useful combination therapy is and when monotherapy will suffice. From my viewpoint, I worry much more about loss of efficacy to infliximab than I worry about medication adverse effects. As such, I will continue to inform families that combination therapy appears to improve infliximab durability.

Related blog posts:

Mount Washburn, Yellowstone

Doctor Scorecards: Affecting Care (but not in the way you think)

Posted on October 21, 2015 by gutsandgrowth

A recent perspective article (L Rosenbaum. NEJM 2015; 373: 1385-8) explains how the use of physician scorecards are negatively affecting patients and the pitfalls in their interpretation. Her article describes a situation, that is ‘not uncommon,’ in which a higher risk cardiology patient will not have a surgical consult for a few days because most surgeons “wouldn’t touch our patient with a 10-foot pole.” In several states, the increase reports of cardiac surgery outcomes has resulted in surgeons avoiding the sickest patients. The author notes that transparency/public reporting needs to be balanced against the potential harms. Other key points:

The public reporting thus far has been deeply flawed, based on insurance claims that are “notoriously inaccurate.” The reports have poor reliability, in part, due to too few surgeries to make accurate conclusions.
The public reports amount to “fear mongering” rather than the “professed commitment to protecting patients.”
“The key question, then, is less about transparency with regard to quality than it is about what constitutes quality in the first place.”
“The irony in hailing the scorecard as a victory for transparency is that its purported objectivity obscures its methodologic limitations.”

My take: While you are looking a surgeon’s scorecard, keep in mind, he/she may decide to not operate on you when he/she looks at your scorecard (of illness). Related blog posts:

What Functional MRI Finds with Anorexia

Posted on October 20, 2015 by gutsandgrowth

In yesterday’s post, functional MRI showed how rapidly anti-TNF agents can improve pain response in patients with Crohn’s disease. A more complete description of this study is available from the AGA Blog: This is Your Brain on Anti-TNF Therapy. This link also includes access to a video abstract discussion with the author.

Another intriguing use of this technology provides insight into why Anorexia is difficult to treat. The study was summarized in the NY Times:

Anorexia May Be Habit, Not Willpower Here’s an excerpt:

The study’s findings may help explain why the eating disorder, which has the highest mortality rate of any mental illness, is so stubbornly difficult to treat. But they also add to increasing evidence that the brain circuits involved in habitual behavior play a role in disorders where people persist in making self-destructive choices no matter the consequences, like cocaine addiction or compulsive gambling…

The researchers used a brain scanning technique to look at brain activity in 21 women with anorexia and 21 healthy women while they made decisions about what foods to eat…

As expected, both the anorexic and the healthy women showed activation in an area known as the ventral striatum, part of the brain’s reward center. But the anorexic women showed more activity in the dorsal striatum, an area involved with habitual behavior, suggesting that rather than weighing the pros and cons of the foods in question, they were acting automatically based on past learning…

My take: This study shows an association between food selection and differences in brain activity between women with anorexia and in controls. These changes do not prove a causal association but provide an important piece of information about what might be going wrong.

Atlanta Botanical Garden, Bruce Munro Exhibit