Image: The Wrong Way to Eat Dinner

Posted on November 5, 2016 by gutsandgrowth

What Happens When Infliximab Is Stopped in Patients with Ulcerative Colitis Remission

Posted on November 4, 2016 by gutsandgrowth

‘If it ain’t broke, don’t fix it’

Perhaps, the above sentiment is needed for patients with ulcerative colitis who are doing well with infliximab therapy according to a recent study (G Fiorino et al. Clin Gastroenterol Hepatol 2016; 14: 1426-32).

In this multicenter retrospective cohort study, 111 patients with ulcerative colitis who had been in remission (>12 months) were followed after stopping infliximab (IFX) and compared with 82 controls who remained on therapy. Here’s what happened (see Figure 1 in study):

Among those who discontinued IFX, 53 patients (47.7%) relapsed in the followup period. This corresponded to an incidence of 23.3 per 100 person-years and with a median time to relapse of 3.6 years.
In comparison, for those who remained on IFX, 14 relapses (17.1%) occurred which corresponded to an incidence of 7.2 per 100 person-years at risk and with a median time to relapse of 7.6 years.
Thiopurine use after stopping IFX seemed to diminish the risk of relapse: 15.0 per 100 person-years compared with 31.2 per 100 person-years for those taking an aminosalicylate alone.
For those who restarted IFX, 77.1% had a response and 51.4% returned to remission; however, 17.1% had infusion reactions.

My take: In a real-life experience, stopping IFX in patients with ulcerative colitis who had been in sustained clinical remission resulted in a higher relapse rate. This finding is consistent with other studies.

Related blog posts:

The Lawn at University of Virginia

Advice on Abdominal Pain for Everyone Who Cares for Children

Posted on November 3, 2016 by gutsandgrowth

A recent editorial (MK Farrell. J Pediatr 2016; 177: 16-17) provides many useful pointers from a master clinician along with commentary on an epidemiology study of recurrent abdominal pain (ML Lewis et al. J Pediatr 2016; 177: 39-43).

The main finding of the study which used an internet survey of mothers (children 4-18) was that 23% of US children met the Rome III criteria for a functional GI disorder. Constipation was the most common.

Key points in commentary:

John Apley’s monograph The Child with Abdominal Pains “should be read by all who care for children.”
Worldwide prevalence of functional GI disorders has been estimated to be 13%. Peak ages were 4-6 years and early adolescence with a greater prevalence in females
“A variety of phamacologic and nonpharmacologic treatments have been proposed, but none have been consistently effective except perhaps cognitive behavioral therapy and hypnotherapy.”
“Negative studies are not reassuring” [to families]

Pithy observations from Apley:

“The more time the doctor spends on the history, the less time he is likely to spend on treatment.”
“Doctors who treat the symptoms tend to file a prescription. Doctors who treat the patient are more likely to offer guidance.”
“It is a fallacy that a physical symptoms always has a physical cause and needs a physical treatment.”
“Anxiety like courage is contagious.”

My take: Dr. Farrell urges more research focus on interventions (diet, behavioral, alternative therapies, medical treatments) to improve outcomes and less focus on epidemiology.

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.

The Lawn, University of Virginia

Topamax and Amitriptyline Did Not Work for Pediatric Migraines

Posted on November 2, 2016 by gutsandgrowth

A recent study (SW Powers et al. NEJM 2016; DOI: 10.1056/NEJMoa1610384) showed that neither topamax nor amitriptyline were more effective than placebo.

Excerpt of summary from NY Times: Two Drugs for Adult Migraines May Not Help Children

Neither of the two drugs used most frequently to prevent migraines in children is more effective than a sugar pill, according to a study published on Thursday in The New England Journal of Medicine.

Researchers stopped the large trial early, saying the evidence was clear even though the drugs — the antidepressant amitriptyline and the epilepsy drug topiramate — had been shown to prevent migraines in adults…

At 31 sites nationwide, 328 migraine sufferers aged 8 to 17 were randomly assigned to take amitriptyline, topiramate or a placebo pill for 24 weeks. Patients with episodic migraines (fewer than 15 headache days a month) and chronic migraines (15 or more headache days a month) were included…

As it turned out, there was no significant difference among the groups: 61 percent of the placebo group reduced their headache days by 50 percent or more, compared with 52 percent of the children given amitriptyline and 55 percent of those who took topiramate. And there was no significant difference among the three groups in reducing the school days or other activities missed…

One child on topiramate attempted suicide. Three taking amitriptyline had mood changes; one told his mother he wanted to hurt himself, while another wrote suicide notes at school and was hospitalized.

My take: Given the overlapping features between migraines and abdominal pain, how (in)effective are these types of medications for abdominal pain? Also, does someone know where I can buy stock in whoever makes placebo -it performed pretty well.

Related blog posts:

Changes in the Use of IBD Biologic Therapy

Posted on November 1, 2016 by gutsandgrowth

A recent study (W-J Lee et al. Inflamm Bowel Dis 2016; 22: 2410-17) offers a great deal of insight into changes in the use anti-Tumor Necrosis Factor Alpha (ant-TNF) therapy from 2009-2013 in patients ≤24 years. The authors utilized databases with about 180 million people and identified 11,962 patients with inflammatory bowel disease (IBD).

Key findings:

3300 of the 11,962 (27.6%) patients were treated with anti-TNF therapy.
Top-down treatment: 1298 of 3300 (39.3%) were treated with top-down therapy which was defined as usage of anti-TNF therapy within 30 days of first IBD medication prescription. Interestingly, over the course of the study, there was a trend towards more top-down (versus step-up) therapy and shorter time to initiation of anti-TNF therapy. In 2009, 31.4% used a top-down approach compared with 49.8% in 2013.
Top-down therapy is associated with lower rates of corticosteroid use.
Infliximab dominant anti-TNF: infliximab was the anti-TNF in 89.2% of patients less than 12, 82.3% of patients 12-17, and 55.1% of patients 18-24. Adalimumab accounted for the vast majority of the other TNF users. Though, the authors note a trend towards increasing use of adalimumab in both adult and pediatric patients in a separate study (Park KT et al. Inflamm Bowel Dis 2014; 20: 1242-49)
Cotherapy: thiopurines and methotrexate were used as cotherapy in 13.5% and 7.2% of top-down group compared with 54.8% and 14.6% respectively in step-up strategy.
Drug therapy among non-TNF users: 25.4% (2199) received a thiopurine, 79.3% (6871) received a 5-aminosalicylate, and 2.3% (201) received methotrexate.
Anti-TNF therapy discontinuation: Using top-down strategy 69.2% persisted on infliximab at 12 months and 56.8% persisted at 24 months. In comparison, using step-up approach with infliximab, it was 72.7% at 12 months and 64.0% at 24 months. The numbers were quite similar with all the anti-TNF agents indicating that step-up approach had significantly lower rate of anti-TNF discontinuation. The authors speculate that one factor could be use of cotherapy or possibly other adverse reactions.

The authors explain some of the limitations of their study in its reliance on databases, particularly with regard to misclassification. However, in my opinion, these limitations do not affect any of the trends that the authors are able to document.

My take: For most of my patients, I have preferred to continue to utilize cotherapy and/or step-up therapy because I think there is likely to be a more durable anti-TNF response. The fairly small differences in anti-TNF durability have huge implications for those who lose anti-TNF responsiveness given the limited treatment options.

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Hidden Lake and Bear Mountain, Glacier National Park

Preventing Sudden Infant Deaths -Latest Guidelines

Posted on October 31, 2016 by gutsandgrowth

Though sudden infant death syndrome and counseling is mainly in the realm of general pediatrics, subspecialists need to be familiar with the latest AAP recommendations as well.

A summary from NPR: Pediatricians Release New Guidance for Preventing Sudden Infant Deaths

Children should sleep in the same room but on a separate surface from their parents for at least the first six months of their lives, and ideally the first year. They say that this can halve the risk of SIDS…

You can read the AAP’s full guidance here. These are a few more of the pediatricians’ recommendations:

Infants under a year old should always sleep lying on their backs. Side sleeping “is not safe and is not advised,” the AAP says.
Infants should always sleep on a firm surface covered by only a flat sheet. That’s because soft mattresses “could create a pocket … and increase the chance of rebreathing or suffocation if the infant is placed in or rolls over to the prone position.”
Any other bedding or soft objects, like pillows or stuffed animals, could obstruct a child’s airway and increase the risk of SIDS and suffocation, according to the AAP.
The pediatricians say breastfeeding reduces the risk of SIDS.
The same goes for pacifiers at nap time and bedtime, although the doctors say the “mechanism is yet unclear.” They add that “the protective effect is observed even if the pacifier falls out of the infant’s mouth.”
Smoking – both during pregnancy and around the infant after birth – can increase the risk of SIDS. Alcohol and illicit drugs during pregnancy can also contribute to SIDS, and “parental alcohol and/or illicit drug use in combination with bed-sharing places the infant at particularly high risk of SIDS,” the pediatricians say.

2016 Pumpkin

The Narrow Path of Personalized Cancer Medicine

Posted on October 30, 2016 by gutsandgrowth

Since I’m not directly involved in oncology care, I have a limited perspective on how quickly molecular medicine may transform cancer care. A recent commentary (IF Tannock, JA Hickman. NEJM 2016; 1289-94) explains the “Limits to Personalized Cancer Medicine.”

While the idea of careful molecular characterization of tumors that lead to targeted therapy with better survival and better patient quality of life has been proven effective in several circumstances, there are a number of reasons why this approach will not be useful for most cancers.

Key points:

Examples of current personalized cancer Rx: trastuzumab for HER2-expressing breast cancer and vemurafenib for BRAF-mutated-expressing melanomas.
Very few studies have shown feasibility/effectiveness of targeted drug treatment
There has been limited success with targeted drugs within and outside studies
Though proponents of targeted therapy expect further advances, tumors typically have heterogeneity which allows a Darwinian evolution to evade these new therapies. “Cancer cells have an almost universal capacity to develop resistance to a single molecular targeted agent by means of upregulation of the partially inhibited pathway, mutation of the target, or activation of alternative pathways.”
Targeted therapies are usually limited by only partial inhibition of the signaling pathways and by toxicity when used in combination therapy.
In some cases, a clonal driver mutation may be present which would be present in all cell lines –however the authors note that success from this approach is likely to be rare.
Cost: “new drugs to treat cancer are marketed at ever-increasing prices…unrelated to value (i.e. to clinical effectiveness)….but the development and marketing of expensive drugs with marginal effectiveness diverts resources from the development of more effective therapies.”

My take (borrowed from authors): “The concept of personalized medicine is so appealing…[but] there should also be a clear message to patients that personalized cancer medicine has not led to gains in survival…and is an appropriate strategy only within well-designed clinical trials.”

Related blog post:

What is Wrong with the Glimmer of “Precision Medicine” | gutsandgrowth

The Lawn, University of Virginia

GI Educational Cartoons For Children

Posted on October 29, 2016 by gutsandgrowth

Diana Lerner and the Medical College of Wisconsin have developed additional GI educational videos. Previously, they had developed cartoon videos explaining endoscopy (prev post: Terrific Educational Videos on Endoscopy). Now there are several more. All of these are in English and some in Spanish.

Topics include inflammatory bowel disease, gastroesophageal reflux, eosinophilic esophagitis, and celiac disease.

Here’s the link: Pediatric Gastroenterology Cartoons For Kids

Related blog post:

Good Educational Two Minute Video on Celiac Disease

October 2016: IBD Studies

Posted on October 28, 2016 by gutsandgrowth

Briefly noted:

E Zittan et al. Inflamm Bowel Dis 2016; 22: 2442-47. In this study with 773 patients with history of ulcerative colitis/ileal pouch-anal anastomosis, there was no significant difference in complications/leak among the 196 with preoperative anti-TNF exposure (n=26, 13.2%) compared with the control group (n=66, 11.7%). Preoperative anti-TNF exposure does not appear to worsen outcomes after surgery.

C Hartman et al. JPGN 2016; 63: 437-444. This cross-sectional survey of 68 children with IBD (57 Crohn’s disease) found frequent nutrient deficiencies based on 3 day diet records. Interestingly, children on exclusive enteral nutrition were much less likely to have inadequate intakes of energy, minerals, or micronutrients. This article provides plenty of reasons for children with IBD, particularly Crohn’s disease, to work with a nutritionist.

M Fischer et al. Inflamm Bowel Dis; 2016; 22: 2402-09. In a cohort study of 67 patients (35 with Crohn’s, 31 with ulcerative colitis, and 1 indeterminate colitis), fecal microbiota transplantation (FMT) for refractory Clostridium difficile infection was successful in 53 (79%) with a single infusion. Four of the 14 failures, subsequently responded to anti-CDI antibiotics. Of the 8 who had a 2nd FMT, 6 were successful; and 1 of 2 responded to 3rd FMT. Thus, 60 of 67 responded overall to FMT. After FMT, IBD disease activity was reported as improved in 25 (37%), no change in 20 (30%) and worse in 9 (13%). In this cohort, 1 needed colectomy and 1 needed diversion. This article indicates that FMT for CDI in IBD was associated with high cure rates and low risk of IBD flare.

A Khoruts et al. Clin Gastroenterol Hepatol 2016; 14: 1433-38. This was a study of 272 consecutive patients that underwent FMT for recurrent CDI. 15% had established IBD and 2.6% were determined to have IBD at time of FMT. 74.4% of IBD patients responded to a single FMT compared with 92.1% of patients without IBD. More than one quarter of IBD patients experienced a clinical flare after FMT.

MA Conrad et al. Inflamm Bowel Dis; 2016: 22: 2425-31. This review of early pediatric experience with vedolizumab in 21 subjects (16 with Crohn’s disease) identified a clinical response in 6/19 (31.6%) evaluable subjects at week 6 and 11/19 (57.9%) by week 22. Steroid-free remission was noted in 3/20 at 14 weeks (15%) and 4/20 (20.0%) at 22 weeks. Overall, this shows a fairly low response rate to vedolizumab in this highly selected cohort. Prospective pediatric studies of vedolizumab are needed to identify which patients are most likely to benefit.

University of Virginia Rotunda

Case Report: Management after Accidental Bolus of Parenteral Nutrition

Posted on October 27, 2016 by gutsandgrowth

Fortunately, most mistakes do not result in long-lasting consequences. The authors’ of a recent report (JPEN J Parenter Enteral Nutr August 2016 vol. 40 no. 6 883-885) note a severe setback for a patient after accidental bolus of parenteral nutrition:

Here’s the abstract:

There is a paucity of data that exists regarding acute toxicity and management in the setting of parental nutrition (PN) overdose. We describe a case of a patient who received an accidental rapid bolus of PN and fat emulsion. She developed a seizure, metabolic acidosis, arrhythmias, myocardial ischemia, altered mental status, hypotension, and hypoxemia likely caused by elevated triglycerides, leading to a hyperviscosity syndrome. After failing standard therapy, she was successfully treated with a single-volume plasma exchange with resolution of symptoms. Fat emulsion or intravenous lipid emulsion and much of its safety have been recently described in its use as a rescue therapy in resuscitation from drug-related toxicity. Elevated serum triglyceride levels can result in a picture similar to a hyperviscosity syndrome. Plasma exchange is a known therapeutic modality for the management of hyperviscosity syndrome and a novel therapy in the treatment of hyperviscosity syndrome due to fat emulsion therapy. In a patient receiving PN with development of rapid deterioration of clinical status, without an obvious etiology, there should be consideration of PN overdose. A rapid assessment and treatment of severe electrolyte abnormalities should be undertaken immediately to prevent life-threatening cardiovascular and central nervous system collapse. If fat emulsion was rapidly coadministered and there are signs and symptoms of hyperviscosity syndrome, then consideration should be given to plasma exchange as an effective therapeutic treatment option.