Salivary Pepsin Doesn’t Pass Muster for Evaluation of Reflux

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For quite a long time, I thought the expression was “Pass Mustard”.

A recent study (F Dy et al. J Pediatr 2016; 177: 53-8) shows that testing salivary pepsin is probably a waste of time in assessing for extraesophageal reflux disease. The authors prospectively recruited 50 children who underwent multiple studies including 24-hour pH-MII testing. The idea of pepsin as a biomarker has some plausibility since it is produced in the stomach and its presence in the oropharynx (or airway) would be unexpected.  Since salivary pepsin does not require invasive diagnostic testing, it would be useful if it had adequate sensitivity and specificity.

Key findings:

  • 21 of 50 (42%) were salivary pepsin-positive with a median concentration of 10 ng/mL.  Pepsin was detected in 6 of 21 with abnormal impedance testing and 8 of 21 with abnormal pH results (per Table 1 –the discussion used a denominator of 11 for each of these results)

  • There was no significant correlation between salivary pepsin-positivity compared with salivary pepsin-negative for reflux episodes, acid reflux, nonacid reflux or any other reflux variable.

  • The authors also reiterate in the discussion that clinical trials, evaluating reflux and chronic cough, “have failed to find a consistent relationship between measure dreflux and clinical response.”
  • The authors note that bronchoscopy pepsin correlation with esophageal reflux monitoring was similarly low in sensitivity
  • The authors note that “one-third of healthy asymptomatic adults have pepsin detected in their saliva.”  In this study, 38% (15 of 39) of children had pepsin detected despite normal impedance results.

My take:  While this study mainly shows that pepsin detected in the saliva has no practical use in correlation with reflux, the bigger picture is the uncertain relationship of reflux as a causal association with chronic cough.

Any of the reflux-esophageal gurus care to comment?

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Carriage Road in Acadia National Park

Carriage Road in Acadia National Park

 

Big Progress with Smoking

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A remarkable public health advance is happening and has not received much attention.  A recent commentary (MC Fiore. NEJM 2016; 375: 1410-12) highlights the substantial and accelerating progress in lowering the use of tobacco/smoking.

The author notes that the rate of decline in smoking is now about 0.78 percentage points per year during the Obama administration which is more than double the rate during the prior 16 years.  This decline, if continued, could mean that the current rate of smoking of 15.3% of U.S. adults could be zero by around 2035.

The author notes that the current administration likely deserves some of the credit for this progress due to legislative acts and leadership.  Legislation has included increases in federal cigarette excise taxes, more FDA oversight of thousands of tobacco products, and better insurance coverage of smoking cessation through the Affordable Care Act. Leadership has involved the CDC, FDA and HHS.  This has led to comprehensive strategic plans which have developed effective educational campaigns, including “Tips from Former Smokers” and “The Real Cost.” More steps to build on this progress has been outlined in the 50th-annisversary of the Surgeon General’s report, The Health Consequences of Smoking (2014).

Potential Further Actions:

  • Further increases in cigarette excise taxes
  • Sustain high-impact national media campaigns
  • Public housing mandates to make smoke-free
  • Federal legislation to ban any tobacco products to persons younger than 21 years
  • Extend smoke-free indoor-air protections to all Americans

My take: This is great news.  Hopefully, there will be a big drop from >36 million Americans who smoke to many fewer in coming years.  This can reduce premature deaths which are expected for about half of people who continue to smoke.

New Family Member: Charlie!

New Family Member: Charlie!

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

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‘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.

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The Lawn at University of Virginia

The Lawn at University of Virginia

Advice on Abdominal Pain for Everyone Who Cares for Children

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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.

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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

The Lawn, University of Virginia

 

Topamax and Amitriptyline Did Not Work for Pediatric Migraines

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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.

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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.

migraine-meds

Changes in the Use of IBD Biologic Therapy

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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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Preventing Sudden Infant Deaths -Latest Guidelines

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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

2016 Pumpkin

 

 

The Narrow Path of Personalized Cancer Medicine

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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.”

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University of Virginia

The Lawn, University of Virginia

GI Educational Cartoons For Children

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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

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