Category Archives: Uncategorized

Big Advance in Cystic Fibrosis –Who Will Benefit?

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Recent studies point to huge advances in cystic fibrosis (CF) therapy. Though as noted in a previous blog (Why Do Canadians with Cystic Fibrosis Live Longer?), medical advances may have limited effect based on a lot of issues including access to care.

Despite that note of caution, it is hard not to be excited about a couple of recent publications which show that triple cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapy has great potential to improve outcomes for CF patients.

  • JC Davies et al. NEJM 2018; 379: 1599-611.
  • D Keating et al. NEJM 2018; 379: 1612-20.
  • Editorial: F Holguin, 1671-2

Background: In the editorial, the pathophysiology of the defect of CF is discussed and how the newer medicines either act as a potentiator of the CFTR (ivacaftor) or as corrector (lumacaftor and tezacaftor).  Potentiators increase CFTR channel opening at the cell surface whereas correctors increase the amount of CFTR protein at the cell surface. One caveat has been that these therapies had not been proven effective, individually, for Phe508del CFTR mutation which occurs in “approximately two thirds of patients.”  Combination therapy has helped in most of this group but not in those with Phe508del-minimal function (MF).

The new studies examine triple therapy with the addition of two new-generation small molecule correctors: VX-445 and VX-659. These new correctors target different sites of the CFTR protein.

Key findings:

  • in the Davies (VX-659) trial, “4 weeks of triple therapy …increased the primary end point of predicted percentage of FEV1, in the Phe508del-MF and Phe508del-Phe508del groups by an averae of 13.3% and 9.7% respectively”
  • In the Keating (VX-445) trial, triple therapy “significantly increased FEV1 in patients with those genotypes by 13.8% and 11.0% respectively.”
  • Overall, triple therapy “improved the percentage of predicted FEV1 more than double-combination therapy” in patients with a Phe508del-Phe508del mutation.  And reported efficacy in the patients with Phe508del-MF CFTR mutation.
  • The majority of patients had at least one adverse event. 3 of the 122 in the VX-445 trial discontinue treatment due to severe adverse events.

My take: These reports “represent a major breakthrough…for improving health and possibly survival in all patients who carry the most common CFTR mutation.”  Long-term outcomes will need to be followed to confirm these findings.

Related blog posts:

This is Figure 2 from Davies study showing immunoblot findings, densitometry findings, and chloride transport in bronchial cells. The most robust responses were with triple therapy

 

#NASPGHAN18 Highlights (Part 2)

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I did not make it to this year’s meeting but did get a chance to catch up on a lot information via the PG 2018 Syllabus and based on information posted online.

Here are a couple of highlights for me:

My favorite slide from postgraduate course -Dr. Robert Kramer

Slides regarding the topic of Treat-toTarget Dr. Eric Benchimol:

Slides regarding GI symptoms and autism from Dr. Kara Margolis:

Slide regarding the frequency of bariatric surgery: Dr. Rohit Kohli:

Slides regarding intestinal failure population from Dr. Conrad Cole:

From Dr. Miranda van Tilburg regarding psychological therapies for functional GI disorders:

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.

#NASPGHAN18 Highlights and Tweets (part 1)

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I did not make it to this year’s meeting but did get a chance to catch up on a lot information via the PG 2018 Syllabus and based on information posted online.

Here are a couple of highlights for me:

Slides from postgraduate course on CVS from Dr. Katja Kovacic

The slide from Dr. Lightdale (pg 22 in Syllabus) below suggests it is OK for scope if platelets >20K and OK for biopsies if platelets >50K. It is worth noting that some adult data indicate that even lower biospy thresholds are reasonable for biopsies (Post: Lower Endoscopic Thresholds for Thrombocytopenia). As always, one needs to consider carefully the risks compared with the benefits.

From Postgraduate Course

 

 

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.

New Button Battery Guidelines –with Honey and Vinegar

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Button batteries –definitely more scary than Halloween.  Here is a link to new guidelines from Poison Control: New Button Battery Guidelines 2018

A recent report from Nationwide Childrens, How Sweet It Is: Honey Attenuates Button Battery-Induced Esophageal Damage, highlights two important advances in button battery management that are now incorporated into the new button battery guidelines:

  1. At time of endoscopy,  “a weak acetic acid rinse (sterile vinegar) can help neutralize tissue pH and protect the esophagus from continued tissue breakdown after battery removal. This irrigation concept has now been successfully used in children around the world with good clinical outcomes.”
  2. Prior to endoscopy, “both honey and sucralfate (Carafate®) were able to effectively neutralize the tissue pH and reduce visible injury.”

“More than 3,000 cases occur per year, mostly among children younger than age 6, and severe cases are on the rise. Lodged button batteries can cause rapid injury, including permanent bilateral vocal cord paralysis and even death.”

Guideline recommendations with regard to acetic acid:

After a battery is removed from the esophagus, inspect the area endoscopically for evidence of perforation. If none is evident, irrigate the injured areas with 50 mL to 150 mL of 0.25% sterile acetic acid (obtained from the hospital pharmacy). Irrigate in increments and suction away excess fluid and debris through the endoscope. For decades toxicologists have advised against neutralization for fear of causing a thermal injury. However, a recent study (Jatana, 2016) using piglet esophagus preparations after button battery removal, showed only a minimal increase in temperature (0-3 oC), effective tissue surface pH neutralization, and decrease in the visible injury using this neutralization strategy. The tissue surface pH neutralization may reduce the development of progressive, delayed-onset esophageal injury after battery removal.

From guideline with regard to honey:

Administer honey immediately and while en route to the ER, if:

  1. A lithium coin cell may have been ingested (if you don’t know what kind of button battery was swallowed, assume it is a lithium coin cell unless it is a hearing aid battery);
  2. The child is 12 months of age or older (because honey is not safe in children younger than one year);
  3. The battery was swallowed within the prior 12 hours (because the risk that esophageal perforation is already present increases after 12 hours);
  4. The child is able to swallow; and
  5. Honey is immediately available.

How to dose honey:

      1. Give 10 mL (2 teaspoons) of honey by mouth every 10 minutes for up to 6 doses. Do not worry about the exact dose or timing.
      2. Use commercial honey if available, rather than specialized or artisanal honey (to avoid inadvertent use of large amounts of honey produced from potentially toxic flowers).
      3. Honey is NOT a substitute for immediate removal of a battery lodged in the esophagus. Honey slows the development of battery injury but won’t stop it from occurring. Do not delay going to an ER.

Why give honey?

Honey is administered to coat the battery and prevent local generation of hydroxide, thereby delaying alkaline burns to adjacent tissue. Efficacy is based on a 2018 study (Anfang et al) assessing the in vitro protective effects of various liquids in the cadaveric porcine esophagus and in vivoprotective effects of honey and sucralfate (Carafate®) compared to saline irrigations of batteries placed in the esophagus of live piglets. Both honey and sucralfate (Carafate®) effectively prevented the expected battery-induced pH increase and decreased the depth of the resulting esophageal injury.

References:

  1. Anfang RR, Jatana KR, Linn RL, Rhoades K, Fry J, Jacobs IN. pH-neutralizing esophageal irrigations as a novel mitigation strategy for button battery injury. The Laryngoscope. 2018 Jun 11. [Epub ahead of print]
  2. Jatana KR, Rhoades K, Milkovich S, Jacobs IN. Basic mechanism of button battery ingestion injuries and novel mitigation strategies after diagnosis and removal. The Laryngoscope. 2017 Jun;127(6):1276-1282.

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.

 

#NASPGHAN18 Abstract: LR for Pancreatitis & Pumpkin Shot

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At NASPGHAN18, an abstract provided more information that indicates that lactated ringer’s is probably the best intravenous fluid for most children with acute pancreatitis

Related blog posts:

 

2018 Pumpkin for our House

Endoscopic Experts Needed In Pediatrics

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A recent study (A Schmidt et al. Gastroenterol 2018; 155: 674-86) shows how a new endoscopic technique, over-the-scope clips (OTSC), are more effective than standard endoscopic therapy for patients with recurrent bleeding of peptic ulcers.

Key finding: A multicenter prospective randomized unblinded study with 66 patients (33 in each arm) with found that hemostasis with OTSC had a failure rate (further bleeding) of 15.2% compared with 57.6% in those with standard therapy.

The authors note that standard endoscopic techniques are effective in more than 90% with rebleeding rates of 2-10%.  In those with rebleeding, followup endoscopy has a much lower success rate.

My take:

  • This study highlights a problem in pediatric endoscopy –the lack of expertise in these rare cases.  To learn even ‘standard’ endoscopic therapy, most pediatric GI fellows will need to collaborate with adult gastroenterologists in order to have exposure to a sufficient number of cases.
  • The development of alternatives like hemospray (Hemospray for GI Bleeding) which is technically-easy should be helpful for pediatric endoscopists with less endoscopic training.

Related article: 

P Tran et al. JPGN 2018; 67: 458-63.  This retrospective analysis of 11 pediatric cases (median age 14.7 yrs) reported technical success in all cases, though 2 patients with anastomotic ulcers requred additional medical intervention. The article has some pretty cool pictures.

Related blog posts:

 

Lake Agnes, Banff

Lake Agnes Teahouse Menu

 

#NASPGHAN18 -Our Poster on Antibiotic Stewardship and PEG Placement

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Thanks to Chelly Dykes for presenting poster later today and to co-authors for collaborating on this project: Jeffery Lewis, Bonney Reed-Knight and Cate Crenson.

Full abstract below.

ABSTRACT:

 Background: While there is general agreement that antibiotic prophylaxis for percutaneous gastrostomy (PEG) tube insertion reduces the risk of infection at the site of placement (Lipp A, Cochrane Review 2013), optimal antibiotic selection and regimen remain unclear; as a result, there is widespread practice variation.  In addition, in order to limit the development of bacterial resistance and complications from antibiotic use (eg. Clostridium difficile infection), antibiotic stewardship programs have aimed to limit antibiotic usage, particularly broad-spectrum antibiotics.

Methods: From December 1, 2016 through May 1, 2018, the charts of all patients who underwent PEG tube placement in our children’s hospital were reviewed.  This period coincided with an optional practice change in antibiotic prophylaxis.  Prior to the study period, the typical patient received prophylaxis with a three-dose regimen of cefoxitin.  During the study period, at the discretion of the gastroenterologist, patients received either a three-dose regimen of cefoxitin (n=38) or treatment with cefazolin (n=109); 73 patients received a single dose of cefazolin prior to PEG placement and 36 received multiple doses.  The initial dose of either regimen was given within thirty minutes of placement.  All patients were observed for at least 24 hours.  In patients with PEG tube site infections based on clinical assessment, rescue antibiotic treatment was prescribed.

Results: In total, 144 subjects had PEG placement. The main indications for PEG placement were swallow dysfunction (56.2%), poor growth (17.6%), feeding aversions (18.9%) and malignancy (6%).  In the cefoxitin group, clinical infection occurred in 3 of 35 (8.6%).  In the cefazolin group, clinical infection occurred in 20 of 109 (18.3%). In the subset of patients who received multiple doses of cefazolin, the clinical infection rate was 6 of 36 (16.7%). Patients in the cefazolin group had a 2.39 times higher odds (95% CI  0.667-8.612) of infection compared to the cefoxitin group. Although rates of infection were more than twice as high in the cefazolin group compared to the cefoxitin group, this association did not differ statistically using a chi square test (x^2 = 1.89, p = 0.20).

Conclusion: This study highlights the ongoing uncertainty regarding optimal antibiotic prophylaxis for PEG tube placement.  The difference in the clinical infection rate between cefazolin and cefoxitin was not statistically significant; however, the absolute rate of infection in the cefazolin group was more than twice as high as the cefoxitin group and this may influence selection of antibiotic prophylaxis for PEG tube insertion.

 

Almost Everybody Needs Flu Shot –IBD Patients at Higher Risk

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Link: CDC Recommendations for Influenza Vaccination

  • Routine annual influenza vaccination is recommended for all persons aged ≥6 months who do not have contraindications.
  • Vaccination should be offered by end of October; however, vaccination should continue to be offered as long as influenza viruses are circulating and unexpired vaccine is available.

 

Expert Advice for Diagnosis and Treatment of Rumination Syndrome

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Full text: M Halland et al Clinical Gastroenterol Hepatol 2018; 16: 1549-1555 provide an excellent review and practical recommendations for rumination syndrome.

The article describes the high prevalence which is ~0.8-0.9% of adults and ~5% of children.  Some populations like patients with eating disorders and fibromyalgia have even higher rates.

Other key points:

  • Long delay in diagnosis: patients “visit an average of 5 physicians over 2.7 to 4.9 years before being diagnosed correctly”
  • The diagnosis is a clinical based on Rome IV criteria, though most patients undergo an esophagogastroduodenoscopy or barium study to rule out other disorders
  • Best Practice Advice 1: Clinicians strongly should consider rumination syndrome in patients who report consistent postprandial regurgitation. Such patients often are labeled as having refractory gastroesophageal reflux or vomiting.
  • Best Practice Advice 2: Presence of nocturnal regurgitation, dysphagia, nausea, or symptoms occurring in the absence of meals does not exclude rumination syndrome, but makes the presence of it less likely.
  • Best Practice Advice 3: Clinicians should diagnose rumination syndrome primarily on the basis of Rome IV criteria after an appropriate medical work-up.
  • Best Practice Advice 4: Diaphragmatic breathing with or without biofeedback is the first-line therapy in all cases of rumination syndrome.
  • Best Practice Advice 5: Instructions for effective diaphragmatic breathing can be given by speech therapists, psychologists, gastroenterologists, and other health practitioners familiar with the technique.
  • This article gives instructions on this technique: “Diaphragmatic breathing can be learned easily by putting a hand on the chest and on the abdomen during respiration, and only allowing the hand on the abdomen to move out with inspiration while the chest remains in position (Figure 3). We instruct patients to take breaths by protruding the abdomen while keeping the chest as stationary as possible. Each inhalation or exhalation should be slow and complete, aiming for 6 to 8 respirations per minute. We recommend diaphragmatic breathing for 15 minutes after each meal, or longer if the sensation of impending rumination remains. The technique also should be practiced in the absence of meals to become expert at the technique. Uncontrolled studies and case series have reported resolution or improvement in rumination symptoms after diaphragmatic breathing in 20%–66% of patients. Figure 3: The patient slowly inhales through the nose while protruding the abdomen and keeping the chest stationary. (B) The patient slowly exhales via the mouth and allows the abdomen to retract.”
  • Best Practice Advice 6: Objective testing for rumination syndrome with postprandial high-resolution esophageal impedance manometry can be used to support the diagnosis, but expertise and lack of standardized protocols are current limitations.
  • Best Practice Advice 7: Baclofen, at a dose of 10 mg 3 times daily, is a reasonable next step in refractory [adult] patients.

My take: This is a useful review article.  Rumination needs to be considered particularly in patients with regurgitation, often labelled vomiting by families, that happens quickly after meals.

Related posts:

In the news…from Washington Post: