Category Archives: Pediatric Gastroenterology Intestinal Disorder

Food-borne Outbreaks and Lack of FDA Transparency

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A recent opinion piece from FoodSafetyNews highlights the lack of transparency from the FDA regarding food-borne outbreaks (several more listed below).

Bill Marler: Publisher’s Platform: A bit more about the FDA and lack of Transparency

Here’s an excerpt:

The Halloween disclosure of a multistate E. coli outbreak linked to romaine lettuce raises another concern about the FDA and transparency — the failure to disclose where consumers purchased the tainted product..

Under the Freedom of Information Act and Title 21 of the Code of Regulations, government agencies — and specifically, the FDA — are told to exempt trade secrets and commercial information from any of their releases…

Formulations, ingredients and how products are made are trade secrets.  Who supplied the tainted raw material, who made the tainted product and where the tainted product was sold are not a trade secrets – especially during an outbreak.  Simplicity, transparency and consistency allows for a visible supply chain and one that consumers can have confidence in. 

Recent outbreaks (thanks to colleague for these references):

Multistate Salmonella Outbreak Linked To Ground Beef Causes One Death, Eight Hospitalizations

  • Reuters (11/1, Maddipatla) reported, “A multistate outbreak of salmonella linked to ground beef has caused one death in California and eight hospitalizations, U.S. health officials said on Friday. A total of 10 people in six U.S. states were infected with a strain of the bacteria called Salmonella Dublin, according to the Centers for Disease Control and Prevention.”
  • TIME (11/2, Carlisle) reported, “Officials have not yet identified a single common source of the ground beef that is believed to be spreading the Salmonella Dublin based on epidemiological and laboratory evidence. According to the CDC, the sick individuals reported eating different brands of ground beef at different locations.”
  • CNN (11/1, Christensen) also reported the story.

Previously Undisclosed E. Coli Outbreak Linked To Romaine Lettuce Sickened Nearly Two Dozen People, FDA Says

  • The Washington Post (11/1, Brice-Saddler) reported, “A previously undisclosed E. coli outbreak linked to romaine lettuce sickened nearly two dozen people between July and early September, the Food and Drug Administration said Thursday – a delayed announcement one food safety lawyer called a ‘lie to the public in all respects.’” The piece added, “Illnesses associated with the outbreak infected 23 people across 12 states from July 12 to Sept. 8, according to the FDA. No patients died of their illnesses, and officials say there is no ongoing public health risk.”

Dozens more fresh vegetable products because of Listeria monocytogenes risk (11/4) (FoodSafetyNews.com)

  • A (Canadian) nationwide recall of freshcut vegetables continues to expand with dozens of products and multiple brands now on the list. Products potentially contaminated with Listeria monocytogenes are cole slaw, riced cauliflower, green beans, noodles, kale salads and more.  Some of the products do not expire for 10 days or more, so consumers and businesses are urged to check their supplies for the recalled products listed here by the Canadian government

My take: Food-borne illnesses cause 48 million cases in U.S. each year (CDC estimates) and 3000 deaths (MMWR 64:2, 2015). More transparency is needed.

Related blog post: Food Safety Lecture-It’s Still A Jungle Out There

 

In the News, New Cystic Fibrosis Study

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More information related to today’s earlier post: In the News: Big Therapeutic Advance for Cystic Fibrosis

Abstract

BACKGROUND

Cystic fibrosis is caused by mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) protein, and nearly 90% of patients have at least one copy of the Phe508del CFTR mutation. In a phase 2 trial involving patients who were heterozygous for the Phe508del CFTR mutation and a minimal-function mutation (Phe508del–minimal function genotype), the next-generation CFTR corrector elexacaftor, in combination with tezacaftor and ivacaftor, improved Phe508del CFTR function and clinical outcomes.

METHODS

We conducted a phase 3, randomized, double-blind, placebo-controlled trial to confirm the efficacy and safety of elexacaftor–tezacaftor–ivacaftor in patients 12 years of age or older with cystic fibrosis with Phe508del–minimal function genotypes. Patients were randomly assigned to receive elexacaftor–tezacaftor–ivacaftor or placebo for 24 weeks. The primary end point was absolute change from baseline in percentage of predicted forced expiratory volume in 1 second (FEV1) at week 4.

RESULTS

A total of 403 patients underwent randomization and received at least one dose of active treatment or placebo. Elexacaftor–tezacaftor–ivacaftor, relative to placebo, resulted in a percentage of predicted FEV1 that was 13.8 points higher at 4 weeks and 14.3 points higher through 24 weeks, a rate of pulmonary exacerbations that was 63% lower, a respiratory domain score on the Cystic Fibrosis Questionnaire–Revised (range, 0 to 100, with higher scores indicating a higher patient-reported quality of life with regard to respiratory symptoms; minimum clinically important difference, 4 points) that was 20.2 points higher, and a sweat chloride concentration that was 41.8 mmol per liter lower (P<0.001 for all comparisons). Elexacaftor–tezacaftor–ivacaftor was generally safe and had an acceptable side-effect profile. Most patients had adverse events that were mild or moderate. Adverse events leading to discontinuation of the trial regimen occurred in 1% of the patients in the elexacaftor–tezacaftor–ivacaftor group.

CONCLUSIONS

Elexacaftor–tezacaftor–ivacaftor was efficacious in patients with cystic fibrosis with Phe508del–minimal function genotypes, in whom previous CFTR modulator regimens were ineffective. (Funded by Vertex Pharmaceuticals; VX17-445-102 ClinicalTrials.gov number, NCT03525444. opens in new tab.)

In the News: Big Therapeutic Advance for Cystic Fibrosis

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Washington Post: Long-Awaited Drug Could Turn Deadly Disease into Manageable Condition

An excerpt:

A new cystic fibrosis therapy dramatically improved patients’ lung function and showed clear signs of targeting the genetic root of the disease, instead of just alleviating symptoms — a breakthrough so long-sought that many doctors and patients are moved to tears when talking about it.

The data, being unveiled Thursday at a national conference in Tennessee and simultaneously published in two leading medical journals, was so persuasive that the Food and Drug Administration last week approved the three-drug combination, called Trikafta — five months ahead of the agency’s deadline. The drug could benefit 90 percent of patients with the disease, a major advance over previous drugs that worked in a tiny fraction of the people with the disease or had more modest effects…

Sarah Carollo, 28, a special needs teacher in Lee’s Summit, Mo., started Trikafta through a clinical trial in late 2018. Carollo… couldn’t walk down a hallway without stopping to rest and catch her breath…

A few days after she began taking the pill, her doctors tested her lung function and were so stunned at the improvement that they had to check whether they were really looking at the results from the right patient. Two weeks ago, Carollo ran a 5K race with another patient, Laurana Blackburn, who was also taking the drug through the clinical trial…

There are more than 1,700 gene mutations that can cause the protein to malfunction, but in the most common mutation, the protein is misfolded and can’t reach the right spot in the cell — and even if it does reach that spot, it doesn’t work properly. The new combination therapy includes one drug that corrects the misfolded protein and two that activate the correctly folded protein when it reaches the right spot in the cell.

In the largest trial, reported in the New England Journal of Medicine, 403 patients who had at least one copy of the most common gene mutation underlying cystic fibrosis received either Trikafta or a placebo. There were improvements in objective tests of lung function, decreases in lung problems and hospitalizations and an increase in people’s quality of life…

It also remains to be seen whether patients have an easy time gaining access to the drug, which will cost $311,000 a year. While that is a tremendous amount, orphan drugs for small patient populations typically carry very large price tags, and physicians are optimistic that insurers will cover the drug.

The NY Times reported on the FDA approval (October 2019), Studies Yield ‘Impressive’ Results in Fight Against Cystic Fibrosis, and noted that the “Institute for Clinical and Economic Review, which evaluates the cost-effectiveness of drugs, found that the cystic fibrosis drugs the company sells should cost as much as 77 percent less. ”

How Good Are Our Tests for Acute Pancreatitis?

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A recent cross-sectional pediatric study (SH Orkin et al. J Pediatr 2019; 213: 143-8),  with a prospective clinical database, provides data on children presenting with acute pancreatitis, n=112 (2013-16).

Acute pancreatitis (AP): requires at least 2 of 3 criteria:

  1. Abdominal pain consistent with AP
  2. Serum amylase and/or lipase activity at least 3 times ULN
  3. Imaging findings compatible with AP

Key points:

  • Among AP patients who had a lipase level, the sensitivity was 95% whereas the sensitivity for amylase was 39%.
  • Among AP patients who had an ultrasound, the sensitivity was 52%.  In those with either CT or MRI, the sensitivity was 78%.
  • In this cohort, 5.4% did not meet diagnostic criteria based on biochemical elevation (amylase or lipase) and instead relied on imaging along with signs/symptoms.

The authors note that lipase has a delayed peak and longer duration of elevation with AP.   Amylase normalizes more rapidly.

My take: This study reinforces the view that an elevated lipase is more sensitive than amylase and that imaging (especially ultrasound) is frequently normal in AP.

Related blog posts:

Island Ford Park, Chattahoochee River

 

#NASPGHAN19 Intestinal Failure Session Part 2

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Our Spooky Pumpkin

Here are some notes and a few slides from NASPGHAN’s plenary session.  There could be errors of transcription in my notes.

Benjamin Gold, NASPGHAN president and part of our GI group, GI Care For Kids, welcomed everyone to the meeting.

Link to NASPGHAN_Annual_Meeting_Program 2019

Beth Carter  Trophic Growth Factors: A Practical View

Key Points:

  • GLP-2 has been approved as agent for intestinal failure for children (May 2019)
  • Studies thus far have shown good safety but concerns remain (?increased risk of polyposis, increased growth of neoplasm) and as such increased surveillance needed for patients receiving GLP-2
  • Cost in adults ~$295,000 per year
  • Most patients need to continue GLP-2 to maintain effect

Arthur Kasti  Abstract 218  Microbial Metabolites as Markers of Intestinal Dysbiosis in Pediatric Short Bowel Syndrome

This was a terrific presentation. Key points:

  • Microbiome in SBS patients is less diverse
  • Current diagnosis of bacterial overgrowth is difficult and definitive diagnosis is often impractical
  • Several metabolites may be helpful in diagnosis of bacterial overgrowth

Disclaimer: This blog, gutsandgrowth, assumes no responsibility for any use or operation of any method, product, instruction, concept or idea contained in the material herein or for any injury or damage to persons or property (whether products liability, negligence or otherwise) resulting from such use or operation. These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) should be confirmed by prescribing physician.  Because of rapid advances in the medical sciences, the gutsandgrowth blog cautions that independent verification should be made of diagnosis and drug dosages. The reader is solely responsible for the conduct of any suggested test or procedure.  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.

#NASPGHAN19 Intestinal Failure Session Part 1

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Here are some notes and a few slides from NASPGHAN’s plenary session.  There could be errors of transcription in my notes.

Benjamin Gold, NASPGHAN president and part of our GI group, GI Care For Kids, welcomed everyone to the meeting.

Link to NASPGHAN_Annual_Meeting_Program 2019

John Kerner  Potential Role of New Fat Emulsions

Key points:

  • Both SMOFlipid and Omegaven help prevent and/or treat parenteral nutrition associated cholestasis.
  • SMOFlipid is much less expensive (see slide below) -50 gm of SMOFlipid ~$5 compared to 10 gm of Omegaven at $35, thus omegaven costs more than 30 times SMOFlipid.
  • Though SMOFlipid is not FDA approved in children, it is being used widely and allows for increased calories compared to lipid minimization with intralipid and could improve neurocognitive outcomes.
  • SMOF dosing (listed below) with goal of 3 g/kg in preterm infants.
  • Resolution of cholestasis does not mean reversal of cirrhosis.  Thus, lipid emulsion intervention at earlier stage may be important.

Bram Raphael  Getting In Line: Towards a Clinical Practice Guideline For CVC Salvage

Key points:

  • Several infections are very difficult to clear, especially yeast, enterococcus, and pseudomonas
  • Salvaging central lines may obviate the need for multi-visceral transplant which carries a 5-year ~50% mortality rate
  • Cefepime provides good gram-negative coverage; consider meropenem in those with septic shock

Disclaimer: This blog, gutsandgrowth, assumes no responsibility for any use or operation of any method, product, instruction, concept or idea contained in the material herein or for any injury or damage to persons or property (whether products liability, negligence or otherwise) resulting from such use or operation. These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) should be confirmed by prescribing physician.  Because of rapid advances in the medical sciences, the gutsandgrowth blog cautions that independent verification should be made of diagnosis and drug dosages. The reader is solely responsible for the conduct of any suggested test or procedure.  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.

CCFA: Updates in IBD Conference (Part 3)

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My notes from Georgia Chapter of CCFA’s conference. There could be errors of omission, transcription and/or errors in context based on my understanding.

Evan Feldman, MD –Atlanta Colorectal Surgery

Surgical Management of Fibrostenotic Crohn’s Disease

Key Points:

  • Endoscopic dilation (by colorectal surgery or GI) may alleviate symptomatic strictures in selected patients and obviate surgery; dilate to 20 mm if possible.  Needs to be a short segment (<5 cm).  Consider biopsies to exclude malignancy.
  • In adults, higher risk with steroid treatment, particularly if more than 20 mg per day.
  • In symptomatic patients who need surgery …Preserve as much small bowel disease as possible.  Crohn’s disease is not curable. No need for microscopically-negative disease.
  • Stricturoplasty techniques and indications reviewed.  No role for stricturoplasty in the colon.
  • For gastroduodenal disease, gastrojejunostomy is procedure of choice.
  • Discussed perianal fistulas briefly.
    • 1st two steps: 1. control sepsis/exam under anesthesia 2. control disease process.
    • Then several options: continued use of seton, remove seton and see if better disease control leads to fistula closure, surgical procedure (eg. LIFT procedure) –preferably one with low risk of incontinence.  Injection of stem cells (when disease is under control) can be considered but is off-label in U.S. and Dr. Feldman has noted low response rates in his experience.

The slide above depicts a Michelassi stricturoplasty which is rarely performed, but considered for long segments of strictured bowel.

Related blog post:

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.

 

CCFA: Updates in IBD Conference (part 2)

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My notes from Georgia Chapter of CCFA’s conference. There could be errors of omission, transcription and/or errors in context based on my understanding.

Sandy Kim, MD –Children’s Hospital of Pittsburgh

Diet in Inflammatory Bowel Disease: Food for Thought

This was a terrific lecture –though much of the topic has been reviewed recently in this blog: Dietary Therapy for Inflammatory Bowel Disease.

Key points:

  • Changes in diet can change microbiome quickly, within 24 hrs
  • Some diets (eg. more fruit/vegetables/fish) may help lower risk of developing IBD
  • Dietary therapy, especially exclusive enteral nutrition (EEN), is effective therapy for Crohn’s disease
  • Why does EEN work?  It is not clear.  There are some changes in microbiome but decrease or little change overall in microbial diversity
  • Reviewed newer dietary approaches: SCD (www.nimbal.org), CD-TREAT, Crohn’s Disease Exclusion Diet

Related blog posts:

Frank Farraye, MD –Mayo Clinic

Health Maintenance in the Adult Patient with IBD

  • Good Practice: Update Vaccinations in IBD population
  • Recent concerns include measles outbreak, and frequent occurrence of Herpes zoster
  • No evidence that vaccination exacerbates IBD
  • New Hepatitis B Recombination Vaccine (Heplisa-B) -2 doses given over one month (for patients older than 18 years. Seroprotective anti-HBs after two doses: 95.4%
  • Shingrix -new recombinant Zoster vaccine.  Overall efficacy 97.2%.  Frequent adverse reactions
  • Women with IBD should undergo annual cervical cancer screening
  • IBD patients should be seen by dermatology
  • Consider depression screening in IBD patients
  • Counsel patients to quit smoking
  • Consider bone density screening in at risk patients

One audience member (Jeff Lewis, MD) pointed out that more attention needs to be paid to depression and anxiety which are much more common and more frequently health-threatening than issues like vaccination.

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.

 

CCFA: Updates in IBD Conference (part 1)

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My notes from a recent Georgia Chapter of CCFA’s conference. There could be errors of omission, transcription and/or errors in context based on my understanding.

Adam Cheifetz, MD —Harvard School of Medicine

Optimizing IBD Treatments

  • Earlier treatment with effective therapies
  • Utilizing therapeutic drug monitoring

Goals are clinical and endoscopic remission

  • Imaging if not visible on endoscopy
  • Biomarker remission -adjunctive goal
  • Symptoms and endoscopy do not have good correlation in Crohn’s disease
  • Endoscopic healing associated with better outcomes
  • Treatment –>assessment –> adjust treatment if goal is not met

Biologic Agents:

  • First agent works best; TNF-exposed patients do not respond as well as TNF-naive patients to subsequent biologic
  • High rate of secondary loss of response

Therapeutic Drug Monitoring:

  • Combination therapy in Sonic study was associated with higher infliximab levels. It appears that optimized monotherapy is as effective as combination therapy (Colombel study).
  • Fistula treatment requires higher biologic levels
  • Lower biologic drug levels associated with development of antidrug antibodies
  • Proactive monitoring –recommended
  • Both infliximab and adalimumab are frequently underdosed, especially in pediatrics –>another reason for proactive monitoring
  • If sicker patients, consider checking TDM at week 10; less sick patients, reasonable to consider TDM at week 14

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.

#NASPGHAN19 Postgraduate Course (Part 4)

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Here are some selected slides and notes from this year’s NASPGHAN’s postrgraduate course. With my notes, there could be errors of omission and transcription on my part.

Link to the full NASPGHAN PG Syllabus 2019 (Borrowed with permission)

Liver/Pancreas Session

150 Miriam Vos, MD, MSPH, Emory University New news in NAFLD

Dr. Vos gave a terrific lecture. Key points:

  • NAFLD screening: recommended around age 10 years (in children with obesity) based on increasing prevalence with age
  • PNPLA3 encodes adiponutrin –> important for clearing stored triglycerides. Common polymorphism PNPLA3 rs738409‐is associated with NAFLD
  • Who to screen –all obese children >10 years. Overweight children  with risk factors: Type II diabetes,  Hispanic,  Family history,  Pituitary  disorders (GH),  Right sided  abdominal pain
  • ALT and ultrasound are imperfect screens
  • Alcohol worsens NAFLD.  Sugar/juice boxes are also culprits
  • #1 Recommendation: Sugar reduction in diet

Related blog post: “The Paramount Health Challenger for Humans in the 21st Century”

161 Saul J. Karpen, MD, PhD, Emory University School of Medicine/Children’s Healthcare of Atlanta New therapies for chronic cholestatic diseases

  • Limited therapies currently available.  A number of treatments appear promising:  Obeticholic acid, Norursodeoxycholic acid
  • For ABCB4, some drugs used for cystic fibrosis may help as well
  • ASBT inhibitor appears promising for Alagille (see ITCH study)

171 Sohail Husain, MD, Stanford Children’s Hospital Diagnosing drug-induced pancreatitis

  • In patients with IBD, thiopurines and mesalamine/ sulfasalazine (mesalamine have greater risk than sulfasalazine) are associated with pancreatitis
  • ~1/3rd of patients with drug-induced pancreatitis have other risk factors

179 Jaimie D. Nathan, MD, FACS, Cincinnati Children’s Hospital Medical Center Pediatric pancreatic masses: Steroids, surgery or surveillance?

Disclaimer: NASPGHAN/gutsandgrowth assumes no responsibility for any use or operation of any method, product, instruction, concept or idea contained in the material herein or for any injury or damage to persons or property (whether products liability, negligence or otherwise) resulting from such use or operation. The discussion, views, and recommendations as to medical procedures, choice of drugs and drug dosages herein are the sole responsibility of the authors. Because of rapid advances in the medical sciences, the Society cautions that independent verification should be made of diagnosis and drug dosages. The reader is solely responsible for the conduct of any suggested test or procedure. Some of the slides reproduced in this syllabus contain animation in the power point version. This cannot be seen in the printed version.