'Fake News' in GI: Getting to the Truth about Gluten, PEG 3350 and PPIs. Carlo Di Lorenzo, M.D

Transcription

1 'Fake News' in GI: Getting to the Truth about Gluten, PEG 3350 and PPIs Carlo Di Lorenzo, M.D Disclosure I have the following financial relationships with the manufacturer(s) of commercial product(s) and/or provider of commercial services discussed in this CME activity: Consultant for: Sucampo, Merck, Allergan, QOL Inc I do intend to discuss unapproved/investigative uses of commercial products/devices in my presentation. 1

2 Social media and fake news bring a new challenge per physicians 2

3 The way people see science news nowadays Why so many fake news in GI and Nutrition? Powerful combination of uncertainty, public interest, influences of industry and celebrities Everybody eats, everybody experiences GI symptoms Challenging to do blinded studies in nutrition science 3

4 Facts about gluten Exposure to gluten causes celiac disease Celiac disease affects ~1% of US people Celiac disease is easy to diagnose (Ig A and ttg) Avoidance of gluten is the only treatment for celiac disease Myth Going gluten free makes me healthier and improves my athletic performance 4

5 The influence of celebrities 5

6 How Many People in the US Are Embracing a GFD? Percentage of U.S. Adults Trying to Cut Down or Avoid Gluten in Their Diets Reaches New High in 2013, Reports NPD Gluten There (or Wheat) are 3 Gluten related - related disorders disorders Wheat Allergy ~0.1% Celiac Disease 1% Non-celiac Gluten Sensitivity?% No gene associated Largely IgE-mediated Children and Bakers HLA-DQ2, DQ8 Autoimmune disease Any age No gene associated Immune-mediated? Mostly adults Serum specific IgE CD autoantibodies Biopsy No diagnostic marker 6

7 Who is on a gluten free diet? *Consumer reports Reasons for avoiding gluten 7

8 Reasons for avoiding gluten Where is the evidence that eliminating gluten helps? 8

9 Collectively the whole group reported the most severe symptoms after placebo (P =.012). The present study showed that the majority of patients with suspected NCGS are not able to identify when challenged with gluten in a double-blind placebocontrolled food challenge, indicating that gluten is not the cause of their symptoms. 9

10 Excess 6/13/2018 Does going gluten free enhance sport performance? Med Sci Sport Exerc 2015; 47: Any downside of a gluten free diet? s Kcal intake Simple CHO Saturated fats Lipids Zinc Magnesium Iron Vit. B Vit. D Calcium Folate Dietary Fiber Deficiencies 10

11 Gluten: take home messages Test for celiac disease before stopping gluten Discourage stopping gluten for other health benefits or athletic improvement Monitor for excessive weight gain and nutrient deficiencies children on a gluten free diet 11

12 Facts about PEG 3350 It has been on the market since 1999 Probably the most investigated drug in pediatric GI (efficacy for clean-outs and maintenance, comparative, colonoscopy prep, different ages) High prevalence of constipation in children with behavioral and psychiatric disorders PEG 3350 recommended as 1 st line rx in current practice guidelines 12

13 Concerns about PEG 3350 Neuropsychiatric events such as seizures, tremors, tics, anxiety, lethargy, aggression, paranoia, mood swings, and obsessive compulsive behaviors such as repetitive chewing and sucking have been observed in patients receiving PEG 3350 for treatment of constipation PEG 3350 might contain trace amounts of ethylene glycol, diethylene glycol, and triethylene glycol and these might contribute to neuropsychiatric adverse events in children Williams KC, et al. J Pediatr

14 Are children with ASD at risk for defecation disorders? Constipation, flatulence and diarrhea more common in children with ASD than in normal children and children with other neurodevelopmental disorders (Autism 2009;13:343-55) Constipation (33% vs 17%) was more common in youth with autism than in a control population in Olmstead County (Pediatrics 2009; 124:680-6) ASD are one order of magnitude more common in the constipation clinic than in the general population (Pediatr Surg Int 2011;27:353-8) 14

15 But PEG is in antifreeze! 15

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17 But remember, there is nothing special about PEG 3350; it is not the Miracle laxative 17

18 Effect of PEG 3350 vs Milk of Magnesia % Children who improved or 30 recovered PEG MOM 1 month follow-up Recovered Improved PEG MOM 3 month follow-up Loening-Baucke V et al. Pediatrics 2006; 118:528 PEG vs MOM: P =ns Compliance rates with the treatment were 95% for PEG and 65% for MOM PEG MOM 6 month follow-up PEG MOM 12 month follow-up PEG 3350: take home messages A lot of success can be achieved in childhood constipation with behavioral interventions PEG 3350 still to be considered an effective AND safe treatment for constipated children No significant advantage of PEG 3350 over other laxatives in terms of efficacy When palatability and compliance are an issue, I still use PEG

19 Facts about acid suppression Problem of erosive esophagitis has been solved PPI-responsive EoE Protection from NSAID induced gastroduodenal lesions Helps with GI bleeding Acid suppression is overused 19

20 FDA and PPI in children Education/Pharmacy-Education-Materials/Downloads/ppi-pediatric-factsheet11-14.pdf The problem 20

21 Overuse of PPI Percent of NICU admissions, where lansoprazole, ranitidine, or metocolpramide was administered, among 4 NICUs within a single healthcare system Barney CK, et al. Advances in Neonatal Care 2009,9:

22 Can an accurate diagnosis of infant GERD be based upon symptoms such as irritability? Diagnosis of GERD in infants? Symptoms including regurgitation, colic/irritability, and vomiting are common among otherwise normal infants (Iacono G et al, Dig Liver Dis, 2005;37:432-8) Symptoms of GER are indistinguishable from those of food allergy (Venter C, et al JACI 2006;1118; Sampson H.A. JACI 2004;806, Savino F et al Eur J Clin Nutr. 2006;1304) 22

23 It may make more sense to switch the formula than to start acid suppression. But if you do, please switch to a hydrolysate formula Also important to remember 23

24 Total minutes of crying per day in normal infants Age (mo) Crying time (min) 121 +/ / / /-79 James-Roberts and Halil, J Child Psychol Psychiat 1991;52:951 GERD or Normal or Hot off the press 24

25 Besides being ineffective when not used for the right indication, are they actually bad for you? 25

26 Complications of PPI Potential risks of prolonged acid suppression Effects on vitamins and mineral absorption: Iron Calcium Magnesium Vitamin B12 Infections: Pneumonia C. Difficile Small bowel bacterial overgrowth Other enteric infections Necrotizing enterocolitis and candidemia Interstitial nephritis (rare, idiosyncratic reaction) Myocardial infarction 26

27 Clostridium Difficile: Retrospective study in children Aliment Pharmacol Ther. 2010;31:754-9 Recurrent C. Difficile Kwok CL et al. Am J Gastroenterol 2012;107: Risk is further increased by concomitant use of antibiotics and PPI, whereas H2RAs may be less harmful 27

28 Pediatrics 2012;129:e40 e45 28

29 Stark CM et al. J Pediatr 2016;168:16-22 Decreased acid barrier Altered microbiome Attenuation of the immune response Direct effects of the bacteria Decreased effectiveness of antibiotics Recently published and all over the lay press 29

30 Dementia 73,679 participants >75 y/o and free of dementia at baseline Patients receiving regular PPI medication (n = 2950) were found to have a significantly increased risk of incident dementia compared with the patients not receiving PPI medication (n = 70,729) Gomm W, et al. JAMA Neurol Feb 15 Difference between association and causation (courtesy of Jose Garza, MD) 30

31 Take home messages Prolonged acid suppression should be used when really needed Try to wean Increased risk of infection probably real Metabolic consequences and increased risk for MI and dementia not convincingly demonstrated Final bit of wisdom in this era of fake news 31

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