Category Archives: Uncategorized

The Quality of Evidence for Dietary Treatments in Inflammatory Bowel Disease

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BN Limketkai et al. Clin Gastroenterol Hepatol 2023; 21: 2508-2525. Open Access! Dietary Interventions for the Treatment of Inflammatory Bowel Diseases: An Updated Systematic Review and Meta-analysis

This was a systematic review of prospective controlled trials (n=27) of solid food diets for the induction or maintenance of remission in IBD.

Key findings:

  • For induction of remission in Crohn’s disease (CD), the Mediterranean diet was similar to the Specific Carbohydrate Diet (low certainty of evidence), and partial enteral nutrition (PEN) was similar to exclusive enteral nutrition (very low certainty of evidence).
  • PEN reduced risk of relapse (very low certainty of evidence), whereas reduction of red meat or refined carbohydrates did not (low certainty of evidence).
  • For ulcerative colitis, diets were similar to controls (very low and low certainty of evidence).

My take: Most of the dietary treatments for IBD have low to very low certainty of evidence regarding their effectiveness. Dietary changes are very likely to be helpful but more studies with rigorous endpoints are still needed.

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Gastroparesis is Frequently Misdiagnosed

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D Cangemi, L Stephens, BE Lacy. Clin Gastroenterol Hepatol 2023; 2670-2672. Misdiagnosis of Gastroparesis is Common: A Retrospective Review of Patients Referred to a Tertiary Gastroenterology Practice

In this retrospective study with adult patients (n=339) referred specifically to a tertiary center for evaluation of gastroparesis (GP) from 2019-2021, the key findings:

  • Nausea was most common symptom (in 89%), followed by abdominal pain (76%, constipation (71%), vomiting (66%), bloating (38%) and early satiety (35%)
  • 196 (58%) had undergone a prior gastric emptying study; though only 23 (7%) had ingested radiolabeled eggs as the test meal.
  • 66 (19.5%) ultimately received a diagnosis of GP; 80.5% received alterative diagnosis including functional dyspepsia in 44.5%. In those with GP, diabetes was more common (40% vs. 17%, P=.017).
  • GP patients more often had retained food in the stomach during EGD (23% vs. 11%, P=.013)

My take: In adults (& probably in children), most individuals labelled as having gastroparesis actually have an alternative explanation, usually functional dyspepsia. The symptoms are indistinguishable and improperly performed scintigraphy contributes to confusion.

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Nelson Rocks, Circleville, WV

Getting over the Stigma of Medicines for Anxiety/Depression and Obesity

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This is a terrific personal account of starting medications for anxiety/depression and obesity.

NY Times: Aaron Carroll 9/9/23, What Obesity Drugs and Antidepressants Have in Common

An excerpt:

Until a few years ago, I had controlled my depression and anxiety through decades of counseling. I was reluctant to try medications because the medical understanding of them seemed vague…We also can’t explain why some people benefit from S.S.R.I.s and others do not. Because of this, many people still believe those who take them don’t really need them. I also believed that, if I was strong enough, I didn’t need medication…

I was wrong to doubt. It’s had a remarkable effect on my mood, and almost everyone around me noticed the difference. I was more optimistic, friendlier and more engaging. I was forced to reconsider why I had avoided taking the medication for so long. I think it’s because — even though I realize this isn’t true — taking it felt like an admission of failure…

I’ve recently faced a similar scenario with new drugs for obesity. I’ve struggled with my weight for most of my life. I’ve always been overweight, and in the last few years, I’ve slipped into obesity, according to my body mass index. I exercise regularly and carry the weight well, but it bothers me immensely. It especially troubles me because I have a fair amount of self-discipline and eat quite healthfully…

Despite all the advances in science, we don’t know why some people, even when they try desperately, can’t seem to lose weight. Because of that, we often assume it must be a lack of willpower…

These drugs are expensive, but I was determined to see what would happen if I took one. It is hard to explain what life is like on this medication to people who don’t have trouble controlling their weight. I’m not hungry all the time. I’m not thinking about food incessantly. I’m not obsessing about what I wish I could eat and what I can’t. My mental health, and even my temperament, improved so much that my whole family rejoiced…

Before writing this essay, I had told just a few people I’m on the drug. I think it’s because, on some level, I still feel shame. I felt the same when I finally started taking an antidepressant…

Medical treatments should not be dismissed just because we don’t fully grasp their mechanisms; people who use them are not cheating.

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Photos from Washington DC

Timing of Cleft Palate Surgery

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C Gamble et al. NEJM 2023; 389:795-807. Timing of Primary Surgery for Cleft Palate

Conclusion from study authors: Medically fit infants who underwent primary surgery for isolated cleft palate in adequately resourced settings at 6 months of age were less likely to have velopharyngeal insufficiency at the age of 5 years than those who had surgery at 12 months of age.

The associated editorial (R Tse, O Jackson, N Engl J Med 2023; 389:857-858. Mind the Gap) notes that “over two thirds of infants who were screened were excluded because their cleft was part of a syndrome, they were deemed to be medically unfit for early surgery, or they had a cleft that was too wide.” Also, “the incidence of additional surgery to treat velopharyngeal insufficiency was greater in the 6-month group than in the 12-month group (30 procedures in 27 children vs. 17 procedures in 16 children), and speech assessments performed after the secondary procedures were used in the analysis. Thus, the trial evaluated the mixed effects of primary surgery and secondary surgery in some patients.” Finally, “the considerations with regard to early surgery include the greater technical complexity of the procedure and the greater risks associated with anesthesia (airway complications and potential neurodevelopmental sequelae). Early surgery may also contribute to midfacial growth restriction, which becomes apparent only later, in adolescence, and may require complex corrective jaw surgery.”

My take: Early cleft palate surgery is not best for all infants with this defect.

Related blog post: Skinny Babies with Cleft Lips and/or Cleft Palates

Risk Factors for Inflammatory Bowel Disease: Antibiotics (Part 2)

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AB Jawad et al. JPGN 2023; 77: 366-372.Early Life Oral Antibiotics Are Associated With Pediatric-Onset Inflammatory Bowel Disease-A Nationwide Study

Key findings:

  • Oral antibiotic exposure during the first 5 years of life was associated with a higher risk of developing pIBD (HR = 1.33,  P <0.0001). The risk was also increased if patients had ≥4 antibiotic prescriptions compared to no antibiotics (HR = 1.33, P <0.0001).
  • Broad-spectrum antibiotics increased the risk of pIBD compared to narrow-spectrum antibiotics (HR = 1.29, P < 0.0001).
  • When stratified by IBD subtypes, only Crohn disease was significantly associated with exposure to antibiotics (HR = 1.37, P = 0.002).

My take: This study indicates that antibiotics (and/or serious infections) are associated with an increased the risk of pediatric Crohn’s disease but the absolute risk is very low. We still have a lot to learn about how environmental exposures, including diet, infections, antibiotics, and pollution, contribute to the increasing prevalence of inflammatory bowel disease.

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Risk Factors for Inflammatory Bowel Disease: Ultra-Processed Food (Part 1)

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N Narula et al. Clin Gastroenterol Hepatol 2023; 21: 2483-2495. Open Access! Food Processing and Risk of Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis

JA Fitzpatrick et al. Clin Gastroenterol Hepatol 2023; 21: 2478-2480 (editorial). Open Access! Ultra-processed Foods and Risk of Crohn’s Disease: How Much is Too Much?

Figure 1 from editorial: The NOVA classification of food

A total of 1,068,425 participants were included (13,594,422 person-years) among 5 cohort studies published between 2020 and 2022. The average age of participants ranged from 43 to 56 years. Key findings:

  • Crohn’s disease:  During follow-up, 916 participants developed CD, and 1934 developed UC. There was an increased risk for development of CD for participants with higher consumption of ultra-processed foods compared with those with lower consumption (HR, 1.71; 95% CI, 1.37–2.14; I2 = 0%) and a lower risk of CD for participants with higher consumption of unprocessed/minimally processed foods compared with those with lower consumption (HR, 0.71; 95% CI, 0.53–0.94; I2 = 11%). 
  • Ulcerative colitis: There was no significant association between risk of UC and ultra-processed foods (HR, 1.17; 95% CI, 0.86–1.61; I2 = 74%) or unprocessed/minimally processed foods (HR, 0.84; 95% CI, 0.68–1.02; I2 = 0%).

The associated editorial by Fitzpatrick et al, notes that “there are plausible mechanisms that explain the associations of higher UPFs and development of CD, such as: (1) displacing the intake of minimally processed foods and subsequently reducing exposure to beneficial micronutrients, antioxidants, and phytochemicals; (2) driving overconsumption of total calories7; and (3) increasing exposure to non-nutritive food substances that have been implicated in the development of CD in pre-clinical studies…The notion is that a lower UPF intake is better, but a cutoff value remains elusive.”8

My take (borrowed from editorial): “the population studies have indicated that the extremes of UPF intake are related to risk of CD and that such associations are underpinned by plausible biological mechanisms, suggesting causality.”

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How to Handle Gastric Intestinal Metaplasia

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I Mansuri et al. JPGN 2023; 77: 332-338. Gastric Intestinal Metaplasia in Children: Natural History and Clinicopathological Correlation

This retrospective single-center study (2013-2019) identified 38 patients with gastric intestinal metaplasia (GM) with a mean age of 12.5 years.

Background: “Gastric intestinal metaplasia (GIM) is defined as the replacement of the normal gastric epithelium by intestinal-type epithelium. GIM is considered a preneoplastic lesion for gastric adenocarcinoma in adults and is found in 25% of Helicobacter pylori ( H pylori ) exposed adults.”

Key findings:

  • The prevalence was 0.53% based on 7104 patients who were 18 or younger who underwent EGDs
  • 2 cases of H pylori were identified; chronic gastritis was noted in 47%
  • Only a third of patients had f/u EGDs; none of these had progression to dysplasia. In fact, GIM was NOT identified in the majority at followup

In their discussion, the authors note that the AGA’s clinical practice guidelines for GIM in adults provides the following recommendation: “Routine surveillance endoscopy in patients with incidental detection of gastric intestinal metaplasia (GIM) is discouraged.”

Also, it is worthwhile to consider that many cases of GIM are likely overlooked given the often patchy distribution.

My take (borrowed from authors): GIM appears to be an incidental gastric biopsy finding of uncertain significance. Unless there are high risk factors for gastric cancer, routine followup is unlikely to be beneficial.

Pictures from Villa Ephrussi de Rothschild:

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.

According to the study which you would never qualify for… (2023)

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In 2012, this blog highlighted a study which showed that “only 31.1% of 206 patients with IBD would have been eligible to participate in any of the selected RCTs.” (Post: According to the study which you would never qualify for…).

A recent study shows the same phenomenon in pediatric IBD studies: O Atia et al. Aliment Pharmacol Ther 2022; 56 (5): 794-801. Open Access! Children included in randomised controlled trials of biologics in inflammatory bowel diseases do not represent the real-world patient mix

This study utilized data for children initiating biologics from two prospective real‐world cohorts and one retrospective cohort.

Key findings:

  • Only 62 of 164 (38%) children with moderate–to‐severe disease would have been eligible for inclusion in the original RCTs.
  • The steroid-free remission rate was higher in the eligible children (51%) than in the ineligible children (31%; OR 2.3 [95%CI 1.2–4.5]; p = 0.01)
  • The main exclusion criterion was prohibited previous therapies (47%)

My take (borrowed from authors): “Remission rates were higher among eligible children raising the concern that results presented in regulatory RCTs in paediatric IBD do not necessarily reflect the patient‐mix in the real‐world and should be interpreted with caution when applied to clinical practice.”

Pictures from VilleFranche-Sur-Mer:

Expect Costs of Liquid Omeprazole to Increase Due to FDA Approval

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Last fall, the FDA approved a liquid version of omeprazole.

9/3/22 Drugs.com: “FDA Approves Konvomep. FDA Approves Konvomep (omeprazole and sodium bicarbonate for oral suspension) for Gastric Ulcer and Reduction of Risk of Gastrointestinal Bleeding in Critically Ill Patients

WOBURN, Mass. (September 2, 2022) – Azurity Pharmaceuticals, Inc., a pharmaceutical company focused on developing innovative dose-forms and formulations of products to serve the needs of overlooked patients, announced today that the U.S. Food and Drug Administration (FDA) has approved Konvomep (omeprazole and sodium bicarbonate for oral suspension).“

Now that this FDA approved product is available, it may be that it will be more difficult to receive a compound version. The cost of this new formulation is much higher. Here are some of the costs from GoodRx.com.

My take: The high cost of this liquid preparation is another good reason to avoid using a PPI in patients with low likelihood of benefit.

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CCFA 2023 (Atlanta) Part 4

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Another terrific lecture from David Rubin: Positioning of Advanced IBD Therapy. Here are my notes and some slides which could include errors in transcription and omission. Can get access to all 46 slides here: IBD Pro CCFA 2023 Atlanta

Many challenges in sequencing treatment -heterogeneity of diseases, loss of response, challenges in interpreting data, understudied issues (perianal disease, extra-intestinal manifestations, psychological health). 

Evolution of therapies: desperation era -limited options, step up era, top down era with anti-TNFs, treat to target era and currently evidence-based by safety era. 

  • It is possible to avoid steroids in many patients with upcoming plans to use an advanced therapy -this is probably beneficial.  This may result in patients remaining symptomatic until these therapies can be started.
  • JAK inhibitors cannot be given as first-line agent in U.S. (but is done in other countries).
  • VARSITY trial enrolled patients with prior anti-TNF exposure (but not adalimumab) which biased the study against adalimumab vs vedolizumab
  • SEAVUE study ~65% in clinical remission at 1 yr with both adalimumab and ustekinumab; though, ustekinumab had better tolerability
  • Ustekinumab better 2nd line treatment for CD after anti-TNF (Parrot et al. AP&T 2022; 55: 380-388
  • Vedolizumab is a good therapy for CD, especially in biologically-naïve
  • Risankizumab good for moderate-severe CD both in biologically-naïve and biologically-experienced
  • Dose reduction in maintenance of Jak inhibitors can result in LOR and 50-75% can achieve response after resumption of higher dosing