The authors retrospectively utilized the University of Manitoba IBD Epidemiology Database includes all Manitobans diagnosed with IBD between 1984 and 2018 (n=5920). Key findings:
Rates of PPI use in control subjects increased gradually from 1.5% to 6.5% over 15 years
Persons with IBD had a higher rate of PPI use, peaking up to 17% within 1 year of IBD diagnosis with a rate ratio (RR) of 3.1
The authors noted an abrupt increase in PPI use within 6 months of an IBD diagnosis which could indicate that IBD-related symptoms are being mistakenly treated with a PPI or that IBD may increase reflux-related symptoms. Given the higher rate of PPI use in pre-IBD diagnosis patients, compared to controls, the authors note that “it is possible that their [PPI] use enhances the likelihood of an IBD diagnosis by their role in altering the gut microbiota.” In addition, they note that “a case-control study found that PPIs were associated with an increased risk of pediatric IBD” (NR Schwartz et al. J Pediatr Pharmacol Ther 2019; 24: 489-496).
My take: PPIs are being used more frequently. Whether PPIs are detrimental before or after a diagnosis with IBD is not clear.
This was a multicenter, randomized, placebo-controlled trial to compare the efficacy and safety of thiopurine-allopurinol versus thiopurine with placebo for adults commencing a thiopurine for IBD in 102 patients. Allopurinol was dosed at 100 mg. Key findings:
A higher proportion achieved the primary outcome (improved clinical score and fecal calprotectin <150) in the thiopurine-allopurinol group (50% vs 35%, p = 0.14) and fewer participants stopped their allocated therapy due to adverse events (11% vs 29%, p = 0.02
Medication exposure and disease outcomes were compared between 3 diagnostic periods: 1988 to 1993 (period [P] 1; pre-IS era), 1994 to 2000 (P2; pre-anti-TNF era), and 2001 to 2011 (P3; anti-TNF era).
Key finding: The risk of colectomy at 5 years decreased significantly over time (P1, 17%; P2, 19%; and P3, 9%; P = 0.045, P-trend = 0.027) and between the pre-anti-TNF era (P1 + P2, 18%) and the anti-TNF era (P3, 9%) (P = 0.013).
In this systematic review, the authors identified 8 eligible articles with 526 pediatric patients with IBD. Key finding: “There is no significant association between preoperative anti-TNF-α therapy and postoperative complications in children with IBD after intestinal resection.”
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.
This retrospective study compared the findings of children with probable autism (ASD) to age- and gender-matched controls with developmental delay (DD) or with typical development (TD), (n= 526 ASD, 526 DD, 1052 TD). Key findings:
Children with ASD had higher rates of abnormal esophageal histology (ASD 38.4%; DD 33.4%; TD 30.4%, P = .008)
Stomach findings did not differ significantly among the groups: histologic inflammation was identified in ASD 13.3%, DD 18.5%, and TD 22.4% (P=.10).
In the duodenum, histologic abnormalities were observed with lower frequency in ASD (ASD 17.0%; DD 20.1%; TD 24.2%, P = .005).
The authors emphasize the importance of the esophageal findings (increased rates of esophagitis). However, there are some important caveats that are not discussed in the paper:
At baseline (prior to study), it was known that the ASD and DD groups had higher rates of eosinophilic esophagitis: ASD 9.1%, DD 9.5%, and TD 7.4% (Table 1). In addition, both of these groups had higher rates of gastroesophageal reflux at baseline: ASD 7.6%, DD 8.0%, and TD 6.5%. This selection bias is likely to negate much of the esophageal differences observed in their study. Also, the ASD group had much higher numbers receiving H2 blockers at time of procedure: ASD 11.4%, DD 10.3%, and TD 6.4%.
In addition, the TD group had a much higher rate of abdominal pain as the indication for endoscopy (TD 26.6%, ASD 17.5%, and DD 20.2%). It is well-recognized that isolated abdominal pain has a low yield on endoscopy.
The authors do not discuss the elephant in the room. What is the significance of microscopic esophagitis (or microscopic gastritis or microscopic duodenitis)? Previous authors have noted that “15% of healthy individuals may have microscopic esophagitis” (Gastroenterology 2018 (volume 154; pages 263-451 -see page 291). When we were looking at the variation of diagnostic yield for endoscopy, we decided to focus on colonoscopy because of the high rates of microscopic inflammation in the upper GI tract (related blog post: Our Study: Provider Level Variability in Colonoscopy Yield)
My take: In their discussion, the authors state that this study represents “significant progress in the understanding of gastrointestinal pathophysiology in children with ASD…suggest a unique fingerprint of findings in children with ASD.” In my view, the authors showed similar yield of EGD histologic abnormalities in all three groups and these microscopic findings are of uncertain significance.
This study analyzed “pH impedance testing in the NICU in 516 infants with symptoms of arching and irritability. A nurse was assigned to document episodes of arching and irritability during the study.”
Key findings:
Acid reflux and impedance bolus characteristics were not significantly different between infants with >72 and ≤72 arching/irritability events (P ≥ .05)
Arching/irritability events had an 8% sensitivity for reflux (3062/39,962). The specificity of arching/irritability for NOT being reflux was 94% (246,462/262,534)
Oral feeding was associated with more arching and irritability than tube feeding
“The study found that <10% of the clinical episodes were associated with acid reflux but episodes of arching and irritability were more common in infants with preterm birth, neurologic injury, or chronic lung disease.”
My take (in part, borrowed from authors): “Acid GER disease is unlikely the primary cause of arching/irritability and empiric treatment should not be used when arching/irritability is present.” Unfortunately, getting physicians to curtail the use of ineffective acid blockers in infants is a not making headway (Unfavorable Trends in Reflux Management of Infants) There is definitely enough material with reflux to devote a whole MythBusters show.
In addition to not being the main reason for arching,
Reflux is not a frequent reason for BRUEs
Reflux cannot be reliably-identified by ENTs. Red airway appearance is NOT indicative of reflux (poor specificity, poor sensitivity)
Reflux in infants does not improve with PPIs (more than placebo)
Fundoplication does not result in fewer hospitalizations or improve pulmonary outcomes
Treating reflux does not improve asthma and probably does not help throat symptoms either
Many kids (and adults) with “reflux” don’t have reflux
This research utilized 40 studies which met the eligibility criteria, including over 288 million participants and 147,668 patients with EoE from 15 countries across the five continents.
Key findings:
The global pooled incidence and prevalence of EoE were 5.31 cases per 100,000 inhabitant-years and 40.04 cases per 100,000 inhabitant-years, respectively.
The pooled prevalence and incidence of EoE were higher in high-income countries, males, and North America.
The pooled prevalence and incidence of EoE have increased from 1976 to 2022.
Time trends of incidence (A) and prevalence (B) of EoE, 1976 to 2022. Pooled estimates, cases per 100,000 inhabitant-years.
“This review summarizes the data leading to FDA approval for dupilumab and provides a practical approach for clinical use of dupilumab.” Dupilumab, a humanized monoclonal antibody that blocks interleukin (IL)-4 receptor alpha, is currently the only FDA-approved medication for EoE. It is noted that in the trials leading to FDA approval, all patients were PPI refractory and ~70% had received topical steroids (with about half either intolerant or nonresponsive).
Dosing: 300 mg weekly injection with a single-dose prefilled autoinjector pen or a syringe with a needle shield. It is recommended that refrigerated medicine is brought to room temperature for at least 45 minutes prior to injection. It “can remain unrefrigerated up to 14 days.”
In Figure 1, the articles details positioning of use of dupilumab in EoE management algorithm:
New diagnosis, patient preference
Additional atopic condition with approved dupilumab use (strong indication)
Lack of response to current treatment (diet, PPI, swallowed steroids) or adverse effects from current treatment (strong indications)
“It is reasonable to repeat endoscopy with biopsy 24 weeks after initiation of dupilumab in many patients…However, endoscopy may be completer earlier” in selected patients.
At least 5 other biologics are in phase 2 or phase 3 studies (listed in Table 1).
My take: EoE is increasing in prevalence and new therapies (often expensive) are emerging.
Also, there is a fairly good patient education 7-page pamphlet from the makers of Dupixent encouraging patients with symptoms suggestive of EoE to speak with their physicians.
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.
The authors performed population pharmacokinetic (popPK) simulations to determine optimal dosing recommendations.
Key points:
Infliximab: “The Q2W SC dosing regimen of infliximab has been selected with the purpose of exceeding a C,trough,ss of 5 mg/L.” This tends to align with 5 mg/kg Q8W IV dosing.
Infliximab: “Patients on Q6W or Q8W IV infliximab can safely switch to Q2W SC infliximab…only patients on Q4W IV infliximab need Q1W SC dosing”
Vedolizumab: “Only patients on Q4W IV vedolizumab should switch to Q1W SC dosing”
Both agents: “Switching 4 instead of 8 weeks after the last IV dose can hit SS[steady state] faster, thereby avoiding the risk of temporary underexposure.”
My take: It is still important to see how switching from IV to SC route affects clinical outcomes in real-world cohorts. This study, though, does provide a good starting point when trying to provide the right dose frequency to achieve good therapeutic troughs.
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.
Thanks to all of you who provided articles, suggestions and encouragement to make this blog better this past year. This has been the 12th year for this blog and it has continued to gain more views each year. Here are links to many of my favorite posts from 2023 along with a few pictures:
In pediatrics, there is often a prevailing view that kids can overcome a lot due to their resiliency. However, just like a a track event, if you trip or fall back in a race, you may never catch up. With many medical conditions, it is unclear whether a delay in diagnosis results in long-term deficits. Recent data have found that a ~1 month delay in the treatment of cystic fibrosis is associated with poorer nutritional/growth outcomes, even 5 years later.
Using the U.S. Cystic Fibrosis Foundation patient registry (CFFPR), the authors examined children born between 2010-2018 who were diagnosed based on newborn screening (NBS). Age at first event (AFE) serves as a proxy for when CF care was likely initiated. Patients were divided into 3 cohorts based on AFE: <14 days (early cohort), 14 days to <33 days, and 33 days or more (late cohort).
Key findings:
Infants in the late cohort were more likely to have a sweat test as their first CF event.
Pulmonary exacerbations were reported as the reason for hospitalization in in 59.1% of late cohort compared with 4.8% of early cohort with hospitalization as their first CF event.
Height-for-age z-scores were consistently lower in the late cohort. At 1 yr and 5 yrs, median z-scores were -0.6 (vs. -0.42) and -0.26 (vs. -0.12 in early group) respectively
The authors note that the early and late groups had differences in parental education attainment which “may be evidence that the late cohort had lower socioeconomic status that could have resulted in barriers to timely evaluation.”
The discussion notes that the introduction of highly effective modulator therapy does not overcome early stunting; which indicates that even with newer therapy, institution of nutritional treatments remains critical.
The study confirms that
NBS/early identification has clear benefits.
There is a need to quickly get suspected patients seen by CF centers.
My take: There was persistently (through at least 5 yrs) reduced height-for-age z-scores in patients with CF who presented just 27 days later.
Dr. Burrell noted that concerns for EoE are increased in those who have more uniform problems with increased textures (rather than selectivity) and in those with more severe feeding disordersSometimes Caregivers will contribute to nutritional disorders by placing on diets like a gluten-free, casein-free diet
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.
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