Category Archives: Uncategorized

IBD Updates: Fatigue Trajectory, Risk of IBD with Derm Findings

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NZ Borren et al. Inflamm Bowel Dis 2021; 27: 1740-1746. Open Access: Longitudinal Trajectory of Fatigue in Patients With Inflammatory Bowel Disease: A Prospective Study

In this prospective study using the CCFA IBD Partners cohort, the authors examined fatigue symptoms with questionnaires (FACIT-F and MDI) at 3 timepoints over a 1 year period. There was likely a strong selection bias among participants (mean disease duration was 18 years) who chose to complete theses questionnaires. Key findings:

  • Persistent fatigue (at baseline and at 6 months) was the most common pattern, affecting two-thirds (65.8%) of patients
  • The strongest predictor of incident fatigue was sleep disturbance at baseline (odds ratio, 2.91.
  • Only 12.3% of those with fatigue at baseline had symptom resolution by 6 months. Resolution was more likely in patients with a diagnosis of ulcerative colitis, quiescent disease, and an absence of significant psychological comorbidity

My take: In those with fatigue, it is often persistent.

Related blog post: #MondayNightIBD and Fatigue

D King et al. Inflamm Bowel Dis 2021; 27: 1731-1739. The Risk of Later Diagnosis of Inflammatory Bowel Disease in Patients With Dermatological Disorders Associated With Inflammatory Bowel Disease

The authors retrospectively studied 7447 patients with dermatological conditions such as erythema nodosum (EN), pyoderma gangrenosum, Sweet’s syndrome, and aphthous stomatitis which can occur with inflammatory bowel disease (IBD) and are considered dermatological extraintestinal manifestations (D-EIMs).

Key findings:

  • 131 (1.8%) subsequent IBD diagnoses in patients with D-EIMs compared with 65 (0.2%) in those without D-EIMs
  • Median time to IBD diagnosis was 205 days (IQR, 44-661 days) in those with D-EIMs

My take: The absolute risk if IBD is low in patients with D-EIMs but still increased 6-fold. This would probably be a good population to screen for IBD with a biomarker (eg. calprotectin)

Related blog post: Review of Pyoderma Gangrenosum

J Shah et al. Inflamm Bowel Dis 2021; 27: 1832-1838. Ocular Manifestations of Inflammatory Bowel Disease Nice review: “ocular manifestations of IBD include keratopathy, episcleritis, scleritis, and uveitis and are among the most common extraintestinal manifestations.” Urgent referral to ophthalmology needed if deep eye pain that can awaken from sleep (?scleritis), if photosensitivity/blurry vision/headache (?anterior uveitis), or if floaters/decreased vision (?posterior uveitis)

Functional Abdominal Pain in Children with Celiac Disease

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F Cristofori et al. Clin Gastroenterol Hepatol 2021; 19: 2551-2558. Functional Abdominal Pain Disorders and Constipation in Children on Gluten-Free Diet

This prospective cohort (2016-2018, n=417, mean age 13.7 y) examined the frequency of functional disorders (based on questionnaire) in children with celiac disease (CD) who were receiving a strict gluten free diet (GFD) for at least one year.

Key findings:

  • Functional abdominal pain disorders (FAPDs) had a higher prevalence s among patients with CD (11.5%) than controls (6.7%)  (P < .05)
  • Irritable bowel syndrome (IBS) and functional constipation (FC) defined by the Rome IV criteria were more prevalent in patients with CD (7.2% for IBS and 19.9% for FC) than controls (3.2% for IBS and 10.5% for FC) (P < .05 and P < .001, respectively)
  • Younger age (P < .05) and a higher level of anti–transglutaminase IgA at diagnosis (P < .04) were associated with FAPDs (in particular for IBS) irrespective of GFD duration
  • A GFD did help with abdominal pain: After starting a GFD, 80% of children with celiac disease had resolution of stomach pain, whereas 9% started to complain of symptoms after starting a GFD

In the discussion, the authors speculate on the reasons for ongoing pain including inadvertent gluten exposure, intestinal inflammation/visceral hyperalgesia, altered microbiome, and refractory CD.

My take: Persistent stomach pain in CD is a common occurrence, even in those trying to adhere to a strict GFD.

Related blog posts:

Chattahoochee River, Atlanta

Why I No Longer Need to Be A Billionaire

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For the past few years, when someone would ask me what I would do if I were incredibly wealthy, I would say that I wanted to start a pharmaceutical company to provide reasonably-priced medications. A good example of the problems with drug pricing was discussed earlier in the week on a prior blog post regarding insulin (Insulin: “Poster Child For Everything That’s Wrong” with U.S Drug Costs). Fortunately, I no longer need to be a billionaire:

NPR: (Jan 24, 2022): Billionaire Mark Cuban launches online pharmacy aimed at lowering generic drug prices

An excerpt:

The Mark Cuban Cost Plus Drug Company announced the opening of its online pharmacy Wednesday. The pharmacy says it will bypass health care industry “middlemen” and help consumers avoid high drug prices by charging manufacturers’ prices plus a flat 15% markup and pharmacist fee…

The pharmacy doesn’t accept health insurance but says prices will still be lower than what people would typically pay at a pharmacy….

The website currently offers 100 generic drugs to treat a variety of illnesses, including diabetes, asthma and heart conditions.

One drug for diabetes patients, metformin, sells for $3.90 for a 30-day supply, compared to a retail price of $20, the pharmacy said. A 30-count of imatinib, which is used to treat leukemia and other cancers, goes for as low as $17.10 at Cuban’s pharmacy compared with $2,502.60 at other pharmacies.

Link to Mark Cuban’s Company: Cost Plus Drug Company

GI Medications:

  • Colcichine is priced at $8.70 (retail $176.23)
  • Entecavir $46.20 (retail $995.75)
  • Esomeprazole Capsule (40 mg) $6.00 (retail $216.66)
  • Lansoprazole Capsule (15 mg) $9.00
  • Mesalamine (Generic for Canasa) $36.90 (retail $959.07)
  • Mesalamine (Generic for Apriso) $36.60 (retail $122.57) ***this is only for 30 pills
  • Methotrexate 2.5 mg (30 capsules) $13.80
  • Omeprazole 40 mg capsules $4.50
  • Pantoprazole is priced at $4.50 (40 mg tablets) (retail $71.40)

GoodRx website also has low prices on many of these medications as well; however, some of these prices at the Mark Cuban pharmacy are terrific. For example, the cost of mesalamine suppositories at GoodRx are about three times as much.

My take: I need to talk to our Epic champion to connect our EMR to this pharmacy service.

Related blog posts:

IBD Shorts: High TNF levels, Biologics in Pregnancy, & Ileocolic Resection Outcomes in Pediatrics

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M Zvuloni et al. JPGN 2021; 73: 717-721. Open Access PDF: High anti-TNFa Concentrations Are Not Associated With More Adverse Events in Pediatric Inflammatory
Bowel Disease

Key findings (retrospective study):

  • Higher trough concentrations (TCs) (>10 mcg/mL) of anti-TNFa were not associated with higher rate of anti-TNFa-related adverse events in 135 patients & >1500 TC measurements
  • Out of the 30 patients who presented with elevated transaminases, 27 (90%) patients had normalized transaminases values by the end of the follow-up
  • Adverse events were noted in 68 of 135 patients (see below)

OH Nielsen et al. Clin Gastroenterol Hepatol 2022; 20: 74-87. Open Access: Biologics for Inflammatory Bowel Disease and Their Safety in Pregnancy: A Systematic Review and Meta-analysis

Forty-eight studies were included in the meta-analysis comprising 6963 patients. Key findings:

  • Biologic therapy in IBD pregnancies was associated with a pooled prevalence of 8% for early pregnancy loss, 9% for preterm birth, 0% for stillbirth, 8% for low birth weight, and 1% for congenital malformations.
  • These rates are comparable with those published in the general population.
  • Importantly, studies with newer biologics (eg. vedolizumab, ustekinumab) had small sample sizes. In addition, ongoing prospective multicenter registries are ongoing.

EA Spencer et al. JPGN 2021; 73: 710-716. Open Access PDF: Outcomes of Primary Ileocolic Resection for Pediatric Crohn Disease in the Biologic Era

Key findings (n=78, retrospective study, 2/3rds received biologic postoperative prophylactic therapy):

  • Endoscopic recurrence was 46% at 2 years (median time to recurrence: 10 months).
  • Histologic recurrence was present in 44% in endoscopic remission
  • At diagnosis and surgery, over a quarter met the criteria for growth failure.. Following surgery, height, weight and BMI z scores improved significantly both at 1 year and last followup

Is Vedolizumab the Best First Line Biologic in Ulcerative Colitis?

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D Lukin et al. Clin Gastroenterol Hepatol 2022; 20: 126-135. Open Access: Comparative Safety and Effectiveness of Vedolizumab to Tumor Necrosis Factor Antagonist Therapy for Ulcerative Colitis

This multicenter, retrospective observational cohort study (2014-2017) studied the outcomes of 722 adults (n=454 vedolizumab (VDZ), n=268 TNF agents (165 IFX, 103 ADA). Key findings:

  • VDZ-treated patients were more likely to achieve clinical remission (hazard ratio [HR], 1.651; 95% confidence interval [CI], 1.229-2.217), steroid-free clinical remission (HR, 1.828; 95% CI, 1.135-2.944), and steroid-free deep remission (HR, 2.819; 95% CI, 1.496-5.310) than those treated with TNF antagonists
  • Safety: Overall, there were no statistically significant differences in the risk of serious adverse events (HR, 0.899; 95% CI, 0.502-1.612) or serious infections (HR, 1.235; 95% CI, 0.608-2.511) between VDZ-treated and TNF-antagonist−treated patients.
  • In TNF-antagonist−naïve patients, VDZ was less likely to be associated with serious adverse events than TNF antagonists (HR, 0.192; 95% CI, 0.049-0.754). Thus, among UC patients with no prior TNF exposure, there was nearly an 80% reduction in any serious adverse event (this difference could be related, at least in part, to patient selection/disease severity)
  • In TNF-exposed patients, VDZ was associated with a significant increased risk for serious infections (HR, 4.295).

The authors note that the clinical remission results are similar to a previous head-to-head study of VDZ vs ADA in which VDZ had OR 1.568 for achieving clinical remission. It should be noted that the potential conflict of interest list of the 36 authors is extensive.

My take: This article supports VDZ as a first-line option for UC and strengthens the argument that it should be the first biologic for most patients with UC.

Related blog posts:

Siesta Key, FL

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.

Quantifying the Risk of Serious Infections in Pediatric Patients with Inflammatory Bowel Disease

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JF Ludvigsson et al. J Pediatr 2021; 238: 66-73. Open Access PDF Serious Infections in Pediatric Inflammatory Bowel Disease 2002-2017—A Nationwide Cohort Study

This study utilized the Swedish nationwide health registry (2002-2017; n = 5767 with IBD) and controls from the general population (n= 58,418). One reason for this study is the increased frequency and changing patterns of immunosuppressive medications that are being used in pediatric IBD. Key findings:

  • 672 serious infections (38.6/1000 person-years) occurred among the children with IBD compared with 778 serious infections in the control group (4.0/1000 person years; adjusted HR 9.46 ). HRs were increased for children with ulcerative colitis 8.48, Crohn’s disease 9.30, and IBD unclassified 12.1
  • Particularly high HRs were also seen in the first year of diagnosis with HR of 12.1 and n children with IBD undergoing surgery, HR 17.1. This 17-fold risk translates to an average of 6 per 100 children having a serious infection among those with operations.
  • 340 of the 672 serious infections were gastrointestinal, including 34 due to Clostridium difficile
  • 20 opportunistic infections were identified during 19,000 person-years

Potential risk factors for infection, besides medications, include malnutrition, chronic inflammation, impaired response to vaccination, and dysregulation of immune responses. A limitation of this study is ascertainment bias as families/patients with underlying disease may be more likely to seek medical attention for otherwise self-limited infections.

My take: This report confirms and quantitates daily clinical practice: children with IBD are more frequently hospitalized due to infections.

Related blog post: Infection or Flareup in IBD: GI PCR Panel Helps

Stillbirths associated with COVID-19: Stillbirths increased from 5.6 per 1,000 baseline to 8 per 1,000 if COVID-19 anytime during pregnancy and to 22.6 per 1,000 if COVID-19 infection began within 28 days of birth in a study of more than 130,000 Scottish births (12/1/20-10/21/21).
Reference: Stock, S.J., Carruthers, J., Calvert, C. et al. SARS-CoV-2 infection and COVID-19 vaccination rates in pregnant women in Scotland. Nat Med (2022). https://doi.org/10.1038/s41591-021-01666-2

Time to Change the Medical Treatment and Attitudes Directed at Obesity?

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NPR: New podcast examines wellness trends and beliefs, like what weight means about health. Interview with Aubrey Gordon and Michael Hobbes who co-host the podcast “Maintenance Phase.”

This interview has a lot of useful ‘food for thought.’

Some excerpts:

  • Every year, millions of Americans go on a diet. Americans also spend billions of dollars on weight loss products. So why, despite all of that, are obesity rates in the U.S. are continuing to rise?….
  • There’s a very clear correlation between weight and bad health outcomes, but weight is not the only thing that’s correlated with health. We know that poverty has a devastating effect on people’s health. The life expectancy in various counties in America can be up to 20 years of difference…And yet, weirdly, when it comes to obesity, it’s like, oh, no, no, we know that the obesity is causing this, right? Like, people have kind of jumped to this causal explanation…
  • Paradoxically, and unfortunately, what we have seen in the years since that redefinition [of obesity as a disease] is a skyrocketing of bias against fat people. That has happened amongst health care providers. It has happened amongst social workers. It has happened amongst the general public in the United States…
  • I think we would all do ourselves a really significant service by actually just focusing on the health markers and not the proxy for the health markers, which is weight…
  • What we find is really consistent stories from fat people of going into the doctor with a migraine headache and their doctor tells them to lose weight. They go in with a car accident, their doctor tells them to lose weight. They go in with a tumor, their doctor tells them to lose weight. This is something that is, like, really, really devastating to the health of fat people that essentially people don’t listen to them.

My take: Diets for weight loss have very low rates of success. Focusing on healthy eating habits (eg. food/beverage composition, eating together) along with encouraging healthy activity levels is likely to be most beneficial for long-term outcomes. .

Related blog posts:

Siesta Key, FL

Improving Outcomes with Proactive Therapeutic Drug Monitoring + Swiss COVID-19 Data

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Another recent study showing the benefits of proactive therapeutic drug monitoring (pTDM):

SW Syverson et al. JAMA. 2021;326(23):2375-2384. Effect of Therapeutic Drug Monitoring vs Standard Therapy During Maintenance Infliximab Therapy on Disease Control in Patients With Immune-Mediated Inflammatory Diseases (The article is only 10 pages; however, the supplementary material (which I did not read) is an additional 258 pages.) Thanks to Ben Gold for sharing article reference. Also, this study was reviewed in Healio Gastro: Link: Therapeutic drug monitoring sustains disease control during infliximab maintenance

Methods: Randomized, parallel-group, open-label clinical trial including 458 adults (mean age, 44.8 years; 49.8% women) with rheumatoid arthritis, spondyloarthritis, psoriatic arthritis, ulcerative colitis (n=81), Crohn disease (n=66), or psoriasis undergoing maintenance therapy with infliximab in 20 Norwegian hospital

Key finding:

  • Sustained disease control without worsening was evident in 73.9% of pTDM group compared with 55.9% in standard infliximab group

Some limitations of this study:

  1. The open-label study was not powered to detect the difference of pTDM in each of the six diseases
  2. The therapeutic goal for maintenance infliximab was 3 to 8 mg/L, which is a little lower than current goals (ACG expert panel suggests a level of at least 5-10)

My take: This study supports recent expert guidance (see blog post below) on the benefit of pTDM as part of evidence-based care. It is likely that pTDM is even more important in children/teens due to growth.

Time to Disease Worsening

Related blog posts:

Also data from Switzerland:

Acid Suppression for Laryngomalacia -Handed This Article to My ENT Colleagues

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DR Duncan et al. J Pediatr 2021; 238: 42-49. Acid Suppression Does Not Improve Laryngomalacia Outcomes but Treatment for Oropharyngeal Dysphagia Might Be Protective

This retrospective cohort study with 236 subjects (55% received acid blockers) provides a compelling argument that acid suppression is unlikely to be beneficial in infants with laryngomalacia and to consider the possibility of aspiration in them as well. Among all subjects, 27% received H2RA, 11% received PPI, and 17% received both.

Key findings:

  • Subjects treated with acid suppression had a greater risk of supraglottoplasty (hazard ratio 3.36, 95% CI 1.36-8.29, P = .009), shorter time to supraglottoplasty (5.64 ± 0.92 vs 7.98 ± 1.92 months, P = .006), and increased respiratory hospitalization risk (relative risk 1.97, 95% CI 1.01-3.85, 0.047), even after adjustment for covariates
  • Subjects receiving thickening had fewer respiratory hospitalization nights and longer time to supraglottoplasty (9.3 ± 1.7 vs 4.56 ± 0.73 months, P = .004), even after adjustment.
  • Subjects with moderate-to-severe laryngomalacia were more likely to have aspiration on a video fluoroscopic swallow study (VFSS)
  • Of the 40 patients who had a supraglottoplasty, only 4 (10%) had a VFSS before and afterwards. All repeat VFSS showed improvement at a mean of 4.7 months after supraglottoplasty

It is noted that 36% of subjects underwent a VFSS and 40% had a clinical feeding evaluation. The authors note that other studies have found “a high rate of silent aspiration in laryngomalacia.”

My take:

  1. Acid blockers are unlikely to be beneficial in infants with laryngomalacia and are potentially detrimental (findings limited by retrospective design in a tertiary care setting)
  2. Symptoms in children with laryngomalacia may be due to aspiration and evaluation is needed in those with significant symptoms

Related blog posts:

WSJ 1/2/22: Why Cloth Masks Might Not Be Enough as Omicron Spreads

Best of IBD in Gastroenterology 2021 from AIBD

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The following link is the same as the QR code below (from twitter feed) and provides PDF access to ~30 influential articles from the journal, Gastroenterology, this past year (many reviewed on this blog previously):

Link: Best of Gastroenterology 2021 AIBD

I’ve included screenshots of many of the articles below.

D Turner, SB Hanauer. Editorial on DINE-CD study
Krugliak et al. In press.

Also, recent data indicate that the omicron strain of SARS-CoV-2 is much less likely to affect sense of smell or taste but more likely to cause a sore throat –from Eric Topol twitter feed: