Elevated Bilirubin in Newborns with Down Syndrome

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Elevated bilirubin in newborns with Down syndrome has been previously reported but the frequency has not been well-described.  A recent retrospective report (TM Bahr J Pediatr 2020; 219; 140-5) compared 357 neonates with Down syndrome to 377,368 controls.

Key findings:

  • Compared with control subjects, neonates with Down syndrome had 4.7 times the risk of having an initial total serum bilirubin exceeding the 95th percentile (23.5% vs 5.0%), 8.9 times the need for phototherapy (62.2% vs 7.0%) and 3.6 times the readmission rate for jaundice (17.4 vs 4.8 per 1000 live births).

The authors note that the basis for the increased risk of hyperbilirubinemia may be early hemolysis related to “neocytolysis” which is due to destruction of RBCs following a change from low to high oxygen exposure. Other factors could include slower bilirubin conjugation/elimination and poor feeding.

My take: This study indicates that infants with Down syndrome have a substantial risk of hyperbilirubinemia.  And, while you are checking a bilirubin, it is worthwhile to obtain a direct bilirubin as cholestasis is increased in infants with Down syndrome too; the latter is often transient and/or associated with other organ involvement.

Related blog post: Neonatal cholestasis and Down syndrome

Island Ford Nat’l Recreation Area/Chattahoochee River, Sandy Springs

COVID Toes

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USA Today (4/27/20): Doctors find more cases of ‘COVID toes’ in dermatological registry. Here’s what they learned

An excerpt:

Dr. Esther Freeman, director of Massachusetts General Hospital Global Health Dermatology and member of the AAD task force on COVID-19, said COVID toes are pinkish-reddish “pernio-like lesions” that can turn purple over time…

While experts can’t confirm why COVID toes appear, they have some educated guesses. One could be inflammation in the toes’ tissue… Another hypothesis is inflammation of the blood vessel wall, medically known as vasculitis. And finally, … it is possible COVID toes could be caused by small blood clots that form inside the blood vessel…

COVID toes have appeared in some cases of asymptomatic patients. The majority of the toe cases manifested simultaneously or after more common COVID-19 symptoms, rather than before.  

My take: During this pandemic, I need to look at my patient’s feet.

Measles Outbreak, 2018-2019 & More on Coronavirus in Georgia

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A recent report (JR Zucker et al. NEJM 2020; 382: 1009-17) highlights an outbreak of a vaccine-preventable disease, measles.  Measles is much more contagious than the recent coronavirus; this is one reason why a vaccine is so crucial.

In total, there were 649 cases confirmed –most of the cases were in a close-knit community in Brooklyn, NY.  86% of the cases with a known vaccination history occurred in those who were unvaccinated. 49 required hospitalization.  The cost to the Department of Health was $8.4 million.

My take:  The health consequences and cost of not preventing measles is staggering -though being eclipsed by the coronavirus pandemic.  The toll in Europe has been much higher.  Worldwide more than 140,000 died from measles in 2018.

Related blog posts:

From Georgia Department of Health: COVID-19 Status Report

It is important to understand that some data, particularly in the last 2 weeks, may not be reported yet.

Related blog post (April 24): Why Georgia Isn’t Ready to Reopen

“Quietly” Testing Famotidine for COVID-19

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Yesterday, I received two emails (first from Steven Liu) about an article in Science and today I’ve already seen this article is referenced in a CNN report:

New York Clinical Trial Quietly Tests Heartburn Remedy Against Coronavirus

Key points:

  • In China, a review of ~6000 patients suggested lower mortality in those taking famotidine (not statistically significant)
  • Famotidine may interfere with viral replication protease in the coronavirus based on computer modeling
  • A randomized trial with IV famotidine (large quantities are not available) is underway in New York using 9 times the dose used for heartburn.
  • The article notes that increased heart problems are common in those with reduced renal function
  • “We still don’t know if it will work or not”

My take: Famotidine may be a hot commodity –at least until studies are completed.  Based on experience with hydroxychloroquine, some of our patients may need to look for alternative acid blockers.

Related blog posts:

 

 

New and Improved Biomarker Blood Test for Crohn’s Disease?

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A recent study (G D’Haens, O Kelly, R Battat et al. Gastroenterol 2020; 158: 515-26,editorial 463) describes the development and validation of a blood test panel to assess Crohn’s disease (CD) endoscopic activity level.  The authors evaluated a blood test which measured 13 proteins in the blood using samples from 278 patients.  Then there were two validation cohorts:

  • 116 biologic-naive CD patients -cohort 1
  • 195 biologic-exposed CD patients -cohort 2

The blood tests were used to develop an endoscopic healing index (EHI) score (0-100). Higher scores indicate greater disease activity.

Key findings:

  • EHI values below 20 identified remission with a sensitivity of 97.1%  and 83.2% in cohorts 1 & 2 respectively; specificity was 69% and 37% respectively.
  • EHI values below 50 points identified patients with highest specificity of 100% and 88% in cohorts 1 and 2 respectively.
  • EHI AUROC (area under the receiver operating characteristic curve) did not differ significantly from that of fecal calprotectin and were higher than measurement of serum CRP (in cohort 1 but not cohort 2).

The editorial notes that the EHI performed much better in younger, biologically-naive patients and that the EHI could potentially be incorporated into a treat-to-target strategy which would potentially entail followup endoscopy in those with EHI >50.

My take: While the stool calprotectin has some logistical barriers in many patients, the EHI is likely a much more expensive test and needs further validation.  For now, the combination of CRP and calprotectin are the best noninvasive biomarkers to assess CD activity.

Briefly noted: Vedolizumab-Induced Pulmonary Toxicity -Case report of a patient with ulcerative colitis who developed interstitial lung disease (Gastroenterol 2020; 158: 478-9).

Related blog posts:

 

Efficacy of Anti-TNF Agents for Internal Fistulas and Study of Antibiotics and Development of IBD

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G Bougen et al. Clin Gastroenterol Hepatol 2020; 18: 628-36.  This retrospective study (n=156, median age 32 years) found that anti-TNF therapy delays or prevents surgery for almost half of patients with Crohn’s disease who had luminal fistulas.  Key findings:

  • With a median followup of 3.5 years, “68 patients (43.6%) underwent a major abdominal surgery.”
  • Fistula healing occurred on average 1 year after the introduction of anti-TNF treatment
  • The presence of a stricture or abscess increased the likelihood of surgery.
  • Three patients died from intestinal adenocarcinomas, one patient died from melanoma (6 months after initiation of anti-TNF therapy), one patient died from sepsis (3 months after initiation of anti-TNF therapy, and 32 patients (20.5%) developed an intestinal abscess.

My take: Therapy with anti-TNF agent, in the setting of a luminal fistula, is a reasonable option, especially in the absence of a concurrent stricture.

FS Troelsen, S Jick. Inflamm Bowel Dis 2020; 26: 440-7, editorial 448-9. Using a UK database, the authors identified 461 cases of ulcerative colitis (UC) and 863 cases of Crohn’s disease (CD) and then matched each case to 4 controls. Key findings:

  • There was no association between ever use of antibiotics and UC, OR 1.02 or CD, OR 1.01 compared to never use of antibiotics
  • CD was associated with antibiotic exposure before age 5 (OR 2.2) in analysis restricted to individuals followed from birth
  • A slight increase was seen for CD in ever users of quinolones (OR 1.76, CI 1.00-3.11) and metronidazole (OR 1.43, CI 0.87-2.34)

In the editorial, Charles Bernstein notes that “it may be that specific types of antibiotics…at specific times in a person’s life have differential risks for IBD development. Also, it may be that what triggers IBD in children is different than what triggers IBD later in life.”

Duke University -late Fall 2019

IBD Pediatric Costs & Cannabis Still No Data for IBD

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Happy birthday to my favorite follower!!!

A recent single-center study (AW Fondell et al. Inflamm Bowel Dis 2020; 26: 635-40, editorial by Joel Rosh, 641-2) examined the first-year costs of children with inflammatory bowel disease (IBD) in 2016.  There were 67 patients (43 with Crohn’s disease (CD), and 24 with ulcerative colitis (UC)).

Key findings:

  • Mean cost was $45,753; $43,095 for CD, $50,516 for UC
  • Severe CD (n=11) was $71,176 and severe UC (n=5) was $134,178; it is notable that only one patient with CD had surgery and only one patient with UC had surgery.
  • Overall cost distribution: 37% from infusion costs, 25% hospital costs, 18% outpatient procedures, 10% outpatient oral medications, 7% outpatient imaging and 3% outpatient visits.
  • 69% of CD patients and 33% of UC patients received biologics
  • 21% (n=9) of CD patients and 45% (n=11) of UC patients were hospitalized
  • Private payer reimbursement was a mean of $51,269 compared to $24,610 mean for Medicaid.

Limitations: 

  • In any cost analysis, many assumptions are needed.  For medications, for example, the author used pharmaceutical retail prices.  The actual costs are near-impossible to calculate as every insurance policy and every hospital system has a multitude of charges based on proprietary negotiations.
  • While this data comes from a referral center, all of the patients in the study were from Connecticut.

Due to the expense of care, Dr. Rosh points out that many insurers have often mandated the use of “standard dosing” of biologic therapy, “ignoring that robust data” indicate that this dosing is “the exception rather than the rule in pediatric IBD patients.”  These type of short-sighted interventions could affect long-term medical outcomes.

My take: There clearly are areas where costs can be reduced (eg. lower infusion costs, lower endoscopy costs, biosimilars).  However, no amount of cost cutting will change the conclusion that good care for IBD is expensive.

Briefly noted: TS Kafil et al. Inflamm Bowel Dis 2020; 26: 502-9.   This study examined evidence for cannabis effectiveness in IBD.  After performing a literature search, the authors could only identify five randomized controlled trials (n=185).  Each study used different doses, formulations and routes of administration.  No studies evaluated maintenance treatment and relapse in CD or UC.  Findings: “no firm conclusions can be made regarding the safety and effectiveness of cannabis and cannabionoids in adults with CD and UC.”

Related blog posts:

 

Cobb County -Concord Covered Bridge Historic District

 

NY Times: Why Georgia Isn’t Ready, You Shouldn’t Drink Disinfectants/Bleach, Masks Help

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Correction: Today’s earlier blog post has been updated:

  • For >1000 [calprotectin], the sensitivity 38%, specificity 100%, PPV 98%, and NPV 92%
  • Previously this line started with the following: “For >100”

From NY Times: Why Georgia Isn’t Ready to Reopen

Key points:

  • Georgia’s infection rates have not started to decline
  • Georgia has a low testing rate compared to other states
  • Georgia’s population rate is vulnerable with increased rates of diabetes and the 4th highest rates of uninsured individuals

Narrowing the Workup for Chronic Abdominal Pain –Carlo DiLorenzo Was Right!

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In the good old days when we could have large meetings, Carlo DiLorenzo gave a terrific summary of recurrent abdominal pain (#NASPGHAN19 Postgraduate Course -part 3).  One of the slides, shown below, is supported by a new study (J Zeevenhooven et al. J Pediatr 2020; 219: 76-82)

In this recent reterospective study, the authors examined 853 patients, of whom 102 (12%) had an organic disorder; all had abdominal pain >2 months. The authors compared two diagnostic strategies:

  • Group 1: anti-TTG IgA, fecal calprotectin, Giardia, along with blood tests (hemoglobin, CRP, ESR)
  • Group 2: anti-TTG IgA, fecal calprotectin, and Giardia (if diarrhea)

Calprotectin was considered normal if <50 mcg/g,  “gray zone” if 51-250, mildly elevated if 251-1000, and elevated/active inflammation if >1000.

Key findings:

  • Sensitivity of the strategies was 90% and 88% for Group 1 and Group 2 respectively
  • In the presence of 1 or more alarm symptoms, the sensitivity was 92% for both strategies.
  • The sensitivity/specificity of calprotectin varied based on the cutoff value.
    • For >50, the sensitivity 75%, specificity 87%, PPV 44%, and NPV 96%
    • For >250, the sensitivity 48%, specificity 99%, PPV 82%, and NPV 93%
    • For >1000, the sensitivity 38%, specificity 100%, PPV 98%, and NPV 92%

Alarm symptoms

  • Alarm symptoms that were statistically different in the organic group included the following:
    • Chronic diarrhea (P <.001), occurred in 32% organic compared to 6% functional
    • GI blood loss (P <.001) , occurred in 35% organic compared to 5% functional
    • Recurrent vomiting (P=.029), occurred in 10% organic compared to 5% functional
    • Perianal complications (P=.001), occurred in 6% organic compared to 1% functional
    • Impaired growth (P=.023), occurred in 4% organic compared to 1% functional
  • Interestingly, the study found that having a positive family history of IBD/celiac/FMF did not differentiate functional and organic patients, occuring in 12% and 15% respectively.
  • Pain in RUQ or lower region also did not differentiate functional and organic patients, occuring in 3% and 4% respectively.
  • The authors note that 30 (29%) patients with organic disease did not have an identified alarm symptom -this compares to 479 (64%) patients with functional disease did not have an identified alarm symptom

From my experience with our recent study (Digestive Diseases (Full Text): Diagnostic Yield Variation with Colonoscopy among Pediatric Endoscopists) which focused on diagnostic yield with colonoscopy, it is clear that there are significant limitations with data collection in a retrospective study regarding recurrent abdominal pain.  Even the definition of chronic diarrhea may vary considerably among practitioners.  At the same time, we did find that an abnormal calprotectin had the highest diagnostic yield (See related blog post for summary: Our Study: Provider Level Variability in Colonoscopy Yield)

It is surprising to me that only 10 patients (1%) in their cohort were identified as having impaired growth.

My take: This study shows that anti-TTG testing and calprotectin are the most useful tests in children with persistent abdominal pain.  The addition of hemoglobin, CRP, and ESR “can be left out in the clinical evaluation of chronic abdominal pain in children.”  The authors advocate, as well, for a prospective cohort study to confirm their observations.

Related blog posts:

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

Timely Tweets & NY COVID-19 Study

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From John Pohl Twitter Feed: Article about mortality/comorbidites from COVID-19 in NYC: Link: Presenting Characteristics, Comorbidities, and Outcomes Among 5700 Patients Hospitalized With COVID-19 in the New York City Area

Methods: Case series of patients with COVID-19 admitted to 12 hospitals in New York City, Long Island, and Westchester County, New York, within the Northwell Health system. The study included all sequentially hospitalized patients between March 1, 2020, and April 4, 2020, inclusive of these dates.

Key findings:

  • The authors report a 88% fatality rate among patients requiring mechanical ventilation, including >97% among those >65 years of age
  • Comorbidities were present in 94% of the 5700 patients.  Most common comorbities included  hypertension (57%), obesity (42%), and diabetes (34%). Asthma was present in 9%.
  • Among patients who were discharged or died (n = 2634), 14.2% were treated in the intensive care unit, 12.2% received invasive mechanical ventilation, 3.2% were treated with kidney replacement therapy, and 21% died.

 

From Emily Perito:

From The Onion