COVID-19: Over 120,000 Children Have Lost a Parent or Caregiver

NY Times: Over 120,000 American Children Have Lost a Parent or Caregiver to Covid-19, Study Says (between April 1, 2020, and June 30, 2021)

“According to the study in Pediatrics, one of every 168 American Indian/Alaska Native children, one of every 310 Black children, one of every 412 Hispanic children, and one of every 612 Asian children have lost a caregiver, compared to one in 753 white children.”

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Updated Bilirubin Nomogram

TM Bahr et al. J Pediatr 2021; 236: 28-33. A New Hour-Specific Serum Bilirubin Nomogram for Neonates ≥35 Weeks of Gestation

This study which encompassed 397,395 total serum bilirubins provides an updated normogram for serum bilirubins in the first days of life. The data for this nomogram is based on 140 times the number of subjects and is derived from 15 years of universal bilirubin screening (Intermountain Healthcare Hospitals).

Key points:

  • The authors state that this study is one step “toward evidence-based phototherapy decision-making”
  • “We are currently using this nomogram [figure below] routinely in our hospitals in Utah for phototherapy initiation (when a neonate has a TSB exceeding the 95th percentile) and for discharge risk stratification.”
  • “This reduces phototherapy usage…to about 5% of well babies, whereas we had previously been administering phototherapy in 8-10% of well babies.”
  • “Newborns with TSB>75 percentile…receive a recommendation for follow-up within 24 hours.”
  • The authors acknowledge the limitations of their study and caution that more long term outcome data are needed in evaluation of their approach.

My take: Overall, the data is fairly similar to prior data but adoption of these slightly higher values would likely reduce the number of infants requiring phototherapy.

Related blog posts:

In this figure, the new data is indicated by the solid lines and
the prior Bhutani data is indicated by dashed lines.

Liver Shorts: PFIC/FIC1, Best Tenofovir, Ascites Practice Guidance

DBE van Wessel et al. Hepatology 2021; 74: 892-906. Open Access: Impact of Genotype, Serum Bile Acids, and Surgical Biliary Diversion on Native Liver Survival in FIC1 Deficiency

This huge collaborative study with 130 patients provides a great deal of information about familial intrahepatic cholestasis type 1 (FIC1). Key findings:

  • Survival analysis showed an overall native liver survival (NLS) of 44% at age 18 years. NLS was comparable among FIC1-A, FIC1-B, and FIC1-C (% NLS at age 10 years: 67%, 41%, and 59%, respectively; P = 0.12)
  • The number of predicted protein truncating mutations did not correlate with natural history or prognosis

H Toyoda et al. Hepatology 2021; 74: 656-666. Treatment and Renal Outcomes Up to 96 Weeks After Tenofovir Alafenamide Switch From Tenofovir Disoproxil Fumarate in Routine Practice

In this study, the researchers 834 patients with CHB previously treated with TDF for ≥12 months who were switched to TAF in routine practice at 13 US and Asian center. Key findings:

  • “Overall, we observed continued improvement in virologic response, ALT normalization, and no significant changes in eGFR following switch to TAF from TDF.”
  • HBV DNA suppression increased from 88% to 92% at 48 weeks post-switch, and then 95% at 96 weeks postswitch
  • Improved renal function: “By week 96, 21% (55/267) of patients with CKD stage 2 at switch improved to stage 1 and 35% (30/85) of CKD stage 3-5 patients improved to stage 2 and 1.2% (1/85) to stage 1.”

SW Biggins et al. Hepatology 2021; 74: 1014-1048. Open Access. Diagnosis, Evaluation, and Management of Ascites, Spontaneous Bacterial Peritonitis and Hepatorenal Syndrome: 2021 Practice Guidance by the American Association for the Study of Liver Diseases

This practice guidance (with 276 references) is an update from similar guidelines published in 2012.

Key Points For Children:

  • Children with cirrhosis and ascites should be referred for evaluation for LT
  • Children undergoing LVP should receive 25% albumin infusion of 0.5-1.0 g/kg, or 6-8 g per liter of ascites removed.
  • Diagnostic paracentesis should be performed in children with ascites and fever, abdominal pain, or clinical deterioration. The risks and benefits of this procedure for use in all children with new ascites but without these symptoms have not been defined.
Atlanta Beltline Murals

Latest on VTE in Pediatric IBD

MA Aardoom et al. JCC 2021; https://doi.org/10.1093/ecco-jcc/jjab171 The incidence and characteristics of venous thromboembolisms in paediatric-onset inflammatory bowel disease; a prospective international cohort study based on the PIBD-SETQuality Safety Registry

Design: 2016-2020: paediatric gastroenterologists prospectively replied to the international Safety Registry, monthly indicating whether they had observed a VTE case in a patient <19 years with IBD. n=24,802 PIBD patients

Key findings:

  • Twenty cases of VTE were identified (30% Crohn’s disease)
  • The VTE incidence was 3.72 [95%CI 2.27 – 5.74] per 10,000 person-years, 14-fold higher than in the general pediatric population (0.27 [95%CI 0.18-0.38], p<0.001)
  • All but one patient had active IBD, 45% were using steroids and 45% hospitalized.
  • Cerebral sinus venous thrombosis was most frequently reported (50%) VTE

My take: The absolute risk of VTE is low in the pediatric population. In those with active disease, the presence of CVC and use of steroids are known risk factors and require consideration of, at minimum, nonpharmacologic interventions.

Related blog posts:

Pregabalin Helpful for Functional Dyspepsia in Small Study

I Kotikula et al. AP&T 2021; 54: 1026-1032. https://doi.org/10.1111/apt.16588. Randomised clinical trial: the effects of pregabalin vs placebo on functional dyspepsia

Key findings (8 week, randomized placebo-controlled study)

  • The self-reported adequate relief rates in the pregabalin and placebo groups were 70.6% and 42.1% at week 4 (P = 0.02), and 70.6% and 44.7% at week 8 (P = 0.03), respectively
  • Pregabalin improved the overall quality of life (P = 0.03)
  • The most common adverse event with pregabalin was dizziness, occurring in 51.6% of patients

My take: In this study, pregabalin led to significant alleviation of dyspeptic symptoms, especially in patients with predominant epigastric pain.

Related blog posts:

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Outcomes of Youth-Onset Type 2 Diabetes

While pediatric gastroenterologists typically are not coordinating the management pediatric patients with Type 2 Diabetes Mellitus (T2DM), we certainly see many with T2DM and often are involved in some aspects of their care (eg. fatty liver disease).

A recent study (TODAY study group. NEJM 2021; 385: 416-426. Long-Term Complications in Youth-Onset Type 2 Diabetes) details the heavy burden due to T2DM.

This “TODAY2” study annually followed 500 participants from the TODAY trial (2011). The age of the participants was 26.4±2.8 years, and the mean time since the diagnosis of diabetes was 13.3±1.8 years.

Key definitions:

  • Hypertension: At 95% or greater for age (at least SBP 130 or DBP 80) on 3 consecutive visits and/or needing medical therapy
  • Dyslipidemia: Consecutive LDL values of at least 130, consecutive triglycerides of at least 150, or values requiring medical therapy
  • Albuminuria: ratio of urine albumin to creatinine of at least 30
  • Diabetic Nerve Disease: based on scores of Michigan Neuropathy Screening Instrument -consecutive values of at least 2 or more (scores range from 0 to 8)
  • Diabetic Eye Disease: based on a grade of at least 20 according to criteria of Early Treatment Diabetic Retinopathy Study criteria (grades range from 10 to 85)

Key findings:

  • The cumulative incidence of hypertension: 67.5%
  • The incidence of dyslipidemia: 51.6%
  • The incidence of diabetic kidney disease:54.8%
  • The incidence of nerve disease: 32.4%.
  • The prevalence of retinal disease: 13.7% (2010 to 2011) and 51.0% (2017 to 2018)

The authors note that the high incidence of complications is “most likely related to extreme metabolic phenotype (which includes severe insulin resistance and rapid worsening of beta-cell function) and to challenging socioeconomic circumstances.”

Study strengths: 15 years of prospective, extensive data and population representative of U.S.

My take: “Taken together, these data illustrate the serious personal and public health consequences of youth-onset” T2DM by age 26 years!! Unless medical therapies improve further, these consequences argue for careful consideration of bariatric surgery.

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From Chesapeake and Ohio Canal National Historic Park (near Washington D.C.)

“We Need More Information to Process This Claim”

After expending a great deal of time and effort on prior authorizations lately, this recent satirical explanation on prior authorizations and the purpose of insurance companies hits the target. Though, insurance companies do make money off interest, I think the main goal of PA is to limit care costs. Some patients will not get the care their doctor recommends due to stalling by the insurance company. Many times it takes a physician hours in order to get approvals. If a patient’s physician is not willing to do this, many times the patient will not get the treatment.

Link: Health Insurance

Related blog post: For the Next Insurance Appeal & Satire on Prior Authorization

Primary Care Physician Looming Shortage

In a recent commentary (K Grumbach et al. NEJM 2021; 385: 1156-8. Revitalizing the U.S. Primary Care Infrastructure), it’s clear a day of reckoning is coming due to a depletion of primary care physicians.

Scope of the problem:

  • “High-quality primary care is vital but undersupported in the United States. In communities with more primary care resources, people live longer, health care costs are lower, and there is greater health equity”
  • “Primary care physicians make up only 30% of the physician workforce…research on primary care garners just 1% of federal agency research awards”
  • “Primary care physicians earn 30% less than other physicians, on average, and they have among the highest rates of physician burnout”
  • “The situation is worsening…between 2005 and 2015, the number of primary care physicians in the United States decreased from 46.4 to 41.4 per 100,000 people, and the proportion of nurse practitioners and physician assistants who work in primary care is dropping”
  • Currently, the number of physician training to become family physicians is “well below the level needed to replace retiring family physicians. Less than one in five internal medicine residency graduates pursue careers in primary care, down from half of such graduates 25 years ago”

The authors propose a government council to develop and implement a plan to address the looming crisis.

My take: Virtually nothing has been done in 25 years to address this problem and I doubt anything substantive will emerge in the near future; though, it would be good policy to incentivize more physicians to go into primary care.

Related blog posts:

National Cathedral, Washington D.C. Scaffolding due to earthquake damage in 2011.

Clever Study to Assess Utility of TTG IgA For Monitoring Response to a Gluten-Free Diet

K Payne et al. JPGN Reports: 2021; August 2021 – Volume 2 – Issue 3 – p e097. Open Access Repeat Biopsy to Assess Duodenal Healing in Children With Celiac Disease and Eosinophilic Gastrointestinal Disorders

Background: “Current standard of care in the management of uncomplicated CD is not to undergo multiple esophagogastroduodenoscopies (EGDs)…  In this study, patients with both CD and eosinophilic gastrointestinal disorders (EGID) …) were identified to explore [the mucosal response to a gluten-free diet], as it is standard for patients with EGID to undergo repeat EGDs for disease surveillance.”

Key findings in this retrospective study from CHOP:

  • At second biopsy, 44% (17/39) of patients showed no histologic evidence of active CD and 36% (14/39) of patients had negative tTG-IgA values
  • 9/15 (60%) of patients with no evidence of CD on biopsy had abnormal tTG-IgA levels
  • 8/14 (57%) of patients with normal tTG-IgA levels had evidence of active disease on biopsy
  • Among the 18 who had been on a GFD for at least 2 years, 94% (17/18) had normal duodenal biopsies after 2 years, and 83% (15/18) had normal tTG-IgA values after 2 years
  • Of the patients with elevated tTG-IgA and normal duodenal biopsies, 66% (6/9) had inflammation elsewhere in the upper gastrointestinal tract, including 4 patients with active EOE and 2 patients with gastritis

My take: This study confirms that tTG-IgA levels are not optimal for monitoring. Current guidelines recognize this and recommend repeat biopsy in patients with persistent or relapsing symptoms even with negative serology

Related blog posts:

Biologic Treatment Effectiveness for Esophageal Crohn’s Disease

J Lui et al. Inflamm Bowel Dis 2021; 27: 1544-1547. The Use of Biologics for the Treatment of Esophageal Crohn Disease

In this retrospective review (1998-2018), the authors identified 39 patients with esophageal Crohn disease (ECD) who met inclusion criteria.

Key findings:

  • 35 (92%) had a clinical response to treatment and 21 (55%) went into clinical remission
  • ECD seems to be associated with more disabling intestinal CD phenotypes. Of the 39 patients, 10 (26%) had stricturing phenotype and 21 (54%) had penetrating phenotype; 19 (49%) had perianal disease
  • “Initial treatment after diagnosis with anti-TNFalpha agents compared to other biologics was associated with greater improvement in clinical (97% vs 71%; P=0.02) and endoscopic response (95% vs. 40%; P<0.01) and in clinical remission (64.5% vs. 14.2%; P=0.01).”
  • Initial treatment with an anti-TNFalpha agent was initial treatment in 18 patients with ECD; 14 had an inflammatory, 3 had a stricturing, and 1 had a fistulizing phenotype.

While this study showed better response to anti-TNFalpha agents compared to other biologics (eg. anti-IL-12/IL-23 agents), this may be due to a selection bias as other biologics are often used as a second-line treatment and are selected more often in refractory disease.

My take: Esophageal Crohn’s disease is a rare diagnosis and appears associated with more severe disease.

Chesapeake and Ohio Canal National Historic Park (near Washington D.C.)