Screenshots and Tweets; MCAT Exposures, Uninsured in Texas, Health Inequalities, a Joke, Other News

Good Reads:

  1. Wired: Bill Gates on Covid: Most US Tests Are ‘Completely Garbage’
  2. MMWR: Hospitalization Rates and Characteristics of Children Aged <18 Years Hospitalized with Laboratory-Confirmed COVID-19 — COVID-NET, 14 States, March 1–July 25, 2020 “Analysis of pediatric COVID-19 hospitalization data from 14 states found that although the cumulative rate of COVID-19–associated hospitalization among children (8.0 per 100,000 population) is low compared with that in adults (164.5), one in three hospitalized children was admitted to an intensive care unit…Among 222 (38.5%) of 576 children with information on underlying medical conditions, 94 (42.3%) had one or more underlying conditions . The most prevalent conditions included obesity (37.8%), chronic lung disease (18.0%), and prematurity (gestational age <37 weeks at birth, collected only for children aged <2 years) (15.4%)end highlight.”  Key finding: Using a multisite, geographically diverse network, this report found that children with SARS-CoV-2 infection can have severe illness requiring hospitalization and intensive care.

COVID-19 Physician’s Personal Experience

Link: MY COVID-19 Excerpts:

 

Online Aspen Webinar -COVID-19, Autoimmune Hepatitis (Part 8)

For those who want to view the actual lectures, you can sign up and view the recordings:  Aspen Webinar Lecture Series


Below I’ve included a few slides and some notes; my notes may have errors of omission or transcription.

COVID-19 and the Liver — Fred Suchy

Key Points:

  • The extent and severity of liver disease related to COVID-19  is still being determined.  Many individuals have mild liver test abnormalities (5-60%)
  • Avoid imaging unless it will change your management (eg. thrombus)
  • In those with worsening/significant liver abnormalities, look for other etiologies of elevated liver tests (eg. other viral hepatitis, drugs, myositis, coinfection, clots, multi-system inflammatory disorder)
  • Currently, no change in immunosuppression is recommended in the post-transplant population WITHOUT COVID-19. In those with severe COVID-19 infection, reduction in immunosuppression is recommended

 

How I Manage Patients with Autoimmune Hepatitis -Diagnosis and Treatment   Amy Taylor.

Key points:

 

 

 

 

NY Times: Opening Schools Safely

NY Times: Opening Schools Won’t Be Easy, but Here’s How to Do It Safely

An excerpt:

  • First, schools cannot reopen safely when community transmission is high and climbing. In our view, schools should open only in places that have fewer than 75 confirmed cases per 100,000 people cumulatively over the previous seven days, and that have a test positivity rate below 5 percent
  • Second, schools should avoid high-risk activities. ..
  • Third, focus on the basics where risks are tolerable — that is at the medium level or lower on our chart. ..
  • [Fourth] Schools must adhere to public health measures and reduce density in classrooms and elsewhere on campus.

Related blog posts:

More School Advice for Organ Transplant Recipients, Plus Another Benefit of the Influenza Vaccine

Link to PDF (from Pediatric Infectious Disease Society:

FAQs Regarding Return to School for Children after Solid Organ Transplant in the United States During the COVID-19 Pandemic

Some excerpts:

Are pediatric SOT recipients at higher risk for getting COVID-19 compared with other children?
Children of any age can get COVID-19, but they seem to have milder disease than adults. Pediatric SOT recipients do not seem to get COVID-19 more often than other children.

If infected with COVID-19, are pediatric SOT recipients at higher risk for developing severe disease or complications?

Based on experience with other viruses, and from reports of COVID-19 in adult SOT patients, there are a few things that may increase the risk of severe COVID-19. These include:
1) Having undergone transplantation in the last 3-6 months
2) Receiving high doses of immunosuppression (such as for treatment of rejection)
3) Having other medical problems such as diabetes, obesity, or certain lung conditions (refer to CDC website under Helpful Resources for more details)
It is not known if the above factors also put children with SOT at risk. In fact, of all the reports among pediatric SOT recipients with COVID-19 published so far, the majority have had mild symptoms and recovered.

Related blog posts:

Renal Disease Associated With Fatty Liver Disease & Dexamethasone-COVID-19 Data

Looking for and managing hypertension has been an important component of care in children and adults with nonalcoholic fatty liver disease (NAFLD)/metabolic syndrome.  In addition, hypertension is frequently associated with renal impairment.

As such, it is perhaps not surprising that in both adults and children, there is a high rate of renal impairment.   The data in children is much more sparse than in adults.  A recent retrospective pediatric cohort study (T Yodoshi et al. J Pediatr 2020; 222: 127-33) adds more information to this problem.

More background information:

  • Chronic kidney disease is highly prevalent in adults with NAFLD: 20-55% (J Hepatol 2020; 72: 785-801; Am J Kidney Dis 2014; 64: 638-52)
  • NAFLD is currently the leading indication for concurrent liver and kidney transplantation
  • In adults, the severity of NAFLD histology is associated with renal impairment
  • The first stage of renal impairment is glomerular hyperfiltration. This is hypothesized to be a precursor of intraglomerular hypertension which leads to albuminuria and glomerular filtration rate (GFR) decline/progressive renal dysfunction
  • Early intervention in high risk patients with angiotensin receptor inhibitors may prevent or delay progressive renal disease

Key findings in 179 patients with biopsy-confirmed NAFLD:

  • 82% non-Hispanic, median age 14 yrs
  • 36 (20%) had glomerular hyperfiltration and 26 (15%) had low GFR (w/in 3 months of liver biopsy) based on Schwartz equation
  • Hyperfiltration was independently associated with higher NAFLD activity score (aOR 2.96)

Discussion:

  • Mechanism: The authors speculate that “it is possible that they [renal and liver disease] are both the end result of the same ‘hit.’ The renin-angiotensin system may play a key role….Notably, there is an ongoing…clinical trial investigating an ATI receptor blocker, losartan, for the treatment of NAFLD in children.” Other potential contributors include fructose and insulin resistance.
  • Limitations: This single center biopsy-confirmed population may not be representative of most children with NAFLD.  Also, as this was a retrospective study, more precise measures of renal function were not available.

My take: This study confirms a high rate of renal dysfunction (35%) in children with NAFLD. As such:

  • Children with NAFLD need to have their blood pressure monitored
  • Clinicians should have a low threshold for nephrology referral if suspected renal impairment.

NEJM Recovery Collaborative Group: July 17, 2020
DOI: 10.1056/NEJMoa2021436: Full Link: Dexamethasone in Hospitalized Patients with Covid-19 — Preliminary Report

Form NEJM Journal blog:

In the open-label RECOVERY trial, some 2100 U.K. patients hospitalized with COVID-19 were randomized to usual care plus oral or intravenous dexamethasone (6 mg once daily for up to 10 days), and 4300 were randomized to usual care alone.

Among patients on invasive mechanical support at the time of randomization, the mortality rate within 28 days was significantly lower with dexamethasone than with usual care alone (29% vs. 41%). A benefit was also seen among those on oxygen without invasive ventilation (23% vs. 26%). However, among patients not receiving respiratory support, mortality rates did not differ significantly between treatment groups.


More Iron Infusions, Less Blood Transfusions in Kids with Inflammatory Bowel Disease; COVID-19 Transmission in Children


Briefly noted: AE Jacobson-Kelly et al. J Pediatr 2020; 222: 141-5. In this retrospective multicenter cohort study (2012-2018), the authors used the Pediatric Health Information System administrative database (n= 8007 with 28 260 admissions, <21 yrs of age). Key findings:

  • Anemia was documented in 29.8% of admissions.  IV iron was given in 6.3% of admissions and blood transfusions in 7.4%
  • A steady increase in the proportion of IBD admissions received IV iron, from 3.5% in 2012 to 10.4% in 2018 ( P < .0001), and the proportion of admissions with red cell transfusions decreased over time from 9.4% to 4.4% ( P < .0001).

Related blog posts:

 

Myth or Fact: Joint Hypermobility is Related to Pediatric Functional Abdominal Pain & Dr. Roy Link

According to a recent study (RJ Shulman et al. J Pediatri 2020; 222: 134-40), the prevalence of joint hypermobility does NOT differ in children with irritable bowel syndrome, functional abdominal pain, or healthy control children.

Methods (to reach this conclusion):

  • Children (median age ~9.5 years) with irritable bowel syndrome (n=109), functional abdominal pain (n=31), and healthy controls (n=69) completed a prospective 2-week pain and stooling diaries.  In addition, children and parents reported on measures of anxiety, depression, and somatization. Children were recruited from both primary care and tertiary care settings
  • Joint hypermobility was determined using Beighton criteria using a goniometer and examined cutoffs at both ≥4 or ≥6).

Key findings:

  • Beighton scores were similar between the groups, as was the proportion with joint hypermobility.  Beighton scores were not related to abdominal pain or stooling characteristics.
  • Beighton score ≥4: IBS 35%, FAP 36%, healthy controls 36%.
  • Beighton score ≥6: IBS 12%, FAP 13%, healthy controls 9%.
  • Children reported depression more frequently in those with Beighton scores ≥6 and somatization was greater in those with a score ≥4.

Discussion:

  • “It is well-recognized that patients with joint hypermobility syndromes (eg, Ehlers-Danlos syndrome, Marfan) commonly have GI symptoms.” However, joint hypermobility is common —in this study’s healthy control group 36% had a score ≥4 and 9% had a score ≥6.
  • This study is in agreement with a school-based study (n=136) (M Saps et al. JPGN 2018; 66: 387-90).
  • Limitations: This study population had a median age of ~9.5 years; thus, these findings need to be determined in an older children

My take: There does not appear to be an increased risk of functional GI disorders in children with joint hypermobility. Thus, looking for joint laxity/hypermobility in children with abdominal pain is not needed.

Related blog posts:

Also, a link to Dr. Roy (Benaroch).  Roy is an Atlanta pediatrician and he explains, with the help of Batman and Luigi, the term ‘index’ case and when one is considered exposed: Dr. Roy Covid Pathway

COVID-19: Universal Mask Wearing (JAMA) and Israel’s Concerning Experience with Opening Schools

JAMA Editorial (July 14, 2020) JT Brooks, JC Butler, RR Redfield (all authors from CDC), JAMA. Published online July 14, 2020. doi:10.1001/jama.2020.13107Universal Masking to Prevent SARS-CoV-2 Transmission—The Time Is Now

An excerpt:

In this issue of JAMA, Wang et al present evidence that universal masking of health care workers (HCWs) and patients can help reduce transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections.1 In the largest health care system in Massachusetts with more than 75 000 employees, in tandem with routine symptom screening and diagnostic testing of symptomatic HCWs for SARS-CoV-2 infection, leadership mandated a policy of universal masking for all HCWs as well as for all patients. The authors present data that prior to implementation of universal masking in late March 2020, new infections among HCWs with direct or indirect patient contact were increasing exponentially, from 0% to 21.3% (a mean increase of 1.16% per day). However, after the universal masking policy was in place, the proportion of symptomatic HCWs with positive test results steadily declined, from 14.7% to 11.5% (a mean decrease of 0.49% per day). Although not a randomized clinical trial, this study provides critically important data to emphasize that masking helps prevent transmission of SARS-CoV-2…. the public needs consistent, clear, and appealing messaging that normalizes community masking. At this critical juncture when COVID-19 is resurging, broad adoption of cloth face coverings is a civic duty, a small sacrifice reliant on a highly effective low-tech solution that can help turn the tide favorably in national and global efforts against COVID-19.

Related blog posts:

Some of the uptick in cases likely related to lack of concern and not using masks

Adjustment of azathioprine dose in NUDT15 intermediate metabolizers, COVID-19 in Georgia & COVID-19 Phase 1 Vaccine Study

LA Jackson et al. NEJM 2020; DOI: 10.1056/NEJMoa2022483. Link:  An mRNA Vaccine against SARS-CoV-2 — Preliminary Report  The mRNA-1273 vaccine induced anti–SARS-CoV-2 immune responses in all participants (n=45), and no trial-limiting safety concerns were identified.

______________________________________________________________________

COVID-19 in Georgia (Data from 7/13/20):


B Kang et al. AP&T 2020; https://doi.org/10.1111/apt.15810. Thanks to Ben Gold for this reference. Full text: Adjustment of azathioprine dose should be based on a lower 6‐TGN target level to avoid leucopenia in NUDT15 intermediate metabolizers

Background: “In addition to TPMT polymorphisms, a recent genome‐wide association study reported that a missense variant of nudix hydrolase 15 (NUDT15 ), which encodes a novel thiopurine‐metabolizing enzyme, was strongly associated with thiopurine‐induced leucopenia especially in Asians”

Key findings:

  • Among the 167 pediatric patients included, leucopenia was observed in 16% (19/119), 44% (20/45) and 100% (3/3) of the NUDT15 normal, intermediate and poor metabolizers respectively ( < 0.001)
  • There was a positive association between 6‐TGN levels and leucopenia among the NUDT15 intermediate/TPMT normal metabolizers
  • In order to reduce the development of thiopurine‐induced leucopenia (<15%) in NUDT15 intermediate metabolizers, adjustment of azathioprine doses should be based on a lower 6‐TGN target level (<167.1 pmol/8 × 108 RBC)

Limitations: single-center, retrospective study and possible selection bias

My take: While 6-TGN levels between 235-400 are typically considered therapeutic, individuals with intermediate metabolism are at increased risk for leukopenia and may respond at lower levels.  This study indicates that careful dosing and close monitoring is needed for NUDT15 intermediate metabolizers

Related blog posts:

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