COVID-19 in Children from Italy

NEJM: Children with Covid-19 in Pediatric Emergency Departments in Italy

Key points:

  • Children younger than 18 years of age who had Covid-19 composed only 1% of the total number of patients; 11% of these children were hospitalized, and none died
  • The Coronavirus Infection in Pediatric Emergency Departments (CONFIDENCE) study involved a cohort of 100 Italian children younger than 18 years of age with Covid-19 (median age 3.3 years)
    • .Common symptoms were cough (in 44% of the patients) and no feeding or difficulty feeding (in 23%) (especially if <2 years)
    •  Fever, cough, or shortness of breath occurred in 28 of 54 of febrile patients (52%)
    •  Of the 9 patients who received respiratory support, 6 had coexisting conditions

My take: This study provides additional data indicating that severe outcomes are rare in children with Covid-19.

Related article from NY Times: How Coronavirus Mutates and Spreads

An excerpt:

Researchers have found that the coronavirus is mutating relatively slowly compared to some other RNA viruses, in part because virus proteins acting as proofreaders are able to fix some mistakes. Each month, a lineage of coronaviruses might acquire only two single-letter mutations.

In the future, the coronavirus may pick up some mutations that help it evade our immune systems. But the slow mutation rate of the coronavirus means that these changes will emerge over the course of years.

That bodes well for vaccines currently in development for Covid-19. If people get vaccinated in 2021 against the new coronavirus, they may well enjoy a protection that lasts for years.

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Improving Obesity Trend in Young Children?

Link (YouTube): William Meyers Inaugural Conference Lecture

Related blog post: William Meyers

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CBS News: Study shows declining obesity rate for preschoolers who receive government food aid

An excerpt:

The obesity rate for preschoolers who receive government food aid has declined, according to a study released Tuesday in the Journal of the American Medical Association. Obesity rates dropped steadily to about 14% in 2016 — the latest data available — from 16% in 2010, the Centers for Disease Control and Prevention reported.

The improvement affected youngsters ages 2 through 4 who receive food vouchers and other services in the federal Women, Infants and Children nutrition program. About 1 in 5 U.S. kids that age were enrolled in 2016…

My take:  This is good news. Hopefully, this report will be one of many indicating that the rates of obesity could actually improve.

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Ledipasvir-Sofosbuvir for Children 6-11 years

Almost two years ago, the FDA approved Ledipasvir-Sofosbuvir (aka Harvoni) for pediatric patients 12-17 years of age with hepatitis C virus (HCV) infection.  Now, a recent study (KF Murray, WF Balistreri, S Bansal et al. Hepatology 2018; 68: 2158-66) is likely to expedite approval for children ages 6-11 years of age.

In this open-label study with 92 patients, 88 had genotype 1, 89 received treatment with ledipasvir-sofosbuvir without ribavirin for 12 weeks, 97% were perinatally-infected, and 78% were treatment naive.  The median age was 9 years. The dose (determined by intense pharmacokinetics) was 45 mg-200 mg (half the adult dosage). Two patients with genotype 3 HCV received ledipasvir-sofosbuvir for 24 weeks along with ribavirin.

Key findings:

  • SVR12 was 99% (91/91).  The single patient without SVR12 had relapsed 4 weeks after completing a 12 week treatment course.
  • Ledipasvir-sofosbuvir was well-tolerated; the common adverse events reported were headache and pyrexia.

The authors note that while most children are considered to have mild symptoms or are asymptomatic, some progress to have significant fibrosis or cirrhosis, a small minority develop hepatocellular carcinoma, and HCV infection can impact both cognitive development and overall health.

My take: This study confirms that effectiveness of DAA therapy with ledipasvir/sofosbuvir in children as young as 6 years of age.

Related study: F Tucci et al. Hepatology 2018; 68: 2434-37. The authors report the successful treatment with ledipasvir/sofosbuvir of an infant with both SCID and HCV infection.

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Mesquite Flat Sand Dunes, Death Valley

More on Hepatitis B Treatment in Children

A recent post (New Hepatitis B Treatment Guidelines -AASLD) described the updated treatment recommendations.  When these guidelines were published, a separate review devoted specifically to pediatrics was published (Hepatology 2016; 63: 307-18).

Some of the key points:

  • This pediatric review included 14 studies with 1425 children.  The authors note that 7 of these trials had a high risk of bias.  Also, the studies are limited by relying on surrogate markers of long-term outcomes as clinical outcomes like cirrhosis, HCC, and death are rare in childhood.
  • Among oral agents, entecavir and lamivudine are approved for use in children ≥ 2 years, whereas adefovir and tenofovir are approved for use in children ≥ 12 years.  Both lamivudine and adefovir are associated with frequent development of viral resistance
  • For children with elevated ALT (>1.5 times upper limit of normal [ULN]), treatment is recommended:

9A. The AASLD suggests antiviral therapy in HBeAg-positive children (ages 2 to <18 years) with both elevated ALT and measurable HBV DNA levels, with the goal of achieving sustained HBeAg seroconversion.

Why not treat everyone?

  • Children with immune-tolerant HBV infection (normal or near-normal ALT [< 1.5-2 times ULN] along with high HBV DNA [>10 million IU/mL]), “are not typically candidates for treatment because treatment with any of the currently available drugs has not been demonstrated to improve HBeAg seroconversion compared with no treatment.”
  • Children with ALT >10 time ULN may be in the process of spontaneous seroconversion “and should be observed for several months before treatment” is initiated.
  • “Prolonged treatment with nucleoside or nucleotide analogs in children who are in immune-tolerant phase has not been associated with substantial benefit and carries a risk of developing antiviral drug resistance…An exception may be those…undergoing immunosuppressive therapy.”
Mina Falls, El Yunque Rainforest

Mina Falls, El Yunque Rainforest

Prucalopride -Not Better Than Placebo for Children with Constipation

Background: There were high expectations for prucalopride for the treatment of constipation based on previous small studies as well as a placebo-controlled trial in adults.  In adults, after 12 weeks of treatment, between 19.5-29% were responders compared to 9.6-12.1% in placebo patients. Prucalopride is a 5-hydroxytryptamine receptor-4  (5HT4) agonist which has been shown to accelerate colonic motility and is similar structurally to agents like cisapride and tegaserod; these latter medications have shown effectiveness as prokinetics but were limited by life-threatening cardiovascular side effects.

Design: Large (n=213), multicenter, placebo-controlled trial (Mugie SM, et al. Gastroenterol 2014; 147: 1285-95, editorial 1214-16). Response to medication indicated by >3 spontaneous bowel movements per week and <1 episode of fecal incontinence every 2 weeks.

Findings:

  • 17% of prucalopride subjects and 17.8% of placebo subjects were considered responders.
  • If based solely on bowel movement frequency, 29.2% of prucalopride achieved >3 BMs/week, whereas 35.5% of placebo-treated patients achieved this frequency.
  • Adverse effects were similar

Why did Prucalopride not work?

The authors and editorial make several speculations.  In children, withholding behavior is much more important in the pathophysiology of functional constipation (FC) than in adults.  In addition, slow transit constipation is much more common in adults than in children. In the adolescents (≥12 to <18) there was a mild response noted: 18.5% compared with 14.8% of placebo-treated patients (P=.38). The editorial notes that the short length of the trial (8 weeks) could explain the negative results, though this is unlikely.

The editorial, by Samuel Nurko and Miguel Saps, notes a much higher response to polyethylene glycol which “is the mainstay of treatment.”  “PEG-based solutions achieved a successful outcome in 56% of participants compared with 29% in the lactulose group.”

Take-home message: “This study does not provide new data to justify a change in the indication of PEG as first line of treatment for FC in children.”

In followup to questions regarding Miralax safety, here is a link from NASPGHAN’s Neurogastroenterology and Motility Committee: Miralax FAQ

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A Sign in Our Office --Needs Clarification

A Sign in Our Office –Needs Clarification

IBD Incidence Increasing: 30 Years of Data from Manitoba

A recent study (JPGN 2014; 59: 763-66) shows a steady trend of increased incidence of IBD in Manitoba. This figure is available online:

 

Increasing IBD Incidence in Children

Increasing IBD Incidence in Children from JPGNonline

Abstract:

Objectives: The aim of this study was to describe the incidence and prevalence of inflammatory bowel disease (IBD) in children <17 years of age in 30 years from 1978 to 2007.

Methods: From January 1, 1978, to December 31, 2007, the sex- and age-adjusted annual incidence and prevalence of pediatric IBD per 100,000 population were calculated based on the pediatric IBD database of the only pediatric tertiary center in the province. The annual health statistics records for the Province of Manitoba were used to calculate population estimates for the participants. To ensure validity of data, the University of Manitoba IBD Epidemiology Database was analyzed for patients <17 years of age from 1989 to 2000.

Results: The sex- and age-adjusted incidence of pediatric Crohn disease has increased from 1.2/100,000 in 1978 to 4.68/100,000 in 2007 (P < 0.001). For ulcerative colitis, the incidence has increased from 0.47/100,000 in 1978 to 1.64/100,000 in 2007 (P < 0.001). During the same time period, the prevalence of Crohn disease has increased from 3.1 to 18.9/100,000 (P < 0.001) and from 0.7 to 12.7/100,000 for ulcerative colitis (P < 0.001). During the last 5 years of the study the average annual incidence of IBD in urban patients was 8.69/100,000 as compared with 4.75/100,000 for rural patients (P < 0.001).

Conclusions: The incidence and prevalence of pediatric IBD are increasing. The majority of patients were residents of urban Manitoba, confirming the important role of environmental factors in the etiopathogenesis of IBD.

Unrelated: As a bonus for those who made it to the bottom of this post : there’s a new Bristol Stool App for iPhones.  Here’s the link: http://www.bristol-stool-scale.com (from John Pohl’s twitter feed)

 

2015 Wish List

A recent policy article (JAMA Pediatr 2014; 168: 1155-63 –thanks to Ben Gold for this reference) outlines “10 urgent priorities for the health and health care of US children.”  These priorities and some of the action steps are as follows:

  1. Poverty: “16.1 million children (22%) live in poverty. ” Action steps include enacting measures to improve employment in families and extending child tax credits.
  2. Food Insufficiency: “>16 million children live in food-insecure homes.” Actions could include investing rather than cutting children’s nutrition programs.
  3. Lack of health insurance: affects “7 million children (9%)” though two-thirds are eligible for coverage by Medicaid and CHIP. Actions could include fully funding CHOP and Medicaid and abolishing ACA family glitch along with improving outreach to enroll eligible children.
  4. Child abuse/neglect (maltreatment): “In 2011, 681,000 children experienced maltreatment and 1570 died” as a consequence.  Everyday, a child is abused or neglected every 47 seconds.  Action steps included focusing on domestic violence and treatment and funding more screening and preventative treatment research.
  5. Obesity: “32% of children are overweight and 17% are obese.”  Actions could include passing FIT kids Act (HR 2178) and maximizing funding for USDA’s Farmers market promotion program and the Fresh fruit and vegetable program.
  6. Firearms deaths/injuries: 5 children die daily by firearms.  Actions could include better background checks, along with regulations to require safer storage and safety classes.  Other options include higher taxation on weaponry and ammunition to “better represent societal costs.”
  7. Racial disparities: Action steps include monitoring and disclosing disparities and working to ensure all children have a medical home.
  8. Mental Health: up to 20% of children experience a mental health disorder annually.  Actions could include increasing the number of qualified mental-health providers (by enhancing reimbursement).
  9. Immigration: “children living in immigrant families are the fastest growing group of US children.” Action could include obtain health insurance for all children.
  10. Research: Increase funding for children.  Overall NIH pediatric funding is 12% of total budget whereas children represent 24% of US population.

The problems faced by this nation’s children will reverberate for a long time.  For example, with childhood poverty, it is “associated with substantially higher mortality rates in adults, regardless of adult socioeconomic status (i.e., even affluent adults who were poor as children have elevated death rates), and this increased mortality risk extends across 2 generations.”

Bottomline: Children receive a disproportionately low share of federal expenditures and this extends to healthcare.  In addition, federal spending on children in 2014 has decreased by more than $20 billion (14%) since 2010.

Blog post:

AASLD/NASPGHAN 2014 Guidelines for Evaluation of Pediatric Liver Transplantation

I want to congratulate the authors of a recent AASLD/NASPGHAN report (Hepatology 2014; 60: 362-98 & JPGN 2014; 59: 112-31) and in particular Rene Romero who has been a terrific colleague in Atlanta.  I’m grateful for his timely advice to me and my colleagues along with the excellent care that he has provided to children referred for liver transplantation (LT).

The link to full article, Evaluation of Pediatric Liver Transplantation, and other AASLD practice guidelines can be accessed from this website: AASLD guidelines.

Some of the useful recommendations include the following:

  • For biliary atresia, “patients who are post hepatoportoenterostomy (HPE) should be promptly referred for LT evaluation if the total bilirubin is greater than 6 mg/dL beyond 3 months from HPE” and should be considered if total bilirubin is ≥2 mg/dL.  According to the authors in the Hepatology article, ‘84% of those with a total bilirubin <2 mg/dL will survive with native liver beyond 2 years of age whereas only 16% will if total bilirubin is >6 mg/dL.’ [Interestingly, this information is stated differently in the JPGN article where the authors state  “up to 70% of patients with BA may have prolonged transplant-free survival if the total serum bilirubin falls below 2 mg/dL” w/in 3 months following HPE.]
  • For biliary atresia: HPE is recommended as 1st line treatment except in infants with “evidence of decompensated liver disease.”
  • Ascites management: can be managed with an aldosterone antagonist.  Reserve more aggressive measures (paracentesis, TIPS, surgical shunt) for those with compromised respiratory effort or severely impaired quality of life.
  • Recurrent disease: families should be informed that autoimmune hepatitis, PSC, and bile salt excretory pump disease can recur post-LT.
  • Recommends screening with use of pulse oxygen with the patient in upright position in all patients with possible portosystemic shunting.
  • Discusses immunizations for child and for family members (all family members need to fully immunized).
  • The review provides recommendations specific for virtually each liver condition, including Alagille, Wilson’s, Tyrosinemia, PFIC, hemangioendothelioma, Cystic fibrosis, urea cycle defects, autoimmune hepatitis, PSC, Hepatoblastoma, Alpha-1 Antitrypsin deficiency, Bile Acid Synthesis Disorders, Glycogen Storage Disease, Fatty Acid Oxidation defects, Parenteral Nutrition-Associated Liver Disease (PNALD), and many others.
  • Contraindicated for LT:  Alper’s syndrome/valproate-associated liver failure, mitochondrial disease with severe extrahepatic disease, Hepatocellular carcinoma with extrahepatic disease and rapid progression, uncontrolled systemic infection, Niemann-Pick Disease Type C, and severe medically-refractory portopulmonary hypertension

Take-home message: This practice guideline is an excellent resource in the evaluation of pediatric liver transplantation and pre-transplant management.  The ease of accessing the entire report online is a big plus too.

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Specific Carbohydrate Diet in Children -Ahead of Print

Here is a link, bit.ly/1xb1kk8, (from JPGN) and the abstract to an article on the Specific Carbohydrate Diet in Children.  This study shows clinical improvement and mucosal healing, confirmed by capsule endoscopy, in response to the specific carbohydrate diet (SCN). Congratulations to my colleagues/partners from GI Care for Kids who published this study in JPGN:

Objective: To prospectively evaluate clinical and mucosal responses to the specific carbohydrate diet (SCD) in children with Crohn’s disease (CD).

Methods: Eligible patients with active CD (Pediatric Crohn’s Disease Activity Index, PCDAI >= 15) underwent a patency capsule and if passed intact, capsule endoscopy (CE) was performed. Patients were monitored on SCD for 52 weeks while maintaining all prescribed medications. Demographic, dietary and clinical information, PCDAI, Harvey Bradshaw (HB) and Lewis score (LS) were collected at 0, 12 and 52 weeks. CE’s were evaluated by an experienced reader blinded to patient clinical information and timing.

Results: Sixteen patients were screened; 10 enrolled; and 9 completed the initial 12 week trial; receiving 85 % of estimated caloric needs prior to, and 101%, on the SCD. HB significantly decreased from 3.3 + 2.0 to 0.6 + 1.3 (p = 0.007) as did PCDAI (21.1 + 5.9 to 7.8 + 7.1; p = 0.011). LS declined significantly from 2153 + 732 to 960 + 433 (p = 0.012). Seven patients continued the SCD to 52 weeks with HB (0.1 + 0.4) and PCDAI (5.4 + 5.5) remaining improved (p = 0.016 and 0.027 compared to baseline) with mean LS at 1046 + 372 and 2 patients showing sustained mucosal healing.

Impressions: Clinical and mucosal improvements were seen in children with CD using the SCD over 12 and 52 weeks. Additionally, CE can monitor mucosal improvement in treatment trials for pediatric CD. Further studies are critically needed to understand the mechanisms underlying SCD’s effectiveness in children with CD.

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