Is It Safe to Exclude Central-Line Infections at 24 hrs?

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A recent study (GL Fell et al. J Pediatr 2020; 227: 69-76. Optimizing Duration of Empiric Management of Suspected Central Line-Associated Bloodstream Infections in Pediatric Patients with Intestinal Failure) showed that 98% of blood cultures returned positive within 24 hrs.

This prospective single-institution cohort study with 73 patients had 128 Central Line-Associated Bloodstream Infections (CLBSI) in 35 patients during the study period (2015-2018).

Key findings:

  • The probability of a blood culture becoming positive after 24 hours was 2.3%; only 1 blood culture became positive after 30 hours (none beyond 48 hrs).
  • The median time from blood sampling to positive culture was 11.1 hours.
  • Elevated C-reactive protein and neutrophil predominance in white blood cell count were associated with positive blood cultures

My take: 98% is not good enough. For now, 48-hours is the safest policy.

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Bahai Temple in Wilmette, IL

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Lots of Room to Improve with H pylori Treatment

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Briefly noted: A recent survey study (N Du et al. JPGN Reports: 2021; 2: p e033. doi: 10.1097/PG9.0000000000000033. Full Text: Assessment of Community Pediatric Providers’ Approach to Children With Helicobacter pylori) found that pediatric providers had poor knowledge and/or adherence to pediatric H pylori guidelines.

Key findings:

  • Over a third of the respondents reported incorrectly testing patients for H. pylori while they were taking proton pump inhibitors.
  • 17% (n=17) incorrectly preferred blood serology as testing modality
  • 63% (n=64) relied on symptom resolution as indication of cure

My take: It would be interesting to compare pediatric gastroenterology provider responses to general pediatric providers. It is likely that a much higher percentage would be following established guidelines. One area of the guidelines that I think should be changed would be encouraging increased use of quadruple therapy in children, especially if resistance testing is not performed; this change would better align with adult guidelines. In adults, quadruple therapy has been associated with increased cure rates.

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Data on Immobilized Lipase Cartridge for Patients with Cystic Fibrosis

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Full text: M Sathe et al. JPGN 2021; 72: 18-23. Evaluation of the Effectiveness of In-line Immobilized Lipase Cartridge in Enterally Fed Patients With Cystic Fibrosis

Background: Traditional pancreatic enzyme replacement therapy is not designed for use with enteral feedings. “Only 1 FDA-approved PERT (PERTZYE, Cheisi, Inc.) has a package insert with instructions on how to deliver the contents of the lowest dose capsule (4000 USP lipase unit) through gastrostomy tubes 14 French or larger…Two recently published studies demonstrated the safety, tolerability, and effect on FA absorption of a new enzyme strategy to aid fat digestion with continuous enteral feedings, a single use digestive cartridge containing immobilized lipase (RELiZORB; Alcresta Therapeutics, Newton, MA). The cartridge connects in-line with an enteral feeding set. As enteral formula flows through the cartridge, immobilized lipase enzyme hydrolyzes intact triglyceride fats within the formula into more absorbable forms, whereas the lipase is retained within the cartridge.”

Key findngs:

  • Weight percentiles reached 50% in 18%, 25.5%, and 28.9% of patients at 0, 6, and 12, respectively.
  • BMI reached 50% in 37.1%, 49.1%, and 50.0% in patients at 0, 6, and 12 months, respectively.

My take: “Immobilized lipase cartridge use demonstrated statistically significant improvements in growth in patients with cystic fibrosis requiring enteral feedings.” Newer and more effective therapies for Cystic Fibrosis may decrease the need for enteral supplementation along with lipase cartridge.

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Does It Make Sense to Look for Celiac Disease in Children with Functional Constipation?

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A recent study (AC Fifi et al. J Pediatr 2020; 227: 77-80.Full text PDF: Celiac Disease in Children with Functional Constipation: A School-Based Multicity Study) shows that celiac disease was not more prevalent in Colombian children with functional constipation(n=203) than in matched healthy controls (n=419). Patients were recruited from public schools.

Key finding:

  • The overall prevalence of celiac disease in the entire cohort was 0.6%. Of those with functional constipation, 1 (0.5%) was diagnosed with celiac disease, and 3 (0.7%) of the control patients

The authors note that some prior publications (references 11 and 12) have found a slight increase risk of celiac disease in children with constipation.

My take: In children with functional constipation, the yield from testing for celiac disease is very low and probably not significantly greater than the general population. In children with irritable bowel syndrome (which is often confused with constipation), the yield is probably a bit higher.

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A New FDA Warning for Tofacitinib

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2/4/21: FDA: Initial safety trial results find increased risk of serious heart-related problems and cancer with arthritis and ulcerative colitis medicine Xeljanz, Xeljanz XR (tofacitinib)

“The U.S. Food and Drug Administration (FDA) is alerting the public that preliminary results from a safety clinical trial show an increased risk of serious heart-related problems and cancer with the arthritis and ulcerative colitis medicine Xeljanz, Xeljanz XR (tofacitinib) compared to another type of medicine called tumor necrosis factor (TNF) inhibitors. FDA required the safety trial, which also investigated other potential risks including blood clots in the lungs and death. Those final results are not yet available….

Patients should not stop taking tofacitinib without first consulting with your health care professionals, as doing so may worsen your condition. Talk to your health care professionals if you have any questions or concerns.”

Related blog post: FDA Warning on Tofacitinib (July 2019)

Growth in Inflammatory Bowel Disease: Better Late Than Never

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Briefly noted: N Gupta et al. Inflamm Bowel Dis 2020; 26: 1880-1889. Continued Statural Growth in Older Adolescents and Young Adults With Crohn’s Disease and Ulcerative Colitis Beyond the Time of Expected Growth Plate Closure

In this retrospective observational longitudinal cohort study with 3007 patients with IBD from the ImproveCareNow Network, the authors found a high rate of continued linear growth after expected growth plate closure (15 years in females, 17 years in males).

Key findings:

  • 80% manifested continued growth beyond the time of expected growth plate closure, more commonly in CD (81%) than UC (75%; P = 0.0002)
  • Median height gain was greater in males with CD (1.6 cm) than in males with UC (1.3 cm; P = 0.0004), and in females with CD (1.8 cm) than in females with UC (1.5 cm; P = 0.025)

My take: This study provides additional information about delayed skeletal maturation in the pediatric population with inflammatory bowel disease. Interestingly, the rate of continued growth with ulcerative colitis was nearly as high as with Crohn’s disease.

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Statin Use May Help in Fatty Liver Disease

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J Lee et al. The American Journal of Gastroenterology: January 2021 – Volume 116 – Issue 1 – p 116-124. Full text link: Effects of Statin Use on the Development and Progression of Nonalcoholic Fatty Liver Disease: A Nationwide Nested Case-Control Study,

Using more than 11 million subjects enrolled in Nationwide Korean database, the authors explored the associations between statin use and fatty liver disease in adults (20 yrs or older).

Key findings:

  • The use of statin was associated with a reduced risk of NAFLD development (adjusted odds ratio [AOR] 0.66; 95% confidence interval [CI] 0.65–0.67). NAFLD was diagnosed by calculating fatty liver index (FLI).
  • The use of statins reduced the risk of significant liver fibrosis (AOR 0.43; 95% CI 0.42–0.44). Fibrosis was based on a BARD score ≥ 2.

The effects of statins may be mediated by anti-inflammatory and antifibrotic actions, which have been evident in experimental models of chronic liver disease.

My take: Statin use appears beneficial in patients with NAFLD. Since dyslipidemia is frequent in patients with NAFLD, there should be a low threshold for using statin therapy.

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“Golden Half Hour in Chronic Pain”

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A recent editorial (NL Schecter et al. JAMA Pediatr. 2021;175(1):7–8. doi:10.1001/jamapediatrics.2020.1798. Full text: The Golden Half Hour in Chronic Pediatric Pain—Feedback as the First Intervention -thanks to Ben Gold for this reference) notes that with pain we need to take a more holistic approach: ” Commonly, patients with chronic pain are evaluated by multiple clinicians, including pediatricians and specialists, each of whom may have addressed only one of the child’s persistent symptoms (ie, headache, abdominal pain, dizziness, nausea, or fatigue). When each symptom is addressed in isolation, it seldom provides comprehensive relief. Moreover, this process can foster a family’s belief that each symptom represents a distinct illness.”

Key points:

  • Brief feedback discussion following an assessment for pediatric chronic pain may be akin to the “golden hour” in trauma or neonatal care.  During this critical time, there is an opportunity to connect with a family, clarify misconceptions, move toward a shared biopsychosocial understanding of pain, and engage families in a comprehensive plan for recovery.”
  • Tips for mastering the golden hour:
    • Elicit Parent and Child Expectations at the Outset “This facilitates a thorough understanding of a family’s main concerns, reduces anxiety, and improves satisfaction. For example, if a parent reports that they expect their child to undergo additional diagnostic testing, this needs to be appreciated and addressed during the feedback.”
    • Validate Symptoms  “Explicitly stating that you do not believe the child is “faking” or that the problem is merely due to psychological stress is critical”
    • Offer a Positive Diagnosis “Although you are special, your symptoms are not unique or mysterious…. If the focus is on what has been ruled out, there are always additional diagnoses that you, the patient, or the internet can introduce.”
    • Provide Education “it can be helpful to explain that chronic pain is like a fire alarm that keeps ringing although there is no fire. “
    • Emphasize a Multidisciplinary Intervention Plan plan for medical intervention, psychological support, and physical activity
    • Stay Connected “Plan follow-up visits (every 4-6 weeks)”
    • Offer an Optimistic Appraisal  “optimistic appraisals are most effective when a clinician has first validated a child’s pain, provided a positive diagnosis and education, and outlined an evidence-based, multidisciplinary approach to care”

My take: This article offers helpful advice. However, whether there is a “golden hour” of opportunity is not clear. Having better outcomes with early intervention could easily be related, at least in part, to selection bias.

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From Ashish Jha Twitter Feed 2/1/21:

Does Reflux Therapy Help Chronic Throat Symptoms? (Probably Not)

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A recent study (J O’Hara et al. BMJ 2021;372:m4903. Full text: Use of proton pump inhibitors to treat persistent throat symptoms: multicentre, double blind, randomised, placebo controlled trial) will probably be another thorn in the side of our ENT colleagues who frequently assert that reflux is likely causing a persistent sore throat. This study is likely to influence empiric treatment by GI physicians as well.

Methods:

  • Random blinded allocation (1:1) to either 30 mg lansoprazole (n=172) twice daily or matched placebo (n=174) twice daily for 16 weeks of patients with persistent throat symptoms.
  • Eligible patients had persistent (>6 weeks) unexplained throat symptoms—principally hoarseness, throat pain, globus sensation, throat clearing, postnasal secretions or excess mucus, cough, or choking sensation
  • Primary outcome was symptomatic response at 16 weeks measured using the total reflux symptom index (RSI) score.

Key finding:

  • No evidence was found of benefit from PPI treatment in patients with persistent throat symptoms. RSI scores were similar between the lansoprazole and placebo groups after 16 weeks of treatment and at the 12 month follow-up.
  • Improvements (reduction in RSI score) were observed in both groups—score at 16 weeks: lansoprazole 17.4 (15.5 to19.4) and placebo 15.6 (13.8 to 17.3). No statistically significant difference was found between the treatment arms. Furthermore, “no trends were in favour of lansoprazole.”
  • Limitation: “Our trial could be criticised for lacking any objective measure of GORD within the methodology or for employing any such test as an inclusion criteria. However, we did address the use of PPIs in an empirical setting, which was a near universal practice at the time of our study.”

My take (borrowed in part from authors): “No evidence supports the empirical use of PPIs to treat persistent throat and voice symptoms.” Despite this finding, “old habits die hard” and I predict that it will be a long time before this finding is widely adopted into clinical practice.

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Progression of Fatty Liver Disease in Children

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SA Xanthakos et al. Gastroenterol 2020; 159: 159: 1731-1751. Progression of Fatty Liver Disease in Children Receiving Standard of Care Lifestyle Advice

This prospective study followed the natural history of NAFLD in children with timed liver biopsy reassessment in children (n=122) using the placebo arms of 2 large multicenter clinical trials; patients received standard of care lifestyle advice. The study population had a mean age of 13 years; 71% were Hispanic participants

Key findings:

  • At enrollment, 31% of the children had definite NASH, 34% had borderline zone 1 NASH, 13% had borderline zone 3 NASH, and 21% had fatty liver but not NASH
  • Over a mean period of 1.6 ± 0.4 years, borderline or definite NASH resolved in 29% of the children, whereas 18% of the children with fatty liver or borderline NASH developed definite NASH
  • Fibrosis improved in 34% of the children but worsened in 23%
  • Progression was more likely with increasing ALT, increasing GGT, type 2 diabetes/increasing HgbA1c
  • Overall, one-third had histologic features of progression within 2 years, in association with increasing obesity and serum levels of aminotransferases and loss of glucose homeostasis.
  • The study conclusions are limited by selection bias, potential liver biopsy sampling errors, limited enrollment of non-Hispanic children, and relatively short duration of follow-up

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