This large retrospective cohort study (2006-2017) identified 960 infants with in utero biologic medicine exposures (most commonly etanercept, anakinra, adalimumab, and infliximab) among 582,759 infants. Key findings:
Receipt of live-attenuated rotavirus vaccine in their first year or measles vaccine during their first 24 months were not at increased risk of prespecified adverse events compared to unexposed children
There was not a significant difference in diarrhea, bloody stools, intussusception, vomiting, encephalitis, myelitis, hepatitis, ataxia, or fevers
Receipt of the recommended number of doses of rotavirus vaccines in the first year of life was lower among biologic-exposed than among unexposed children (81.00% vs 85.20%, adjusted OR = 0.74)
Examples of guideline recommendations with regard to live-virus vaccination:
In their discussion, the authors note that this “provide some reassurance to parents and pediatricians regarding live-attenuated vaccines for children exposed to BRM [biologics] in utero. Professional societies may want to consider reevaluating their live-attenuated vaccines recommendations for these children as new safety data accumulates.”
My take: There are clearly theoretical concerns about biologic-exposures of infants in utero since some are actively transported across the placenta barrier and can remain in infants for up to 12 months after birth. However, this study could not identify significant adverse effects in exposed infants.
Methods: 48 patients who had fully responded to a 12-week induction course of budesonide 2 mg BID oral suspension were randomized to continuation of therapy or to placebo, for 36 weeks.
Patients randomized to placebo experienced relapse at a numerically higher rate than those who continued budesonide (43.5% vs 24.0%; p=.13). This reached statistical significance in a per-protocol analysis
In a separate arm, 13% of the 106 patients with previous partial or no response did subsequently fully respond to budesonide
Budesonide therapy was well-tolerated; candidiasis-related events occurred in 17 patients overall and were mild to moderate, and abnormal adrenocorticotropic hormone stimulation tests were reported in 5%
My take: Most patients who respond to induction with budesonide will continue to respond to ongoing treatment. A high rate of relapse is seen in those randomized to placebo.
Design: In a multicenter and multicountry randomized crossover trial, patients (n=230) undergoing CRC screening or surveillance were enrolled in 8 centers (Italy, UK, US), and randomized (1:1) to undergo 2 same-day, back-to-back colonoscopies with or without AI (deep learning computer aided diagnosis endoscopy) in 2 different arms, namely AI followed by colonoscopy without AI or vice-versa.
Key finding: There was an approximately 50% reduction of the miss rate of colorectal neoplasia, mainly due to a decreased miss rate of flat and small lesions.
“Tandem studies are more often positive than parallel design studies. In a parallel design study, endoscopist bias toward any study arm is mitigated by the clinical and medical-legal demands to protect patients from colorectal cancer in a single withdrawal.”
“Detection gains for AI are largely for diminutive lesions.3 This is generally true for detection gains from ancillary devices, because powering trials for improved advanced lesion detection is not practical”
Slow Uptake of AI:
First, other adjunctive detection devices have received approval from the US Food and Drug Administration and then failed to reach widespread use…the limited adoption of this entire category suggests that physicians attach a relatively low price point to the value of detection gains produced by add-on devices…Incorporating detection devices with add-on cost is particularly problematic in US ambulatory surgery centers.”
The authors indicate that an endoscopy company could add AI to standard equipment as one way to advance use of this technology
My take: AI will likely improve interpretation and usefulness of colonoscopy, whether for cancer surveillance and other reasons. Cost and familiarity are current barriers to early adoption.
Anti-TNF durability was 90% at 1 year, 75% at 3 years, and 55% at 5 years
Patients with Crohn’s disease had better durability than those with UC/IBD-U (Hazard ratio 0.17)
The most common reason for discontinuation of anti-TNF were loss of response in 24 (57%) children
67 (66%) received combined therapy with an immunomodulator and this was associated with improved anti-TNF durability (Hazard ratio 0.30). However, authors note this was in era preceding widespread therapeutic drug monitoring.
The majority of children in the current study did not undergo testing for monogenic mutations
My take: Data for use of anti-TNF agents in this age group (< 6 yrs) has been limited. This study suggests similar effectiveness of anti-TNF agents in VEO-IBD compared to older groups. Given this groups increased risk for monogenic mutations, it is still a good idea, if feasible, to test for these disorders.
In this retrospective study (2013-2018), the authors examined outcomes in 105 children treated with a 90:10 enteral feeds (90% formula).
44/105 (42%) patients completed 8–12 weeks
After induction, 18 continued EN maintenance with a 80:20 then 70:30 protocol; however, only 10 remained on EN at 6 months and 4 remained on EN at 12 months
The associated editorial (pg: 1-2) make several points:
While EEN is effective and safe, this study and others have shown poor adherence
It is unclear how exclusive enteral nutrition needs to be in order to be effective. And, many patients instructed to receive 90% of their calories as formula are likely consuming higher amounts of table foods
We still are working out which foods need to be excluded
My take: This study shows that EEN is NOT a practical option for most patients beyond induction. Only 4 patients remained on EEN at 12 months.
This lengthy review (27 pages) authored by a multispecialty team makes 17 graded recommendations regarding gastrostomy tubes/gastrostomy tube (GT) placement. The authors state that this review was based on nearly 900 publications with 58 influencing final recommendations.
Here are several of them:
Trial of home nasogastric feeding is safe and should be strongly considered before GT placement, especially for patients who are likely to learn to eat by mouth
Routine contrast studies are not indicated before gastrostomy placement
Laparoscopic placement is associated with the best safety profile
For most patients, a low-profile balloon GT is preferred
Elaborating on these recommendations::
Home NG: The authors note that Lagatta et al found that infants sent home with NG from nursery had shorter length of stay and fewer readmissions/emergency encounters than patient sent home with GT. However, this statement ignores the significant differences in the patient characteristics in the two groups noted in this article (see related blog post: Impact of NG Feeding Program for NICU Graduates). Interestingly, many of the return visits are due to dislodgements of button GTs.
Preoperative workup: While the authors discourage use of preoperative UGI and except in patients not achieving adequate enteral nutrition due to emesis, they also recommend “GT should only be pursued after appropriate workup has been performed to investigate the underlying medical diagnosis.” I find this vague recommendation to be problematic. Shortly before making this recommendation, the authors state “proper identification and management of the underlying diagnosis (eg. diet modification for eosinophilic esophagitis) may obviate the need for GT placement.” So, do the authors want every child who may need a GT to undergo an EGD? Or perhaps even more, such as an MRI or full exome sequencing? Also, which diet trial do they recommend for potential eosinophilic esophagitis -does this mean an amino acid based formula or is a hydrolysate sufficient?
GT technique: The review of the techniques of GT placement cite data comparing the techniques and complication rates (though noting critical risk of bias in these studies):
open gastrostomy (n=1471) vs PEG (n=679): 3.2% vs 4.1% (P=.35)
laparoscopic gastrostomy (n=787) vs PEG (n=1321) 1.2% vs 5.4% (P<.0001)
IR placement (n=321) vs PEG (n=417): 3.7% vs 1.9% (P=.04)
the authors note the decision needs to consider specific patient characteristics and institutional factors
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This report describes the “newly developed and validated PBMST (Pediatric Bowel Management Scoring Tool) is a reliable tool for evaluating bowel management strategies in children with constipation.”
“This study shows that use of the PBMST (see below) can better guide management of childhood constipation, with its fair reproducibility indicating that it is stable over a specified time period. Indeed, consistent use of the PBMST can objectify the patient’s clinical condition over a longer period. Consequently, the score provides feedback regarding the effect of the applied bowel management strategy for each individual patient.”
My take: 6 key questions for constipation visits: stool form, anorectal pain, abdominal pain, soiling, support from parents, and social limitations.
Methods: Nonconcurrent retrospective analysis of 2 cohorts of 483 very low birth weight (VLBW) infants not exposed and exposed to Binfantis EVC001 probiotic at Oregon Health & Science University from 2014 to 2020
The cumulative incidence of NEC diagnoses decreased from 11.0% (n = 301) in the no EVC001 (unexposed) cohort to 2.7% (n = 182) in the EVC001 (exposed) cohort (P < .01); this was a 73% risk reduction of NEC
NEC-associated mortality decreased from 2.7% in the no EVC001 cohort to 0% in the EVC001 cohort (P = .03)
There was a lack of adverse events (including probiotic sepsis)
Key points from editorial:
“The first cohort study showing a significant decrease in necrotizing enterocolitis (NEC) with the routine administration of probiotic dietary supplements [was] more than 20 years ago”
“The most recent Cochrane Database systematic review 2 included 56 randomized or quasi-randomized trials in which 10 812 infants participated. Meta-analysis found evidence for decreased risk of NEC (Risk ratio [RR] 0.54)”
Both the AGA and ESPGHAN have recommended routine probiotics administration to preterm infants. However, the AAP recommends “against routine probiotic administration citing ‘the lack of FDA-regulated pharmaceutical-grade products in the United States, conflicting data on safety and efficacy, and potential for harm in a highly vulnerable population.’”
“Recognizing that many neonatologists have opted to adopt routine probiotic administration to infants born preterm, the recent American Academy of Pediatrics statement6 recommends that an informed consent process for utilizing probiotics. Dr. Underwood counters: “there is no mention of a need to discuss these risks and benefits by those well-informed clinicians who may not believe that the data support administering probiotics. Inclusion of parents in decision-making in the NICU improves parent satisfaction and infant outcomes.”
My take: It is hard to understand that, despite 20 years of research showing probiotics can reduce mortality and morbidity in premature infants, we have not been able to manufacture a consistent, reliable high-quality probiotic capable of meeting FDA standards.
TL (vs EL) had lower rates of CVC breaks (1.11 vs 5.19/1000 CDs, P < 0.001), occlusions (0.83 vs 4.06/1000 CDs, P= 0.01) and repairs (1.94 vs 5.64/1000 CDs, P= 0.01)
There was no significant difference in CRBSI rates: 0.83/1000 CDs for TL vs 2.03/1000 CDs for EL (P= 0.25)
My take: Taurolidine, when available in U.S., may be a suitable alternative to ethanol, when available in U.S., in preventing CRBSI. In addition, taurolidine locks appear to have fewer mechanical risks.
The expression ‘90% of Success is Showing Up’ has been attributed to Woody Allen. With dietary and medical treatments, adherence is the equivalent of showing up.
In this study, the authors measured fecal gluten immunogenic peptides (GIP), a biomarker of gluten intake, in 45 children (3– 17 years) with Crohn’s disease to assess adherence to enteral nutrition. This, in turn, was correlated with fecal calprotectin (FC) levels.
FC decreased in patients with undetectable GIP at both 33 and 54 days of EEN (mean decrease, 33 days: −743 mg/kg, 54 days: –1043 mg/kg, P< 0.001) but not in patients who had detectable GIP levels
At EEN completion, patients with undetectable GIP had a lower FC by 717 mg/kg compared with patients with a positive GIP result (P = 0.042) and demonstrated a greater decline from baseline FC (–69% vs +5%, P = 0.011)
13% and 23% had detectable GIP levels at 33 days and 54 days respectively. It is noted that GIP levels are only indicative of short-term consumption (eg. prior 1-2 days) of gluten-containing foods
My take: Dietary therapies are really difficult for most people. This study shows that those with poor compliance are unlikely to benefit.