Oral Pan-Genotypic HCV Drugs Approved For Children Starting at Age 3 Years

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AAP News (Nov 2021): First oral pan-genotypic HCV drugs approved for children as young as 3 years

“The Food and Drug Administration (FDA) has approved Epclusa (sofosbuvir and velpatasvir) and Mavyret (glecaprevir and pibrentasvir) for treatment of chronic hepatitis C virus (HCV) infection in pediatric patients as young as 3 years. These products are the first all-oral, pan-genotypic (genotypes 1-6) HCV treatment regimens for pediatric patients 3 years and older…Both products are available as oral tablets and as newly approved oral pellets in dosing strengths suitable to accommodate the recommended weight-based dosing in pediatric patients.”

From HCVGuidelines.org (updated September 2021):

The following images are from Abbvie patient-provider handouts. I do not receive any funding from any pharmaceutical company but think these instructions are useful.

Disclaimer: This blog, gutsandgrowth, assumes no responsibility for any use or operation of any method, product, instruction, concept or idea contained in the material herein or for any injury or damage to persons or property (whether products liability, negligence or otherwise) resulting from such use or operation. These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) should be confirmed by prescribing physician.  Because of rapid advances in the medical sciences, the gutsandgrowth blog cautions that independent verification should be made of diagnosis and drug dosages. The reader is solely responsible for the conduct of any suggested test or procedure.  This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition.

Fix the Feeding Pump, Don’t Call DFACs

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J David et al. JPGN 2021; 73: 599-603. Unexpected Poor Growth in Pediatric Patients on Food-based Enteral Therapy: Case Series and Suggested Practice Changes

In this chart review with five patients, weight loss occurred when patients received only a fraction of their feeds due to feeding pump inaccuracy.

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Briefly Noted: Pediatric Achalasia

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S Woodhull, DR Segar N Engl J Med 2021; 385:e64. DOI: 10.1056/NEJMicm2108193

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Dietary Therapy for Adults with Crohn’s Disease

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H Yanai et al. The Lancet 2021; The Crohn’s disease exclusion diet for induction and maintenance of remission in adults with mild-to-moderate Crohn’s disease (CDED-AD): an open-label, pilot, randomised trial https://doi.org/10.1016/S2468-1253(21)00299-5

In this open-label trial of adults with mild-to-moderate biologic naive Crohn’s disease, key findings:

  • At week 6, 13 (68%) of 19 patients in the CDED plus partial enteral nutrition group and 12 (57%) of 21 patients in the CDED group had achieved clinical remission (p=0·4618)
  • Among the 25 patients in remission at week 6, 20 (80%) were in sustained remission at week 24 (12 patients in the CDED plus partial enteral nutrition group and eight in the CDED alone group)
  • 14 (35%) of 40 patients were in endoscopic remission at week 24 (eight patients in the CDED plus partial enteral nutrition group and six in the CDED alone group)

My take: Dietary therapy may be effective option for motivated adult patients with Crohn’s disease.

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Correlating Calprotectin with Disease Severity in Pediatric IBD

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E Crawford et al. JPGN Reports 2021; 22 – Issue 4 – p e129. Open Access: Association of Fecal Calprotectin With Endoscopic and Histologic Activity in Pediatric Inflammatory Bowel Disease

This retrospective study used data from 331 patients (n=107 with IBD). Fecal calprotectin (FC) was done between 30 days and 1 day before colonoscopy.

Key findings:

  • Correlation with endoscopy: median FC was lowest for all IBD patients with no active disease (181 μg/g) and highest in severe disease (921 μg/g), with significant difference between no disease and moderate and severe disease (P = 0.019, 0.003), and between mild and severe disease (P = 0.012)
  • Correlation with histology: median FC was lowest with no active disease (328 μg/g) and highest in severe disease (895 μg/g), with significant difference between no disease and moderate and severe disease (P = 0.021, 0.018)
  • The control population had median FC of 35.5 compared to 181 μg/g for the IBD population in endoscopic remission (P = 0.018).

My take: Calprotectin levels are particularly helpful as a screen for IBD (probably using threshold of at least 120) and its use to monitor clinical response. This study shows it has some utility in predicting disease severity.

Figure 1: Fecal calprotectin association with endoscopic disease severity of IBD
(A), Crohn’s disease (B) and ulcerative colitis (C). IBD = inflammatory bowel disease.

“How to Remember What Your Doctor Says”

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NY Times (October 26, 2021): How to Remember What Your Doctor Says

Key points:

  1. “When faced with someone in a white coat, don’t go mute. Assert yourself, particularly if you’re confused. Try repeating what you’re hearing”
  2. “People recalled less than half of what their doctors told them a week earlier”
  3. ”In practice, though, patients bring up as many as 15 different issues during a visit. Show up with a list of the three main things you want to talk about, and go over all three before your doctor starts talking.”
  4. “Communication onus should be on medical providers. Still, as a patient, you have agency. ‘When people participate, they remember better'”

My take: This article makes some good points. I think in this era, more written information (after visit instructions) are being provided which helps as well.

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Also, briefly noted, U.S was rated as being in 54th place in its vaccine rates compared to other countries.

Financial Times: Global Vaccine Tracker

Recurrent PSC in Children After Liver Transplantation

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M Martinez et al. Hepatology 2021; 74: 2047-2057. Recurrence of Primary Sclerosing Cholangitis After Liver Transplant in Children: An International Observational Study

In this retrospective study, the authors examined recurrent PSC (rPSC) in children who had undergone liver transplantation (LT) with 3 yrs of median followup. Key findings:

  • rPSC occurred in 36 children, representing 10% and 27% of the subjects at 2 years and 5 years following LT, respectively
  • Subjects with rPSC were younger at LT (12.9 vs. 16.2 years), had faster progression from PSC diagnosis to LT (2.5 vs. 4.1 years), and had higher alanine aminotransferase (112 vs. 66 IU/L) at LT (all P < 0.01)
  • After LT, rPSC subjects had more episodes of biopsy-proved acute rejection (mean 3 vs. 1; P < 0.001), and higher prevalence of steroid-refractory rejection (41% vs. 20%; P = 0.04)

My take: rPSC, not surprisingly, was associated with a more agressive, immunoreactive phenotype prior to LT characterized by younger age, faster progression to end-stage liver disease, higher prevalence of IBD and more frequent/difficult allograft rejection

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Bahamas (courtesy of Mark Martin)

Carlo DiLorenzo: Lessons Learnt Over 30 Years

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Recently, Carlo DiLorenzo came to Atlanta as the speaker for the William Meyers Lectureship. He provided a terrific talk and was the perfect speaker for this lectureship which honors Billy.

Some of the key points:

  • When giving a lecture, often ‘a great study is one that supports the speaker’s view’
  • Physicians often have biases against patients with functional disorders as compared to those who have “rightful” suffering (eg. cancer, pancreatitis)
  • Key part of patient-physician relationship is listening (by the physician). Patients report better satisfaction and perceive to be understood better when a physician is sitting (while listening). “The most important technological advance in the practice of medicine was the invention of the chair. For you to sit in. While you take the history” (Mark Reid, MD)
  • Diagnoses have side effects
  • Families remember our words for years
  • We are not well-equipped to deliver good news: “This is one of the best colons I have ever seen…Your child has irritable bowel and no other tests are needed.”
  • The most under prescribed treatment: 30 minutes of physical activity everyday
  • 2nd most under prescribed treatment is a good night’s sleep.  Increased symptoms when tired
  • “Psychobezoar,” referring to a fear of discomfort with eating, could be used as an alternative to ARFID
  • Most effective treatment for IBS: cognitive behavioral therapy
  • Distraction is helpful tool for pain but need to teach parents to accept this tool
  • Some of the axioms in the lecture are attributed to Mark Reid, MD

Related blog post: #NASPGHAN19 Postgraduate Course -part 3

Here are some of the slides from this talk:

“Esophageal Hypervigilance” and Outcomes in Eosinophilic Esophagitis

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TH Taft et al. Gastroenterol 2021; 161: 1133-1144. Open Access: Esophageal Hypervigilance and Symptom-Specific Anxiety in Patients with Eosinophilic Esophagitis

Commentary: RD Naik, DA Patel. Gastroenterol 2021; 161: 1099-1110. Open Access: Unlocking the Mind Might Be Critical in Management of Eosinophilic Esophagitis: Expanding Beyond Drugs, Dilation, and Diet

Taft et al performed a retrospective study of 103 adult patients with eosinophilic esophagitis. Patients completed the following questionnaires immediately before to endoscopy:

  • Esophageal Hypervigilance and Anxiety Scale (EHAS)
  • Brief Esophageal Dysphagia Questionnaire (BEDQ)
  • Eosinophilic Esophagitis Symptom Activity Index (EEsAI)
  • Northwestern Esophageal Quality of Life Scale (NEQOL).

Endoscopic severity of EoE was graded using the EoE Endoscopic Reference Score System (EREFS). Dysphagia was the primary symptom in 73% of the patients.

Key findings:

  • Patient’s symptom severity (via EEsAI or BEDQ) did not correlate with histology (distal or proximal peak eosinophil count), endoscopic severity of the disease (EREFS), or the distensibility index (measured via functional lumen imaging probe)
  • Symptom severity was correlated with the Esophageal Hypervigilance and Anxiety Scale (EHAS)
  • There was no correlation between EHAS and histologic activity, endoscopic severity (EREFS), or the presence of a stricture

The associated commentary emphasizes some of the study limitations including taking surveys prior to endoscopy (increased anxiety).

My take: This study indicates that with eosinophilic esophagitis, similar to other organic diseases (eg. IBD), patient symptoms do not always correlate with disease severity, and addressing the impact of anxiety and hypervigilance is critical, especially in refractory symptoms.

Figure 1 from commentary

Anonymous Nondirected Liver Donors

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D Yoeli et al. Liver Transplantation 2021; 27: 1392-1400. Challenging the Traditional Paradigm of Supply and Demand in Pediatric Liver Transplantation Through Nondirected Living Donation: A Case Series

This case series of 13 nondirected liver donors (ND-LLDs) (from 2012-2020) helps highlight this increasing trend of motivated donors who do not have a predetermined recipient. The Scientific Registry of Transplant Recipients documented 105 patients who underwent a living donor liver transplantation (LDLT) from ND-LLDs 2000-2019, with 39 in 2019 alone.

Key points:

  • While the article states that carefully selected ND-LLDs at high volume centers have excellent outcomes, the associated editorial (pg 1373-74) notes that there is a 0.2% living donor operative mortality. And, a significant number experience negative physical and socioeconomic effects of donation
  • The authors advocate more use of SPLIT livers to increase the donor pool (currently at 10 centers) to lower pediatric deaths on the waitlist
  • The authors note that the likelihood of receiving a LT is increased at high-volume pediatric centers (85%) compared to low-volume centers (41%). “Center expertise and volume is an important consideration…especially true for pediatric liver transplantation, which is relatively infrequent…551 [in 2019]” compared to 8345 adult liver transplants.

The commentary places some context regarding the donors.

  • 70% had previously donated a kidney (“Repetitive donor disorder?”)
  • Yet, “in some sense, nondirected donors may be the best qualified donors, as they are free of coercion”
  • The authors advocate for a “safe, well-informed” process and for national guidelines to address risks and the components of evaluation, medical and psychosocial

My take: It is amazing how much some individuals are willing to sacrifice to help others, especially in age when some react so harshly to being asked to consider the needs of their community.

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Hyde Farm, Marietta, GA