This and That: Chores, Understanding Vomiting, Helping Crying Babies

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Psychology Today (11/1/22): Best Age for Kids to Start Doing Chores

  • “Science suggests that chores make kids happy and that you should start assigning little jobs early, even when they are toddlers.”
  • “Seemingly insignificant chores like setting the table or folding laundry are valuable building blocks toward a child’s independence.”

NY Times (11/1/22): How Brains Send a Signal That It’s Time to Vomit (in mice) Reference article: Z Xie et al. Cell: The gut-to-brain axis for toxin-induced defensive responses “They traced the effect to certain neurons in the brain that released neurotransmitters when the drug [eg. chemotherapy] or the toxin [eg. bacterial] reached the gut. Following those messages back, they discovered cells in the small intestine that reacted to the presence of these noxious substances. A central player in the pathway to nausea and retching was an immune system molecule called interleukin 33, or IL33. Keeping mice from making IL33 significantly reduced their symptoms.”

N Ohmura et al. Current Biology 2022; 32,  P4521-4529. A method to soothe and promote sleep in crying infants utilizing the transport response

  • “Infant cry is attenuated by transport, but not by motionless holding”
  • “5-min transport promotes sleep for crying infants even in the daytime”
  • “Laydown of sleeping infants into a cot either interrupts or deepens infants’ sleep”
  • “Laydown at 5 to 8 min after the sleep onset tends to prevent infant awakening”

What is the Difference Between Burnout and Depression?

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S Sen. NEJM 2022; 387: 1629-1630. Is It Burnout or Depression? Expanding Efforts to Improve Physician Well-Being

Key points:

  • “This growing attention has helped to reduce the stigma associated with burnout, highlighting the health care system, rather than the individual, as the primary driver of the problem.”
  • What is burnout? “One review identified 142 different definitions of physician burnout in 182 studies.3 …the most commonly used is the Maslach Burnout Inventory, which assesses continuous scores for three domains: emotional exhaustion, depersonalization, and reduced sense of personal accomplishment.”
  • There is a lot of overlap with depression especially with emotional exhaustion. However, depression is still stigmatized as due to individual weakness. “Work-related stress is the primary driver of depression among physicians. A stark illustration of this dynamic is the fact that the prevalence of depression among training physicians before they enter residency is similar to that among young adults in the general population, but depression rates quintuple immediately after residency begins.”
  • “Whether burnout is meaningfully distinguishable from depression, the argument that depression and burnout are caused by fundamentally different precipitants is unsupported by the evidence to date”

My take (borrowed from the author): “Crucially, identification and treatment of depression can help reduce the risk of suicide among physicians. Unfortunately, when we encourage clinicians to consider themselves burned out rather than depressed, they tend not to seek or receive the individual-level interventions that can improve well-being.”

Related NPR Story (11/11/22): Study: Mindfulness-based stress reduction works as well as a popular anxiety drug. This report is based on the following reference:

Review: Infectious Esophagitis

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JEM O’Donnell, U Krishnan. JPGN 2022; 75: 556-563.Infectious Esophagitis in Children

Key points:

  • Three most common causes of infectious esophagitis in children: Candida, HSV and CMV. Asperigillus (& other fungi) as well as bacterial esophagitis are rarely seen. Rare viral infections include human papilloma, varicella zoster and EBV
  • For Candida, this is typically a benign commensal organism but can become pathogenic due to changes in immunity (immunocompromised including corticosteroids), altered motility and sometimes after antibiotics (with or without PPI therapy). EoE can present with similar-appearing mucosa; thus, biopsy and/or brushing is needed.
  • With HSV, pediatric case series have reported higher rates in immunocompetent children
  • Typical treatments: fluconazole for Candida, and Acyclovir for HSV. For CMV, potential treatments include ganciclovir, valganciclovir, foscarnet or cidofovir.

My take: This is a short, good review of the infections that can cause esophagitis in children.

Related blog post: Image Only: Candida Esophagitis

From JPGN twitter feed: Kodsi classification of esophageal candidiasis.

IBD Updates: Dietary Patterns and Disease Activity, Ustekinumab in SUSTAIN study, INSPECT Study for Perianal Fistulas

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BN Limketkai et al. Inflamm Bowel Dis 2022; 28: 1627-1636. Open Access! Dietary Patterns and Their Association With Symptoms Activity in Inflammatory Bowel Diseases. This retrospective study with dietary surveys of 691 participants found the following:

  • Compared with WD1 (typical Western Diet), PB2 (Plant-based diet 2) was associated with lower odds of active symptoms for CD (odds ratio [OR], 0.32
  • PB1 (Plant-based diet 1) was associated with lower odds of active symptoms for participants with UC (OR, 0.45; 95% CI, 0.23-0.90) but not for participants with CD (OR, 0.95

Diet PB1 (“Plant-based Diet 1”) was characterized by much higher intake of fruits, vegetables, plant-based proteins, and cooked grains than most other dietary clusters. There was low water intake in favor of juices and other beverages. There was otherwise average intake of added fats and oils, sugars, seafood, and dairy products, and modest intake of meats, eggs, mixed grains, and breads.

Diet PB2 (“Plant-based Diet 2”) was characterized by high intake of fruits, vegetables, plant proteins, and cooked grains and low intake of animal proteins (especially red and cured meats), added fats, sweetened beverages, sweet bakery products, other desserts, eggs, and breads. There was also a reduction of other beverages in favor of water. There was otherwise an average intake of seafood and dairy products.

M Chaparro et al. Inflamm Bowel Dis 2022; 28: 1725-1736. Open Access! Long-Term Real-World Effectiveness and Safety of Ustekinumab in Crohn’s Disease Patients: The SUSTAIN Study In this retrospective study, 97% of the 463 patients had received prior biological therapy.

  • At week 16, 56% had remission, 70% had response
  • 26.1% required dose escalation or intensification
  • After a median follow-up of 15 months, 356 (77%) patients continued treatment.
  • Previous intestinal surgery and concomitant steroid treatment were associated with higher risk of ustekinumab discontinuation.
  • Neither concomitant immunosuppressants nor the number of previous biologics were associated with ustekinumab discontinuation risk

J Panes et al. Inflamm Bowel Dis 2022; 28: 1737-1745. Open Access! INSPECT: A Retrospective Study to Evaluate Long-term Effectiveness and Safety of Darvadstrocel in Patients With Perianal Fistulizing Crohn’s Disease Treated in the ADMIRE-CD Trial

Background: The current chart review study evaluated the longer-term effectiveness and safety of darvadstrocel (expanded allogeneic adipose-derived mesenchymal stem cells).; n=43 treated patient and n=46 controls.

Key findings:

  • At 52, 104, and 156 weeks posttreatment, clinical remission was observed in 29 (67.4%) of 43, 23 (53.5%) of 43, and 23 (53.5%) of 43 darvadstrocel-treated patients, compared with 24 (52.2%) of 46, 20 (43.5%) of 46, and 21 (45.7%) of 46 control subjects, respectively.

Fewer Malpractice Cases Per National Practioner Data Bank

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DM Studdert, MA Hall. NEJM 2022; 387: 1533-1537. Medical Malpractice Law — Doctrine and Dynamic

This article reviews the topic of malpractice and the hurdles for plaintiffs to establish liability. Some of the interesting points:

  • “Patients lose about 80% of medical malpractice trials.3 However, fewer than 1 in 20 claims end in courtroom verdicts; about one third are settled out of court with a payment to the patient, and the remainder are dropped or dismissed.3“
  • “NPDB data reveal a remarkable phenomenon: the number of paid claims against physicians has decreased by 75% in the past 20 years.” The potential reasons include tort reform, greater openness about medical errors may have reduced patients’ inclination to sue, better medical care (no evidence of this), and incomplete NPDB data. With regard to incomplete data, this can occur with “corporate shielding” in which institutions assume liability and payment responsibility in claims against physicians, thus averting reporting requirements).

In the graph, “payments have been adjusted to 2021 dollars using the consumer price index for all urban consumers (https://data.bls.gov/PDQWeb/cu. opens in new tab).”

Related blog post: “Physician-Patient Relationship is Not Necessary to Sue Docs for Malpractice”

Mailing Letters to People and Risk of Colorectal Cancer

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A widely covered news story in October 2022 was the disappointing results/modest benefits of a colonoscopy screening study. This study actually supports the use of colonoscopy to reduce colorectal cancer deaths but shows that typical screening programs may not work well if patients don’t show up for the test.

M Bretthauer et al. NEJM 2022; 387: 1547-1556. Effect of Colonoscopy Screening on Risks of Colorectal Cancer and Related Death

Methods: This was “a pragmatic, randomized trial involving presumptively healthy men and women 55 to 64 years of age drawn from population registries in Poland, Norway, Sweden, and the Netherlands between 2009 and 2014. The participants were randomly assigned in a 1:2 ratio either to receive an invitation to undergo a single screening colonoscopy (the invited group) or to receive no invitation or screening (the usual-care group).”

There were 84,585 participants in Poland, Norway, and Sweden — 28,220 in the invited group,

Key findings:

  • Only 11,843 (42.0%) in the invited group underwent colonoscopy screening
  • During a median follow-up of 10 years, 259 cases of colorectal cancer were diagnosed in the invited group as compared with 622 cases in the usual-care group
  • The risk of colorectal cancer at 10 years was 0.98% in the invited group and 1.20% in the usual-care group, a risk reduction of 18%
  • The risk of death from colorectal cancer was 0.28% in the invited group and 0.31% in the usual-care group (risk ratio, 0.90; 95% CI, 0.64 to 1.16)
  • The risk of death from any cause was 11.03% in the invited group and 11.04% in the usual-care group

If all invited participants had received a colonoscopy, the authors estimate the risk of colorectal cancer would have decreased from 1.22% to 0.84% and the risk of colorectal cancer death would have been reduced from 0.3% to 0.15% (a 50% drop).

My take: Colonoscopy as a screening tool only works if it is performed. Given the low response rate for screening, other tools like an annual fecal immunochemical test (FIT) need to be considered as alternatives.

Related blog posts:

MMP-7 Helps Sort Out Biliary Atresia from Parenteral Nutrition-Associated Liver Disease

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PS Salvi et al. J Pediatrics 2022; 249: 97-100. Open access! Comparing Serum Matrix Metalloproteinase-7 in Parenteral Nutrition-Associated Liver Disease and Biliary Atresia

In this single-center retrospective study with 19 patients, MMP-7 and GGT values were compared in children who were diagnosed with Parenteral Nutrition-Associated Liver Disease (PNALD, n=15) and Biliary atresia (n=4). Key findings:

  • Median MMP-7 values for PNALD patients 37.8 ng/mL was much lower than MMP-7 values for biliary atresia 112.3 ng/mL.
  • GGT values were not statistically significantly different 116 for PNALD vs 248 for biliary atresia
  • In this cohort, a MMP-7 threshold of 52.8 ng/mL had a sensitivity of 100% and specificity of 93.5% for biliary atresia.

My take: MMP-7 values reduce diagnostic uncertainty between PNALD and biliary atresia. However, there are infrequent cases of biliary atresia with lower values of MMP-7.

Related blog posts:

Two Sisters Pierre-August’s Renoir

Docosahexaenoic Acid (DHA) for Preterm Infants and Intelligence

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JF Gould et al. NEJM 2022; 387: 1579-1588. Neonatal Docosahexaenoic Acid in Preterm Infants and Intelligence at 5 Years

Background: “Because its accretion into the brain is greatest during the final trimester of pregnancy, infants born before 29 weeks’ gestation do not receive the normal supply of DHA.”

In this randomized placebo-controlled study of infants born prior to 29 weeks gestation, DHA supplementation 60 mg/kg/day was given to the study group and cognitive outcomes were measured at 5 yrs. 480 (73%) had an full-scale intelligence quotient (FSIQ) score available — 241 in the DHA group and 239 in the control group.

Key findings:  FSIQ scores were 95.4±17.3 in the DHA group and 91.9±19.1 in the control group. Adverse events were similar in the two groups.

Short take video: DHA in Premature Infants

Related blog posts:

CMV Colitis Rarely Identified

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Q Buck et al. JPGN 2022; 75: 462-465. Routine Histology-Based Diagnosis of CMV Colitis Was Rare in Pediatric Patients

Key findings from this retrospective review (2011-2019):

  • Of 1801 cases of histologic colitis, 11 patients had CMV found by histology (mean age 15.4, 72.7% female), with an incidence of 0.6%
  • Nine out of these 11 (81.8%) patients were immunocompromised and 4 (36.4%) had inflammatory bowel disease (IBD) as an underlying diagnosis of whom 2 had new-onset ulcerative colitis
  • 5 of 6 post-transplant patients with CMV colitis had preexisting CMV viremia
  • An independent analysis of 54 consecutive IBD-associated colectomy cases at TCH showed no histologic evidence of CMV

The study finding that half of the cases of CMV in the IBD population were identified prior to treatment indicates that the underlying IBD may be a more important susceptibility factor than the immunosuppressive medications.

My take: This study indicates that CMV colitis remains important in the post-transplant population but is rarely consequential in the pediatric IBD population.

Related blog posts:

Little O’Malley Peak Trail, near Anchorage AK.
Denali is visible in background, even though it is ~180 miles away.

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