Reason for Optimism

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While yesterday’s post (No exaggeration: too many children are dying in U.S.) highlighted the numerous unnecessary childhood deaths in this country and previous posts have discussed the drop in life expectancy in this country, there are still reasons for optimism.

It has been said that newspapers/news programs never report on the thousands of airplanes that don’t crash everyday.  Similarly, it is easy to think that with so many challenges that we face everyday that the world is falling apart.  A recent NY Times commentary by Nicholas Kristof points out that 2018 was in fact the best year ever.

Why 2018 Was the Best Year in Human History!

An excerpt:

[In 2018] Each day on average, about another 295,000 people around the world gained access to electricity for the first time, according to Max Roser of Oxford University and his Our World in Data website. Every day, another 305,000 were able to access clean drinking water for the first time. And each day an additional 620,000 people were able to get online for the first time.

Never before has such a large portion of humanity been literate, enjoyed a middle-class cushion, lived such long lives, had access to family planning or been confident that their children would survive…

Child deaths are becoming far less common. Only about 4 percent of children worldwide now die by the age of 5. That’s still horrifying, but it’s down from 19 percent in 1960 and 7 percent in 2003…

Until about the 1950s, a majority of humans had always lived in “extreme poverty,” defined as less than about $2 a person per day. When I was a university student in the early 1980s, 44 percent of the world’s population lived in extreme poverty. Now, fewer than 10 percent of the world’s population lives in extreme poverty, as adjusted for inflation.

My take: This commentary points out that worldwide people are living longer and living better.

From Golden Gulch Trail, Death Valley

No Exaggeration: Too Many Children Are Dying in the U.S.

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A recent report (RM Cunningham et al. NEJM 2018; 379: 2468-75; editorial 2466-7) highlights the poor outcomes for children in the U.S. based mainly on the CDC WONDER (Wide-ranging Online Data for Epidemiologic Research) database.

Key findings:

  • “The sad fact is that a child or adolescent in the United States is 57% more likely to die by the age of 19 years than those in other wealthy nations.”
  • Motor vehicle accidents (MVA) are the number one cause of deaths in children/adolescents, accounting for 20% of such deaths.  The U.S. rate of death from MVAs is “triple that in other developed countries.”  Overall, MVA deaths had dropped in half from 1999-2013 but have increased in last few years; this increase is thought to be related to distracted driving/walking due to cellphones.
  • Firearm-related deaths accounted for 15% of deaths in children/adolescents in U.S.  In U.S., children/adolescents are “36 times as likely to be killed by gunshots.”  Unlike adults in U.S., the majority of these gunshots are homicides (59%) rather than suicides (35%); unintentional firearm deaths accounted for 4% (2% undetermined firearm-related death).  Among U.S. adults, 62% of deaths from firearms were from suicide.
  • Malignant neoplasms were the third leading mortality cause in children/adolescents, 9%. This rate is similar to other countries.

The figures in the study are very helpful:

  • Figure 2: Deaths from MVAs for the U.S. pediatric population are more similar to low-to-middle income countries (Figure 2A) whereas firearm-related deaths are much greater than all of the countries shown in Figure 2B (including Sweden, England, Hungary, Australia, Austria, Thailand, Tajikistan, Romania, Mongolia).
  • Figure 3. Deaths in U.S. rural areas are roughly double from MVAs than from the average of urban/suburban areas.  Deaths from firearms are similar in all three areas.  There are several factors which could explain the high rate of fatal MVAs in rural areas: longer time to get medical attention, faster speeds in less populous areas, less seat belts, lower enforcement of traffic laws, and impaired driving.

My take: The increased risk of death from MVAs and firearms identified in this study should not be considered “accidents” but failures.  Is it too much to expect that a child born in the U.S. could have the same chance to reach adulthood as a child in Canada or a child in Europe?

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Vonoprazan versus Lansoprazole for Initial Heartburn Relief

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A recent study (T Oshima et al. Aliment Pharmacol Ther 2019; 49: 140-6) showed that a new potassium-competitive acid blocker (P-CAB) can more rapidly improve symptoms than lansoprazole. Thanks to Ben Gold for this reference.

This small study with 32 adult patients with endoscopically-confirmed erosive esophagitis with frequent heartburn were randomized in a double-blind study and received either lansoprazole 30 mg or vonoprazan 20 mg before breakfast.  The authors note that with PPIs, there is a slow onset of action, such that ‘half of all patients remain symptomatic even after 3 days of treatment.” In contrast, vonoprazan can increase intragastric pH to almost 7 within 4 hours.

Key finding:

  • Heartburn relief occurred quicker with vonoprazan.  Complete relief was noted in 31.3% at day 1 compared with only 12.5% in the lansoprazole group.

My take: Vonoprazan is currently approved in Japan.

Related article: Update on the Use of Vonoprazan DY Graham, MP Dore; Gastroenterol 2018; Volume 154, Issue 3, Pages 462–466

Mesquite Flat Sand Dunes, Death Valley

Vedolizumab Drug Levels –Are They Needed?

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A recent retrospective study (E Dreesen et al Clin Gastroenterol Hepatol 2018; 16: 1937-46) with 179 consecutive patients (66 with ulcerative colitis, and 113 with Crohn’s disease) found that vedolizumab (VDZ) trough concentrations were correlated with response.

Key findings:

  • VDZ trough >30 mcg/mL at week 2, >24 mcg/mL at week 6, and >14 mcg/mL during maintenance were associated with effectiveness endpoints including endoscopic healing, physician global assessment and biochemical response (based on CRP).
  • Median VDZ trough levels during induction were 27.7 mcg/mL at week 2, 27.4 mcg/mL at week 6. With standard dosing, the maintenance VDZ trough was 13.5 mcg/mL at week 14
  • Higher BMI and more severe disease, based on CRP, albumin, and/or hemoglobin, were associated with lower VDZ trough levels and lower probability of mucosal healing (P<.05).

Interestingly, in the discussion the authors note that VDZ troughs above  3 mcg/mL completely saturate α4β7 intergrin.  This physiologic phenomenon is hard to reconcile with data showing better response with higher VDZ levels.  The authors note that “at present, there are not enough data in our study to support the role for TDM to guide clinical decision-making on dose escalation for vedolizumab.”

My take: This study implies that VDZ levels may help predict response but are not necessarily helpful in determining whether dose escalation is warranted.

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Riverwalk, Chattanooga

Blood Test is Better Than a Liver Biopsy for Biliary Atresia

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A recent study (L Yang et al. Hepatology 2018; 68: 2069-72) confirms the utility of Serum Matrix Metalloproteinase-7 (MMP-7) as a biomarker for biliary atresia (BA). The authors studied MMP-7 among healthy controls (n=72 with 54 <6 months) and among 135 with cholestasis (75 with BA, 60 with non-BA).  BA samples were taken at a median age of 54 days.

Key findings:

  • Median concentration for MMP-7 was 2.86 ng/mL in healthy controls, 11.47 ng/mL for non-BA cholestasis, and 121.1 ng/mL for BA.
  • Using a cutoff value of 52.85 ng/mL, the diagnostic sensitivity and specificity were 98.67% and 95.0% respectively.
  • The AUC for MMP-7 in BA was 0.99 compared for AUC for GGT of 0.72.  The sensitivity and specificity for GGT was much lower at 64% and 72% respectively with a cutoff of 314 U/L.
  • The predictive value for MMP-7 was particularly impressive, 74 of 75 BA  subjects were correctly identified as having BA.  Only 3 non-BA patients were incorrectly assigned a BA diagnosis based on MMP-7 values.
  • The authors noted that MMP-7 testing indicates that there are no substantial changes in its values for normal subjects extending to 54 years of age.
  • One limitation the authors note is the relatively small number of patients with non-BA syndromatic intrahepatic cholestasis which made up less than 30% of their non-BA cohort.  Thus, more testing in specific populations is needed.

My take: The diagnostic performance of MMP-7** appears to be superior to that of a liver biopsy (though this was not directly compared in this study) in predicting BA and could obviate the need for most liver biopsies in infants with cholestasis.  Those with high MMP-7 values would proceed directly to intraoperative cholangiogram with possible hepatoportojejunostomy. Those with non-BA MMP-7 values and persistent cholestasis could undergo additional investigation with genetic panels and/or other metabolic/infectious testing.

**This assay is likely to be commercially-available in the coming weeks according to a colleague at Cincnnati Children’s Hospital.  The expectation is an approximagely 2-day turnaround.

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Moon over Zabriskie Point, Death Valley before Sunrise

Resolution: Eradication of Hepatitis C

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Eradication of hepatitis C virus (HCV) is going to be difficult despite the huge improvements in treatment.  One obstacle that has been highlighted previously has been the increase in HCV transmission associated with the opioid epidemic.  Another basic problem is establishing a ‘cascade of care’ that makes sure that those with HCV receive appropriate treatment and followup.

In a recent study (RL Epstein et al. J Pediatr 2018; 203: 34-40, editoria by KB Schwarz, W Karnsakul 7-8) describe the deficiencies in the followup of women in an obstetric clinic serving women with substance use disorders. The authors reviewed electronic records of 879 women over a 10 year period.  Key findings:

  • 85% of women were screened for HCV.  Of the 68% who were seropositive, only 72% had HCV RNA testing and 71% were viremic.
  • There were 404 infants born to women who were HCVB seropositive.  Only 45% of these infants completed AAP-recommended perinatal HCV screening.

In the commentary, the authors point to the suboptimal rates of followup.  They note that there is a “huge gap between infected women and the linkage of their infected progency to care.” Furthermore, the AASLD has recommended that “all children with HCV infection in age groups for which direct-acting antiviral agents are approved should be treated.”

My take: this study identifies gaps in followup and treatment that need to be addressed systematically if we are to realize the goal of HCV eradication.

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NASPGHAN Toolbox App -Review

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To all my colleagues and to others who follow this blog, I wish you a happy new year.  Thank you to all of you, especially to those who provide feedback to help improve the content and usefulness.

Recently NASPGHAN released an App, titled NASPGHAN Toolbox.  There are some very useful features but also some areas where more work is needed.

Work in progress: Many of the algorithms that are listed are dated and no longer accurate.  To list a few examples:

  • The UC Algorithm suggests holding off on anti-TNF therapy in severe disease for 7-14 days
  • The EoE Algorithm lists only diet treatments and topical steroids and does not list PPIs as a treatment option
  • The GERD guidelines are from 2001 rather than more recent recommendations

Also, this ‘algorithms’ section should probably be renamed into ‘algorithms and tables’ as a large amount of the information is not algorithmic.

What I Like:

  • Scores and Calculators for items like MELD score, PUCAI score, Mayo score
  • Extensive patient education handouts and image atlas -this could facilitate “airdrop”ing or messaging of these items to families.  (To be picky –the normal esophagus image could be better)
  • Formula charts –though the lists for infants and older children could be more comprehensive
  • Bristol charts (especially children version) -listed in algorithm section

My take: This is a very good start and a very helpful toolbox for pediatric gastroenterologists but I would not rely on the algorithms.

 

Late-Night Pages –Are they a Conspiracy?

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A few thoughts while I’m still in a post-call daze:

One of my biggest gripes is that there must be a hidden camera in my bedroom.  Someone must monitor this camera whenever I am on call.  Because everytime, every single time it seems, someone calls me 15-20 minutes after I get in bed.  As soon as I get nice and cozy and start to doze off, it is a guarantee that I will get a page.  In addition, it is usually something that could have been called hours earlier.  Last night, at 11:22 pm, a nurse from the hospital called me to say that a 12 year old girl (who was well-nourished) had not been eating all evening and wanted to know if we should put in an NG tube.

Despite my antipathy for late-night calls, particularly some pointless ones, I try to always project a pleasant demeanor on the phone.  I might grumble after a call but not during.  There have been so many times when I have received timely information from nurses which have made important changes in a patient’s care.

Unwanted phone calls remind me of an anecdote that I heard in fellowship.  My mentor said he had received a pointless call from a family at 4 am about their young son.  So, he decided to set his alarm clock for 4 am the next morning and asked the parents how the son had been doing.  Later that morning, the family called the GI division to report the phone call.  They said, ‘When he called us at 4 am, we realized that he could not sleep because he was so worried about our child.  He is an amazing doctor.’

On another topic, can someone explain to me why it seems that whenever I am retrieving a foreign body that the forceps always line up parallel to the object rather than in the optimal perpendicular?

I sometimes tell colleagues that when I am post-call that I don’t realize how it has affected me.  Sometimes I am ‘punch-drunk’ and think everything is funny.  Sometimes I am irritable –but in my view –always justified.  The next day is sometimes like the difference portrayed in the snickers bar commercial where Betty White is transformed into a young adult.

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