Mortality Risk from Childhood Inflammatory Bowel Disease

A recent study (O Olen et al. Gastroenterol 2019; 156: 614-22) was summarized quite succinctly by NEJM journal watch:

Using the Swedish National Patient Registry data, investigators identified 9442 incident cases of IBD diagnosed in patients under age 18 years from 1964 through 2014. Based on 139,000 person-years of follow-up, results were as follows:

  • There were 259 deaths among people with IBD (133 were from cancer and 54 from digestive disease).
  • The all-cause mortality rate in these patients was 2.1/1000 person-years, compared with 0.7 in matched reference individuals from the general population.
  • The average age at death was 61.7 compared with 63.9 years in the reference group.
  • The hazard ratio for death was 3.2 and was higher in those with ulcerative colitis (HR, 4.0), especially if they had concomitant primary sclerosing cholangitis (HR, 12.2), a first-degree relative with ulcerative colitis (HR, 8.3), or a history of surgery (HR, 4.6).
  • Mortality risks were similar when limited to the period after the introduction of biologics (2002–2014).

My take: This study found that having IBD diagnosed in childhood increased the risk of mortality (~1 extra death for every 700 patients followed for 1 year) especially in patients with concomitant PSC and in patients with severe ulcerative colitis.  The study did not see an effect of the newest therapies but was underpowered to directly assess this effect.

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Chattahoochee River, near Azalea Drive

 

Interleukin 6 and Liver Disease Mortality

Briefly noted: J Remmler et al. Clin Gastroenterol Hepatol 2018; 16: 730-7.  This retrospective study with 474 patients showed that blood levels of interleukin 6 were associated with mortality.  In this cohort, those with levels in the lowest quartile (< 5.3 pg/mL) had zero fatalities within 1 year.  In those with the highest quartile (37 pg/mL or more), had a 67.7% mortality rate within 1 year.  The associated editorial (pg 630-32) notes that IL6 functions include liver regeneration, infection defense, and metabolic homeostasis.  “IL6 is synthesized during inflammatory conditions…persistent activation of the IL6 pathway may have detrimental effects in the livers and in other tissues.”

Pine Mountain Trail

Opiates, Inflammatory Bowel Disease and Mortality

A recent retrospective study (NE Burr et al. Clin Gastroenterol Hepatol 2018; 16: 534-41) with 3517 patient’s with Crohn’s disease (CD) and 5349 with ulcerative colitis (UC) examined the frequency of opioid prescriptions and the relationship to fatal outcomes.

Key findings:

  • Compared to 1990-93, the period of 2010-13 saw a sharp rise in the use of opiods in England: 10% compared to 30%.
  • Prescription of strong opioids (>3 prescriptions per calendar year) was associated with premature mortality: Hazard ratio 2.18 for CD and 3.3 for UC.

This study is in agreement with other data showing increasing use of opiate prescriptions worldwide for chronic noncancer pain (although there has been a drop in the past year).  As with other studies of patients with inflammatory bowel disease, this study shows an association between opioid use and mortality.

My take: Needing an opioid may be a marker for more severe disease. Whether the opioid use directly contributes to mortality remains unclear.

 

What’s Happening on the Edge of Viability

A study (N Younge et al. NEJM 2017; 376: 617-28) provides some data on the slowly changing survival and neurodevelopmental outcomes among periviable infants (22-24 weeks gestation).

From epoch 1 (2000-2003), to epoch 3 (2008-2011), there has been some improvements. Overall survival increased from 30% to 36% and the percentage without neurodevelopmental impairment increased from 16% to 20%.

Mortality and Neurodevelopmental Outcomes at ~18 months of age (combined data and 11 centers)

Mortality and Neurodevelopmental Outcomes at ~18 months of age (combined data and 11 centers)

The insightful commentary (pgs 694-6) notes that there has not been improvement in survival in infants born at 22 weeks.  Furthermore, in reviewing multiple studies on outcomes, neurodevelopmental impairment was >94% in patients born at 22 weeks and between 80-90% for infants born at 23 weeks.  At 24 weeks, neurodevelopmental impairment was present between 51-72%

screenshot-137

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The Dark Cloud Inside the Silver Lining -What’s Really Going on with Hepatitis C Infection

Despite the flood of articles touting the success and costs of the new hepatitis C virus (HCV) treatments, direct-acting antivirals (DAA), currently hepatitis C remains more dangerous than HIV and it is likely to continue to exert a huge mortality and morbidity for at least three more decades in the United States.

One study and an associated editorial look into this subject further:

  • J Chhatwal et al. Hepatitis C Disease Burden in the United States in the Era of Oral Direct-Acting Antivirals.  Hepatology 2016; 64: 1442-1450.
  • JM Pawlotsky. The End of the Hepatitis C Burden: Really?

In the study, the authors used a validated HCV burden simulation model (HEP-SIM) and noted the following:

“Even in the oral DAA era, 320,000 patients will die, 157,000 will develop hepatocellular carcinoma, and 203,000 will develop decompensated cirrhosis in the next 35 years.”

Part of the problems will be a large number of individuals who remain unaware of their diagnosis (560,000 by year 2020) but other barriers include medication costs.

From the editorial -some pushback on the cost-savings argument:

  • “Although current drug regimens were reported to be cost-effective, nothing justifies the current prices, except financial considerations on the drug makers’ side. On the one hand, one could consider that the money saved on liver disease-related expenses is not truly saved. Being cured from HCV and not dying from its complications will not prevent the same individual from dying from another cause at a very high cost.”

My take: To bend the HCV curve faster, there will need to be increased HCV screening, increased treatment capacity, and reasonable costs.

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Acadia Natl Park

Acadia Natl Park

Zip Code vs. Genetic Code

Several posts have highlighted the importance of poverty contributing to high mortality, including the following:

The following infographic shows again how your zip code is likely more important than your genetic code.

Lower Teen Birthrate

Lower Teen Birthrate