Reappraisal of the Risk of Autoimmune Disease with Celiac, Plus One

Posted on August 10, 2016 by gutsandgrowth

Using a matched cohort design with 1215 cases of celiac disease and 6075 controls, C Canova and colleagues (J Pediatric 2016; 174: 146-52) provide data from 1989-2011 regarding the development of hypothyroidism and diabetes. This retrospective, longitudinal, population-based Italian study relied on data from the integrated National Health Service.

Key findings:

Over this >20 year period, the risk of developing hypothyroidism was HR 4.64 and the risk of developing type 1 diabetes mellitus was HR 2.50 (not statistically significant)
The risk of hypothyroidism was more prevalent in males with HR 20.00.

The authors note: “The most plausible mechanism explaining the association between CD and T1DM/ATD [autoimmune thyroid disease] is a shared genetic background.”

Also noted: NASPGHAN Clinical Report on the Diagnosis and Treatment of Gluten-related Disorders. ID Hill et al. JPGN 2016; 63L 156-63. Recommended monitoring for celiac disease, from Table 5:

At diagnosis: CD serology, CBC, Iron profile, HFP, Thyroid tests (TSH, free T4), Calcium, Vit D.
At 3-6 mo after diagnosis: CD serology (TTG IgA or DGP-IgG)
Annually: CD serology, CBC, Thyroid tests (TSH, free T4), Vit D.

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Congaree National Park (SC) and the “knees” of the Bald Cypress trees

Why Asthma Study is Important: Hygiene Theory

Posted on August 9, 2016 by gutsandgrowth

In my view, one of the most important pediatric studies this year was just published (reference below). For a long time, it has been recognized that growing up on farms can reduce the likelihood of developing conditions like asthma, as well as inflammatory bowel disease (Related post: NYT: Educate Your Immune System | gutsandgrowth). This study: Innate Immunity and Asthma Risk in Amish and Hutterite Farm Children provides an in depth assessment of 60 children and helps uncover the reason for these epidemiologic results.

Here’s the quick 2 minute summary: Innate Immunity and Asthma Risk in Amish and Hutterite Farm Children

Fecal Calprotectin Monitoring Helpful at Identifying Relapse in IBD

Posted on August 8, 2016 by gutsandgrowth

Thanks to Ben Gold for this reference: Y. Zhulina et al. Aliment Pharm Ther 2016; 44: 495-504.

Methods:

Patients aged 18 years or older, with a known diagnosis of IBD in clinical remission, were prospectively studied. Patients provided faecal samples every third month and were prospectively followed until the ﬁrst clinical relapse or the end of the 2-year follow-up period.
Relapse was deﬁned as increasing symptoms necessitating intensiﬁed medical therapy or surgery.

Key finding:

Among 104 patients, Crohn’s disease (n = 49) and ulcerative colitis (n = 55), 37 had a relapse. A doubling of faecal calprotectin level between two consecutively collected samples was associated with a 101% increased risk of relapse (HR: 2.01; 95% CI: 1.53–2.65; P < 0.001).

My take: Another study showing that stool calprotectin is quite useful. How long will it be until I will not need to write letters to insurance companies to get this test covered?

Also noted in the same issue:
“The safety of autologous and metabolically fit bone marrow mesenchymal stromal cells in medically refractory Crohn’s disease – a phase 1 trial with three doses” (pages 471–481) T. Dhere, I. Copland, M. Garcia, K. Y. Chiang, R. Chinnadurai, M. Prasad, J. Galipeau and S. Kugathasan. Aliment Pharm Ther 2016; 44: 471-81. This study examined the use of mesenchymal stromal cells in 12 patients.

In conclusion, a single infusion of fresh autologous bone marrow-derived mesenchymal stromal cells propagated ex vivo using a non xenogeneic human platelet lysate growth supplement at doses ranging 2–10 million cell/kg BW was well tolerated in patients with medically refractory moderate to severe Crohn’s disease in this preliminary study. Our data neither addressed long-term safety nor sustained efficacy. However, this study informs that a future phase 2 study

A previous study of mesenchymal stromal cells was briefly discussed in a previous blog: Sanjay Gupta is Wrong…about Stem Cell Therapy

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Is Obamacare Causing Skyrocketing Premiums?

Posted on August 7, 2016 by gutsandgrowth

Not yet according to a recent commentary: BD Sommers. NEJM 2016; 375: 201-3. The graph below provides some perspective. In addition, the author cautions those who have voiced early alarm bells regarding upcoming rates. He notes the same alarms have been raised in the previous 2 years. Though, he notes, “there are reasons to suspect that marketplace premium growth for 2017 will exceed this year’s levels. Two of the law’s provisions designed to reduce financial risk to insurers in the new markets expire after 2016 — the risk corridor and reinsurance provisions…the country’s continued emergence from the aftermath of the Great Recession may well spur increasing rates of health care inflation for the general population, as well as for the ACA exchanges”

“Premium growth — even when it does reach into the double-digit range that sparks such substantial media attention — is a policy challenge to be examined and addressed and is also part of the general historical pattern that precedes the ACA.” Those who argue “the law as a whole should be scrapped ignore the devastating effect that repeal would have on the estimated 20 million Americans who have thus far gained insurance under the law.”

My take (from commentary): “Regardless of what ends up happening this year, it seems likely that next spring will bring renewed claims that the sky is falling — when experience should make clear that it isn’t.”

Image from CGH: Duodenal Diverticulum

Posted on August 6, 2016 by gutsandgrowth

Clin Gastroenterol Hepatol 2016; 14: e93

DOI: http://dx.doi.org/10.1016/j.cgh.2015.12.035

Intraluminal duodenal diverticulum is a rare duodenal congenital abnormality caused by an anomalous process of recanalization of the primitive foregut. It has a characteristic radiographic appearance on contrast studies, resembling a “windsock web” or “thumb of a glove”

An upper gastrointestinal (GI) endoscopy was then performed that revealed a 3-cm pedunculated mass in the second part of the duodenum that was biopsied (Figure A), and the patient was referred for an endoscopic ultrasound. A repeat endoscopy before the endoscopic ultrasound revealed a large intraluminal diverticulum that had the appearance of a mass when inverted. Subsequently (Figure B), an upper GI series was performed that showed a large elongated tubular diverticulum arising from the second portion of the duodenum, 2.5 × 12 cm in size, with rapid filling and peristalsis with oral contrast, which extended to the left aspect of the spine when maximally distended

Bedtime in Preschool-Aged Children and Risk for Adolescent Obesity

Posted on August 5, 2016 by gutsandgrowth

An upcoming article (Journal of Pediatrics, (DOI: http://dx.doi.org/10.1016/j.jpeds.2016.06.005)shows an association between bedtime and the development of obesity:

Full-text link: Bedtime in Preschool-Aged Children and Risk for Adolescent Obesity

Abstract:

Objective

To determine whether preschool-aged children with earlier bedtimes have a lower risk for adolescent obesity and whether this risk reduction is modified by maternal sensitivity.

Study design

Data from 977 of 1364 participants in the Study of Early Child Care and Youth Development were analyzed. Healthy singleton-births at 10 US sites in 1991 were eligible for enrollment. In 1995-1996, mothers reported their preschool-aged (mean = 4.7 years) child’s typical weekday bedtime, and mother-child interaction was observed to assess maternal sensitivity. At a mean age of 15 years, height and weight were measured and adolescent obesity defined as a sex-specific body-mass-index-for-age ≥95th percentile of the US reference.

Results

One-quarter of preschool-aged children had early bedtimes (8:00 p.m. or earlier), one-half had bedtimes after 8:00 p.m. but by 9:00 p.m., and one-quarter had late bedtimes (after 9:00 p.m.). Children’s bedtimes were similar regardless of maternal sensitivity (P = .2). The prevalence of adolescent obesity was 10%, 16%, and 23%, respectively, across early to late bedtime groups. The multivariable-adjusted relative risk (95% CI) for adolescent obesity was 0.48 (0.29, 0.82) for preschoolers with early bedtimes compared with preschoolers with late bedtimes. This risk was not modified by maternal sensitivity (P = .99).

Conclusions

Preschool-aged children with early weekday bedtimes were one-half as likely as children with late bedtimes to be obese as adolescents. Bedtimes are a modifiable routine that may help to prevent obesity.

My take: Another potential reason to heed Samuel Jackson’s advice: Go the F- to Sleep (early)

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Vickery Creek

How often are acid blockers used in neonates?

Posted on August 4, 2016 by gutsandgrowth

A recent study (JL Slaughter et al. J Pediatric 2016l 174: 63-70) shows a high rate of acid blockers in neonatal intensive care units. This study retrospectively analyzed the Pediatric Health Information System database (PHIS) from 2006-2013.

Of 122,0002 infants: 23.8% received either a histamine-2-receptor antagonist (H2RA) or proton pump inhibitor (PPI).
19.0% had received an H2RA
10.5% had received a PPI

My take (borrowed from authors): “despite limited evidence and increasing safety concerns, H2RAs/PPIs are frequently prescribed to extremely preterm neonates…Our findings support the need for innovative studies.” Wouldn’t it be nice if there was proof of efficacy in this population?

Vickery Creek, Roswell

Preventing Neonatal Hepatitis B Transmission with Tenofovir

Posted on August 3, 2016 by gutsandgrowth

A recent study (CQ Pan et al. NEJM 2016; 374: 2324-34) showed that tenofovir administered to mothers starting at 30-32 weeks of gestation lowered the rate of perinatal hepatitis B virus (HBV) acquisition.This was a multi center, open-label, randomized parallel-group design trial. The maternal tenofovir dose was 300 mg.

Key points:

200 mothers with HBeAg and HBV DNA >200,000 IU/mL in this study
68% achieved an HBV DNA level <200,000 IU/mL (compared with 2% of controls). Above this threshold has been shown to be associated with increased HBV transmission.
5 of 97 (5%) in the treatment group acquired HBV compared to 18 of 100 in the control group. However, in the per-protocol analysis which excluded infants born to women who withdrew consent, were lost to follow-up, or discontinued therapy there were 0 cases of transmission (0 of 88).
There were no specific safety signals identified in this study. In the discussion, the authors note that the Antiretroviral Pregnancy Registry which includes data from 4013 women who received tenofovir, the rate of birth defects with TDF was 2.4% compared to the general population rate of 2.7%.

My take: This study provides more evidence that antivirals can prevent perinatal HBV infection.

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Intellectual Disability in Pediatric Liver Transplantation

Posted on August 2, 2016 by gutsandgrowth

A recent study (A Wightman et al. JPGN 2016; 62: 808-12) describes the prevalence of intellectual disability in a retrospective cohort from 2008-2013. The importance and the discomfort of the topic is referenced in the introduction:

“A 2005 survey of pediatric liver transplant programs (n=12) found that 33% of centers reported that cognitive disability was “always or usually” considered in their decision. No pediatric centers, however, considered mild or moderate cognitive disability alone (IQ 35-70) to be a relative or absolute contraindication to transplantation.”
The 2005 AASLD guideline states that “children with mental retardation pose significant logistical and ethical challenges” but does not comment on whether this is a contraindication.

This retrospective study of children who underwent an isolated liver transplant from 2008-2013 (n=254).

Key findings:

15% of all first pediatric liver transplantation recipients have intellectual disability
Graft function and patient survival were similar among those with and without intellectual disabilities. Metabolic disease, as the indication for liver transplantation, was the etiology more commonly among children with intellectual disability.

This study had numerous limitations. Due to these limitations (eg. selection bias, lack of a standardized mechanism of measuring intellectual disability), it is likely that intellectual disability occurs more commonly than in 15% of pediatric liver transplant recipients. In fact, a previous study showed 42% of recipients required special education and 29% had IQ <85 (Cognitive Outcomes after Liver Transplantation | gutsandgrowth).

Related neurocognitive recommendations from the 2014 AASLD Pediatric Liver Transplantation Guidelines:

28. “Neurocognitive testing should be performed in children awaiting LT to identify areas warranting early intervention to minimize later cognitive diffi- culties (2-B).”
75, 76, and 92. LT is contraindicated with Alper’s disease, multiorgan mitochondrial disease, and Niemann-Pick type C.
In nearly 40 pages of recommendations, this guideline offers very little guidance on this topic.

AASLD 2014 Pediatric Transplantation Guidelines

“Explain It To Me Like I’m a Six Year Old”

Posted on August 1, 2016 by gutsandgrowth

Sometimes when I read an article, I wish it was presented in a much simpler manner. In the movie “Philadelphia,” the lawyer played by Denzel Washington tells his clients to “explain it to me like I’m a six-year-old.”

A recent clinical report (MI Ardura et al. JPGN 2016; 63: 130-55) probably would have benefitted from this idea to some degree. This report examines infectious disease issues with regard to patients receiving tumor necrosis factor-α (TNFα) inhibitors. All in all, it is very thorough and reviews more than 20 infectious agents (bacteria, fungi, mycobacteria, and viral agents).

Table 2 is most helpful. In this table, the authors recommend that before starting TNF inhibitors:

Risk factor screening for Brucella (eg exposure to animals, unpasteurized dairy products), Bartonella (eg exposure to kitten), Listeria (eg dietary history), Salmonella (eg exposure to reptiles), Aspergillus (eg exposure to construction), coccidioidomycosis (exposure to endemic area), Histoplasma (long list of exposures listed in Table 3 includes barns, caves, chicken coops, old buildings), and Hepatitis C virus
Direct testing is recommended for Mycobacterium tuberculosis, Hepatitis B virus, HIV (≥ 13 yrs if in hospital or ≥15 years), and Varicella zoster virus

Table 4 lists recommended vaccines. For live virus vaccines, the authors recommend to avoid unless they can be administered at least 4 weeks prior to immunosuppressive therapy.

Other useful information:

“Granulomatous infections caused by bacteria, mycobacteria, and fungi are the most frequently described infections in patients receiving anti-TNFα therapies.”
Infection rates of 239/100,000 reported with infliximab between 1998-2002.
More than 70% of these infections occurred within 3 to 6 months of starting infliximab therapy, “suggesting the possibility of reactivation of latent infection.”
M tuberculosis was most common (54/100,000)
“In general, anti-TNFα therapy should be discontinued during any severe infection.”

My take: This report offers a lot of information. Its impact on daily practice would be much greater if the authors created a simple one-sheet screening questionnaire form with recommended bloodwork and vaccines.

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Shem Creek Pelican Art