Could Obesity Be Cured/Created at Birth with Manipulation of Microbiome?

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A concise review (NJEM 2014; 371: 2526-28) quickly describes the latest science on microbiota, antibiotics, and obesity chiefly by summarizing the work of Cox LM et al (Cell 2014; 158: 705-21).

Key points:

  • In mice, studies have shown that low-dose penicillin in early life induces marked effects on body composition (eg. excessive weight gain) lasting into adulthood
  • Prenatally administered penicillin to the mother and high-fat diet also induced fat mass of male mice.
  • Gut microbiota transferred from penicillin-moderated flora mice (at 18 weeks) into the cecums of 3-week-old germ-free mice also resulted in excessive fat mass compared to controls who received gut microbiota transfer from control mice (who did not receive penicillin).
  • “These results suggest that immunologic and metabolic changes are not caused by direct effects of antibiotics but rather by derived changes in the gut microbiota.”
  • “It may even be speculated that in families in which obesity is a problem, specific antibiotic treatment at birth could reverse the adverse effect of obesogenic microbiota transferred from mother to infant during delivery.”

Take-home message: Understanding the microbes in our bodies may lead to much more than curing intestinal infections and intestinal maladies.

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Dr. Oz Gives Out Wrong/Baseless Advice More Often Than Right

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Dr. Oz, “America’s doctor,” while wildly popular, continues to receive bad press regarding the accuracy of his advice.  Recent Washington Post link: “Half of Dr. Oz’s Medical Advice is Baseless or Wrong” (Thanks to Eric Benchimol’s twitter feed for this link)

An excerpt:

The British Medical Journal, which on Wednesday published a study analyzing Oz’s claims along with those made on another medical talk show. What they found wasn’t reassuring. The researchers, led by Christina Korownyk of the University of Alberta, charged medical research either didn’t substantiate — or flat out contradicted — more than half of Oz’s recommendations. “Recommendations made on medical talk shows often lack adequate information on specific benefits or the magnitude of the effects of these benefits,” the article said. “… The public should be skeptical about recommendations made on medical talk shows.”

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How Common is Hepatitis E in the U.S.?

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In a recent study (Hepatology 2014; 60: 815-22), data from the National Health and Nutrition Evaluation Survery (NHANES) 1988-94 was compared with the NHANES 2009-2010 with regard to Hepatitis E virus (HEV) epidemiology.  In addition, the most recent surgery coupled with a high performance HEV assay.  A total of 8,814 individuals were included in the analysis.

Key findings:

  • The seroprevalence of HEV was estimated at 6.0% in the U.S. which is only one-third as high as previous estimates.
  • Birth outside the U.S., Hispanic race, and increasing age were all factors associated with increased HEV seroprevalence.  The associations of hispanic origin and birth outside U.S. as risk factors disappear when age is taken into account.

Also noted: Hepatology 2014; 60: 1082-89.  “Liver transplantation in the management of porphyria” –useful review.

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Can the Mediterranean Diet Change Your DNA?

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According to a recent BMJ study, the Mediterranean diet may protect your chromosomes.  From the NY Times link –here’s an excerpt:

They found that the diet is associated with longer telomeres, the protective structures at the end of chromosomes. Shorter telomeres are associated with age-related chronic diseases and reduced life expectancy.

Researchers used data on 4,676 healthy women, part of a larger health study, whose diets were ranked on a scale of one to nine for similarity to the ideal Mediterranean diet. Researchers measured their telomere lengths with blood tests and followed them for more than 20 years with periodic examinations.

The study, published in the journal BMJ, controlled for body mass index, smoking, physical activity, reproductive history and other factors, and found that the higher the score for adherence to the diet, the longer the telomeres. The difference in telomere length for each point on the adherence scale, the researchers estimate, was equivalent to an average 1.5 years of life.

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Implementing High-Value Care

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A recent commentary (NEJM 2014; 371: 2145-47) describes some early successes and failures with efforts at “getting more performance from performance measurement.”

The authors note that “the current measurement paradigm..does not live up to its potential.”  There have been a proliferation of measurements “without commensurate results.”

Areas of progress:

Reducing hospital readmissions: “national readmission rates, which hovered around 19% between 2007 and 2011, had dropped to approximately 17.5% by 2013…recent research suggests that the measured decrease resulted from actual changes in care and not simply greater use of observation units or emergency department care.”

Rates of early elective deliveries: “the rate of early elective deliveries had stayed fixed for many years, even though there was evidence that the practice led to a greater need for neonatal intensive care, higher risks of maternal and neonatal complications, and health problems later in the children’s lives…the rates of early deliveries fell from 17% in 2010 to 4.6% in 2013 (www.leapfroggroup.org/tooearlydeliveries)”  This change happened due metrics in pay-for-performance or not paying for such deliveries along with educational efforts.

Areas Were Not Helpful (aka The Road Paved with Good Intentions)

“Unfortunately, for every instance in which performance initiatives improved care, there were cases …[that] simply enraged colleagues or inspired expenditures that produced no care improvements.”

Early Antibiotics for Community-Acquired Pneumonia:  Due to data suggesting that antibiotics within 6 hours of presentation positively influenced the outcome of community-acquired pneumonia (i.e. lower in-hospital mortality), this became a Centers for Medicare and Medicaid Services (CMS) metric.  “The measure led to inappropriate antibiotic use in patients without community-acquired pneumonia, had adverse consequences such as Clostridium difficile colitis, and did not reduce mortality.”

Bottomline: More work is needed to avoid needless busy work and improve patient outcomes.

As quoted in a previous blog entry:

“Not everything that counts can be counted, and not everything that can be counted counts.” –Albert Einstein

2015 Wish List

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A recent policy article (JAMA Pediatr 2014; 168: 1155-63 –thanks to Ben Gold for this reference) outlines “10 urgent priorities for the health and health care of US children.”  These priorities and some of the action steps are as follows:

  1. Poverty: “16.1 million children (22%) live in poverty. ” Action steps include enacting measures to improve employment in families and extending child tax credits.
  2. Food Insufficiency: “>16 million children live in food-insecure homes.” Actions could include investing rather than cutting children’s nutrition programs.
  3. Lack of health insurance: affects “7 million children (9%)” though two-thirds are eligible for coverage by Medicaid and CHIP. Actions could include fully funding CHOP and Medicaid and abolishing ACA family glitch along with improving outreach to enroll eligible children.
  4. Child abuse/neglect (maltreatment): “In 2011, 681,000 children experienced maltreatment and 1570 died” as a consequence.  Everyday, a child is abused or neglected every 47 seconds.  Action steps included focusing on domestic violence and treatment and funding more screening and preventative treatment research.
  5. Obesity: “32% of children are overweight and 17% are obese.”  Actions could include passing FIT kids Act (HR 2178) and maximizing funding for USDA’s Farmers market promotion program and the Fresh fruit and vegetable program.
  6. Firearms deaths/injuries: 5 children die daily by firearms.  Actions could include better background checks, along with regulations to require safer storage and safety classes.  Other options include higher taxation on weaponry and ammunition to “better represent societal costs.”
  7. Racial disparities: Action steps include monitoring and disclosing disparities and working to ensure all children have a medical home.
  8. Mental Health: up to 20% of children experience a mental health disorder annually.  Actions could include increasing the number of qualified mental-health providers (by enhancing reimbursement).
  9. Immigration: “children living in immigrant families are the fastest growing group of US children.” Action could include obtain health insurance for all children.
  10. Research: Increase funding for children.  Overall NIH pediatric funding is 12% of total budget whereas children represent 24% of US population.

The problems faced by this nation’s children will reverberate for a long time.  For example, with childhood poverty, it is “associated with substantially higher mortality rates in adults, regardless of adult socioeconomic status (i.e., even affluent adults who were poor as children have elevated death rates), and this increased mortality risk extends across 2 generations.”

Bottomline: Children receive a disproportionately low share of federal expenditures and this extends to healthcare.  In addition, federal spending on children in 2014 has decreased by more than $20 billion (14%) since 2010.

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Can an Altered Microbiome Explain Persistent Symptoms in Treated Celiac Disease?

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A recent study (Am J Gastroenterol dii:10.1038/ajg.2014.355) from Helsinki examined 177 patients with celiac disease.  Their goal was to investigate whether altered intestinal microbiota may be associated with persisting gastrointestinal symptoms in celiac patients who had been following a strict gluten-free diet (GFD) for at least 3 years.

After administering a questionnaire (Gastrointestinal Symptom Rating Scale or GSRS) to those with negative celiac antibodies and normal small bowel mucosa (n=164), the researchers identified the 18 subjects with the highest total score (persistent symptom group) and compared them to the 18 subjects with the lowest total score.  Three duodenal biopsies during endoscopy had been frozen and were subsequently analyzed for their microbial DNA.  In each group, one microbial profile was unsuccessful.

Key findings:

  • In the persistent symptom group, there was lower relative abundance of Bacteroidetes (15% vs. 25%, P=0.01), lower Firmicutes (33% vs 46%, P=0.05) and higher relative abundance of Proteobacteria (40% vs 21%, P=0.04).
  • The “microbial richness,” measured as a number of detected genera or operational taxonomic units (OTUs), was reduced in patients with persistent symptoms.  On average, patients with persistent symptoms had 32 genera and 72 OTUs per sample; in contrast, those without symptoms, on average had 37 genera and 106 OTUs.

Some of the strengths of this study include the normal villous architecture for all of the patients; this helps exclude refractory celiac disease as an etiology for the persistent symptoms.  In the discussion, the authors note that the “intestinal microbiota composition in healthy adults is relatively stable and can tolerate normal stress in the intestine caused by, e.g. daily changes in diet.” The speculate that long-term untreated celiac disease “may disrupt a stable intestinal microbiota community that, in some patients, could then reform in a dysbiotic state.”

The limitations of this study include the difficulty of excluding small intestinal bacterial overgrowth which could be related and the difficulty of excluding coexisting irritable bowel syndrome.  Like most studies regarding the micro biome, this study cannot “show causality or distinguish the effects of different bacteria to the persistent symptoms.”

Bottomline: Treated celiac patients with persistent symptoms have a different duodenal microbiome compared to treated celiac patients whose symptoms resolved with a gluten-free diet.

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Moving to MRE

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A recent review (JPGN 2014; 59: 429-39) regarding imaging for inflammatory bowel disease reiterates the accepted view that magnetic resonance enterography (MRE) is typically the most useful imaging test for children with inflammatory bowel disease; in Table 5, MRE is listed for each indication, though CT scan is recommended “if emergent or after hours.”  The review reviews prior pediatric publications, radiation risks (with non-MRE studies), and alternative imaging.  The discussion on costs is minimized, though the authors note that MRE is the most expensive and can be compromised by motion artifact. As a practical matter, I think giving a typical charge (or range) for each of the imaging techniques would be helpful.  Also, another important issue is assuring that radiologists have the technical expertise to obtain quality imaging.

Another study (Clin Gastroenterol Hepatol 2014; 12: 1702-07) retrospectively looked at 1095 emergency room visits by 613 individuals (average age ~40 years) to determine if they could develop a model to limit unnecessary CT scans.  Of the 1095 CT scans, 24.8% were normal; 10.9% had either perforation or non-perianal abscess.  In their discussion, they note that the equation “no scan for ESR (mm/h) + 5*CRP (mg/dL) ≤10” would avoid 18.5% of CT scans.  Implementation of a more complex model could eliminate up to 43% of the CT scans.  The algorithm (Figure 2) suggested by the authors:

  • Assess for obstruction.  If suggestive symptoms, obtain abdominal X-rays.  If concerns for obstruction remain, consider CT scan.
  • If not concerned about obstruction, is there a high likelihood of perforation or abscess? If yes proceed with CT scan.  If not, consider anti-inflammatory therapy if CD symptoms present (without imaging).

Here’s the link to the abstract –supplementary materials can be obtained by those who log in.   http://dx.doi.org/10.1016/j.cgh.2014.02.036

Bottomline: Cross-sectional imaging is particularly helpful at determining whether complications are developing in patients with inflammatory bowel disease.  Increasing use of MRE will reduce radiation risks.

With regard to costs, a recent NPR story discussed “How Much Is That MRI, Really? Massachusetts Shines A Light.” While this story discussed costs related to a Massachusetts law which mandates that insurers reveal the costs of various tests, it did not relate any information regarding quality.  The study implied that an MRI at one institution would be equivalent to an MRI at another.  This is not the case.

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Sorting Out Discrepancies in Hepatitis B Testing

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A recent study (J Pediatrics 2014; 165: 773-8) highlighted the clinical problem of discrepant hepatitis B virus (HBV) testing in pregnant women.

Design: The Centers for Disease Control and Prevention analyzed a nonrandom sample of discordant cases of HBV reported by US Perinatal Hepatitis B Prevention Program.  Discordant cases indicated that there were differences between an initial HBsAg result and a subsequent test.  Among 142 cases, 89 had sufficient information to determine accuracy of the initial test.

Key finding: 14 (15.7%) of these cases were true positives, the remainders were false-positives.

How did authors sort out cases?

Negative testing for “total anti-HBc or no detectable HBV DNA result indicating no HBV infection…A positive total anti-HBc indicates current or past HBV infection, is not elicited by vaccination, and usually persists for life.”

Pointers regarding serology:

  • IgM anti-HBc -acute or recent infection and can persist for more than 6 months.
  • HBV DNA confirms active infection and can detect infection at levels below those of HBsAg assays.  This can occur either due to “occult HBV infection” or due to a mutant HBV strain that results in non-reactive test for HBsAg.
  • There were at least 11 HBsAg assays that have been FDA-approved –most but not all of them will confirm results before reporting.

It is important to sort out patients with discrepant HBV serology.  In infants who are not identified with HBV testing (false-negatives), this results in suboptimal post exposure prophylaxis and increased likelihood of chronic HBV.  Whereas, infants with false-positive results, incur unnecessary prophylaxis and costs.  The authors note that “total anti-HBc was the most useful single test to resolve HBsAg discrepancies.

Also noted: J Pediatr 2014; 165: 767-72.  “Factors Affecting the Natural Decay of Hepatitis B Surface Antigen in Children with Chronic Hepatitis B Virus Infection during Long-Term Followup”  This study followed 349 Taiwanese children over 20 years and noted annual HBsAg clearance of 0.58% (42 cleared HBsAg).  Spontaneous clearance was more common in HBeAg-seroconverters, infants with low initial HBsAg level <1000 IU/mL, and to those born to non-HBsAg-carrier mothers.

What is Panayiotopoulos Syndrome?

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Recently, Panayiotopoulos syndrome was mentioned on the GI Listserv as a possible explanation for a child with seizures following vomiting and gagging.  I hope that I was not the only one to wonder what that was.

According to Pediatrics Review Article:

Panayiotopoulos syndrome is a common idiopathic childhood-specific seizure disorder formally recognized by the International League Against Epilepsy. An expert consensus has defined Panayiotopoulos syndrome as “a benign age-related focal seizure disorder occurring in early and mid-childhood. It is characterized by seizures, often prolonged, with predominantly autonomic symptoms, and by an EEG [electroencephalogram] that shows shifting and/or multiple foci, often with occipital predominance.”

Autonomic epileptic seizures and autonomic status epilepticus are the cardinal manifestations of Panayiotopoulos syndrome. Autonomic seizures in Panayiotopoulos syndrome consist of episodes of disturbed autonomic function with emesis as the predominant symptom. Other autonomic manifestations include pallor (or, less often, flushing or cyanosis), mydriasis (or, less often, miosis), cardiorespiratory and thermoregulatory alterations, incontinence of urine and/or feces, hypersalivation, and modifications of intestinal motility.

Bottomline: If a parent is convinced that vomiting or retching is triggering seizures, the child’s neurologist needs to consider this disorder.