Blind Men and The Elephant: Lasting Consequences of Enteric Infections

Recently, Ben Gold handed me a supplement which alluded to the case of “the blind men and the elephant.”  So, of course, I wanted to know more about this.

According to Wikipedia:

In various versions of the tale, a group of blind men (or men in the dark) touch an elephant to learn what it is like. Each one feels a different part, but only one part, such as the side or the tusk. They then compare notes and learn that they are in complete disagreement. The stories differ primarily in how the elephant’s body parts are described, how violent the conflict becomes and how (or if) the conflict among the men and their perspectives is resolved.  In some versions, they stop talking, start listening and collaborate to “see” the full elephant. When a sighted man walks by and sees the entire elephant all at once, the blind men also learn they are all blind. While one’s subjective experience is true, it may not be the totality of truth. If the sighted man were deaf, he would not hear the elephant bellow.

It has been used to illustrate a range of truths and fallacies; broadly, the parable implies that one’s subjective experience can be true, but that such experience is inherently limited by its failure to account for other truths or a totality of truth. At various times the parable has provided insight into the relativism, opaqueness or inexpressible nature of truth, the behavior of experts in fields where there is a deficit or inaccessibility of information, the need for communication, and respect for different perspectives.

The rest of the supplement regarding chronic health consequences following acute enteric infections was less interesting but probably more important than learning a new anecdote.

The introduction notes that nearly 600,000 children under 5 years die from dehydrating diarrhea each year.  Many more suffer from consequences of disease-associated malnutrition with both physical and cognitive deficits.

Articles in supplement:

  • Am J Gastroenterol Suppl 2016; 3: 4-11. –details diarrhea-associated years lived with disability 51 per 100,000 in developed regions compared with 685 in developing regions.
  • Am J Gastroenterol Suppl 2016; 3: 12-23. –details the likelihood of consequences following enteric infections, including functional GI disorders, inflammatory bowel disease, celiac disease (data limited), Guillain-Barré syndrome, hemolytic uremic syndrome, chronic fatigue, and neurologic sequelae.
  • Other articles in the supplement describe changes in the microbiome, the micorbiome-gut-brain axis, and the relationship between autoimmunity and irritable bowel.

 

Nutrition Guidelines for Cystic Fibrosis

Wilschanski et al (JPGN 2016; 63: 671-5) provide a summary (“highlights”) of a full report (Turck D et al. Clin Nutr 2016; 35: 557-77) on nutritional recommendations for infant and children with cystic fibrosis.

What’s in here:

Table 1: criteria for adequate nutritional status including

  • Age <2 yrs: 50% for weight & height compared to healthy-age peers
  • Age 2-18 yrs: 50% BMI compared to healthy peers

Table 2: nutritional assessment and followup

  • Assess elastase-1 annually if pancreatic sufficient
  • Assess pancreatic enzyme supplementation
  • Annual blood tests: CBC/d, iron status, fat-soluble vitamins, LFTs.  Possibly: fatty acids
  • If older than 10 years, annual glucose tolerance
  • Dietary review every 3 months
  • Bone density assessment between 8-10 yrs and then every 1-5 yrs

Table 3: Energy requirements

  • Anticipate need for 110-200% compared with healthy peers

Table 4: Pancreatic enzyme replacement therapy (PERT)

  • 0-1 yr: 2000-4000 units lipase/120 mL of formula/breast milk & 2000 units lipase/gram of dietary fat
  • 1-4 yrs: 2000-4000 units of lipase/gram of dietary fat (max 10,000 units lipase/kg/day)
  • >4 yrs: starting dose; 500 units lipase/kg/meal -titrate up to 1000-2500 units lipase/kg/meal (max 10,000 units lipase/kg/day)

Table 5: Fat-soluble vitamin/vitamin guidelines

Table 6: Sodium supplementation

  • 0-6 months: 1-2 mmol/kg/day –give salt in small portions throughout the day, “diluted in water or fruit juice”.  In some infants, up to 4 mmol/kg/day if increased losses (eg. due to heat, gastrointestinal losses)
  • Older children: anticipate need for additional salty foods or use sodium chloride capsules, especially when excessive sweating (eg. fever, sports, hot weather)

Related blog posts:

Disclaimer: These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) should be confirmed by prescribing physician.  This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition.

Maine Coast, near Acadia

Maine Coast, near Acadia

 

Peanut Allergy Prevention Guidelines

From USA Today: Peanut allergy: Everything they told you was wrong

LINK::

An excerpt:

Research suggests the method to stopping a lifelong peanut allergy is to, well, feed your baby peanut foods.

The National Institute of Allergy and Infectious Diseases, part of the federal government’s National Institute of Health, issued new guidelines to health care providers and parents Thursday…

The guidelines are based on whether a child has eczema or an egg allergy, good indicators of peanut allergies. Fauci suggests parents check with their doctor before moving forward with peanut foods.

The guidelines are as follows:

– For infants deemed a high risk for developing a peanut allergy, based on eczema or egg allergies, experts suggest feeding them food with peanuts as early as four to six months old.

– Infants with mild to moderate eczema should be introduced to peanuts at six months old.

– For babies without eczema or egg allergies, researchers say parents can start giving them peanut foods when they see fit.

 

From NBC News: Peanut Allergy Prevention (includes video)

High-risk infants

Babies with with severe eczema or an egg allergy should be tested at a specialist’s office when they’re 4 to 6 months old and have started taking solid food.

screenshot-59

Related blog posts:

 

Treatment Outcomes in Children and Adolescents with Hypercholesterolemia

A recent study (MM Mendelson et al. J Pediatr 2016; 178: 149-55) provides some useful data indicating that statin therapy for children and adolescents is typically effective based on cholesterol reduction levels.

This observational study prospectively collected data from 2010-2014 among 1521 pediatric patients seen for a lipid disorder.  In this cohort, 1260 patients (83%) did not receive statin therapy during the study period.  Ultimately, 97 patients (6% of clinic cohort) had received statin therapy and had adequate data for evaluation.

  • 70 patients received simvastatin: 1 at 5 mg/day, 26 at 10 mg/day, and 43 for 20 mg/day.
  • 24 patients received atorvastatin: 22 at 10 mg/day and 2 at 20 mg/day
  • 3 patients received pravastatin: 2 at 10 mg/day and 1 at 20 mg/day

Primary outcome for therapy: LDL-C <130 for patients without high risk factors and <110 for patients with high risk condition(s) (eg. diabetes mellitus, end-stage renal disease, heart transplant, Kawasaki disease with aneurysms)

Key findings:

  • Median baseline LDL-C was 215.
  • LDL-C decreased by 37% on average (83 mg/dL) within the first 60 days of therapy
  • Achieved primary outcome: 60% at 1 year,  73% at 2 years, and 87% at 3 years
  • No patients presented with relevant hepatic or myopathic side effects. 2 of 97 had transient epiosde of ALT > 3 x ULN.

Discussion:

  • Overall, the reported outcomes in this select cohort were at least as good as outcomes reported in studies of adults in the general population.  This may be due to parental supervision or perhaps due to a better physiologic response. In addition, as this was an observational study, poorly adherent patients may be lost to follow-up and would not be accounted for.
  • Currently statin therapy is recommended if lifestyle modifications are not sufficient to lower LDL-C.  Thus, “it is estimated that more than 700,000 US children and adolescents may be eligible for statin therapy according to the 2011 NHLBI guidelines.”

My take: Since cholesterol and LDL-C are biomarkers of treatment, the long-term benefit (& possible risks) of statin therapy remains unclear .  However, more data on meaningful endpoints like heart attacks and strokes could take decades.  Until then, the best evidence available suggests that the potential benefit of statin therapy could be quite substantial.

Related posts:

waterwarriors

Understanding Why Vitamin D Deficiency is Not So Common Afterall

An excellent commentary (JE Marrison et al. NEJM 2016; 375: 1817-20) throws a bunch of cold water on the idea that there is a massive vitamin D deficiency pandemic.  The main contention of the authors is that physicians, and by extension patients, focus too closely at specific thresholds which are poorly understood.

They explain the term “Estimated Average Requirement” (EAR) which is the median of the distribution of human requirements.  Whereas, the RDA or recommended daily allowance “reflects the estimated requirement for people at the highest end of the distribution.”  So, at least 97.5% of people will have a requirement below the RDA.  However, due to Vitamin D’s importance, particularly with bone health, “the EAR is set at 400 IU per day for persons 1 to 70 years of age and 600 IU per day for persons older than 70.”

Other key points:

  • The EAR and RDA assume minimal to no sun exposure.
  • The RDAs of 600 IU/day and 800 IU/day correspond to 25(OH)D level of  16 ng/mlL and 20 ng/mL.
  • “A common misconception is that the RDA functions as a ‘cut point’ and that the entire population must have a serum 25(OH)D level above 20 ng per millimeter to achieve good bone health.”
  • “Approximately half the population has a requirement of 16 ng per milliliter (the EAR) or less.”
  • “Many studes establish ‘inadequacy’ using the RDA, though it is actually at the upper end of the spectrum of human need.” Thus, most people who are labelled as deficient are misclassified.
  • Using correct methodology, the authors assert that 13% of Americans 1-70 years are ‘at risk’ and <6% are deficient (with 25(OH)D < 12.5 ng/mL.

The problem with excessive Vitamin D testing and excessive treatment:

  • If 97.5% of the population has levels of Vitamin D exceeding 20 ng/mL, there are likely to be adverse effects in addition to increased costs of testing/treating.

Who to screen?

  • Those with risk factors for vitamin D deficiency: osteoporosis, osteomalacia, malabsorption, medications that can affect vitamin D metabolism (eg. anticonvulsants), or institutionalization
  • “For healthy patients, routine screening is not recommended by most medical organizations.” Though, the authors do recommend that “the RDA will nearly always meet the needs of generally healthy people.”

My take: This article makes a good argument for less testing along with avoidance of overprescribing vitamin D.  Nevertheless, for healthy people taking the RDA for vitamin D is quite sensible.

Related blog posts:

Disclaimer: These blog posts are for educational purposes only. Specific dosing of medications/diets (along with potential adverse effects) should be confirmed by prescribing physician/nutritionist.  This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition.

Victoria Chimes -Maine's Ship on their state quarter

Victoria Chimes -Maine’s Ship on their state quarter

In the News: UCSF Soda Ban

NY Times: Putting Sugary Soda Out of Reach

An excerpt:

Last year, U.C.S.F. removed sugar-sweetened beverages from every store, food truck and vending machine on its campus. Even popular fast-food chains on the campus, like Subway and Panda Express, have stopped selling Sprite, Coca-Cola and their sugary brethren at the university’s request….

“We’re a public health institution, and there’s something not right about us making money off of products that we know are making people sick,” said Laura Schmidt, a professor at the medical school who spearheaded the beverage initiative…

Nationwide, at least 30 medical centers have restricted the sale of soda and full-calorie sports drinks, including the Cleveland Clinic in Ohio and the University of Michigan Health System…

the beverage industry argues that the strategy is flawed. It points out that obesity rates have been climbing even as America’s soda intake has declined in recent years. And it says that focusing blame on soda alone, rather than calories from all foods, is misguided.

Related blog posts:

 

Autism Drugs: Fat and Happy?

“The reason fat people are happy is that their nerves are well protected.”
– Luciano Pavarotti

It is not uncommon to see kids with behavioral problems that are also obese.  Many times, medications which help improve behavioral problems may contribute to obesity by increasing appetite.

A recent study (K Shedlock et al. J Pediatr 2016; 178: 183-7) provides some insight into this issue. In this retrospective study, using the Military Health System database (2000-2013) with 48,762 individuals with autism spectrum disorder and with 243,810 matched controls, children with autism spectrum disorder (ASD) had significantly higher rates of obesity with OR 1.85 along with obesity-related conditions.  These conditions include type 2 diabetes, hypertension, hyperlipidemia, and NAFLD/NASH.

Key points:

  • In children with ASD, mood stabilizers, antipsychotics, antiepileptic drugs, and selective serotonin reuptake inhibitors (SSRIs) were associated with obesity.  Mood stabilizers had the greatest risk in this study, with adjusted OR of 1.41; the other medications had fairly small risk with adjusted ORs between 1.13 to 1.16.
  • When kids with ASD develop complications like NAFLD/NASH or hyperlipidemia, they may be less likely to adhere with recommended lifestyle changes.  This can be due to sensory aversions and social deficits.

My take: Children with autism spectrum disorder are likely at increased risk for obesity at baseline; some of the medications to treat behavior problems may contribute to obesity, though they may be partly an epiphenomenon or a marker of a more severe autism spectrum disorder.

Portland Head Light

Portland Head Light

Fatty Liver Improved with Exercise

A recent study (LA Orci et al. Clin Gastroenterol Hepatol 2016; 14: 1398-1411) analyzed data from 28 randomized trials (>1600 patients) and performed a meta-analysis regarding the utility of exercise for nonalcoholic fatty liver disease (NAFLD).

Key finding:

  • Physical activity, independently from diet change, was associated with improvement in intrahepatic lipid content (-0.69) and with reduction in alanine aminotransferase.

The authors note that the effects of lipid reduction due to exercise is considered moderate-to-large.  In several trials, another effect of exercise that was measured was a reduction in insulin resistance.

Limitations:

  • The duration of the effect of exercise is not known and there is not a clear “dose” of exercise.
  • Lack of histologic data (only 2 studies had histology data)

My take: This study suggests that exercise by improving metabolic status is important in improving NAFLD; thus, a fatty liver is not just about being fat.

Bar Harbor at Sunset

Bar Harbor at Sunset

Case Report: Management after Accidental Bolus of Parenteral Nutrition

Fortunately, most mistakes do not result in long-lasting consequences.  The authors’ of a recent report  (JPEN J Parenter Enteral Nutr August 2016 vol. 40 no. 6 883-885note a severe setback for a patient after accidental bolus of parenteral nutrition:

Here’s the abstract:

There is a paucity of data that exists regarding acute toxicity and management in the setting of parental nutrition (PN) overdose. We describe a case of a patient who received an accidental rapid bolus of PN and fat emulsion. She developed a seizure, metabolic acidosis, arrhythmias, myocardial ischemia, altered mental status, hypotension, and hypoxemia likely caused by elevated triglycerides, leading to a hyperviscosity syndrome. After failing standard therapy, she was successfully treated with a single-volume plasma exchange with resolution of symptoms. Fat emulsion or intravenous lipid emulsion and much of its safety have been recently described in its use as a rescue therapy in resuscitation from drug-related toxicity. Elevated serum triglyceride levels can result in a picture similar to a hyperviscosity syndrome. Plasma exchange is a known therapeutic modality for the management of hyperviscosity syndrome and a novel therapy in the treatment of hyperviscosity syndrome due to fat emulsion therapy. In a patient receiving PN with development of rapid deterioration of clinical status, without an obvious etiology, there should be consideration of PN overdose. A rapid assessment and treatment of severe electrolyte abnormalities should be undertaken immediately to prevent life-threatening cardiovascular and central nervous system collapse. If fat emulsion was rapidly coadministered and there are signs and symptoms of hyperviscosity syndrome, then consideration should be given to plasma exchange as an effective therapeutic treatment option.

AAP Recommendations on Preventing Obesity and Eating Disorders

From AAP Committee on Nutrition, Pediatrics, August 2016Full text: Preventing Obesity and Eating Disorders in Adolescents

  1. Discourage dieting, skipping of meals, or the use of diet pills; instead, encourage and support the implementation of healthy eating and physical activity behaviors that can be maintained on an ongoing basis. The focus should be on healthy living and healthy habits rather than on weight.
  2. Promote a positive body image among adolescents. Do not encourage body dissatisfaction or focus on body dissatisfaction as a reason for dieting.
  3. Encourage more frequent family meals.
  4. Encourage families not to talk about weight but rather to talk about healthy eating and being active to stay healthy. Do more at home to facilitate healthy eating and physical activity.
  5. Inquire about a history of mistreatment or bullying in overweight and obese teenagers and address this issue with patients and their families.
  6. Carefully monitor weight loss in an adolescent who needs to lose weight to ensure the adolescent does not develop the medical complications of semistarvation.
Gardens at University of Virginia

Gardens at University of Virginia