Ordering Tests and Good Health

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A provocative article from the NY Times discusses the fact that more testing does not always lead to good health outcomes.  Here’s an excerpt:

A cadre of test skeptics at Dartmouth Medical School specialize in critically examining our test-based approach to well adult care. If you are confused about mammography, colonoscopy or the PSA test for prostate cancer, these folks deserve much of the blame: They have repeatedly demonstrated that these tests and many others do not necessarily ameliorate a healthy person’s health, any more than standardized testing in grade school improves a child’s intellect…

… systems that rate doctors by how well their patients’ blood pressure is managed are likely to invite trouble. Doctors rewarded for treating aggressively are likely to keep doing so even when the benefits begin to morph into harm…One study found that nursing home residents taking two or more effective blood pressure drugs did remarkably badly, with death rates more than twice that of their peers. In another, dementia patients taking blood pressure medication with optimal results nonetheless deteriorated mentally considerably faster.

Yet no quality control system that I know of gives a doctor an approving pat on the head for taking a fragile older patient off meds. Not yet, at least. Someday, perhaps, not ordering and not prescribing will mark quality care as surely as ordering and prescribing do today.

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Keeping Up with Clostridium Difficile

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It is difficult to keep up with all of the relevant publications regarding Clostridium difficile–there are so many.  This likely reflects its emergence as a frequent and important pathogen.

Recent references:

  1. Sandberg KC et al. “Disproportionate Rise in Clostridium difficile Associated Hospitalizations Among US Youth with Inflammatory Bowel Disease, 19978-2011.” JPGN 2015; 60: 486-92 (editorial 421-22).
  2. Leffler DA, Lamont JT. NEJM 2015; 372: 1539-48.

In the first study, the researchers note that there has been a 5-fold increase in inflammatory bowel disease (IBD) hospitalizations with concomitant Clostridium difficile infection (CDI).  Whereas, the hospitalization without CDI increased 2-fold.  Associated with this 5-fold increase in hospitalizations, there were increased costs and longer length of stays.  Interestingly, IBD patients with CDI had a  lower likelihood (OR 0.31) of colectomy in this study. This epidemiology yields more questions than answers.  Certainly, a significant fraction of this increase is due to the use of more sensitive PCR-based assay. In addition, many of these patients may not be symptomatic due to CDI; it can be difficult to determine if IBD symptoms are due to IBD or due to CDI. Even treatment with antibiotics like vancomycin does not fully differentiate as the response could be nonspecific.

In the second review, severe useful points were made.

Risk factors:

  • Antibiotics –this remains most important risk factor
  • Older age (especially if >65 years)
  • Possible acid suppression -not confirmed in some studies when adjusting for coexisting conditions
  • Inflammatory bowel disease
  • Immunosuppression
  • Chronic kidney disease

Diagnosis:

  • Use of DNA assays has allowed for detection of “low levels of toxigenic organisms of uncertain clinical significance.”  Thus, these assays may detect clinically-insignificant infections.
  • Endoscopy is rarely needed, but sometimes helpful in ovelapping conditions like coexistent CDI from IBD
  • Negative PCR assay has a negative predictive value of “more than 95% in average-risk groups.”
  • Testing and treating persons with solid stools is not recommended

Prevention:

  • Probiotics “have an uncertain effect on the prevention of C difficile infection, and their routine use for the prevention or treatment of active infection is not recommended.”  The authors note that initial favorable studies of antibiotic-associated diarrhea were underpowered and that more recent studies have shown mixed results.  In studies of patients with unusually high rates of CDI, probiotics were shown to confer benefit.

Treatment:

  • Metronidazole and vancomycin remain 1st line treatments.
  • Fidaxomicin use has been limited due to expense, but has been shown to reduce recurrence of CDI in those who do not have the b1/NAP1/027 strain.
  • Alternative antimicrobials, including rifaximin, nitazoxanide and others, are “not recommended except in cases of unacceptable adverse effects.”
  • For recurrent infection, 1st line approach is retreatment with either metronidazole & vancomycin. Second recurrences are often treated with fidaxomicin or tapered vancomycin course.
  • Fecal microbial transplantation –noted to be highly effective and safe as salvage therapy. The precise components that are important are uncertain; however, “the phyla Bactteroidetes and Firmicutes are thought to comprise critical components.”  “More work is neede to understand the possible role for fecal microbial transplantation for primary CDI”

Bottomline: CDI remains an important pathogen and significantly complicates the management of IBD.

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Another Big Study: No Link between MMR vaccine and Autism (Plus one)

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In a study with 95,727 children, there was no link between receipt of the MMR (measles, mumps, rubella) vaccine and autism, even in children at high risk (eg. sibling with autism).

Here’s a summary from USA Today: No link between MMR and Autism

Original JAMA article (free & entire article)

Related blog: “Too many vaccines and autism” is debunked | gutsandgrowth

An unrelated commentary, “Social Distancing and the Unvaccinated,” (NEJM 2015; 372: 1481-83) notes that a recent ruling (Phillips v City of New York) upholds the state’s authority to bar unvaccinated children from school during outbreaks.  This practice is referred to as social distancing to lessen likelihood of further transmission. This “reiterated the Supreme Court decision in the 1905 case Jacobson v. Massachusetts, which clearly found vaccine mandates constitutional.”

GI Care For Kids: Our group has been very supportive of the Crohn’s and Colitis Foundation of America (CCFA) and especially active in staffing the yearly Camp Oasis for more than 20 years.  Throughout the year, there are a number of other events to support CCFA.  This past weekend many of us participated in “Taking Steps.”  Here are a few pictures:

Super Poopers: Ben Gold, Larry Saripkin, Dinesh Patel, Seth Marcus, and Jay Hochman

Super Poopers: Ben Gold, Larry Saripkin, Dinesh Patel, Seth Marcus, and Jay Hochman

Dr. Spandorfer’s team raised a great deal of money (50K) and he/his family were featured in the Atlanta Journal Constitution (Local Family Takes Big Steps to Raise Awareness).  His son, Jack, spoke at the event, and was honored as this year’s hero.  They also had pretty clever T-shirts

With 'Pip" Spandorfer (whose team raised $50,000)

With ‘Pip” Spandorfer (whose team raised $50,000)

Dinesh Patel and Kimberly Sheats

Dinesh Patel and Kimberly Sheats

 

 

 

Briefly Noted: E-Cigarette Use Increasing Rapidly in Kids & Gilead Profits

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From NPR (accessed 4/24/15): The statistical findings, published in this week’s issue of Morbidity and Mortality Weekly Report, come from the CDC’s National Youth Tobacco Survey. The latest survey found that the use of e-cigarettes increased from 1.1 percent in 2013 to 3.9 percent in 2014 among middle school students, and from 4.5 percent to 13.4 percent among high school students. That translates to a total of 450,000 middle school students now using e-cigs, alongside 2 million high school students.

Related blog post: Tobacco 21 & ENDing Combustible Tobacco Use | gutsandgrowth

 

Also, from NY Times, Gilead is making a lot of money on its Hepatitis C medications ,$4.55 billion in 1st quarter:

Sales of Gilead Sciences’ drugs to treat hepatitis C reached $4.55 billion in the first quarter, far exceeding already lofty Wall Street expectations but likely to focus attention once again on the overall costs to the health care system of the medicines.

Gilead said on Thursday that its new drug, Harvoni, had overall sales in the quarter of $3.58 billion, of which $3.02 billion was in the United States. This was the first full quarter of sales for Harvoni, which was approved in October.

Sales of Sovaldi, the older hepatitis C drug, fell to $972 million in the quarter from $2.27 billion in the first quarter of 2014 because it was supplanted by Harvoni. Combined, hepatitis C drug sales in the first quarter were double that of a year earlier.

University of Chicago

University of Chicago -Midway

Medical Marijuana -Update

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While medical marijuana is not a frequent concern of many pediatric gastroenterologists, our nurses have been getting questions with the recent passage of legislation.  In Georgia, as in many states, marijuana is allowed for certain medical conditions. “Georgia’s medical marijuana law [Haleigh’s Hope Act] does not legalize the production or sale of marijuana, it simply decriminalizes its possession by certain qualified individuals.” –GeorgiaCann Website

in Georgia the patient must suffer from one of these qualifying illnesses:

  1. Cancer, when such diagnosis is end stage or the treatment produces related wasting illness, recalcitrant nausea and vomiting.
  2. Amyotrophic Lateral Sclerosis (ALS), when such diagnosis is severe or end stage.
  3. Seizure disorders related to diagnosis of epilepsy or trauma related head injuries.
  4. Multiple Sclerosis, when such diagnosis is severe or end stage.
  5. Crohn’s Disease
  6. Mitochondrial Disease
  7. Parkinson’s Disease, when such diagnosis is severe or end stage.
  8. Sickle Cell Disease, when such diagnosis is severe or end stage.

While I will not be recommending medical marijuana for my patients, here is a link for How to Legally Obtain Medical Marijuana Oil in Georgia (thanks to AM for information).

Also, Georgia Department of Public Health -Low THC Oil Registry Page

Related blog posts:

From CNN:

University of Chicago

University of Chicago

“This Is A Stick Up — Your Money or Your Life”

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When I read a recent Hepatology editorial (Hepatology 2015; 61: 1106-8), I could not help think of the aforementioned title of this blog.

Here’s the scoop:

The two most commonly used medications for Wilson’s disease are trientine (Syprine) and D-penicillamine (Cupramine). For about 20 years, the original manufacturer of these medications kept the consumer cost at ~$1 per 250 mg tablet.  Currently the cost of Syprine is ~$200 per 250 mg tablet and Cuprimine costs ~$55 per 250 mg tablet.  This 200-fold increase translates into a yearly cost of ~$300,000.

How did this happen?

  • Little competition
  • Profit motive
  • Patients are reluctant to protest (they need this medication to be manufactured)

Why is this outrageous?

This increase in cost was not driven by any new discovery or research innovation.

Are there options?

Zinc is inexpensive and may be an option after initial period of chelation/normalization of liver biochemistries.  Zinc needs to be taken two to three times per day and “well away from meals for best absorption.”

Bottomline: These medication prices are outrageous.

Briefly noted:

  • “Molecular pathophysiology of portal hypertension”  Hepatology 2015; 61: 1406-15. Terrific review with excellent figures.
  • “Ezetimibe for the treatment of Nonacloholic Steatohepatitis” (MOZART trial) Hepatology 2015; 61: 1239-50. This randomized double-blind, placebo-controlled trial with 50 patients (biopsy-proven NASH) showed that Ezetimbe was not significantly different from placebo in histologic response rates, serum aminotransferases, or in magnetic resonance elastography findings.
  • Van Biervliet et al. “Clinical Zinc Deficiency as Early Presentation of Wilson Disease” JPGN 2015; 60: 457-9. Case report.

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Chronic Pancreatitis in Pediatrics -Descriptive Study

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“Genius is one percent inspiration and ninety-nine percent perspiration.” – Thomas A. Edison

I thought about this saying as I was reading an editorial titled: “Understanding Pediatric Chronic Pancreatitis: Inspiration and Hard Work Required” (Pant C, Sferra TJ. J Pediatr 2015; 166: 798-800). The editorial was reviewing the article “Pediatric Chronic Pancreatitis Is Associated with Genetic Risk Factors and Substantial Disease Burden” (Schwarzenberg SJ et al. J Pediatr 2015; 166: 890-6).

The study comes from the International Study Group of Pediatric Pancreatitis: In Search of a Cure (INSPPIRE) consortium.  None of the findings in the study are particularly surprising; nevertheless, a descriptive study of the patients in the registry who had strictly defined chronic pancreatitis (n=76) is still an important early step in improving our understanding of this dreaded problem.

Chronic pancreatitis required either:

  • Abdominal pain consistent with pancreatic pain with imaging findings suggestive of chronic pancreatic damage
  • Evidence of exocrine or endocrine pancreatic insufficiency and imaging findings suggestive of chronic pancreatic damage
  • Histology (surgical biopsy) findings suggestive of chronic pancreatitis

Key points:

  • Two-thirds of patients with genetic testing had identified genetic mutations: PRSS1 (n=33), SPINK1 (n=14), CFTR (n=11), chymotrypsin C (CTRC) (n=2).  Mutations in more than 1 gene were noted in 9 patients, including 6 of the 11 with CFTR mutations.  Several newer mutations, like calcium-sensing receptor and carboxypeptidase A1, were not evaluated in any of the patients.
  • Pancreas divisum was present in 15 patients; however, 8 of 15 of these patients had an identified genetic mutation as well.
  • Radiographic findings of chronic pancreatitis were most commonly ductal abnormalities and pancreatic atrophy. This is in contrast to adults in which pancreatic calcifications are common.
  • The researchers also document severe disease burden with patients reporting a median of 3 emergency dept visits and 2 hospitalizations in the previous year. In addition, 70% (n=47) had missed 1 day of school in the past month and 34% had missed 3 or more days.
  • Medical treatment (eg. pancreatic enzymes) was ineffective in the majority of patients.
  • 43% had undergone ERCP and two-thirds noted improvement from this intervention
  • Surgical procedures were performed in 39% and were helpful in the majority.  Total pancreatectomy with islet autotransplantation was the most common surgery in this cohort and was helpful in 20 of 21 patients.
  • The authors recommend avoidance of CT scans due to concerns of accumulating excess ionizing radiation exposure.

Take home message: For me, this study helps define the problem.  As a practical matter, it would be helpful to have a genetic panel to check for the lesser frequent mutations if PRSS1, SPINK1, and CFTR are normal.

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Stool Color Cards -Not Flashy but Effective

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A recent report (Gu YH et al J Pediatr 2015; 166: 897-902) shows the cumulative experience of 19 years of using stool color cards to detect biliary atresia.  Cards were distributed to all pregnant women (Tochigi Prefecture, Japan) prior to or during the postnatal one-month health check.

Key findings:

  • 34 patients detected among 313,230 live births. Reported sensitivity: 76.5% and specificity 99.9%.
  • Mean age for performance of Kasai was 59.7 days.
  • Improved long-term retention of native liver: 88% at 5 years, 77% at 10 years, and 49% at 15 years.

Limitation: Children in Western countries have had lower success rates following Kasai procedure, so it is unclear whether stool cards would be as effective in different regions.

Take-home message: Detecting biliary atresia earlier will improve outcomes.  Stool color cards should be an easy low-tech option.  Other options would include stool color apps and checking bloodwork.

Image below from Screenshot from John Pohl’s twitter feed:

Embedded image permalink

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Conflicting Cholesterol Guidelines –Massive Undertreatment or Massive Overtreatment?

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A fascinating article (Gooding HC et al. JAMA Pediatr doi:10.1001/jamapediatrics.2015.0168) studies a cross-sectional analysis of the National Health and Nutrition Examination Survery (NHANES) population and determines the frequency of the need for statin therapy for hyperlipidemia based on two separate guidelines.

  • 2011 Integrated Guidelines for Cardiovascular Health and Risk Reduction in Children and Adolescents of the National Heart, Lung, and Blood Institute (Pediatrics 2011; 128 (sup 5): S213-S256) PEDS RECS
  • 2013 Guidelines on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults from the American College of Cardiology and American Heart Association (Circulation 2014: 129 (25) (supl 2) S1-S45) ADULT GUIDELINES

Specifically, the design of the study focused on 17-21 year olds in which the guidelines had overlapping recommendations. While the NHANES population involved only 6338 patients, this representative sample was used to calculate the likelihood of statin therapy more broadly among the US population of 20.4 million in this age group.

Key Findings:

  • Among the cohort of 6338, 2.5% would qualify for statin treatment using PEDS RECS compared with 0.4% under ADULT GUIDELINES.
  • This finding extrapolates to 483,500 patients nationwide compared with 78,200, respectively.  This is a difference of more than 400,000 and reflects a 6-fold difference.

Why the discrepancy?

  • ADULT GUIDELINES recommend use of statins only if LDL-C is >190. PEDS RECS extend to as low as 130 or 160 if additional risk factors (highly prevalent) are present, including hypertension, obesity, and smoking.
  • ADULT GUIDELINES are based on randomized clinical trials, though “they advocate for physician’s judgement in areas where the evidence base is insufficient.” PEDS RECS use extrapolated evidence for lifetime risk of coronary vascular disease.

Bottomline: While these guidelines highlight differences among 17-21 year olds, the decision regarding statin therapy extends across the age spectrum in terms of whether a low or high threshold should be in place.  Also, it is unfortunate that the additional modifiable risk factors (smoking, hypertension, and obesity) are so prevalent as to create this divergence in approach.

Related references:

  • NEJM 2015; 372: 1489-99. Alirocumab, a monoclonal antibody that inhibits PCSK9, lowered LDL 62% in patients receiving maximal statin therapy. Randomized, placebo-controlled study with 2341 patients.
  • NEJM 205; 372: 1500-09. Evolocumab, a monoclonal antibody that inhibits PCSK9, lowered LDL 61% in two open-label randomized trials (n=4465).

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Sandy Springs

Sandy Springs

Inequality in Pediatric Health Care

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“Of all the forms of inequality, injustice in health care is the most shocking and inhuman.”

-Martin Luther King, Jr

This quote is part of an editorial (Flores G, “Dead Wrong: The Growing List of Racial/Ethnic Disparities in Childhood Mortality” J Pediatr 2015; 166: 790-3). The author discusses the disparities among African-American (AA) and Latino children in comparison to white children.

Key points:

  • AA children and young adults had ~6 times the death rate for drowning in swimming pools, 4 times more likely of dying after liver transplant, and about twice the likelihood of dying due to acute lymphoblastic leukemia.
  • Latino children have higher cancer death rates with about twice the likelihood of dying due to acute lymphoblastic leukemia and increased drowning death rate as well.
  • One new study (pages 812-8) shows that black children have increased in-hospital mortality (OR 1.66) after complications following congenital heart surgery and that hispanic children have an increased complication rate following surgery (OR 1.13). This was a retrospective study using the Kids’ Inpatient Database with approximately 3 million discharge abstracts for three separate years.
  • A second study (pages 819-26) with a data set of 98,833 children shows that birth defects resulted in higher 8-year adjusted hazards of death for black, latino, and Asian/Pacific Islander children.

Recognizing these disparities inevitable leads to the question of why. Dr. Flores postulates several factors.

  • Genetic differences.  For example, some ethnicities have more difficult to treat cancers, either due to genetic mutations or due to metabolism of medications.
  • Delays in diagnosis and treatment.  Patients who present at a later stage of diagnosis often have lower cure/response rates. The author notes that black children receive a diagnosis of autism a mean of 1.4 years later than white children.
  • Barriers to specialty care.  Specialty care can result in improved outcomes.
  • Bias in healthcare delivery, both conscious and unintentional.

Bottomline: The problems of racial inequality is not just a matter of relationships between the police and the community.  It is clear that more needs to be done to improve outcomes in healthcare as well.

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Unrelated Link: Surgeon General Tells Elmo to Get His Vaccines