Category Archives: Pediatrics

Immunization Recommendations from CDC 2013

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The following was copied from the ImproveCareNow Circle Newsletter (conta.cc/145rO5T):

The Centers for Disease Control and Prevention (CDC) offers easy-to-print schedules for regular childhood immunizations and “maintenance”. These are good resources for parents and patients to keep track of their vaccine schedule. You can access them here:

It is important to note: Patients taking immunosuppressant drugs (such as prednisone, 6MP, Methotrexate, biologic agents like Remicade or Enbrel) CANNOT receive a “live vaccine” because they can become ill as a result of the vaccine. This is especially important during fall when the flu vaccine is recommended. The intranasal flu vaccine (flu mist) is a live vaccine and should NOT be given to patients taking immunosuppressant drugs.

Yearly flu [injection] shots are encouraged for kids with IBD because the flu can be very serious in someone taking immunosuppressant drugs or who has a chronic illness.  Also, because the flu is a viral infection it can stimulate the immune system and could cause a flare.

Related blog link:

Protecting the most vulnerable | gutsandgrowth

Injection Flu Vaccine Safe for Patients with IBD

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A recent article from Pediatrics, published online May 6, 2013
(doi: 10.1542/peds.2012-3567), confirms that influenza vaccination (injection/inactivated vaccine) is safe in patients with inflammatory bowel disease:

“Safety and Utilization of Influenza Immunization in Children With Inflammatory Bowel Disease”  Eric I. Benchimol, Steven Hawken, Jeffrey C. Kwong, and Kumanan Wilson

Abstract:

OBJECTIVE: Influenza immunization is recommended for children with IBD, however safety concerns may limit uptake. This study assessed whether immunization was associated with adverse events in IBD patients using a population-based database of children with IBD.

METHODS: All children <19 years diagnosed with IBD in Ontario, Canada between 1999–2009 were identified using health administrative data, and matched to non-IBD controls. Self-controlled case series (SCCS) analyses determined health services event rates (outpatient visits, hospitalizations and emergency visits) in any 2-week risk period to 180 days post-immunization compared to a no-risk control period. Relative incidence (RI) was calculated for overall and IBD-related events and rates were compared between IBD cases and controls using relative incidence ratios (RIR).

RESULTS: 4916 IBD patients were matched to 21,686 controls. IBD patients were more likely to have received immunization than controls (25.3% vs. 13.2%, P < .001). No increased event rates existed in IBD cases during risk periods (pooled RI 0.95, 95% CI 0.84–1.07), including hospitalizations and emergency visits. There was a slightly higher event rate in IBD cases versus controls for days 3–14 (RIR 1.60, 95% CI 1.05–2.44, P = .03). IBD-related visit rates were lower in risk periods compared to control period (pooled RI 0.81, 95% CI 0.68–0.96).

CONCLUSIONS: There was no increase in health services use in the post-vaccine risk period in IBD patients, and there was evidence for a protective effect of influenza immunization against IBD-related health services use. Influenza immunization is safe in children with IBD and should be encouraged to improve poor coverage rates.

Gluten-free, Casein-free -No Improvement in Autism

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From Kipp Ellsworth’s twitter feed:

The gluten-free, casein-free diet and autism: limited return on family investment

From Journal of Early Intervention

goo.gl/uulzis  (link to entire article)

Excerpt:

Abstract

The gluten-free, casein-free (GFCF) diet is widely used by families of children with autism spectrum disorders (ASD). Despite its popularity, there is limited evidence in support of the diet. The purpose of this article was to identify and evaluate well-controlled studies of the GFCF diet that have been implemented with children with ASD. A review of the literature from 1999 to 2012 identified five studies meeting inclusion criteria. Research rigor was examined using an evaluative rubric and ranged fromAdequate to Strong. In three of the studies, no positive effects of the diet were reported on behavior or development, even after double-blind gluten and casein trials. Two studies found positive effects after 1 year but had research quality concerns. Reasons why families continue to expend effort on GFCF diets despite limited empirical evidence are discussed. Recommendations are that families should invest time and resources in more robustly supported interventions and limit GFCF diets to children diagnosed with celiac disease or food allergies.

We still see this

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Despite a number of previous studies regarding transient benign hyperphospatasemia which date back to 1954, pediatric gastroenterologists still see kids referred for this.  A new study analyzes 142 previous reports which included 813 cases (JPGN 2013; 57: 167-71).

Most of the alkaline phosphatase is produced in the liver and bone. “Sometimes a marked increase in alkaline phosphatase values is found in infants and toddlers without evidence of liver or bone disease…The temporary increase in alkaline phosphatase resolves without intervention within 16 weeks…is termed transient benign hyperphosphatasemia.”  With this disorder, the alkaline phosphatase is commonly ≥ 5 times the upper reference range.

Findings:

  • 733 cases were in patients <19 years of age; 80 cases were in those ≥ 19 years
  • Among infants and toddlers, the prevalence may be between 1.1% and 3.5%
  • The duration of elevation was ≤4 months in 80%
  • A preceding infection often preceded the reported cases
  • Our analysis “indicates that isoenzyme studies are not useful.” In about 50% the most prevalent isoform is from bone, though this may reflect poor clearance from the circulation.

Evaluation recommended by authors: aminotransferases, bilirubin, γ-glutamyl transferase, calcium, phosphorus, urea, and creatinine (eg. CMP, phosphorus, & GGT) –though they indicate that these may be waived by many experienced clinicians.

Bottom-line: Transient benign hyperphosphatasemia is likely the most common cause of elevated alkaline phosphatase in healthy infants and toddlers.  Sometimes this occurs in older children and adults. Recognition of this disorder may help avoid unnecessary investigation.

“Too many vaccines and autism” is debunked

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Based on false science, many parents think that refusing or delaying vaccinations will be safer for their children and decrease the risk of autism.  While the scientific underpinnings for such a concept have no basis (Pediatrics 2004; 114: 793-804, and Institute of Medicine. Immunization safety review: vaccines and autism. Washington, DC: National Academies Press; 2004), lingering concerns persist.  Into this background, another rigorous study (J Pediatr 2013; 163: 561-7) has concluded that there is “no association between exposure to antigens from vaccines during infancy and the development of autism spectrum disorder (ASD),” autism, or ASD with regression.

So how did the authors reach this conclusion?

Using a case-control study from three managed care organizations (MCOs) of 256 children with ASD and 752 control children, the authors examined exposure to total antibody stimulating proteins and polysaccharides from vaccines.  They utilized vaccine registries and medical records.  The children in this study were born between 1994-1999 and were aged 6-13 years at the time of data collection.

The results showed that with each 25-unit increase in total antigen exposure, the adjusted odds ratio (aOR) for ASD was 0.999 for cumulative exposure to age 3 months. The aOR stayed the same at 7 months and 2 years.  When autism or autism with regression were examined, similarly there was no increased risk.

One of the strengths of this study was that members of these MCOs have routine immunizations as a covered benefit; this helps minimize socioeconomic factors which could influence results.  A small number of ASD cases (5%) and controls (2%) had an older sibling with autism; results were unchanged when these children were excluded.

In many ways, this finding is completely anticipated and in agreement with the Institute of Medicines most recent 2013 report on immunizations (The Childhood Immunization Schedule and Safety: Stakeholder …).  As the authors note in their discussion, “beginning at birth, an infant is exposed to hundreds of viruses and other antigens, and it has been estimated that an infant theoretically could respond to thousands of vaccines at once.”

Bottom-line: Vaccines prevent disease without causing autism.  Vaccine refusal increases the risk of disease for those who refuse and creates collateral damage as well.

Related blog entries:

 

What to do with ALTEs?

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While apparent life-threatening events (ALTEs) in infants are quite disturbing, the best management for these events is far from clear. A recent systematic review of ALTEs in infants was undertaken and included studies from 1970-2011 (J Pediatr 2013; 163: 94-9). The authors ultimately identified 37 relevant studies: 18 prospective observational studies and 19 retrospective observational studies.

Results:

  • None of the 37 studies yielded “a high level of evidence for diagnostic or prognostic investigations.”
  • Risk factors for ALTE: prematurity, previous ALTEs, and suspected child maltreatment.
  • Routine screening for gastroesophageal reflux, meningitis, bacteremia, and seizures are “highly unlikely to be helpful in patients who are well-appearing and have no other findings suggestive of a diagnosis.”
  • Testing for GERD “is unnecessary in children with ALTEs.”  “A positive test does not necessarily inform management because causation cannot be established.”  Patients with recurrent ALTEs “may benefit from pH monitoring in combination with symptom recording.

Additional references:

NASPGHAN Consensus guidelines on GERD (2009)

Link: Gastroesophageal Reflux Disease in the Pediatric … – NASPGHAN.o

  • In premature infants, a relationship between GER (i.e. reflux) and pathologic apnea and/or bradycardia has not been established.Despite a lack of convincing evidence, if pathological apnea occurs in the face of pre- existing reflux, then the following two statements are the most common features:
  • Although reflux causes physiologic apnea, it causes pathologic apneic episodes in only a very small number of newborns and infants.
  • When reflux causes pathological apnea, the infant is more likely to be awake and the apnea is more likely to be obstructive in nature.
  • A diagnosis of an acute life-threatening event (ALTE) warrants consideration of causes other than GER (i.e. reflux).Reflux of gastric acid seems to be related to ALTEs (episodes of combinations of apnea, color change, change in muscle tone, choking, and gagging) in < 5 % of infants with ALTE. 
  • -J Pediatr 2009; 155: 516. Bradycardia not improved in preemies treated for GER. n=18. Editorial 464 urges not using GER Rx in neonates –outside clinical trials.
  • -J Pediatr 2009; 154: 374. Apnea associated with reduction in LES tone in premature infants; therefore, GER may be secondary to apnea rather than the reverse. Small study -12 apneic event in 7 infants.
  • -J Pediatr 2008; 152: 365. Compared risk factors with SIDS. One of 153 (0.6%) with ALTE died.
  • -Pediatrics 2005; 116: 1059 & 1217 (editorial). Apnea in preemies is unrelated to GER.
  • -Pediatrics 2004; 113: e128-132. Apnea is unrelated to GER in most preemies; airway problems due to GERD is hard to establish.
  • -J Pediatr 2000; 137: 321 & 298. Poor temporal association between GER & apnea in ALTE patients.
  • -J Pediatr 2001; 138: 355. Metoclopropramide/cisapride do not help apnea in preemies with GER
  • -Pediatrics 2002; 109: 8-11. GER does not cause apnea of prematurity.

Ketamine for chronic pain –is this a good idea?

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A recent phase 1 study explored the use of oral ketamine for chronic pain (J Pediatr 2013; 163: 194-200).

Ketamine has several mechanisms of actions in improving pain.  It is frequently used in emergency room settings because of its analgesic and dissociative amnestic qualities.  In addition, it has relatively little cardiorespiratory impact, a short half-life, and is better tolerated in children than adults.

Given the frequency of chronic pain in children and the relative paucity of treatment options, the authors aimed to determine whether ketamine in a short-term study (2 weeks) would be safe and effective.  This prospective study enrolled 12 patients who received ketamine 3 times per day at dosages of 0.25-1.5 mg/kg/dose .**

Pain diagnoses included chronic pancreatitis, Crohn’s disease, esophageal spasm, headache, joint pains, and other causes.  Median age was 16 years (range 11-19).

Results:

  • Two participants, both treated with 1.5 mg/kg/dose, experienced dose-limiting toxicities: sedation and anorexia.
  • Of the 12 patients, 5 had improvement in pain scores; 2 of these patients had complete resolution of pain which lasted >4 weeks off ketamine treatment.
  • There was evidence of norketamine accumulation in many patients.  Norketamine is the major metabolite of ketamine.

**Note: All medication dosages should be checked in standard references for individual patients.  This blog may have transcription errors with regard to dosages.

Related blog posts:

What physicians can learn from fast-food restaurants and retail shops

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Going to a physician is worse than going to a jeweler.  At a jeweler’s, it is commonly said that if you have to ask how much it costs, then you probably cannot afford it.  When seeing a physician, in all likelihood the costs of various tests are not completely known (until the bill arrives).  In contrast, when going to a fast-food restaurant or to most shops, the price is clearly posted and this helps make an informed decision.

Not surprisingly, a recent study from Johns Hopkins has shown that physicians order less tests when the fee for the test was displayed (JAMA Intern Med 2013; 173: 903-08).

This study randomly assigned 61 inpatient diagnostic laboratory tests to an “active” arm with the fee displayed or to a control arm with no fee displayed.  The displayed fee was based on the Medicare.  During a 6-month baseline period 208-2009, no fees were displayed.  allowable fee.  Pediatrics was one of the smallest hospital services involved in this study (0.8%); internal medicine service accounted for 52.1% and intensive care 26.6%.

Results: Rates of test ordering were reduced from 3.72 tests per patient-day in baseline period to 3.40 tests per patient-day in the intervention period (8.59% decrease).  In contrast, the control arm tests increased during the same period from 1.15 to 1.22 (5.64% increase).  The net result was $400,000 charge reduction in a 6-month period.

The study limitations included the practice setting where most orders are placed by residents. In addition, it is not known whether the reductions in testing led to any detrimental affects.

Trying to sort out the price of laboratory tests, imaging, and procedures for the individual are complicated by the unfathomable world of insurance contracting and discounts. Yet, providing the baseline cost, even without knowing what part insurance would cover, would be worthwhile.  Presumably, somebody is paying.

Bottomline: How many physicians know how much that blood test, the endoscopy, or the CT scan is going to cost? In medicine, physicians frequently discuss risk-benefit ratio.  I think an effort to understand the cost should be part of the equation as well.

Related blog entries:

Risk from CT scans -Best Data to Date

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Thanks to Mike Hart for forwarding the following reference:

BMJ 2013; 346: f2360 doi: 10.1136/bmj.f2360

This study examines the risk of cancer among a cohort of nearly 11 million Australian children and adolescents since 1985.  Among this cohort, 680,000 (6.2%) pediatric patients were identified who had been exposed to a CT scan. This study was accomplished by analyzing CT scans funded by the Australian Medicare system which provides health services for all Australians.

One of the remarkable aspects of this study was the efforts the authors took to exclude reverse causation.  First of all, the data was analyzed with an exclusion period of a year “because of the possibility that the scan was part of the cancer diagnostic procedure…but we repeated the main analyses with lag periods of five and 10 years to explore the possibility of reverse causation.”  In addition, the authors analyzed all non-brain cancers in patients who had had cranial CT scans.  Despite all of the parameters, an increased risk of cancer was maintained among those who had prior CT and the risk was heightened by obtaining studies at younger ages and by having increased number of CT scans.

Key findings:

  • Almost 60% of CT scans were of the brain. Only 5% of CT scans were of abdomen or pelvis.
  • CT scan incidence increased over time.  Between 1985-89, 95,249 (14%) CT scans were ordered.  Whereas between 2000-2005, 266,971 (39%) were ordered.
  • The average CT dose was about 4.5 mSv per scan.
  • The increased relative risk (IRR) for brain cancers after a scan to a site other than the brain was 1.51 (confidence interval 1.19-1.91).
  • Each seivert (Sv) of effective dose was associated with 0.125 cancers; thus, by 2007, with average followup of 9.5 years, one cancer resulted from every 1800 CT scans.  This number is likely to climb with more time.
  • Among brain CT scans, the numbers are trickier due to the possibility of slow-growing tumors (which could trigger symptoms for imaging and still be difficult to detect).  However, up to one excess brain cancer would occur for every 4000 brain scans.
  • All solid cancers IRR 1.25, All lymphoid/hematologic cancers IRR 1.19, Brain cancers after CT IRR 2.44, Brain cancer after other scans 1.51.

There are several limitations to the study including the difficulty of knowing specific doses of radiation at various CT scanners, the possibility of CT scans funded outside the Australian Medicare system, or obtaining screening scans due to precancerous genetic conditions. Nevertheless, the magnitude of the cohort in this study along with its general agreement with a number of other studies provide ample evidence that these risks are real.

Take-home point: While CT scans have the potential for great benefits, they increase the risk of developing cancer; in many cases, an MRI or an ultrasound can provide similar information without this risk.  In this study, for lag (exclusion) period of one, five, and 10 years, the incidence rate for all cancers combined increased by 24%, 21%, and 18% respectively in the CT exposed group.  Eventual lifetime risk is likely to climb with longer followup.

Related blog posts:

Uncertainty and Mindfulness

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Two complementary perspective articles are worth a look:

  • NEJM 2013; 368: 2445-48
  • NEJM 2013; 368: 2448-50.

The first article discusses cognitive bias. The authors note that diagnostic failure rates are typically in the range of 10-15%, but lower for “visual specialties” like radiology and pathology where the rate is closer to 2%.  Why is the diagnostic failure rate so high?  The authors describe the mind’s vulnerability due to biases, and assumptions. “More than 100 biases affecting clinical decision-making have been described.”

The authors note that decision-making relies on either intuitive processes or analytic processes.  Intuitive processes are either hard-wired or acquired through repeated experiences.  These processes are subconscious and fast.  In contrast, analytic processes are deliberate, slower, but much more reliable.  “Despite the ubiquity and usefulness of intuitions, they are not reliable enough for us to use them to send a spaceship to Mars.”  In more complex issues, analytic processes are needed.

The main problem with analytical thinking is that it is more time-consuming and more resource-intensive.  “It would be impractical to deal with each clinical decision analytically.”  Keeping mindful of when critical thinking is needed is the challenge.

The second article discusses uncertainty, especially with regard to prognosis.  Key points:

  • Normalize the issue of uncertainty with patients. “Patients are bombarded…with the notion that high-tech advances…have resulted in definitive answers.” “Clinicians should be honest…’I understand that you want more accurate information about the future.  The reality is that it’s like predicting the weather–we can never be absolutely certain about the future. I wish I could be more certain.'”
  • Help families manage uncertainty.  “The search for certainty may impede the ability …to live in the present.” Clinicians should avoid propagating this issue.  Instead of “We need more time to be sure,” the authors suggest “What can we do to help you now, given that we are unsure of exactly what the future will bring?”