SAFETY ISSUES
| VACCINE SAFETY UPDATE—Neal A. Halsey, MD, Professor, Department of International Health, Johns Hopkins
University Bloomberg School of Public Health, and Professor, Department of Pediatrics, Johns Hopkins University
School of Medicine, Baltimore, MD
|
 | Varicella-zoster vaccines: available in 3 titers; reports of adult formulation (ie, Zostavax) inadvertently administered
to children; resulted in headache and fever in 2 children 1 wk after vaccination, and rash in one child, but
no serious adverse events; monitor child if accidentally given adult vaccine; accidental administration of adult
vaccine not associated with decrease in immunogenicity, therefore reimmunization not necessary (adult vaccine
has higher titer)
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| Combined measles-mumps-rubella-varicella (MMRV) vaccine: MMRV produces higher antibody response; despite
same concentration of measles virus as in MMR vaccine; MMRV associated with small increase in rate of
fever after vaccination (usually occurs within 6-12 days; no increase in febrile seizures)
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| Human papillomavirus (HPV) vaccine: syncope most common side effect requiring medical attention; 26 cases of
syncope or “dizziness” associated with HPV vaccine; serious head injury occurred in 6 patients, who fainted after
administration of HPV vaccine (adolescents majority of cases; can result in long-term neurologic complications
and death); prevent syncope and secondary injuries by instructing patient to sit or lie down for 15 min after
immunization
|
| Rotavirus vaccine: controlled clinical trials show RotaTeq vaccine not associated with increased risk for intussusception
within first 42 days and 1 yr after vaccination; controlled clinical trials show no increased rate of fever,
vomiting, diarrhea, or hematochezia; Food and Drug Administration (FDA) released “information update” on
RotaTeq vaccine in February 2007; FDA reported 3.5 million doses distributed, and 28 reports of intussusception
(does not exceed number expected; FDA requested product label and patient product information be updated)
|
| Meningococcal conjugate vaccine (Menactra): 19 reports of Guillain-Barré syndrome (GBS) that occurred ≤6 wk
after administration of vaccine; analysis of data showed not statistically significant; risk for GBS associated with
Menactra vaccine currently unknown; FDA updated label and product information, but made no change in recommendations
for universal use; cluster analysis suggests GBS most likely to occur during second week after
vaccination
|
| Live attenuated influenza vaccine: 3 of 4 studies indicated live attenuated formula more effective than inactivated
(possibly due to carryover efficacy to second year and greater coverage against drifted strains); licensure not yet
approved in 12- to 59-mo-old children; subgroup analysis shows 6- to 11-mo-old infants have 3% increase in
medically significant wheezing and 3.5% increase in hospitalization rates ≤180 days after last dose of vaccine;
significant increase in risk for hospitalization among 6- to 11-mo-old infants, in both those with and without history
of wheezing; live attenuated vaccine more beneficial in children >12 mo of age without history of wheezing;
manufacturer seeking approval for children ≥12 mo of age and who do not have history of wheezing
|
| Adverse events and standard vaccination schedule: recent study showed no association between infant vaccinations
and recurrent wheezing in infants <12 mo of age; also showed no association between infant vaccinations and eczema
during first year of life
|
| Case of eczema vaccinatum: occurred in child of military personnel (military vaccinates recruits traveling to Iraq
and Afghanistan); father had history of eczema as child (associated with specific immune deficiency that predisposes
for increased severity of eczema); child treated with experimental antiviral agent; mortality rate 10% to
20%
|
| Thimerosal preservative and autism: ecologic analysis comparing mercury exposure and autism-like diagnosis of
children in United States from 1987 to 1998 (sponsored by groups seeking educational services for autism in
California); showed autism rate increasing; however, increase in cases of autism has continued despite decreased
exposure to thimerosal; increasing rates of autism seen even in countries where thimerosal use discontinued; increased
reporting probably due to increased recognition, diagnosis, and acceptance by parents and broadening of
spectrum of this disorder; Institute of Medicine (IOM) published review of data on vaccines and autism; no
causal relationship found between MMR vaccine and autism or between thi-merosal-containing vaccines and autism;
Centers for Disease Control and Prevention (CDC) study on impact of thimerosal on developmental delay
looked at 1200 children 7 to 9 yr of age who received varying doses of thimerosal in first 7 mo of life; preliminary
results showed thimerosal had no effect on development; currently, CDC gathering data for case-controlled
study looking at prenatal exposure to thimerosal, exposure during first 28 days of life (ie, hepatitis B vaccine),
and from birth to 7 mo of age (results expected in 2008)
|
| Persistence of measles virus and autism: study found no evidence of measles virus in peripheral blood of children
with autism
|
| Public perception of safety: public perceives link between vaccines and autism, despite lack of evidence; currently,
most vaccines (except for some influenza formulations) do not contain thimerosal as preservative; some vaccines
contain residual amounts (<0.5 µg) of thimerosal; state legislation—23 states have had bills formerly introduced
and 13 more with bills in preparation; 7 states have adopted laws that limit or exclude use of vaccines with thimerosal
(most allow for trace amounts), and most allow for exceptions or suspensions of law in public health emergencies
|
| Conclusions: safety (and perceptions about safety) as important as efficacy; new vaccines carefully monitored after
licensure; more information made public by FDA, even if evidence not supportive of causal relationships; physician-reporting
to Vaccine Adverse Event Reporting System (VAERS) keystone for monitoring safety; important
to educate parents, press, and legislators regarding causal assessments
|
| MEDICATION SAFETY IN THE AMBULATORY SETTING—Stephen D. Wilson, MD, PhD, Associate Clinical
Professor of Pediatrics, and Director, Pediatric Hospital Medicine, University of California, San Francisco, School of
Medicine
|
| Medication safety: scope of problem—according to 2006 IOM report, medication errors harm 1.5 million Americans
annually, with annual cost of $175 billion dollars; 75% of medication errors occur in ambulatory setting; 1 of
every 131 outpatient deaths attributable to medication errors; National Center for Health Statistics reports 9000
deaths per year directly attributable to acknowledged medication errors; unacknowledged medication errors that directly
or indirectly contributed to mortality estimated at 4 to 5 times that number; medication errors responsible for
45,000 deaths per year (similar to mortality rates for breast cancer and motor vehicle accidents)
|
| Medication errors: mortality and adverse events—deaths due to medication errors increased during past 2 decades,
compared to decrease in all transportation-related deaths; rate of serious medication errors and adverse effects
(including death) per prescription 6 to 7 times rate that occurs in hospital setting; other studies suggest rate of
significant errors among outpatient prescriptions, 6% to 15% (pediatric settings at high end of range); types of
errors—incorrect medication for condition, incorrect dose due to knowledge error, incorrect dose due to calculation
error, incorrect frequency, medication prescribed to allergic patient, and medication prescribed while patient
taking dangerously interacting medication; errors of omission—condition recognized, but medication not prescribed
(eg, not prescribing inhaled steroid for patient with chronic asthma); supporting medication indicated, but
not prescribed (eg, patient on high dose of furosemide and not given potassium-sparing agent); errors of
transmission—illegible handwriting; verbal or phone prescription not properly understood; errors involving
sound-alike or look-alike medications; dispensing errors—wrong medication dispensed; wrong dose dispensed;
wrong instructions or duration given; serious error rate at chain pharmacies estimated at 1% to 2% of all prescriptions;
number of errors exacerbated by shortage of pharmacists nationwide, while number of prescriptions increasing;
growing reliance on pharmacy technicians who have more active role in filling prescriptions because of
shortage of pharmacists; compliance errors—currently, system has no direct feedback between pharmacy and
physician; errors include failure to fill prescription and prescription not covered by insurance
|
| Potential solutions: start with things most easy to change; prescribing process—50% of outpatient errors arise during
prescribing process; consider use of electronic personal references on personal data assistant (PDA), electronic
personal prescription-writing software (produces legible prescriptions; may calculate dosages), prescription software
with advanced decision support, prescription software linked to patient’s electronic medical record, and prescription
software with electronic transmission to commercial pharmacies; conclusions from IOM 2006 report—
electronic prescribing most promising for reducing drug-related mistakes (can eliminate legibility errors, allows introduction
of decision support tools, and allows inclusion of patient-specific considerations [eg, allergies and drug
interactions]); electronic prescribing could avoid >2 million adverse drug events annually, eliminate >100,000 life-
threatening reactions, and save billions of dollars; most current systems severely limited in effectiveness; IOM
recommendations—all healthcare providers should have plans in place to write prescriptions electronically by
2008 (speaker believes ambitious, but unrealistic); providers should use electronic prescribing systems, and pharmacies
should receive prescriptions electronically by 2010; Agency for Healthcare Research and Quality (AHRQ)
should lead development and implementation of prescription-writing information technology systems; Medicare
Modernization Act of 2003—charged Secretary of Health and Human Services with establishing federal electronic
prescribing standards for all patients enrolled in Medicare Part D
|
| Electronic prescribing systems: National E-prescribing Patient Safety Initiative (NEPSI)—funded by private consortium;
5-yr goals include providing physicians with standard electronic web-based prescribing system; backed
by Centers for Medicare and Medicaid Services, Center for Health Transformation, and several private insurance
companies; web-based, only need Internet connection and web browser to access system; design features include
—providing patient medication reviews; cross-checking for drug interactions; continuous uploading of updated
formularies from insurance companies; connection to major commercial pharmacies; linkage to medical search
engine designed by Google; system developed by Palm, Inc—2 approaches; 1) self-contained PDA-based system
(can provide local printing); contains access to formularies and some decision-making support; 2) electronic
prescription system; provides web-based transmission to pharmacies and web-based linkage to formularies;
disadvantages—NEPSI prescribing system free for first 5 yr, but expect subscription fee or proprietary software
upgrades may be required at end of free period; electronic prescribing associated with increased amount of time
and substantial cost; associated with new kinds of errors (eg, drop-down menus); studies concluded first-generation
systems do not necessarily make large difference in outcomes
|
| Ways to reduce medication errors now: handwriting—use legible handwriting; take time to spell out everything;
terminology—avoid “use as directed”; dosage—double-check dosage calculations; other
recommendations—avoid errors by writing prescriptions in setting without interruptions; avoid use of abbreviations
(eg, write daily instead of qd, unit instead of U); avoid use of decimals and terminal zero (eg, write 1 mg instead
of 1.0 mg); recommend using pre-printed prescriptions for frequently prescribed medications; when calling in
prescription to pharmacy, spell drug name, include 2 patient identifiers, and request “read back” from pharmacist
of entire prescription; advise patients and families to check prescriptions after pick-up from pharmacy; invest in
electronic decision support tools; begin to evaluate prescription-writing software options (look for decision support
features, compatibility with commercial pharmacy software, ability to expand later, and potential for expansion
into outpatient electronic medical records)
|
Suggested Reading
Cimino MA et al: Assessing medication-prescribing errors in pediatric intensive care units. Pediatr Crit Care Med
5:124, 2004; Classen DC et al: Improving medication safety: the measurement conundrum and where to start. Int J
Qual Health Care 15:i41, 2003; Clifton JC II: Mercury exposure and public health. Pediatr Clin North Am 54:237,
2007; D'Souza Y et al: No evidence of persisting measles virus in peripheral blood mononuclear cells from children
with autism spectrum disorder. Pediatrics 118:1664, 2006; Grossman JM et al: Physicians' experiences using
commercial e-prescribing systems. Health Aff 26:w393, 2007; Halsey NA et al: Mercury in infants given
vaccines containing thiomersal. Lancet 361:698, 2003; Hviid A: Postlicensure epidemiology of childhood vaccination:
the Danish experience. Expert Rev Vaccines 5:641, 2006; Jacobs B et al: Electronic medical record, error detection,
and error reduction: a pediatric critical care perspective. Pediatr Crit Care Med 8:S17, 2007; King WJ et
al: The effect of computerized physician order entry on medication errors and adverse drug events in pediatric inpatients.
Pediatrics 112:506, 2003; Potts AL et al: Computerized physician order entry and medication errors in a pediatric
critical care unit. Pediatrics 113:59, 2004; Salmon DA et al: Factors associated with refusal of childhood
vaccines among parents of school-aged children: a case-control study. Arch Pediatr Adolesc Med 159:470, 2005;
Salmon DA et al: Enhancing public confidence in vaccines through independent oversight of postlicensure vaccine
safety. Am J Public Health 94:947, 2004; Shevell M et al: Autism and MMR vaccination or thimerosal exposure:
an urban legend? Can J Neurol Sci 33:339, 2006; Varkey P et al: The effect of computerized physician-order entry
on outpatient prescription errors. Manag Care Interface 20:53, 2007; Wu RC et al: Cost-effectiveness of an electronic
medication ordering and administration system in reducing adverse drug events. J Eval Clin Pract 13:440,
2007.
Educational Objectives
| The goal of this program is to improve patient safety, specifically in the areas of vaccination and potential medication
error in the ambulatory setting. After hearing and assimilating this program, the clinician will be better able to:
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| 1. Discuss the safety of the varicella-zoster and the combined measles-mumps-rubella-varicella (MMRV) vaccines.
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| 2. Describe the most common adverse events associated with administration of the human papillomavirus (HPV)
and meningococcal conjugate vaccine.
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| 3. Evaluate the live attenuated influenza virus vaccine for efficacy and potential for adverse events.
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| 4. Discuss the potential causal relationship between vaccines and autism, and describe the most recent findings,
which do not currently support this hypothesis
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| 5. Discuss the types of medication errors, and potential solutions for avoiding these errors, in the pediatric ambulatory
population.
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Faculty Disclosure
In adherence to ACCME Standards for Commercial Support, Audio-Digest requires all faculty members to disclose
relevant financial relationships within the past 12 months that might create any personal conflicts of interest. Any
identified conflicts were resolved to ensure that this educational activity promotes quality in health care and not a proprietary
business or commercial interest. For this program, the following has been disclosed: Dr. Halsey receives research
support from Wyeth Laboratories for studies in Guatemala, and one-day consultancies from Merck, Novartis,
and Medimmune.
Acknowledgements
Dr. Halsey was recorded in Baltimore, MD, at the 35th Annual Pediatric Trends, presented April 16-20, 2007, and
sponsored by the Johns Hopkins Children’s Center. Dr. Wilson was recorded in San Francisco, CA, at the 40th Annual
Advances and Controversies in Clinical Pediatrics, presented May 31 through June 2, 2007, and sponsored by
the Department of Pediatrics, University of California, San Francisco, School of Medicine. The Audio-Digest Foundation
thanks Drs. Halsey and Wilson and the sponsors for their cooperation in the production of this program.
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