Cochrane for Clinicians
Putting Evidence into Practice
Vaccines for Preventing
Influenza in Healthy Children
|The Cochrane Abstract below is a summary of
a review from the Cochrane Library. It is accompanied by an interpretation that
will help clinicians put evidence into practice. Steven E. Roskos, M.D.,
presents a clinical scenario and question based on the Cochrane Abstract,
followed by an evidence-based answer and a full critique of the review.
A healthy one-year-old girl presents in the
fall for well-child care and an immunization update. The girl's mother asks you
whether her child should have an influenza vaccination.
Would an influenza vaccination prevent
illness in this patient, and would it be safe?
Influenza vaccines have good efficacy
(i.e., prevention of influenza) in children older than two years, and live,
attenuated vaccine is more efficacious than trivalent, inactivated vaccine.
Effectiveness (i.e., prevention of influenza-like illness, perhaps a clinically
more important measure) is poor for all influenza vaccines in healthy children.
Safety outcomes have not been analyzed. In children younger than two years,
trivalent inactivated vaccine is no better than placebo and there are no
good-quality safety data. There is some evidence that vaccines are effective in
reducing school absence.1
Influenza in otherwise healthy children
most commonly causes a febrile respiratory illness that leads to school (and,
for their parents, work) absenteeism; however, it can result in hospitalization
and, rarely, death. Hospitalization rates for influenza in children up to one
year of age are comparable with those reported for 65-year-old adults.
Influenza was responsible for an estimated 92 deaths per year in the 1990s
among children younger than five years. One study revealed that 70 percent of
deaths caused by influenza in children two to 17 years of age were in patients
without an underlying medical condition.2
In 2002, the vaccination for influenza of all
children six to 23 months of age was encouraged by the universal
recommendations of the Advisory Committee on Immunization Practices (ACIP) of
the Centers for Disease Control and Prevention,3 which is endorsed by the American Academy of
Family Physicians. The vaccine was included in the Vaccines for Children
program in 2003.4 Recommendations for the
2005-2006 influenza season included administration of influenza vaccine to all
children six to 23 months of age and any persons wishing to reduce the
likelihood of becoming ill with influenza or of transmitting influenza to
others.2 Support for extending vaccination to
healthy younger children is provided largely by a two-year randomized study
involving children six to 24 months of age.5
In this study, a high rate of seroconversion was found among children given the
influenza vaccine, but there was only a small decrease in the rate of influenza
during year 1 (culture-proven influenza was identified in 5.5 percent of
children in the vaccination group versus 15.9 percent of those in the placebo
group) and no difference in rates during year 2.5 Influenza vaccination did not reduce the
likelihood of otitis media.5
children and adults, the consequences of influenza mainly are absences from
school and work; however, the risk of complications is greatest in children and
in persons older than 65 years.
appraise all comparative studies evaluating the effects of influenza vaccines
in healthy children, to assess vaccine efficacy (i.e., prevention of confirmed
influenza) and effectiveness (i.e., prevention of influenza-like illness), and
to document adverse events associated with receiving influenza vaccines.
The reviewers1 searched the Cochrane
Central Register of Controlled Trials (CENTRAL; Cochrane Library Issue 1,
2005), OLD MEDLINE (1966 to 1969), MEDLINE (1969 to December 2004), EMBASE
(1974 to December 2004), Biological Abstracts (1969 to December 2004), and
Science Citation Index (1974 to December 2004). They wrote to vaccine
manufacturers and a number of corresponding authors of studies in the
Criteria: Any randomized controlled trials (RCTs) and cohort or
case-control studies of any influenza vaccine in healthy children younger than
Data Collection and
Analysis: Two authors independently assessed trial quality and extracted
Results: Fifty-one studies involving a total of 263,987 children were
included. Seventeen papers were translated from Russian. Fourteen RCTs and 11
cohort studies were included in the analysis of vaccine efficacy and
effectiveness. From RCTs, live vaccines showed an efficacy of 79 percent (95%
confidence interval [CI], 48 to 92) and an effectiveness of 33 percent (95% CI,
28 to 38) in children older than two years compared with placebo or no
intervention. Inactivated vaccines had a lower efficacy (59 percent; 95% CI, 41
to 71) than live vaccines but similar effectiveness (36 percent; 95% CI, 24 to
46). In children younger than two years, the efficacy of inactivated vaccine
was similar to placebo. Thirty-four reports containing safety outcomes were
included: 22 of live vaccines, eight of inactivated vaccines, and four of both
types. The most commonly presented short-term outcomes were temperature and
local reactions. The variability in design of studies and presentation of data
was such that meta-analysis of safety outcome data was not feasible.
Conclusions: Influenza vaccines are efficacious in children older than
two years, but little evidence is available for children younger than two
years. There was a marked difference between vaccine efficacy and
effectiveness. That no safety comparisons could be carried out emphasizes the
need for standardization of methods and presentation of vaccine safety data in
future studies. It was surprising to find only one study of inactivated vaccine
in children younger than two years given recent recommendations to vaccinate
healthy children from six months of age in the United States and Canada. If
immunization in children is to be recommended as public health policy,
large-scale studies assessing important outcomes and directly comparing vaccine
types are urgently required.
These summaries have been
derived from Cochrane reviews published in the Cochrane Database of Systematic
Reviews in the Cochrane Library. Their content has, as far as possible, been
checked with the authors of the original reviews, but the summaries should not
be regarded as an official product of the Cochrane Collaboration; minor editing
changes have been made to the text (http://www.cochrane.org).
Two influenza vaccines are available for use in
children. The trivalent, inactivated vaccine is given by intramuscular
injection and is approved for children six months of age. It is given annually,
except in previously unvaccinated children younger than nine years, for whom
two doses are recommended, one month apart, with the second dose given before
December. The live, attenuated vaccine is given by intranasal spray and is
approved for healthy patients five to 49 years of age. It also is given
annually, except in previously unvaccinated children five to nine years of age,
who should receive two doses separated by six to 10 weeks.2
The Cochrane authors reviewed the literature and
included randomized controlled trials (RCTs) and cohort and case-control
studies.1 Efficacy and effectiveness results
were taken mainly from 14 RCTs. Safety outcomes could not be combined for
analysis because of the variability in study design and the diversity of safety
outcomes reported, as well as the variable presentation of data. There are some
lower-quality safety data available for trivalent, inactivated vaccine and
live, attenuated vaccine in children, including those six to 23 months of age,
from event-reporting networks and population-based studies.2 The most commonly reported adverse events from
reporting networks and observational studies were fever, rash, injection-site
reactions, irritability, insomnia, and seizures. Causality could not be proved,
and in some studies the seizures were thought to be febrile seizures. One
placebo- controlled study and one population-based study showed no increase in
significant adverse events, but neither met criteria for inclusion in the
Family physicians should present parents with the
ACIP recommendations, explain that there is limited evidence that the vaccine
is effective for children younger than two years, advise that the vaccine may
reduce school absence in school-age children, and let parents decide. Future
research is needed to clarify the benefit and safety of influenza vaccines in
1. Smith S, Demicheli V, Di Pietrantonj C,
Harnden AR, Jefferson T, Matheson NJ, et al. Vaccines for preventing influenza
in healthy children. Cochrane Database Syst Rev 2006;(1):CD004879.
2. Harper SA, Fukuda K, Uyeki TM, Cox NJ, Bridges
CB, for the Advisory Committee on Immunization Practices, Centers for Disease
Control and Prevention (CDC).
Prevention and control of influenza.
Recommendations of the Advisory Committee on Immunization Practices (ACIP)
[Published correction appears in MMWR Morb Mortal Wkly Rep 2005;54:750]. MMWR
Recomm Rep 2005;54(RR-8):1-40.
3. Bridges CB, Fukuda K, Uyeki TM, Cox NJ,
Singleton JA, for the Advisory Committee on Immunization Practices. Prevention
and control of influenza. Recommendations of the Advisory Committee on
Immunization Practices (ACIP). MMWR Recomm Rep 2002;51(RR-3):1-31.
4. Campos-Outcalt D. Influenza vaccine: new
recommendations for infants and children aged 6 to 23 months. J Fam Pract
5. Hoberman A, Greenberg DP, Paradise JL,
Rockette HE, Lave JR, Kearney DH, et al. Effectiveness of inactivated influenza
vaccine in preventing acute otitis media in young children: a randomized
controlled trial. JAMA 2003;290:1608-16.
STEVEN E. ROSKOS, M.D., is assistant professor in
the Department of Family Medicine at the University of Tennessee Graduate
School of Medicine, Knoxville.
to Steven E. Roskos, M.D., Dept. of Family Medicine, University of Tennessee
Graduate School of Medicine, 1924 Alcoa Highway, U-67, Knoxville, TN 37920
Reprints are not available from the author.
This clinical content conforms to AAFP
criteria for evidence-based continuing medical education (EB CME). EB CME is
clinical content presented with practice recommendations supported by evidence
that has been reviewed systematically by an AAFP-approved source. The practice
recommendations in this activity are available at
Expectant Management vs.
Surgical Treatment for Miscarriage
What is the safety and effectiveness of
expectant management versus surgical treatment for first-trimester
Expectant management and surgical treatment
are safe and effective for first-trimester miscarriage. Among patients who
choose expectant management, there is a lower rate of pelvic infection but
higher rates of mild bleeding, need for unplanned surgical treatment, and
When a nonviable first-trimester pregnancy
is diagnosed, women have the option of waiting for the uterine contents to
pass, choosing medical management with medications such as misoprostol
(Cytotec), or undergoing dilation and curettage. Without intervention, more
than 65 percent of missed abortions and 80 percent of incomplete and
first-trimester abortions pass naturally within two to six weeks.1 Misoprostol 600 to 1,200 mcg vaginally on day 1,
with a repeat dose if indicated on day 3, has been proven safe and effective.
Success rates approach 95 percent, and women find their experience
satisfactory.2,3 Surgical management includes
vacuum extraction, suction curettage, or sharp curettage with or without
dilation. Surgical management is the definitive treatment when other methods
Nanda and colleagues reviewed the literature for
trials comparing expectant management with surgical treatment for miscarriage.
They found five trials with a total of 689 participants.
Expectant management had higher rates of incomplete
miscarriage, need for unplanned surgical treatment, and bleeding, but a lower
rate of pelvic infection (relative risk 0.29; 95% confidence interval, 0.09 to
0.87). Rates of infection ranged from 0 to 10 percent. Overall, there were two
women in expectant management groups who required blood transfusion. However,
rates of hemorrhage greater than 500 mL and bleeding requiring transfusion were
not statistically significant between expectant management and surgical
treatment groups. Two to 20 percent of women in the expectant management groups
needed surgery. Unplanned surgical management usually was attributed to
unacceptable pain, bleeding, or patient request. There were no differences in
serious adverse events between the expectant management and surgical treatment
Rates of complete abortion varied by study. In one
study, the rate of complete abortion in the expectant management group was 81
percent at less than two weeks and 93 percent at seven weeks. Surgical
treatment had a complete abortion rate of 97 percent at less than two weeks; no
patients required second procedures. There is no clear indication for routine
surgical management; therefore, patient preference should be respected.
Nanda K, et al. Expectant care versus surgical treatment for
miscarriage. Cochrane Database Syst Rev 2006;(2):CD003518.
1. Butler C, Kelsberg G, St Anna L, Crawford P.
Clinical inquiries. How long is expectant management safe in first-trimester
miscarriage? J Fam Pract 2005;54:889-90.
2. Nguyen TN, Blum J, Durocher J, Quan TT,
Winikoff B. A randomized controlled study comparing 600 versus 1,200 microg
oral misoprostol for medical management of incomplete abortion. Contraception
3. Creinin MD, Huang X, Westhoff C, Barnhart K,
Gilles JM, Zhang J, for the National Institute of Child Health and Human
Development Management of Early Pregnancy Failure Trial. Factors related to
successful misoprostol treatment for early pregnancy failure. Obstet Gynecol
Exercises for Mechanical Neck
How effective is exercise therapy for
mechanical neck pain?
There is some evidence that a variety of
exercises help patients with mechanical neck pain. Evidence is strongest for a
multimodal approach that includes exercise and mobilization or manipulation of
the cervical spine, although this research has been criticized for having an
imperfect control group.
Mechanical neck pain is caused by a variety
of injuries and disease processes, including whiplash, myofascial neck pain,
and degenerative cervical spine disease. Kay and colleagues reviewed the
literature for randomized and quasi-randomized clinical trials on treatments
for neck pain. Most studies (24) were of mechanical neck pain alone. The
researchers also found one study of mechanical neck pain with some radicular
signs, three studies of headache of cervical origin, and three involving a
mixed group of patients with neck pain and neck disorder associated with
headache or radicular symptoms. Studies were of fair quality. Although an
earlier version of this systematic review was inconclusive, subsequent
systematic reviews by other groups have found a benefit with exercise.
The authors found limited evidence of benefit for
mechanical neck pain with a variety of types of exercise activity: active
range-of-motion exercises without resistance, stretching and strengthening
exercises, strengthening exercises alone, and eye-fixation exercises to improve
proprioception. The strongest evidence, from four studies, was found for a
multimodal approach that included exercise and mobilization or manipulation of
the cervical spine (number needed to treat = 4 to 5).
The Philadelphia Panel, a panel of physicians and
methodologic experts from the United States and Canada, developed an
evidence-based guideline for the treatment of musculoskeletal disorders.1 According to this guideline, there is good
evidence (grade A for pain and function, grade B for patient global assessment)
to include supervised exercise programs alone, including proprioceptive and
traditional exercises, for the management of chronic neck pain (i.e., lasting
longer than 12 weeks).1 The Philadelphia Panel
does not endorse manual therapy (i.e., cervical mobilization or manipulation)
because the control group did not receive sham manual therapy.
TM, et al. Exercises for mechanical neck disorders. Cochrane Database Syst Rev
1. Philadelphia Panel evidence-based clinical
practice guidelines on selected rehabilitation interventions for neck pain.
Phys Ther 2001;81:1701-17.
The series coordinator for AFP is Clarissa Kripke, M.D., Department of Family
and Community Medicine, University of California, San Francisco.
Copyright © 2006 by the American
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