CME
Evidence-Based Practice
Answering clinical questions▲
with the best sources
VOLUME 9
NUMBER 10
OCTOBER 2006
WHAT’S INSIDE
H P V U P D AT E S U P P L E M E N T
3
HIV UPDATE
Long-term outcome of a
multivalent HPV vaccine
FROM THE EDITOR
HELP DESK
4
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5
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7
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3
4
Do smokers of low-tar cigarettes have
a lower risk of lung cancer than smokers
of higher-tar cigarettes?
What is the safest and most effective
form of emergency contraception
available in the United States?
What are the criteria for admitting
a patient suspected of having
community-acquired pneumonia?
Does obesity affect outcomes for patients
undergoing total knee replacement
for osteoarthritis?
Is the combination of calcipotriene
(Dovonex®) and betamethasone
more effective than either agent alone
for treating psoriasis?
B E H AV I O R A L H E A LT H M AT T E R S
Nonpharmacological interventions
for insomnia in adults
W O M E N ' S H E A LT H U P D AT E
10
Gabapentin: Another alternative
for hot flashes?
DRUG PROFILE
10
Levemir®: Comparable to Lantus®?
9
Stronger evidence supports
protective value of male
circumcision in HIV transmission
The direct impact of male circumcision on the rate of HIV
transmission remains controversial. However, results of a
recent study, in which adult men at high risk of
acquiring HIV were randomized to immediate or delayed
circumcision, have shed new light on this important topic
Epidemiologists have noted that areas of Africa with higher rates of
male circumcision tend to have lower HIV infection rates.1 But indepth analyses of this association have produced conflicting results.
For example, a meta-analysis from 2000 looking at data from 27 studies from sub-Saharan Africa concluded that male circumcision
reduced the risk of acquiring HIV by about 50%.2 In contrast, a 2003
Cochrane review3 identified 35 quality observational studies, 19 conducted in high-risk populations. The Cochrane review conclusion
was that while there was a definite epidemiological association, evidence was insufficient to support circumcision as a means to reduce
transmission.
The problem, of course, is that cultures that circumcise are different from those that do not, and circumcision may be a marker for
a host of other risk-lowering behaviors.
To attempt to determine if male circumcision can reduce HIV
risk, researchers conducted a randomized, nonblinded study in the
semiurban area of Orange Farm, near Johannesburg, South Africa.4
Community-wide recruitment sought men ages 18 to 24 who wanted
to be circumcised, but who would agree to be randomized to immediate circumcision or to circumcision at the end of the study period.
Patients who were already HIV positive (4.4% of the men assessed for
eligibility) were excluded. Patients found to be HIV positive at any
time during the study were referred for antiretroviral therapy.
continued
HIV UPDATE
The study included 3,724 men, half of whom
were randomized to immediate circumcision and
half to delayed circumcision. More than 90% of
them had been sexually active with a partner on at
least 1 occasion, with an average age of first sexual
experience between 16 and 17 years. Most participants reported between 1 and 3 lifetime sexual partners. As a group, 0.07% of their sexual partners had
been men and only 3 participants had ongoing sexual partnerships with men. About 2% of participants were married or living as married. All patients
were counseled about sexually transmitted disease
and had access to condoms. Circumcision costs
were covered by the investigators and were conducted by 3 local general practitioners. Patients
receiving circumcisions were instructed not to have
any sexual activity for 6 weeks while their incisions
healed. Patients were reevaluated and had their
HIV status checked at 3, 12, and 21 months.
The trial was stopped early. At a mean followup of 18 months, the researchers recorded 20 HIV
infections in the intervention group and 49 in the
control group. The circumcised men had a relative
risk of contracting HIV of 0.40 (95% CI, 0.24–0.68;
P<.001). When controlled for behavioral factors,
including the fact that the men who were circumcised reported more sexual behaviors than controls,
the relative risk of contracting HIV among the circumcised group was 0.39 (95% CI, 0.23–0.66). The
timing of the HIV infections suggested that the 6week postponement of sexual activity in the circumcised group did not contribute significantly to
the protective effect.
Two similar trials are currently under way, 1 in
Kenya and 1 in Uganda, with a combined total of
more than 7,700 patients.5 The results of these studies are expected sometime in 2007. In the mean
time, the demand for adult male circumcision has
already increased significantly in South Africa.
Mathematical modeling suggests that, if the results
of the Orange Farm study can be generalized, a
program of circumcision could save 3 million lives
and prevent 6 million new infections in subSaharan Africa over the next 20 years.1 Based on the
low cost of circumcision in developing countries
(around US$25 in some areas), the cost of preventing 1 case of HIV might be as low as US$1,052.5
A key limitation of the Orange Farm study was
its brief duration. The study also took place in a
2 Evidence-Based Practice
developing country with a high HIV prevalence and
predominantly heterosexual transmission, limiting
its direct application to areas where health care and
HIV spread are different. It was also not a blinded
study, and this could have biased the results. As the
study was conducted among consenting adults, one
must be cautious about extrapolating the outcome
to infant circumcision. Finally, circumcision did not
fully prevent transmission, and the need for continued education and vigorous public health measures
EBP
is unlikely to be reduced.
Jon O. Neher, MD, University of Washington
REFERENCES
1.
Williams BG, Lloyd-Smith JO, Gouws E, et al. The potential impact of male circumcision on HIV in sub-Saharan Africa. PLoS Med 2006; 3:e262. [LOE 2b]
2.
Weiss HA, Quigley MA, Hayes RJ. Male circumcision and risk of HIV infection
in sub-Saharan Africa: a systematic review and meta-analysis. AIDS 2000;
14:2361–2370. [LOE 1a]
3.
Siegfried N, Muller M, Volmink J, et al. Male circumcision for prevention of heterosexual acquisition of HIV in men. Cochrane Database Syst Rev 2003;
(3):CD003362. [LOE 1a]
4.
Auvert B, Taljaard D, Lagarde E, Sobngwi-Tambekou J, Sitta R, Puren A.
Randomized, controlled intervention trial of male circumcision for reduction of
HIV infection risk: the ANRS 1265 trial [published correction appears in PLoS
Med 2006; 3:e298]. PLoS Med 2005; 2:e298. [LOE 1b]
5.
Wise J. Demand for male circumcision rises in a bid to prevent HIV. Bull World
Health Organ 2006; 84:509–511.
CME CREDIT
This activity has been planned and implemented in accordance with the Essential
Areas and policies of the Accreditation Council for Continuing Medical Education
through the joint sponsorship of Michigan State University College of Human
Medicine and the Family Physicians Inquiries Network (FPIN). The Michigan State
University College of Human Medicine is accredited by the ACCME to provide continuing medical education for physicians.
It is estimated that this educational activity will require 3 hours to complete.
Credit Designation statement
Michigan State University, College of Human Medicine, designates this educational
activity for a maximum of three (3) hours in Category 1 credit toward the AMA
Physician’s Recognition Award. Each physician should claim only those hours of credit that he/she actually spent in the activity.
The learning objectives of the Evidence-Based Practice newsletter are to become
knowledgeable about evidence-based solutions to commonly encountered clinical problems, to understand how ground-breaking research is changing the practice of family
medicine, and to become conversant with balanced appraisals of drugs that are currently being marketed to physicians and/or consumers.
The editors of this educational material may review studies that discuss commercial
products or devices as well as the unapproved/investigative use of commercial products/devices. The editors of this educational material report that they do not have significant relationships that create, or may be perceived as creating, a conflict relating to
this educational material.
Statements and opinions expressed in abstracts and communications herein are those
of the author(s) and not necessarily those of the Publisher. The Publisher of this newsletter does not guarantee warrant, or endorse any methods, product, instructions, procedures, techniques, or ideas mentioned in the newsletter. The Publisher and Editors disclaim any liability, loss or risk, personal or otherwise, which may arise, directly or indirectly, from any use or operation of any methods, products, instructions, procedures,
techniques, or ideas contained in the material herein.
Evidence-Based Practice (ISSN 1095-4120) is published monthly by the Family
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Columbia, MO 65202. Telephone: 573-256-2066, Fax: 573-256-2078. E-mail:
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Physicians Inquiries Network, Inc.
From the Editor
HPV Update
Long-term outcome of a
multivalent HPV vaccine
New information strongly supports shortand long-term efficacy of multivalent HPV
vaccination
In the last issue of Evidence-Based Practice, the new multivalent
human papillomavirus (HPV) vaccine Gardasil® was reviewed.1
Gardasil vaccinates against 2 strains of HPV associated with cervical cancer and 2 strains associated with visible anogenital warts.
In that review, readers may have noticed that the key evidence of
the efficacy of Gardasil was based on 2 large studies available in
abstract form that, while ongoing, only reported data out to 2
years.2,3 Data on efficacy out to 4 years were discussed in the
review, but only for an experimental monovalent HPV-16 vaccine.4
However, longer term (>4 year) data have been recently published on an experimental vaccine that contained both HPV-16 and
HPV-18 antigens. Because these are the same cancer-associated
HPV strains found in Gardasil, these data should provide a better
estimate of the cancer-preventing value of Gardasil over a longer
time frame.
In this trial more than 1,000 young women (age 15–25) were
recruited from 32 medical centers; they had no history of abnormal
Pap smears and were seronegative for HPV types 16 and 18.5 They
were randomized to receive either bivalent HPV vaccine or placebo
at 0, 1, and 6 months. Pap smears for cytology and HPV DNA testing, and serum for HPV antibodies, were obtained every 6 months.
At 27 months, using an intent-to-treat analysis, persistent HPV
infection developed in 4% of women in the placebo group, compared
to 0.5% of women in the vaccinated group (P<.0001; number needed to treat [NNT]=29). For the outcome of the development of cytological abnormalities associated with HPV-16 and HPV-18 infection,
vaccination was shown to have a significant protective effect (4.9%
in placebo group vs 0.4% in vaccine group; P<.0001; NNT=23).
The authors then followed a subset of these women (the 776
who had received all 3 doses of the vaccine or placebo) and reported on the outcomes after an average of 4.5 years.6 Efficacy for protection against persistent HPV infection remained high (vaccine
efficacy 94.3%; 95% CI, 63.2%–99.9%). Significantly, no women
in the vaccine group, compared to 1.7% of those in the placebo
group, developed CIN 1 or worse during the 4 years of follow-up.
Comparable information will not be available for Gardasil, a
vaccine that is being marketed now, for another 2 years. However,
this information strongly supports both the short- and long-term
efficacy of multivalent HPV vaccination to prevent chronic infecEBP
tion and the development of cytological abnormalities.
Collecting state quarters and HDAs
I want to take this opportunity to personally thank the United
States Mint for coming up with the 50 State Commemorative
Quarter Program that started in 1999. Ever since January of that
year, every dull trip to the convenience store for a gallon of milk
has become a miniature scavenger hunt as I try to find new state
quarters in my pocket change. I am particularly fond of the 2004
Wisconsin quarter, since nothing says state pride like a tiny picture of an ear of corn, a cow, and a cheese wheel. However, the
2006 designs minted so far have been lovely, too, and I eagerly
look forward to searching for a new issue every time the milk runs
low. If by December I have not found all 5 new quarters minted
this year, I will head down to my local coin shop where I can get
any new quarter for the bargain price of 75 cents.
Collecting state quarters involves more than just finding the
things, however. Even when I have the quarters, if they are all
mixed up with pennies, nickels, and dimes in a pasta sauce jar in
the kitchen cabinet, I don’t have a real collection. A proper collection requires that I have my quarters organized, and for that job I
use a custom coin folder. In another two and a half years, I will have
my 50-slot coin folder finally filled. For the sake of my trips to the
store, I can only hope they start minting custom dimes about then.
I also have another rapidly expanding collection—back
issues of Evidence-Based Practice. These are neatly lined up on
the shelf behind me, but, as I am sure you have noticed, they are
not the easiest things to use as a point-of-care resource.
Fortunately, the problem of creating a workable collection out of
EBP newsletters has already been solved. All the HDAs published
in Evidence-Based Practice are incorporated into PDA-based
comprehensive reference software for your handheld or on the
Web: PEPID PCP (Portable Electronic Physicians Information
Database for Primary Care Plus). This tool keeps the HDAs organized in just the right way—by clinical problem—and embeds
them in detailed monographs addressing the full spectrum of
family medicine. FPIN’s Clinical Inquiries, as published in the
The Journal of Family Practice and American Family Physician,
are similarly embedded in PEPID PCP. PEPID PCP is available
from the Family Physicians Inquiries Network (www.fpin.org).
So having an organized, working HDA collection is now about
as easy as collecting state quarters. There is no need to clip and
file, or flip through old issues of the newsletter. You can lean back
and enjoy reading the discoveries in each new issue without fear of
ever losing them.
Through your affiliation with FPIN as an EBP subscriber, receive a
10% discount on PEPID PCP, by visiting www.pepid.com/fpin. EBP
Regards,
David White, MD, Columbia, Missouri
Jon O. Neher, MD, University of Washington
Jon O. Neher, MD
refrences continued on page 8
Evidence-Based Practice
3
Help Desk
CONCISE ANSWERS TO PHYSICIANS’ CLINICAL QUESTIONS
Do smokers of low-tar cigarettes have
a lower risk of lung cancer than smokers
of higher-tar cigarettes?
low (8–14 mg tar), medium (15–21 mg tar), and
high ≥22 mg tar). All of the high-tar cigarettes
were nonfiltered. Men and women who smoked
very-low-tar and low-tar brands had risks of lung
cancer indistinguishable from participants who
smoked medium-tar brands.
Men and women who smoked high-tar nonfilter brands were found to have about a 50%
increase in risk of cancer-specific mortality than
participants smoking medium-tar brands (hazard
ratio [HR] 1.44; 95% CI, 1.20–1.73 in men, and
HR 1.64; 95% CI, 1.26–2.15 in women).
Evidence-Based Answer
There is no difference in lung cancer mortality
among persons who smoke low- or ultra-low-tar
cigarettes and those who smoke regular filtered cigarettes. However, individuals who smoke unfiltered
(and consequently very-high-tar) cigarettes do have
a significantly higher risk of lung cancer than
smokers of filtered brands. (SOR B, based on a single inception cohort study.)
David White, MD, Columbia, Missouri
To assess risk of lung cancer among smokers of
cigarettes with varying levels of tar, researchers
recruited 175 smokers who had smoked at least 15
cigarettes per day over the preceding year.1 From
questionnaire responses, the brand each participant smoked was classified as regular (>14.5 mg
tar), light (>6.5–14.5 mg tar), and ultralight ≤6.5
mg tar), based on Federal Trade Commission standards. The distribution of smokers based on tar
level was 26.9% for regular, 45.7% for light, and
27.4% for ultralight cigarettes. Urine levels for 2
biomarkers for lung carcinogen, 1-hydroxypyrene
(1-HOP) and 4-(methylnitrosamino)-1-(3pyridyl)-1-butanol (NNAL), were measured,
along with urinary total cotinine concentration
(related to nicotine uptake).
No significant differences were found for any
of the biomarkers among any of the 3 tar level
groups (all P≥.50), demonstrating that uptake of
nicotine and certain lung carcinogens was identical
regardless of cigarette tar level assignment.
These findings were reflected in the results of
a large prospective cohort study2 that enrolled
364,239 men and 576,535 women, aged at least 30
years, who had either never smoked, were former
smokers, or were currently smoking. The primary
outcome was death from primary cancer of the
lung, trachea, or bronchus during the ensuing 6
years. During the 6-year follow-up, 2,622 men and
1,406 women died from these cancers.
Analysis showed that lung cancer death rates
were markedly higher for smokers than for participants who had never smoked or who had quit
smoking. For smokers, cigarette brands were categorized into tar ratings of very low (≤7 mg tar),
4 Evidence-Based Practice
1.
Hecht SS, Murphy SE, Carmella SG, et al. Similar uptake of lung carcinogens
by smokers of regular, light, and ultralight cigarettes [published correction
appears in Cancer Epidemiol Biomarkers Prev 2006; 15:1568. Dosage error in
text]. Cancer Epidemiol Biomarkers Prev 2005; 14:693–698. [LOE 2b]
2.
Harris JE, Thun MJ, Mondul AM, Calle EE. Cigarette tar yields in relation to
mortality from lung cancer in the cancer prevention study II prospective cohort,
1982–8. BMJ 2004; 328:72. [LOE 1b]
What is the safest and most effective form
of emergency contraception available
in the United States?
Evidence-Based Answer
Three options for emergency contraception are currently available in the United States: levonorgestrel
(Plan B®, recently approved for use in adults without a prescription), the Yupze method using combined oral contraceptives, and insertion of a coppercontaining intrauterine device (IUD). Insertion of
an IUD should be offered to women presenting to a
physician for emergency contraception because it
has both the highest efficacy rate and the potential
for use as a long-term contraceptive. Plan B (given
in a 1- or 2-dose regimen) is the preferred hormonal option because of its greater availability, efficacy,
simplicity, and lower side effect profile than combined oral contraceptives. (SOR A, based on systematic reviews and evidence-based guideline.)
A copper-containing IUD should be considered as a
first-line choice for emergency contraception, particularly if long-term contraception is desired.1 An
IUD can be inserted up to 5 days after the first
episode of unprotected intercourse and may be
inserted beyond 5 days if it can be determined that
insertion will not occur beyond 5 days after ovula-
Help Desk
tion. Nulliparity, young age, sexually transmitted
disease risk, and history of ectopic pregnancy are not
considered absolute contraindications to use.
A Cochrane review of interventions for emergency contraception included a randomized trial
comparing insertion of an IUD to no treatment in
300 women presenting within 4 days of unprotected
intercourse. The nontreated group had a significantly higher number of pregnancies (relative risk
[RR]=0.09; 95% CI, 0.03–0.26).2 The incidence of
complications was not reported. Data from 5 nonrandomized trials, not included in the Cochrane
review, suggest a failure rate for IUDs of 0.2% (3
pregnancies/1,470 women).2 A meta-analysis of 20
papers showed postcoital IUD insertion had an
effectiveness rate of 98.7%.3 In contrast, studies of
combined oral contraceptive and levonorgestrel
methods demonstrated efficacy rates of about 75% to
89%, respectively.
Two trials (n=2,878 women) comparing levonorgestrel 750 µg every 12 hours for 2 doses with
the Yuzpe method found levonorgestrel more effective for preventing pregnancy (RR=0.51; 95% CI,
0.31–0.83).2 Nausea (RR=0.43; 95% CI, 0.39–0.48),
vomiting (RR=0.24; 95% CI, 0.18–0.31), dizziness
(RR=0.72; 95% CI, 0.61–0.85), and fatigue
(RR=0.61; 95% CI, 0.54–0.70) were all less common with levonorgestrel. Headache, breast tenderness, and abdominal pain were also less common,
but the statistical difference was marginally significant. Spotting or bleeding and time to resumption of
menses were similar in both groups.
Two trials compared use of a single dose of levonorgestrel 1.5 mg versus the standard 2 doses of 750
µg.2 One of the trials enrolled 1,160 women who
had an episode of unprotected intercourse within 72
hours; the other trial included 4,136 women presenting before 120 hours. No clinically or statistically significant differences were noted for prevention
of pregnancy between the groups (RR=0.77; 95%
CI, 0.45–1.30). With the exception of headache in
women using the single-dose regimen (RR=1.23;
95% CI, 1.04–1.47), no differences were noted in
side effects between the 2 groups.
The World Health Organization (WHO)
states there are no medical contraindications to the
use of hormonal emergency contraception.1 Liver
enzyme-inducing agents (eg, St. Johns wort) may
decrease the efficacy of hormonal emergency contraception. Although most trials of hormonal
emergency contraception have excluded women
who had unprotected intercourse more than 72
hours prior, at least 1 large randomized trial conducted by WHO showed reduction in rates of
pregnancy up to 120 hours.
Andrea Mielke, PharmD candidate
Connie Kraus, PharmD, BCPS
University of Wisconsin School of Pharmacy
1.
Faculty of Family Planning and Reproductive Health Care Clinical Effectiveness
Unit. FFPRHC Guidance April 2006. Emergency contraception. J Fam Plann
Reprod Health Care 2006; 32:121–128. [LOE=1a]
2.
Cheng L, Gulmezoglu, Oel CJ, Piaggio G, Ezcurra E, Look PF. Interventions for
emergency contraception. Cochrane Database Syst Rev 2004; (3):CD001324.
[LOE=1a]
3.
Dunn S, Guilbert E, Lefebvre G, et al. Emergency contraception. J Obstet
Gynaecol Can 2003; 25:673–679 and 680-687. [LOE=1a]
What are the criteria for admitting a patient
suspected of having community-acquired
pneumonia?
Evidence-Based Answer
The pneumonia severity index (PSI) scoring system
is superior to other predictive models with respect to
accurately discriminating high- and low-risk
patients who present with community-acquired
pneumonia. Patients with pneumonia classified as
level IV or V on the index should be hospitalized.
(SOR A, based on a validated clinical decision rule.)
Three prognostic rules have been validated for
stratifying mortality rates in patients presenting
with community-acquired pneumonia. These are
the PSI, the CURB (Confusion, elevated blood
Urea nitrogen, elevated Respiratory rate, low systolic or diastolic Blood pressure), and the CURB-65
(CURB criteria plus age over 65). In a prospective
study, researchers found that the PSI had a higher
discriminatory power for short-term mortality,
defined a greater proportion of patients at low risk,
and was more accurate in identifying patients at
low risk than either CURB score.1
Derived from data on 14,199 inpatients with
community-acquired pneumonia and validated
with data from 38,039 inpatients and 2,287 patients
Evidence-Based Practice
5
Help Desk
EVIDENCE-BASED PRACTICE
Editor-in-Chief
Jon O. Neher, MD
University of Washington
in an inpatient/outpatient study,2 the PSI is based on numerical scores from 20 variables, including age, comorbid conditions, physical findings, and laboratory test results.3 According
to the total score, patients are stratified according to 5 different levels of mortality risk (I–V). Level I patients (very low
risk) can be safely treated as outpatients, and level IV and V
patients (high risk) should be hospitalized. A table of these
findings and their associated numerical scores can be viewed
at http://www.annals.org/cgi/content/full/138/2/109/F2.3 An
online PSI risk score calculator is available at
http://pda.ahrq.gov/clinic/psi/psicalc.asp.4
For patients with intermediate levels of risk (II and III),
researchers performed a randomized trial of 224 immunocompetent adults comparing inpatient with outpatient management.5 Patients, who all presented with communityacquired pneumonia and PSI scores placing them in level II
or III risk strata, were randomly assigned to outpatient or
inpatient care. Outpatients received oral levofloxacin (500
mg/d, mean duration 10 days) and had a home evaluation
by a nurse at 2 days. Inpatients received intravenous levofloxacin (500 mg/d) and switched to the same oral dose
administered daily using a prespecified set of criteria (mean
combined duration 10 days). All patients were evaluated 7
and 10 days after diagnosis.
The primary research outcome was the percentage of
patients with an overall successful clinical outcome, defined
as meeting all of 7 predefined criteria (cure of pneumonia,
absence of adverse drug reactions, absence of medical complications during treatment, no need for additional visits, no
changes in initial treatment with levofloxacin, absence of
subsequent hospital admission in the 30 days after randomization, and absence of death from any cause in the 30 days
after randomization). Other outcomes of interest were
patients’ health-related quality of life and satisfaction with
the care received for pneumonia.
Successful outcome was achieved in 83.6% of outpatients and 80.7% of hospitalized patients (absolute difference, 2.9%; 95% CI, –7.1% to 12.9%). Patients treated as
outpatients were more satisfied with their care, and no
quality-of-life differences were noted between the groups.
David White, MD, Columbia, Missouri
1.
Aujesky D, Auble TE, Yealy DM, et al. Prospective comparison of three validated prediction
rules for prognosis in community-acquired pneumonia. Am J Med 2005; 118:384–392.
[LOE 1a]
2.
Fine MJ, Auble TE, Yealy DM, et al. A prediction rule to identify low-risk patients with community-acquired pneumonia. N Engl J Med 1997; 336:243–250. [LOE 1a]
3.
Metlay JP, Fine MJ. Testing strategies in the initial management of patients with community-acquired pneumonia. Ann Intern Med 2003; 138:109–118. [No LOE – topic review]
6 Evidence-Based Practice
Section Editors
Drug Profile
Rex Force, PharmD
Idaho State University
Maternity Care
Beth Potter, MD
University of Wisconsin
Pharmacy HDAs
Connie Kraus, PharmD, BCPS
University of Wisconsin
Behavioral Health Matters
Laurie Ivey, PsyD
University of Colorado
Evidence in Nutrition
Mindy Schwartz, MD
University of Chicago
Patient Education
Janet Hale, RN
Rockbridge Baths, VA
Jean Blackwell, MLS
University of North Carolina-Chapel Hill
Executive Editor
Bernard Ewigman, MD, MSPH
University of Chicago
Consulting Editor
Sarah Lovinger, MD
Chicago, IL
Medical Copy Editor
Melissa L. Bogen, ELS
Chester, NY
Layout and Design
Robert Thatcher
Midland Park, NJ
Project Manager
Jonathan W. Crowell
Columbia, MO
[email protected]
Statement of Purpose
Evidence-Based Practice (EBP) addresses the most important
patient care questions asked by practicing family physicians, using
the best sources of evidence in a brief, clinically useful format.
Newsletter Topics
Transforming Practice: Research evidence on diagnostic testing or
treatment periodically accumulates to a “tipping point” that warrants a change in practice. Each month the editors select one topic
for which a substantial change in clinical practice seems justified.
Alternates monthly with News Alert.
News Alert: A discussion of current issues that affect family medicine today. Alternates monthly with Transforming Practice.
Help Desk: EBP authors search the highest quality sources for best
evidence (PrimeEvidence and the TRIPS database) in a concise,
clinically useful format. If definitive answers are not available from
these sources, the editors turn to high-quality, well-referenced
sources. Other resources are used at the editors’ discretion.
Topics in Maternity Care: To keep readers current with trends and
new evidence regarding obstetrics and maternity care
Behavioral Health Matters/Evidence in Nutrition: Two features which
alternate monthly, and present the most current evidence relating to
their respective disciplines.
Drug Profile: Pharmaceutical information is promoted directly to
consumers as well as physicians, and is readily available on the
Internet and in other mass media. In each issue of EBP, the editors
objectively review the advantages and disadvantages of a featured
medication based on scientific evidence.
Patient Education: An evidence-based patient summary of a Clinical
Inquiry, provided as a tear-out page to be copied and distributed to
your patients.
Help Desk
4.
Pneumonia Severity Index Calculator. Rockville, Md: Agency for Healthcare
Research and Quality; December 2003. Available at: http://pda.ahrq.gov/
psicalc.asp. Accessed September 6, 2006.
5.
Carratala J, Fernandez-Sabe N, Ortega L, et al. Outpatient care compared with
hospitalization for community-acquired pneumonia: a randomized trial in lowrisk patients. Ann Intern Med 2005; 142:165–172. [LOE 1b]
analyzed as a subgroup. A third analysis found no
differences in outcomes between patients weighing
more than or less than 100 kg at baseline.
The mean body mass index for the obese cohort
was 34.2 kg/m2, and only 6 patients were morbidly
obese (body mass index >40 kg/m2). The authors
stated that these 6 patients had satisfactory knee
scores and no complications at 5 years. Nevertheless,
the results of this study should not be extrapolated to
predict outcomes for morbidly obese populations.
Does obesity affect outcomes for patients
undergoing total knee replacement
for osteoarthritis?
Evidence-Based Answer
The best evidence to date suggests that there are no
important differences in outcomes for obese versus
nonobese patients undergoing total knee replacement for osteoarthritis as many as 5 years after surgery. (SOR B, based on cohort studies.)
Studies have had conflicting results regarding the
influence of obesity on important outcomes for
patients undergoing total knee replacement for
osteoarthritis. A short-term cohort study found that
for 1 year postsurgery, obesity did not affect outcomes for a series of 180 consecutive patients.1 In
contrast, a case-control study of 68 obese patients
and 68 matched controls found that any degree of
obesity, defined as a body mass index of 30 kg/m2 or
more, was associated with poorer outcomes over a
mean of 6 years.2 The results of a larger 5-year
study have recently been published.3
In this study, a consecutive series of 320
patients undergoing 370 total knee replacements
for osteoarthritis were followed for 5 years. Patients
were evaluated clinically and radiographically at 6,
18, 36, and 60 months. Evaluations included a
Knee Society score, which is a 0- to 100-point scale
that includes knee joint findings (pain, stability,
range of motion) as well as functional parameters
(walking distance and stair climbing).
Using a cutoff of a body mass index of 30 kg/m2
or more for obesity, no difference was noted in the
outcomes of Knee Society scores between obese
and nonobese patients at any of the evaluation
points. Similarly, no significant differences were
noted in complication rates for obese versus
nonobese patients (P>.05 for the comparisons of
wound infection, deep venous thrombosis, perioperative mortality, and the number of surgical revisions at 5 years). Additionally, no differences were
noted between obese and nonobese women, when
David White, MD, Columbia, Missouri
1.
Deshmukh RG, Hayes JH, Pinder IM. Does body weight influence outcome after
total knee arthroplasty? A 1-year analysis. J Arthroplasty 2002; 17:315–319.
[LOE 1b]
2.
Foran JR, Mont MA, Etienne G, Jones LC, Hungerford DS. The outcome of total
knee arthroplasty in obese patients. J Bone Joint Surg Am 2004; 86A:1609–1615. [LOE 3b]
3.
Amin AK, Patton JT, Cook RE, Brenkel IJ. Does obesity influence the clinical
outcome at five years following total knee replacement for osteoarthritis? J Bone
Joint Surg Br 2006; 88:335–340. [LOE 1b]
Is the combination of calcipotriene (Dovonex®)
and betamethasone more effective than either
agent alone for treating psoriasis?
Evidence-Based Answer
Used individually, calcipotriene is equivalent or
superior to other commonly used agents for psoriasis, including potent topical corticosteroids. The
combination of calcipotriene and betamethasone is
more effective than either agent alone. (SOR B,
based on a RCT.)
A systematic review found that the synthetic vitamin D3 analogue, calcipotriene (Dovonex), is
equivalent or superior to other agents commonly
used to treat psoriasis.1 Thirty-seven randomized
controlled trials (6,038 patients) using calcipotriene compared with placebo or some other
active treatment for plaque psoriasis were identified. All trials lasted 6 to 8 weeks. Data from trials
were pooled for each of the individual treatment
comparisons, and the primary outcome for the
meta-analysis was the rate ratio, defined as the proportion of patients achieving at least marked
improvement in the calcipotriene group compared
with the control group. Adverse effects were also
estimated using the rate ratio, along with rate differences and numbers needed to treat.
continued
Evidence-Based Practice
7
Help Desk
Calcipotriene was at least as effective as potent
topical corticosteroids, calcitriol, short contact
dithranol, tacalcitol, coal tar, and combined coal
tar 5%, allantoin 2%, and hydrocortisone 0.5%.
For the specific comparison with potent corticosteroids, although calcipotriene was significantly
more beneficial at 6 weeks, no differences were
noted between groups at 8 weeks. Calcipotriene
was related to more adverse reactions, predominantly lesional or perilesional irritation, than
potent corticosteroids (risk difference 0.10; 95%
CI, 0.03–0.17; P<.05; number needed to
harm=10).
A subsequent RCT evaluated the efficacy and
safety of the combination of calcipotriene and
betamethasone compared with either agent alone
(in a vehicle that could accommodate either
agent) for patients with psoriasis.2 A total of 1,043
patients aged at least 18 years with psoriasis vulgaris were randomized to use calcipotriene 50
µg/g in vehicle, betamethasone dipropionate 0.5
mg/g in vehicle, both agents in vehicle, or the
vehicle alone. The formulation was applied to
affected areas (excluding face and scalp) twice
daily for 4 weeks.
HPV Update Supplement
continued from page 3
For the outcome of response, defined as at least a
75% reduction in a psoriasis activity severity index,
the combination was superior to all 3 of the other
treatment arms (proportion of responders 76.1% for
combination vs 55.8% for betamethasone vs 33.4%
for calcipotriene vs 7.5% for the control group;
P<.001 for all comparisons). The numbers needed
to treat, for 1 additional patient to respond, were 4 for
combination versus calcipotriene alone and 5 for
combination versus betamethasone alone. No significant differences were noted in rates of adverse events
between any of the groups.
On January 9, 2006, the Food and Drug
Administration approved a fixed combination preparation of calcipotriene (0.005%) plus betamethasone
dipropionate (0.064%) ointment (Taclonex®) for topiEBP
cal use in adults with psoriasis vulgaris.3
David White, MD, Columbia, Missouri
1.
2.
3.
WOMEN'S HEALTH UPDATE
Neher JO. First HPV vaccine approved. Evidence-Based Practice 2006;
9(9):1–3, 8.
2.
Sattler C. Efficacy of a prophylactic quadrivalent human papillomavirus (HPV)
(types 6, 11, 16, 18) L1 virus-like particle (VLP) vaccine for the prevention of
cervical dysplasia and external genital lesions. Abstract presented at: 45th
Annual Meeting of the Interscience Conference on Antimicrobial Agents and
Chemotherapeutics; December 16–19, 2005; Washington, DC. [LOE 1b]
3.
Koutsky L. Prophylactic quadrivalent human papilloma virus (HPV) (types 6,
11, 16, and 18) L1 virus-like particle (VLP) vaccine (Gardasil™) reduces cervical intraepithelial neoplasia (CIN) 2/3 risk. Abstract presented at: 43rd
Annual Meeting of the Infectious Diseases Society of America; October 6–9,
2005; San Francisco, Calif. [LOE 1b]
4.
Moa K, Koutsky LA, Ault KA, et al. Efficacy of human papillomavirus-16 vaccine to prevent cervical intraepithelial neoplasia: a randomized controlled trial
[published correction appears in Obstet Gynecol 2006; 107:1425]. Obstet
Gynecol 2006; 107:18–27. [LOE 1b]
5.
Harper DM, Franco EL, Wheeler C, et al. Efficacy of a bivalent L1 virus-like particle vaccine in prevention of infection with human papillomavirus types 16 and
18 in young women: a randomised controlled trial. Lancet 2004;
364:1757–1765. [LOE 1b]
6.
Harper DM, Franco EL, Wheeler CM, et al; for the HPV Vaccine Study group.
Sustained efficacy up to 4.5 years of a bivalent L1 virus-like particle vaccine
against human papillomavirus types 16 and 18: follow-up from a randomised
control trial. Lancet 2006; 367:1247–1255. [LOE 1b]
8 Evidence-Based Practice
CONTINUED FROM PAGE 10
patients given gabapentin, developing in every
fourth patient in the gabapentin group.
In summary, small studies have shown that
gabapentin effectively reduces the frequency and
severity of hot flashes in postmenopausal women,
and that the magnitude of this benefit may be similar to that associated with estrogen therapy. Some
trials report a clinically significant increased risk of
EBP
adverse effects in patients taking gabapentin.
REFERENCES
1.
Ashcroft DM, Po AL, Williams HC, Griffiths CE. Systematic review of comparative efficacy and tolerability of calcipotriol in treating chronic plaque psoriasis.
BMJ 2000; 320:963–967. [LOE 1a]
Papp KA, Guenther L, Boyden B, et al. Early onset of action and efficacy of a
combination of calcipotriene and betamethasone dipropionate in the treatment
of psoriasis. J Am Acad Dermatol 2003; 48:48–54. [LOE 1b]
US Food and Drug Administration, Center for Drug Evaluation and Research.
CDER drug and biologic approvals for calendar year 2006: updated through
March
31,
2006.
Available
at:
http://www.fda.gov/cder/rdmt/
InternetNDA06.htm. Accessed August 28, 2006.
David White, MD, Columbia, Missouri
REFERENCES
1.
2.
3.
Loprinzi L, Barton DL, Sloan JA, et al. Pilot evaluation of gabapentin for treating hot flashes. Mayo Clin Proc 2002; 77:1159–1163. [LOE 4]
Guttuso T Jr, Kurlan R, McDermott MP, Kieburtz Ket al. Gabapentin’s effects
on hot flashes in postmenopausal women: a randomized controlled trial. Obstet
Gynecol 2003; 101:337–345. [LOE 1b]
Reddy SY, Warner H, Guttuso T Jr, et al. Gabapentin, estrogen, and placebo for
treating hot flushes: a randomized controlled trial. Obstet Gynecol 2006;
108:41–48. [LOE 1b]
Behavioral Health Matters
Nonpharmacological interventions for insomnia in adults
Summary
Effective nonpharmacological
interventions for treating
insomnia include sleep restriction, relaxation therapy, cognitive interventions, paradoxical
intention, stimulus control,
biofeedback, and multicomponent therapies (SOR A, based
on meta-analyses), as well as
exercise (SOR B, based on 1
small RCT).
TABLE
Effect sizes* of nonpharmacological interventions on sleep parameters2
Nonpharmacological
Intervention
Sleep-Onset Time Awake After Number of Total Sleep
Latency
Sleep Onset
Awakenings
Time
Stimulus control
0.81
0.70
0.59
0.41
Sleep restriction
0.98
—
—
—
Relaxation, somatic
0.83
—
0.56
—
Relaxation, cognitive
1.20
—
—
—
Biofeedback
1.00
0.70
—
—
Multicomponent therapies
1.05
0.70
—
0.75
—
—
—
0.46
Paradoxical intention
*An effect size of 0.6 is considered moderate and 1.2 is considered large.
The Evidence
As many as 12% of the general adult population and
as many as 30% of the elderly have insomnia.1
Behavioral interventions are often preferred treatments because of the limited therapeutic effect and
adverse side effects of prescription drugs.2
A meta-analysis identified 59 controlled studies
(2,102 patients) that examined the effect of nonpharmacological interventions on the following outcome variables: sleep-onset latency, time awake after
sleep onset (the symptom most commonly targeted
by physicians), number of awakenings, and total
sleep time.2 Nonpharmacological interventions
included sleep hygiene, stimulus control, sleep
restriction, somatic relaxation therapy (progressive
muscle relaxation, autogenics, biofeedback), cognitive relaxation therapy (imagery training, thought
stopping, meditation), and paradoxical intention.
The Table shows the effect sizes for the various
outcomes according to specific nonpharmacological
interventions. Sleep-onset latency was consistently
reduced below or near the 30-minute cutoff criterion
typically used to define insomnia. Increases in total
sleep time were also generally around 30 minutes.
Another meta-analysis examining behavioral
therapies for insomnia examined 23 studies of
adults.1 The studies were grouped into 3 behavioral
intervention types: omnibus CBT (cognitive behavioral interventions and imagery training); relaxation-based therapy (progressive relaxation, biofeedback, hypnosis, etc); and behavioral intervention
only (stimulus control, sleep compression, paradoxical intention, etc). Sleep outcomes included quality
(224 patients), latency (n=676), total sleep time
(n=643), sleep efficiency (n=308), and awakening
after sleep onset (n=551). Sleep efficiency was the
only outcome that differed in response to type of
intervention. Significant effect sizes were found for
omnibus CBT and behavioral intervention only
(effect size 1.47 and 0.67, respectively). The effect
size for relaxation-based therapy was not significant.
In a nonblinded cohort study of 43 elderly persons
with insomnia who were not depressed or demented,
moderate-intensity exercise for 16 weeks (30–40 minutes of low-impact aerobics or brisk walking, 4 times
per week) led to improvements in sleep-onset latency,
total sleep time, and sleep quality.3 Exercise reduced
sleep-onset latency by an average of 11.5 minutes
(P=.007); lengthened total sleep time by an average of
42 minutes (P=.05); and significantly improved scores
on a sleep quality measure (95% CI, 1.9–5.4; P<.001).
Laurie C. Ivey, PsyD
Swedish Family Medicine Residency
Littleton, Colorado
REFERENCES
1.
2.
3.
Irwin MR, Cole JC, Nicassio PM. Comparative meta-analysis of behavioral interventions for insomnia and their efficacy in middle-aged adults and in older
adults 55+ years of age. Health Psychol. 2006; 25:3–14. [LOE 1a]
Morin CM, Culbert JP, Schwartz SM. Nonpharmacological interventions for
insomnia: a meta-analysis of treatment efficacy. Am J Psychiatry. 1994;
151:1172–1180. [LOE 1a]
Montgomery P, Dennis J. Physical exercise for sleep problems in adults aged
60+. Cochrane Database Syst Rev. 2002; (4): CD003404. [LOE 2b]
Evidence-Based Practice
9
WOMEN'S HEALTH UPDATE
Gabapentin: Another alternative for hot flashes?
The Problem
Hot flashes, which occur in about half of women
going through menopause, are characterized by an
intense sensation of warmth in the upper body and
face with flushing of the skin and perspiration. An
individual episode may last 30 seconds to 30 minutes, although a typical hot flash generally lasts several minutes. They may occur hourly, daily, or less
frequently at apparently random intervals. Given
the wide spectrum of symptom intensity, it is not
surprising that some women are little inconvenienced, while others seek medical attention.
Standard Care
Estrogen therapy is the gold standard for hot flashes, as declining estrogen levels are believed to trigger the symptoms. However, because of the potential medical risks of estrogen, other therapies have
been sought. The list of natural compounds purported to be helpful for hot flashes reads like a compendium of phytopharmacology: black cohosh, soy,
red clover, dong quai, licorice, chasteberry, evening
primrose oil, and wild yam. An adequate replacement for estrogen has not been found.
Gabapentin
Now, evidence points to gabapentin as perhaps
another option. In an early case series, 24 patients
who had been experiencing at least 14 hot flashes
per week, for at least 1 month, were placed on
gabapentin therapy.1 The protocol called for
patients to take 300 mg gabapentin at bedtime for 1
week, 300 mg twice daily for the second week, and
then 300 mg 3 times daily for the next 2 weeks. For
the week prior to initiation of therapy and for the
next 4 weeks, participants were asked to make diary
entries recording hot flash frequency and severity.
The primary outcomes were hot flash frequency,
and the hot flash score, which was defined as the
hot flash severity times the hot flash severity score
(weekly rating; 1 to 4 scale). Four patients did not
return any data.
For the 20 patients who returned data, hot flash
severity and hot flash scores were reduced from the
baseline week by 66% and 70%, respectively, during
the 4th treatment week. Four patients discontinued
the drug due to perceived side effects. In 3 of these
4, the primary adverse effect was dizziness.
In a subsequent clinical trial, 59 postmenopausal women with at least 7 hot flashes per
day were randomized to receive either 300 mg
gabapentin 3 times daily or matching placebo for 12
weeks.2 Patients were instructed to take 1 capsule at
bedtime for 3 days, 1 capsule twice daily for 3 days,
and then 1 capsule 3 times a day for the duration of
the study. Hot flash frequency and hot flash severity
scores were recorded in a diary, as in the case series
described above.
At the end of 12 weeks, gabapentin was associated with a significant reduction in flash frequency
and hot flash scores compared with placebo (45% vs
29%, P=.02; and 54% vs 31%, P=.01, respectively).
In the gabapentin group the most common adverse
effects were somnolence (20%) and dizziness
(13.3%). More patients taking gabapentin withdrew
from the study due to adverse effects (13.3% vs 3.4%
in the placebo group).
In a recent trial, investigators compared the efficacy of gabapentin with that of oral estrogen therapy and placebo for reducing the frequency and
severity of hot flashes.3 Sixty women with postmenopausal hot flashes were randomly assigned to
gabapentin (titrated to 2,400 mg daily in divided
doses), conjugated estrogen (0.625 mg daily), or
placebo for 12 weeks. Patients recorded hot flash frequency and severity scores for 2 weeks prior to the
intervention, and continued to do so for the duration of the study. The primary outcome was hot
flash score, which combined the frequency and
severity scores, as in the previously described studies.
Using an intent-to-treat analysis, at the end of
the study both gabapentin and estrogen were associated with greater reductions in hot flash scores compared to placebo (71%, P=.004, and 72%, P=.016,
respectively, vs 54% in the placebo group). No statistically significant difference was found between the
gabapentin and estrogen therapies. Although no differences were found between groups for individual
adverse effects, the cluster of headache, dizziness,
and disorientation was more common among
continued on page 8
10 Evidence-Based Practice
DRUG PROFILE
®
®
Levemir : Comparable to Lantus ?
The Bottom Line
Although associated with less hypoglycemia and weight gain when compared to NPH insulin, insulin detemir
has not been shown to be superior to its true competitor, insulin glargine, in randomized controlled trials. For
patients who have small to moderate insulin requirements, insulin detemir needs to be dosed twice daily, compared to insulin glargine’s once-daily dosing.
Key Points
• Two long-acting insulins are currently available on the market, insulin glargine (Lantus) and insulin
detemir (Levemir).
• Both long-acting insulins have superior adverse effect profiles when compared with NPH insulin.
• Onset of action for insulin glulisine is clinically comparable to insulin lispro and insulin aspart
• Insulin detemir, launched in May 2006, needs to be compared head to head with insulin glargine to
assess relative performance.
The Pitch
Norvo Nordisk has recently
launched long-acting insulin
detemir (Levemir). With the
withdrawal of Ultralente insulin at
the end of 2005, only 2 long-acting
insulins, glargine (Lantus) and
detemir, are available on the US
market. Pharmaceutical representatives are claiming that insulin
detemir possesses “a light touch”
due to a lower incidence of hypoglycemia and weight gain in comparison with NPH insulin.
TABLE
Characteristics of insulin used for basal therapy7
Glargine
Detemir
NPH
Peak (hours)
No significant peak
6–8
4–10
Onset (hours)
4–6
1
2–4
Duration (hours)
24
if dosed at
≥0.4 units/kg per day
• 10–12 if dosed at
≤0.4 units/kg per day
10–24
$77.99/10-mL vial
$29.85–$47.88/
10-mL vial
Cost*
Clinical pearls
$73.77/10-mL vial
• 16–20
upon injection • Twice-daily dosing
may be necessary
due to low pH
• May be mixed with
• Should NOT be
aspart or lispro if
mixed due to the
injected immediately pharmacokinetic
alteration of other
insulins
• Pain
is related to
a greater incidence
of hypoglycemia
• May mix with lispro,
aspart, and regular
insulins
• Peak
The Data
The data being used to promote
the weight and hypoglycemic *Prices are from drugstore.com. Accessed on July 2, 2006.
benefit of insulin detemir come
which slows systemic absorption. The duration of
from an observational study in which the research
action of insulin detemir ranges from 5.7 hours,
protocol was not specifically designed to rigorously
increasing with increasing doses, to 23.2 hours
test the weight effects of the different treatments.1
Both insulin detemir and insulin glargine have been
(Table).5 In clinical trials, insulin detemir dosed 0.4
associated with a lower incidence of hypoglycemia
units/kg lasted approximately 16 to 20 hours,
2–4
when compared to NPH insulin.
whereas a dose of 0.2 units/kg had a duration of
The prolonged action of insulin detemir is
about 12 hours. Doses that achieved a full 24-hour
mediated by the slow systemic absorption of insulin
duration were not specifically defined.2,5
5
Both insulin detemir and insulin glargine were
detemir molecules from the injection site. A high
concentration of insulin detemir (ie, a higher dose)
compared to twice-daily NPH insulin to receive
yields a stronger self-association with albumin,
FDA approval. However, when compared to NPH
Evidence-Based Practice
11
DRUG PROFILE
Evidence-Based Practice
insulin, insulin glargine was used once daily whereas insulin detemir was used once or twice daily.2,5,6
It has been shown that mixing insulin detemir
with NovoLog® (insulin aspart) reduces insulin
aspart levels by 40%7; therefore, both agents should
not be used in the same injection. Although Aventis
does not recommend mixing insulin glargine with
other forms of insulin, studies show that mixing it
with Humalog® (insulin lispro) or insulin aspart
does not affect glycemic control.8,9
So what dose is needed to make insulin detemir
a 24-hour basal insulin? This question remains
unanswered. But patients who only need a basal
insulin of 0.1 to 0.3 units/kg will have to inject
themselves twice daily to cover their basal insulin
needs for a full 24 hours. Insulin glargine, in most
patients, has a duration of 24 hours regardless of
dose. To combat the problem of waning compliance
with additional injections per day, patients might be
tempted to mix insulin detemir with their bolus
insulin, but due to the pharmacokinetic changes
described above, this strategy is not recommended.
Head-to-head, randomized controlled trials have
not been carried out with the 2 agents to compare
rates of weight gain or hypoglycemia. The package
insert for insulin detemir mentions an unpublished
study that shows insulin detemir once or twice daily
obtains similar, but not superior, decreases in HbA1c
when compared to insulin glargine once daily.5
Family Physicians Inquiries Network, Inc.
409 West Vandiver Drive
Building 4, Suite 202
Columbia, MO 65202
As of now, the clinical advantage of using
insulin detemir over insulin glargine remains
unclear. Expect to see further studies comparing
EBP
these 2 insulins later this year.
Megan Kowitz, PharmD candidate
Cara Liday, PharmD, CDE
Idaho State University
REFERENCES
1.
2.
3.
4.
5.
6.
7.
8.
9.
Dornhorst A, Merilainen M, Ratzmann K-P. Insulin detemir with or without OAD
improves glycemic control without weight gain in OAD-treated insulin naïve
patients with type 2 diabetes: results from a German subgroup of the PREDICTIVE study. Poster presented at: American Diabetes Association 66th Annual
Sessions; June 9–13, 2006; Washington, DC. Abstract 462-P. [LOE 4]
Hermansen K, Davies M, Derezinski T, et al. A 26-week, randomized, parallel,
treat-to-target trial comparing insulin detemir with NPH insulin as add-on therapy to oral glucose-lowering drugs in insulin-naive people with type 2 diabetes.
Diabetes Care 2006; 29:1269–1274. [LOE 1b]
Rosenstock J, Dailey G, Massi-Benedetti M, Fritsche A, Lin Z, Salzman A.
Reduced hypoglycemia risk with insulin glargine: a meta-analysis comparing
insulin glargine with human NPH insulin in type 2 diabetes. Diabetes Care
2005; 28:950–955. [LOE 1a]
Eliaschewitz FG, Calvo C, Valbuena H, et al; for the HOE 901/4013 LA Study
Group. Therapy in type 2 diabetes: insulin glargine vs. NPH insulin both in
combination with glimepiride. Arch Med Res 2006; 37:495–501. [LOE 1b]
Levemir® (insulin detemir [rDNA origin] injection) [package insert]. Princeton,
NJ: Novo Nordisk Inc; October 19, 2005. Available at: http://www.levemirus.com/prescribing_information.pdf. Accessed September 6, 2006.
Home PD, Rosskamp R, Forjanic-Klapproth J, Dressler A; for the European
Insulin Glargine Study Group. A randomized multicentre trial of insulin glargine
compared with NPH insulin in people with type 1 diabetes. Diabetes Metab Res
Rev 2005; 21:545–553. [LOE 1b]
Comparison of insulins. Pharmacist’s Letter/Prescriber’s Letter 2006; 22(3):220309.
Kaplan W, Rodriguez LM, Smith OE, Haymond MW, Heptulla RA. Effects of
mixing glargine and short-acting insulin analogs on glucose control. Diabetes
Care 2004; 27:2739–2740. [LOE 1b]
Fiallo-Scharer R, Horner B, McFann K, Walravens P, Chase HP. Mixing rapidacting insulin analogues with insulin glargine in children with type 1 diabetes
mellitus. J Pediatr 2006; 148:481–484. [LOE 1b]
PRESORTED
STANDARD
U.S. POSTAGE
PAID
LINCOLN, NE
PERMIT # 365
Copy for your patients
CLINICAL INQUIRIES: PATIENT EDUCATION
Information you can trust. Information you can use.
Patient Handout
Based on the Clinical Inquiries® by the Family Physicians Inquiries Network™
Can type 2 diabetes be prevented through diet and exercise?
Journal of Family Practice, January 2005, Vol. 54, No. 1.
Talking With Your Doctor About Diabetes
Diabetes is the most common cause of blindness, kidney failure, and amputations in adults. It is also a major
cause of heart disease and stroke. If you have a family history of diabetes, have had elevated blood sugar tests,
and are approaching middle age, you may be at increased risk for developing diabetes and wondering how
you can reduce that risk.
If you have already been diagnosed with diabetes, your doctor may have prescribed medication and advised
you to check your blood sugar at home. Your doctor or diabetes educator has probably mentioned “lifestyle
changes” as a way to keep your blood sugar within normal limits and prevent further medical problems.
Studies have shown that long-term weight loss of 5% to 7%, along with moderate exercise for more than 2.5
hours a week, greatly reduces the risk of developing diabetes. Losing weight and exercising is easier said than
done, however, and it is often difficult to see how sacrifices you make today will improve your health and prevent medical problems in the future.
Taking medicine is only part of the answer. You must do 95% of the work in keeping blood sugar and other
risk factors under control, so it is important to consider how much time and effort you can manage on a daily
basis to keep your blood sugar at a healthy level.
Visiting with a dietitian can be very helpful in changing your eating habits, but it will involve extra time in the
grocery store and preparing meals. Exercise involves setting aside time each day to exercise and finding an
activity you like to do. It is always hard to make changes and fit new things into an already busy life.
Be honest with your doctor about what you can and cannot do. Talk about your greatest fears concerning
diabetes. Ask your doctor what he or she thinks are your greatest risks—both immediate and long term.
Together you can decide what your priorities are, what you are willing to try, and what will help you achieve
your goals, one step at a time.
For more information
National Diabetes Education Program
http://www.ndep.nih.gov/index.htm
Diabetes Learning Center (American Diabetes Association)
http://www.diabetes.org/all-about-diabetes/chan_eng/channel.htm
Diabetes (MedlinePlus)
http://www.nlm.nih.gov/medlineplus/diabetes.html
OCTOBER 2006
Evidence-Based Practice
CME
CONTINUING MEDICAL EDUCATION TEST
OCTOBER 2006
For each question, please mark the single best answer by checking the appropriate box.
1. Which of the following topical treatments have been
shown to be superior to calcipotriene (Dovonex) for
the treatment of psoriasis?
❏ a. Potent topical corticosteroids
❏ b. Coal tar
❏ c. Dithranol
❏ d. None of the above
5. The Orange Farm study of circumcision to
reduce HIV transmission was unique in that
it was the first such study that was:
❏ a. Randomized
❏ b. Double-blinded
❏ c. Retrospective
❏ d. Statistically significant
2. Which of the following nonpharmacologic therapies
improves sleep parameters?
❏ a. Stimulus control
❏ b. Progressive relaxation
❏ c. Sleep restriction
❏ d. All of the above
6. Which of the following provides the
most effective form of emergency contraception?
❏ a. A copper-containing IUD
❏ b. The Yupze method using combined
oral contraceptives
❏ c. Plan B (2-dose regimen)
❏ d. Plan B (1-dose regimen)
3. Which of the following statements about
insulin detemir is true?
❏ a. It is given once daily regardless of dose
❏ b. It is marketed as a long-acting insulin
❏ c. It causes more weight gain than NPH insulin
❏ d. It is more effective than insulin glargine
4. Which one of the following statements is true?
❏ a. Ultra-low-tar cigarettes are associated with
lower cancer rates than regular-tar cigarettes
❏ b. Unfiltered cigarettes are associated with
higher cancer rates than filtered cigarettes
❏ c. Most smokers prefer regular-tar cigarettes to
lower-tar alternatives
❏ d. Urine biomarkers of lung carcinogens vary directly
with the tar content of the cigarett
7. For patients undergoing total knee replacement for
osteoarthritis, obesity adversely affects which of the
following outcomes at 5 years?
❏ a. Complication rates
❏ b. Functional status
❏ c. Knee joint function (stability, range of motion)
❏ d. None of the above
8. Which one of the following statements is correct?
❏ a. Gardasil is a monovalent HPV vaccine.
❏ b. Four-year outcome data are available for
an HPV-16/18 vaccine.
❏ c. Six-year outcome data are available for Gardasil.
❏ d. Ten-year outcome data on HPV vaccination are
available from Europe.
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