Transcript Study Design

Update in
General Internal Medicine
2006
Laura Zakowski MD
No financial disclosures
Learning objectives
 Recognize that famciclovir can be used to




treat herpes labialis
Recall that all patients with inguinal
hernias do not need referral for repair
Understand a rationale for use of rapid
strep culture for pharyngitis
Recognize α-Lipoic Acid as a treatment for
diabetic neuropathy
Identify a risk factor for abnormal Pap
smears in postmenopausal women
Famciclovir for herpes labialis
Spruance et al. J Am Acad Derm 2006;55:47-53
 Rationale: For the many patients
experience “fever blisters” is there an
effective treatment?
 Industry-sponsored
 N = 701 outpatients in US, Canada and
Australia
 Included: patients with 3 or more
outbreaks over a year, prodromal sxs,
Study design
 Randomized to three groups:
 1500 mg once
 750 BID for one day
 Placebo
 Began treated within one hour of
symptoms
 Returned to clinic and recorded sxs with
lesion
Results
 Time to healing
better in both
treatment groups
 Similar adverse
effects in all groups
 Headache
 Nausea
Placebo
1500 once
7
6
D
A
Y
S
5
4
3
2
1
0
750 BID
Bottom line
 Single daily dose of 1500 mg famciclovir
 Reduces time to healing by two days
 Comparable to other treatments
Valacyclovir 2000 mg BID: 1 day faster
Penciclovir cream: q2 hr x4 days: 0.7 day faster
Acyclovir 400 mg 5x/day x5 days: 1 day faster
 No study compares treatments directly
Repair of inguinal hernia
Fitzgibbons et al. JAMA. 2006;295:285-292
 Should we send all patients with inguinal





hernias to the surgeons?
Referred by PCC, surgeons, self
N = 720 men of a potential 3074
Asymptomatic or minimally symptomatic
18 years of age or older, mean age 57
Excluded:
 Pain, discomfort, undetectable hernias
Study design
 Randomized and watched for 2-4.5 years
 Examined regularly
 Primary outcome: pain and discomfort
interfering with normal activities
Results at 2 years
 Intention to treat:
 Pain interfering with activities: 2-5%
 Both groups had less pain after two years
 More pain reduction in surgical group
 Complications:
 Medical: 1.8/1000 patient-years (n=2)
 Surgical: 25%
 Cross-over
 To surgery: 23%
 To watchful waiting: 17%
Probability of Crossover From
Watchful Waiting to Surgery
Fitzgibbons, R. J. et al. JAMA 2006;295:285-292.
Copyright restrictions may apply.
Bottom line
 Waiting for hernia repair is reasonable
 Pain does improve after hernia repair
Management of Acute Pharyngitis in
Adults
Humair J-P, et al. Arch Intern Med
2006;166:640-644
 What should we use: Centor criteria, Rapid
Strep or culture?
 Swiss university-based primary care clinic
 N = 372 patients
 Pharyngitis
 Between 2 and 4 clinical symptoms:
 Fever
 Tonsillar exudate
 Tender cervical adenopathy
 Absence of cough
Study Design
 Determined Centor criteria
 Obtained rapid strep and culture
 Assumed certain costs:
 $25 for PCN
 $5 for rapid strep
 $18 for throat culture
 Analyzed different strategies
Results
 Symptoms:




Temperature: 60%
Tonsillar exudate: 70%
Painful lymph nodes: 74%
No cough: 75%
 Centor criteria:
 2: 40%
 3: 42%
 4: 18%
Results
3 or 4
Centor
60
Culture
% PCN
Rapid
Strep
37
% overuse
3
32
0
% underuse
3
9
0
% Appropriate
94
59
100
Cost
$15
$25
$32
38
Bottom line
 Use of rapid strep test can limit over and
underuse of antibiotics
 This approach is also cost-effective
α-Lipoic Acid for Diabetic
Neuropathy
Ziegler, et al. Diabetes Care 2006;29:2365-2370
 Does this supplement improve diabetic




neuropathy?
Nutritional supplement
Liver and renal excretion
Initial worsening of neuropathy symptoms
In combination with any diabetic
medication: increased risk of
hypoglycemia
Study Design




N = 181
Industry sponsored
Conducted in Israel and Russia
Ages 18-74
 type 1 or type 2
 Other causes of neuropathy ruled out
 Excluded:
 Hepatic or renal disease
 PVD
 Measured TSS: Pain, paresthesia, numbness
Results at 5 weeks
70
50% reduction in TSS
60
50
Placebo
600 mg
1200 mg
1800 mg
40
30
20
10
0
NNT = 3 (CI 2,6)
Adverse effects
 No hypoglycemic events reported
(%)
Placebo
Nausea
0
Vomiting
0
Vertigo
0
Overall
21
600 mg
13
2
4
27
1200 mg 1800 mg
21
48
4
26
4
11
43
54
Bottom Line
 α-Lipoic Acid improved symptoms of




diabetic neuropathy
A dose of 600 mg is best
An uncontrolled supplement
Cost is about $5 per month
No comparison to other effective
treatments
Cervical cytological
abnormalities with aging
Yasmeen, et al. Obstet Gynecol 2006;108:410-9
 USPTF recommends against screening
after 65. Is this appropriate?
 N = 16,608 in WHI study
 Ages 50-79 with normal Pap or LSIL
 Excluded: cancers including cervical
Study Design
 Follow-up cytology at years 3 and 6
 Collected information on potential cervical
cancer risk factors
 Age, ethnicity, history of smoking
 Married
 Not married, not sexually active
 Not married, sexually active
 Recorded incidence of Pap abnormalities
 Results for 13,546 at year 3
and 3,398 at year 6
Results
Reported in person-years
Any
abnormality
HSIL
Cervical
cancer
E+P
179*
23
6
Placebo
130*
31
4
Results: HSIL or cancer
Hazard
Ratio
1.0
P value
Not married, no sexual activity
2.3
.02
Not married, sexual activity
3.5
.005
Placebo
1.0
Estrogen and Progestin
.9
Married or living as married
.75
Bottom Line
 Living as not married with ongoing sexual
activity a risk factor for abnormal Pap
smears
 Estrogen with progestin:
 did not affect incidence of HSIL or cervical
cancer
 Did cause more cytologic abnormalities