|| JAMA Highlights
Cognitive-Behavioral Therapy, Imipramine, or Their Combination for
A Randomized Controlled Trial
David H. Barlow, PhD; Jack M. Gorman, MD; M. Katherine Shear, MD; Scott W. Woods, MD
Context Panic disorder (PD) may be treated with drugs, psychosocial intervention,
or both, but the relative and combined efficacies have not been evaluated
in an unbiased fashion.
Objective To evaluate whether drug and psychosocial therapies for PD are each
more effective than placebo, whether one treatment is more effective than
the other, and whether combined therapy is more effective than either therapy
Design and Setting Randomized, double-blind, placebo-controlled clinical trial conducted
in 4 anxiety research clinics from May 1991 to April 1998.
Patients A total of 312 patients with PD were included in the analysis.
Interventions Patients were randomly assigned to receive imipramine, up to 300 mg/d,
only (n=83); cognitive-behavioral therapy (CBT) only (n=77); placebo only
(n=24); CBT plus imipramine (n=65); or CBT plus placebo (n=63). Patients were
treated weekly for 3 months (acute phase); responders were then seen monthly
for 6 months (maintenance phase) and then followed up for 6 months after treatment
Main Outcome Measures Treatment response based on the Panic Disorder Severity Scale (PDSS)
and the Clinical Global Impression Scale (CGI) by treatment group.
Results Both imipramine and CBT were significantly superior to placebo for the
acute treatment phase as assessed by the PDSS (response rates for the intent-to-treat
[ITT] analysis, 45.8%, 48.7%, and 21.7%; P=.05 and P=.03, respectively), but were not significantly different
for the CGI (48.2%, 53.9%, and 37.5%, respectively). After 6 months of maintenance,
imipramine and CBT were significantly more effective than placebo for both
the PDSS (response rates, 37.8%, 39.5%, and 13.0%, respectively; P=.02 for both) and the CGI (37.8%, 42.1%, and 13.0%, respectively).
Among responders, imipramine produced a response of higher quality. The acute
response rate for the combined treatment was 60.3% for the PDSS and 64.1%
for the CGI; neither was significantly different from the other groups. The
6-month maintenance response rate for combined therapy was 57.1% for the PDSS
(P=.04 vs CBT alone and P=.03
vs imipramine alone) and 56.3% for the CGI (P=.03
vs imipramine alone), but not significantly better than CBT plus placebo in
either analysis. Six months after treatment discontinuation, in the ITT analysis
CGI response rates were 41.0% for CBT plus placebo, 31.9% for CBT alone, 19.7%
for imipramine alone, 13% for placebo, and 26.3% for CBT combined with imipramine.
Conclusions Combining imipramine and CBT appeared to confer limited advantage acutely
but more substantial advantage by the end of maintenance. Each treatment worked
well immediately following treatment and during maintenance; CBT appeared
durable in follow-up.
Standard Short-Course Chemotherapy for Drug-Resistant Tuberculosis
Treatment Outcomes in 6 Countries
Marcos A. Espinal, MD, DrPH; Sang Jae Kim, ScD; Pedro G. Suarez, MD; Kai Man Kam, MB; Alexander G. Khomenko, MD; Giovanni B. Migliori, MD; Janette Baéz, MD, MPH; Arata Kochi, MD, PhD; Christopher Dye, DPhil; Mario C. Raviglione, MD
Context No large-scale study has investigated the impact of multidrug-resistant
tuberculosis (TB) on the outcome of standard short-course chemotherapy under
routine countrywide TB control program conditions in the World Health Organization's
(WHO) directly observed treatment short-course strategy for TB control.
Objective To assess the results of treatment with first-line drugs for patients
enrolled in the WHO and the International Union Against Tuberculosis and Lung
Disease's global project on drug-resistance surveillance.
Design and Setting Retrospective cohort study of patients with TB in the Dominican Republic,
Hong Kong Special Administrative Region (People's Republic of China), Italy,
Ivanovo Oblast (Russian Federation), the Republic of Korea, and Peru.
Patients New and retreatment TB cases who received short-course chemotherapy
with isoniazid, rifampicin, pyrazinamide, and either ethambutol or streptomycin
between 1994 and 1996.
Main Outcome Measure Treatment response according to WHO treatment outcome categories (cured;
died; completed, defaulted, or failed treatment; or transferred).
Results Of the 6402 culture-positive TB cases evaluated, 5526 (86%) were new
cases and 876 (14%) were retreatment cases. A total of 1148 (20.8%) new cases
and 390 (44.5%) retreatment cases were drug resistant, including 184 and 169
cases of multidrug-resistant TB, respectively. Of the new cases 4585 (83%)
were treated successfully, 138 (2%) died, and 151 (3%) experienced short-course
chemotherapy failure. Overall, treatment failure (relative risk [RR], 15.4;
95% confidence interval [CI], 10.6-22.4; P<.001)
and mortality (RR, 3.73; 95% CI, 2.13-6.53; P<.001)
were higher among new multidrug-resistant TB cases than among new susceptible
cases. Even in settings using 100% direct observation, cases with multidrug
resistance had a significantly higher failure rate than those who were susceptible
(9/94 [10%] vs 8/1410 [0.7%]; RR, 16.9; 95% CI, 6.6-42.7; P<.001). Treatment failure was also higher among patients with any
rifampicin resistance (n=115) other than multidrug resistance (RR, 5.48; 95%
CI, 3.04-9.87; P<.001), any isoniazid resistance
(n=457) other than multidrug resistance (RR, 3.06; 95% CI, 1.85-5.05; P<.001), and among patients with TB resistant to rifampicin
only (n=76) (RR, 5.47; 95% CI, 2.68-11.2; P<.001).
Of the retreatment cases, 497 (57%) were treated successfully, 51 (6%) died,
and 124 (14%) failed short-course chemotherapy treatment. Failure rates among
retreatment cases were higher in those with multidrug-resistant TB, with any
isoniazid resistance other than multidrug resistance, and in cases with TB
resistant to isoniazid only.
Conclusions These data suggest that standard short-course chemotherapy, based on
first-line drugs, is an inadequate treatment for some patients with drug-resistant
TB. Although the directly observed treatment short-course strategy is the
basis of good TB control, the strategy should be modified in some settings
to identify drug-resistant cases sooner, and to make use of second-line drugs
in appropriate treatment regimens.
Association of Hostility With Coronary Artery Calcification in Young
The CARDIA Study
Carlos Iribarren, MD, MPH, PhD; Stephen Sidney, MD, MPH; Diane E. Bild, MD, MPH; Kiang Liu, PhD; Jerome H. Markovitz, MD, MPH; Jeffrey M. Roseman, MD, MPH, PhD; Karen Matthews, PhD
Context Psychosocial factors, including personality and character traits, may
play a role in the development and expression of coronary artery disease.
Objective To evaluate whether hostility, a previously reported predictor of clinical
coronary artery disease, is associated with coronary calcification, which
is a marker of subclinical atherosclerosis.
Design Prospective cohort study.
Setting and Participants Volunteer subsample from Chicago, Ill, and Oakland, Calif, consisting
of 374 white and black men and women, aged 18 to 30 years at baseline, who
participated in the Coronary Artery Risk Development in Young Adults (CARDIA)
study. Cook-Medley hostility assessment data were collected at baseline from
1985 to 1986 and at year 5 examinations from 1990 to 1992. After the 10-year
examinations in the 1995-1996 year, electron-beam computed tomographic scans
Main Outcome Measures Presence of any detectable coronary artery calcification (coronary calcium
score >0), and coronary artery calcium scores of 20 or higher.
Results In logistic regression analysis adjusting for age, sex, race, and field
center comparing those with hostility scores above and below the median of
the distribution of the present sample, the odds ratio of having any coronary
calcification was 2.57 (95% confidence interval, 1.31-5.22), and the odds
ratio of having a calcium score of 20 or higher was 9.56 (95% confidence interval,
2.29-65.9) for calcium scores of 20 or higher. The associations with any coronary
artery calcification persisted after adjusting for demographic, lifestyle,
and physiological variables. Results using a cynical distrust subscale were
somewhat weaker than for those using the global hostility score. Power was
inadequate to perform sex- or race-specific analyses.
Conclusion These results suggest that a high hostility level may predispose young
adults to coronary artery calcification.