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Back To Vidyya JAMA Highlights


Cognitive-Behavioral Therapy, Imipramine, or Their Combination for Panic Disorder

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 alone.

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 discontinuation.

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.

JAMA. 2000;283:2529-2536

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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.

JAMA. 2000;283:2537-2545

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Association of Hostility With Coronary Artery Calcification in Young Adults

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 were performed.

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.

JAMA. 2000;283:2546-2551

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