Duloxetine 60 mg once daily in the treatment of milder major depressive disorder.

There is ongoing debate regarding the effectiveness of antidepressants in patients with milder major depressive disorder (MDD). This post-hoc analysis evaluated the efficacy and tolerability of duloxetine in the subset of 159 (75 duloxetine and 84 placebo) patients with milder MDD (baseline HAMD17 total score > or = 15 and < or = 18) who were treated once daily with duloxetine 60 mg or placebo in two identical, 9-week, randomised, double-blind trials. At endpoint, change from baseline on HAMD17 was greater in the duloxetine group (-7.0) than in the placebo group (-4.1) (p = 0.005). Response and remission rates, and improvement on the Clinical Global Impressions-Severity (CGI-S) scale, the Patient Global Impressions-Improvement (PGI-I) scale, and measures of painful symptoms were also significantly better in the duloxetine group (p < 0.05). Tolerability was consistent with that seen in previous studies of duloxetine in patients with more severe depression. In conclusion, duloxetine 60 mg/day is effective and well tolerated in milder MDD.

Recombinant human antithrombin III restores heparin responsiveness and decreases activation of coagulation in heparin-resistant patients during cardiopulmonary bypass.

OBJECTIVES: We sought to evaluate the efficacy of recombinant human antithrombin III for restoration of heparin responsiveness in heparin-resistant patients scheduled for cardiac surgery. METHODS: This was a multicenter, randomized, double-blind, placebo-controlled study in heparin-resistant patients undergoing elective cardiac surgery. Patients were considered heparin resistant if the activated clotting time was less than 480 seconds after 400 U/kg heparin. Fifty-two heparin-resistant patients were randomized into 2 cohorts. One cohort received a single bolus (75 U/kg) of recombinant human antithrombin III (n = 28), and the other, the placebo group (n = 24), received a normal saline bolus. If the activated clotting time remained less than 480 seconds, this was defined as treatment failure, and 2 units of fresh frozen plasma were transfused. Patients were monitored for adverse events during hospitalization. RESULTS: Six (21%) of the patients in the recombinant human antithrombin III group received fresh frozen plasma transfusions compared with 22 (92%) of the placebo-treated patients ( P < .001). Two units of fresh frozen plasma did not restore heparin responsiveness. There was no increased incidence of adverse events associated with recombinant human antithrombin III administration. Postoperative 24-hour chest tube bleeding was not different in the 2 groups. Surrogate measures of hemostatic activation suggested that there was less activation of the hemostatic system during cardiopulmonary bypass in the recombinant human antithrombin III group. CONCLUSION: Treatment with recombinant human antithrombin III in a dose of 75 U/kg is effective in restoring heparin responsiveness and promoting therapeutic anticoagulation for cardiopulmonary bypass in the majority of heparin-resistant patients. Two units of fresh frozen plasma were insufficient to restore heparin responsiveness. There was no apparent increase in bleeding associated with recombinant human antithrombin III.

A current assessment of rurally linked exposures as potential risk factors for sarcoidosis.

PURPOSE: To identify and quantify the risk of developing sarcoidosis associated with specific rural exposures previously recognized as potential risk factors for this disease. METHODS: A matched case-control design was carried out with a 2-to-1 ratio of controls to cases. Case exposure histories were determine from a detailed questionnaire collecting self-reported information covering the period from birth through disease development and comparing that to exposure histories for the corresponding period in age-, race-, and gender-matched controls identified using Random Digit Dial survey methodology. Conditional logistic regression was used to analyze the matched data while controlling for several baseline variables. RESULTS: A number of exposures were found to be univariately associated with the development of sarcoidosis including: the use of wood stoves, the use of fireplaces, the use of nonpublic water supplies, and living or working on a farm. A dose-response gradient was detected from exposure to wood stoves and fireplaces continued to be significantly associated with sarcoidosis in multivariable models. CONCLUSIONS: The results of this study provide further support for the hypothesis that behaviors associated with rural living play some role in the development of sarcoidosis. This study further suggests that exposures involving the handling or burning of wood such as using wood stoves or fireplaces for home heating may, in part, explain this rural association.

A double-blind, placebo-controlled outpatient trial of pergolide for cocaine dependence.

Results of preclinical studies suggest that pergolide, a mixed D(1)/D(2) dopamine receptor agonist, may be useful in treating cocaine dependence. To empirically investigate this possibility, we conducted a 5-year, double-blind, placebo-controlled clinical trial of two doses of pergolide (0.05 and 0.25 mg bid) in subjects with cocaine dependence and combined cocaine/alcohol dependence. Data analysis was performed on an intent to treat population (N=358) and a per protocol population (N=108) with urine drug screens (UDS) used as the main outcome measure. There were no significant effects on UDS at either pergolide dose. Pergolide had no significant effect on alcohol use in the comorbid alcohol/cocaine dependence group. Pergolide does not appear to have clinical value in the treatment of cocaine dependence or in decreasing alcohol use in cocaine-dependent individuals at the presently studied doses.

Cardiac and mood-related changes during short-term abstinence from crack cocaine: the identification of possible withdrawal phenomena.

Studies assessing withdrawal phenomenon during short-term abstinence from chronic cocaine use have been limited. Although cocaine abusers are reported to be at increased risk for cardiac disorders, little research has assessed cardiac parameters in cocaine abusers and subsequent changes in these parameters that may be associated with the discontinuation of cocaine use. In this study, we categorize 441 chronic cocaine abusers into three groups based on self-reported length of abstinence from cocaine use at entry into a trial approved by the National Institute on Drug Abuse (NIDA) assessing the use of pergolide mesylate in treating relapse and craving in crack cocaine abuse. Electrocardiogram (ECG) PR intervals were found to be correlated positively with length of abstinence, returning to normal population levels within 30 days. In addition, levels of generalized anxiety, nervousness, and heart racing were found to be correlated negatively with length of abstinence from crack cocaine. This work provides preliminary evidence of cardiac and mood-related parameters that are associated with cocaine abstinence and that may indicate specific withdrawal phenomena in chronic users. In addition, these results suggest that the risk of cardiomyopathies associated with abnormal atrial-ventricular polarization may dissipate relatively quickly in abusing individuals.

Geographic variation in sarcoidosis in South Carolina: its relation to socioeconomic status and health care indicators.

Geographic patterns of sarcoidosis have been detected and studied on a global scale. However, the associations between these disease patterns and population characteristics have not been determined. The authors studied the geographic pattern of sarcoidosis in South Carolina and its relation to socioeconomic status (SES) and health status indicators. Hospitalization rates for the period 1985-1995 were used as geographic indicators of sarcoidosis. Rates were assessed for the 46 counties in South Carolina, adjusting for differences in SES, availability/accessibility of health care, diagnostic practices, and hospital utilization. Patterns in geographic variation were assessed based on physiographic characteristics and proximity to the Atlantic coastline. Significant variation was identified with an increase in sarcoidosis rates proximal to the Atlantic coastline. Population characteristics were identified that appeared to explain regional variation in sarcoidosis in Caucasians; however, regression analysis was unable to explain the regional differences in disease distribution by variation in SES, diagnostic practices, accessibility/availability, or hospital utilization in African Americans. These results suggest that the development of sarcoidosis is associated with a geographically linked risk factor in African Americans. This work supports the need for additional studies that will identify this risk factor(s).

Pergolide mesylate. Adverse events occurring in the treatment of cocaine dependence.

In this preliminary report from a placebo-controlled, double-blind, dose-response study on the use of pergolide mesylate for cocaine dependence in outpatients 8 out of 235 subjects noted adverse events requiring breaking of the blind. Events occurred at or within 7 days of receiving the first dose of medication and included side effects (four cardiovascular, one psychiatric); drug-drug interactions (one): and clinical exclusions (two pregnancies). Two anecdotes of illicit abuse are reported. Although efficacy is unestablished, pergolide appears to be safe in the early treatment of cocaine dependence except where there are relative contraindications.