The use of the Panic and Agoraphobia Scale (P & A) in a controlled clinical trial.

BACKGROUND: A new 13-item scale has been developed for measuring severity of illness in patients with panic disorder and agoraphobia, the Panic and Agoraphobia Scale (P & A). The scale has five subscales covering the main factors that reduce quality of life in panic disorder patients (panic attacks, avoidance, anticipatory anxiety, disability and worries about health). The application of this scale in a double-blind placebo-controlled panic disorder trial is described. At the same time, the aim of the study was to compare the therapeutic effects of aerobic exercise with a treatment of well-documented efficacy. METHODS: Patients with Panic disorder (DSM-IV) were randomly assigned to three treatment modalities: running (n=45), clomipramine (n=15) or placebo (n=15). Treatment efficacy was measured with the Panic and Agoraphobia Scale (P & A) and other rating scales. RESULTS: According to the P & A and other scales, both exercise and clomipramine led to a significant decrease of symptoms in comparison to placebo treatment. Clomipramine was significantly more effective and improved anxiety symptoms significantly earlier than exercise. The evaluation of the P & A subscales revealed that exercise exerted its effect mainly reducing anticipatory anxiew and panic-related disability. CONCLUSIONS: The new Panic and Agoraphobia Scale was shown to be sensitive to differences between different panic treatments. Analysis of the scales five subscores may help to understand mechanisms of action of panic disorder treatments.

Haematological abnormalities in early abstinent alcoholics are closely associated with alterations in thrombopoietin and erythropoietin serum profiles.

Numerous reports exist on haematological pathology in alcoholism. However, no data are available regarding a potential involvement of haematopoietic growth factors in the recovery from alcohol-induced haematological abnormalities upon abstinence. Therefore, thrombopoietin (TPO) and erythropoietin (EPO) serum levels along with haematological and other routine laboratory parameters were closely followed in 14 thoroughly characterized male alcoholic patients over one to five months of controlled abstention from alcohol. Haematological changes in these early abstinent alcoholics consisted predominantly of (a) the well known rebound surge of platelets, (b) an early reticulocyte peak, and (c) persistently low haematocrit levels over months without signs of recovery. Observations on EPO and TPO during early abstinence can be summarized as follows: (1) Increased TPO levels precede the rebound thrombocytosis by several days, (2) both EPO and TPO concentrations are higher in anaemic than in nonanaemic alcoholics, with (3) nonanaemic subjects exhibiting levels of TPO in the range of healthy controls but levels of EPO below controls and (4) TPO concentrations show a stronger correlation with initial haematocrit values than with thrombocyte counts. To conclude, haematological recovery in early alcohol abstinence appears to be, at least in part, growth factor-driven, involving both TPO and EPO, and may reflect an intense interaction of erythro- and thrombopoiesis.

Application of a new statistical approach to evaluate a clinical trial with panic disorder patients.

In clinical trials in psychiatry, changes in severity are usually measured with ordinal level scales which are applied repeatedly during the trial, showing a constant decline in psychopathology scores as treatment leads to improvement. Previous non-parametric tests for repeated measures in factorial designs did not test the hypothesis that scale scores decrease constantly during the trial. A recently developed "rank test for ordered alternatives in a mixed model" was developed and applied to the data of a clinical trial in panic disorder. Thirty-seven outpatients with panic disorder and agoraphobia (PDA) were treated with imipramine (75-150 mg/day) in an 8-week open, prospective trial. Patients with intercurrent agoraphobia were instructed in practising self-exposure in their agoraphobic situations. The total score on the Panic and Agoraphobia Scale, the Hamilton Anxiety Scale (HAMA) and the Clinical Global Impression Scale (CGI) were used as the main efficacy measures. The new rank test showed significant treatment results in all scales applied. Treatment results were excellent, as was shown by a decrease in the average Panic and Agoraphobia Scale severity scores from 28.9 (range 14-45) to 13.3 (range 0-37; rank statistic Tn = 6.7; p < 0.0001). The largest effect size r(w) of all clinician-rated scales was seen with the observer-rated version of the Panic and Agoraphobia Scale, although closely followed by the CGI and the HAMA. Among the self-rated scales, the Panic and Agoraphobia Scale also showed the largest effect size. All five subscores of the Panic and Agoraphobia Scale showed significant improvements. The highest treatment effect sizes were seen in the "panic attacks" subscore, followed by the "anticipatory anxiety" subscore. The new statistical test applied in this study, which has some advantages in comparison with previously applied tests, is suitable for psychiatric treatment evaluations since it can also be applied in the case of discrete repeated measurements.

Elevated serum levels of astroglial S100beta in patients with liver cirrhosis indicate early and subclinical portal-systemic encephalopathy.

Portal-systemic encephalopathy is the prototype among the neuropsychiatric disorders that fall under the term Hepatic Encephalopathies. Ammonia toxicity is central to the pathophysiology of Portal-systemic encephalopathy, and neuronal ammonia toxicity is modulated by activated astrocytes. The calcium-binding astroglial key protein S100beta is released in response to glial activation, and its measurement in serum only recently became possible. Serum S100beta was determined by an ultrasensitive ELISA in patients (n=36) with liver cirrhosis and transjugular intrahepatic portosystemic stent-shunt. Subclinical portal-systemic encephalopathy and overt portal-systemic encephalopathy were determined by age-adjusted psychometric tests and clinical staging, respectively. Serum S100beta, was specifically elevated in the presence of subclinical or early portal-systemic encephalopathy, but not arterial ammonia. S100 levels elevated above a reference value (S100beta < or = 110pg/ml) or the cut off value determined in our group of patients (112pg/ml) predicted subclinical portal-systemic encephalopathy with a specificity and sensitivity of 100 and 56.5%, respectively. Serum S100beta was significantly dependent on liver dysfunction (Child-Pugh score), but was more closely related to cognitive impairments than the score. Serum S100beta seems to be a promising biochemical surrogate marker for mild cognitive impairments due to portal-systemic encephalopathy.

Psychological profiles of patients with laryngeal contact granulomas.

The association between laryngeal contact granuloma and demographic/psychological variables was examined by using a psychosomatic approach to health research. A stepwise procedure of logistic regression analyses was utilized to get a final multivariate model of variables associated with the clinical finding of a laryngeal contact granuloma. The subjects consisted of 47 patients with contact granulomas and 110 patients with voice disorders due to other causes. Our analysis of 22 variables uncovered the following statistically significant factors for developing a contact granuloma: male gender (P = 0.0001), low achievement orientation (P = 0.0007), fear of physical lesions (P = 0.0038), impulsiveness (P = 0.0016), age > 60 years (P = 0.0012), low extraversion (P = 0.004), high achievement orientation (P = 0.0079), fear of appearing in public (P = 0.0216) and strain (P = 0.03). These results show that a variety of variables are important for predicting the development of a laryngeal contact granuloma. The usefulness of this set of risk variables for predicting a contact granuloma remains to be proved in a prospective study. It is possible that not only the nature but the number of risk factors are the prime determinants of outcome.

The use of the Panic and Agoraphobia Scale in a clinical trial.

A new scale for assessing severity in PDA (Panic Disorder with/without Agoraphobia) has recently been developed: the Panic and Agoraphobia Scale [P & A (Bandelow, 1995)]. The objective of this study was to test whether the scale is sensitive to changes during a treatment trial. Thirty-seven patients (mean age, 32.7; S.D., 6.3) with PDA were treated with imipramine (75-150 mg/day) for 8 weeks in an open prospective trial. Patients with concurrent agoraphobia were instructed in practising self-exposure to agoraphobic situations. The total scores on the P & A, the Hamilton Anxiety Scale (HAMA) and the Clinical Global Impression Scale (CGI) were used as the main efficacy criteria. Treatment results were excellent, as could be shown by a decrease in the average severity scores of the P & A observer-rated version from 28.9 (S.D., 8.1) to 13.3 (S.D., 11.8; rank statistic T(N) = 6.7; P < 0.0001). The largest effect size r(w) of all clinician-rated scales was seen with the observer-rated version of the P & A, although closely followed by the CGI and the HAMA. Among the self-rated scales, the P & A (self-rated version) also showed the largest effect size. All five subscores of the P & A showed significant improvements. The highest treatment effect sizes could be seen in the 'panic attacks' subscore, followed by the 'anticipatory anxiety' subscore. The new Panic and Agoraphobia Scale (P & A) is a useful tool for measuring treatment efficacy in panic disorder trials.