Assessing fibromyalgia-related fatigue: content validity and psychometric performance of the Fatigue Visual Analog Scale in adult patients with fibromyalgia.

OBJECTIVES: To document 1) the content validity and 2) measure improvements in fatigue, using the Fatigue Visual Analogue Scale (VAS) assessment tool in patients with fibromyalgia. METHODS: The relevance and comprehensiveness of the Fatigue VAS were tested through a qualitative analysis of 20 subjects' verbatim transcripts from semi-structured qualitative interviews. Data from two randomised, controller trials in fibromyalgia (n=1121) were used to conduct correlation analyses with the Fatigue and Tiredness items from the Fibromyalgia Impact Questionnaire (FIQ) and the Short Form-36 Vitality scale. Known-groups and cross classification analyses were conducted to demonstrate the ability to measure improvement in fatigue using the Fatigue VAS. RESULTS: All subjects spontaneously reported that fatigue was an important symptom to capture in fibromyalgia. The Fatigue VAS was well understood by most subjects (n=18/20). High correlations (Pearson r>0.75) and good agreement (k>0.66) were found between the Fatigue VAS and the FIQ tiredness items no. 16 and 17 and SF-36™ Vitality scale. In both clinical trials there was a substantial separation of approximately 20 points on the mean change in the Fatigue VAS score between responders (>30% improvement in pain VAS) and non-responders. CONCLUSIONS: Previous studies have confirmed that fatigue is a major component of the fibromyalgia experience. This current study reports that fibromyalgia patients spontaneously rated fatigue as a highly significant feature of their illness, and supports the use of the Fatigue VAS as a valid questionnaire in fibromyalgia clinical trials.

Assessing sleep in fibromyalgia: investigation of an alternative scoring method for the Jenkins Sleep Scale based on data from randomized controlled studies.

OBJECTIVES: To investigate the validity of a rescored version of the Jenkins Sleep Scale (JSS) to assess the extent of possible bias of a 4-week recall period in assessing sleep in patients with fibromyalgia. METHODS: A rescoring algorithm of the JSS was developed. The psychometric properties of the rescored JSS were examined using blinded, observed data from a Phase 2 trial (n=195) in subjects with fibromyalgia. In addition, data from two Phase 3, randomised, controlled trials (n=1,121) in subjects with fibromyalgia were used to further validate the rescored JSS by conducting correlation analyses with other assessments expected to correlate with sleep. These included fatigue and tiredness items from the Fibromyalgia Impact Questionnaire (FIQ), the Functional Outcomes of Sleep Questionnaire (FOSQ), and the Short Form-36 (SF-36™) Vitality scale. RESULTS: Construct validity of the rescored JSS was found to be acceptable, with an internal consistency reliability of α=0.70. Test-retest reliability on stable subjects, defined using the FIQ total score, was also acceptable (ICC=0.70). Moderate to high correlations (Pearson r>0.66) were found with two FIQ items, addressing fatigue and non-restorative sleep, and the SF-36™ Vitality scale; correlations with the original JSS were similar. Both JSS versions were found to be responsive (p<0.0001), and the rescored version accounted for 90% of the variance captured in the original version. CONCLUSIONS: These results showed the rescored JSS performed similarly to the original scale, suggesting the original scale's 4-week recall period did not introduce substantial bias in capturing the experience of fibromyalgia-related sleep disturbances.

Stimulation by interleukin-6 and inhibition by tumor necrosis factor of cortisol release from bovine adrenal zona fasciculata cells through their receptors.

Interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) are synthesized and released from adrenal cells. Therefore, the effects of TNF-alpha and IL-6 on cortisol release from bovine zona fasciculata (ZF) cells were investigated. IL-6 (10-1000 pg/mL) significantly increased basal and adrenocorticotropic hormone (ACTH)-stimulated cortisol release in a concentration-dependent manner. This stimulatory effect of IL-6 became apparent at intervals as short as 4 h and continued through 24 h. IL-6 also potentiated the cortisol release stimulated by the adenylyl cyclase activator forskolin. By contrast, TNF-alpha (0.1-10 ng) inhibited basal and ACTH-stimulated cortisol release in a concentration-dependent manner. The inhibitory effects of TNF-alpha on cortisol release were significant at time intervals as short as 4 h and continued through 24 h. TNF-alpha inhibited forskolin-stimulated cortisol release. Binding studies demonstrated that ZF cells have IL-6 receptors (100 receptors/cell, Kd of 7.5 x 10(-11)) and TNF receptors (200 receptors/cell, Kd of 2.4 x 10(-9) M). Immunohistochemical analysis provided evidence that the majority of ZF cells have IL-6 receptors, TNF type 1 receptors, and TNF type 2 receptors. Because IL-6 and TNF-alpha are released from the adrenal cortex and these cytokines modify the release of cortisol from the ZF, IL-6 and TNF-alpha may play a paracrine or autocrine role in the regulation of adrenal function.

Perioperative morbidity and mortality in combined vs. staged approaches to carotid and coronary revascularization.

Between 1986 and 1994 we identified 57 patients who underwent carotid endarterectomy (CEA) and coronary artery bypass grafting (CABG) during the same hospitalization. Simultaneous CABG and CEA was performed in 28 patients (mean age 70.5 years, 58% male). Indications for CABG in these patients were myocardial infarction in two crescendo angina in 19, congestive heart failure in two and left main or triple-vessel coronary artery disease noted during carotid preoperative evaluation in five. Indications for CEA were transient ischemic attack (TIA) in 12, crescendo TIA in six, cerebrovascular accident (CVA) in five, and asymptomatic stenosis in five. There were no postoperative myocardial infarctions or perioperative deaths. Two patients developed atrial fibrillation, and four patients had CVAs (two were ipsilateral to the side of CEA). Twenty-nine patients underwent staged procedures (i.e., not performed concomitantly but during the same hospitalization). Indications for CABG and CEA were comparable to those in the group undergoing simultaneous procedures. In 17 patients CEA was performed before CABG. There was a single CVA, the result of an intracerebral hemorrhage. Five of the 17 patients had a myocardial infarction and two died; one patient had first-degree heart block requiring a pacemaker. Four additional patients developed atrial fibrillation, one of whom required cardioversion. The remaining 12 patients had CABG followed by CEA. There were no CVAs, myocardial infarctions, arrhythmias, or deaths in this subgroup. These data demonstrate that the performance of simultaneous CABG and CEA procedures is associated with increased neurologic morbidity (14.3%), both ipsilateral and contralateral to the side of carotid surgery in contrast to staged CABG and CEA (3.4%). In addition, when staged carotid surgery preceded coronary revascularization in those with severe coronary artery disease, the combined cardiac complication and mortality rate was significantly higher than when coronary revascularization preceded CEA. This evidence suggests that when CABG and CEA must be performed during the same hospitalization, the procedures should be staged with CABG preceding CEA.

Treatment of AIDS-related bronchopleural fistula by pleurectomy.

Spontaneous pneumothorax in patients with acquired immunodeficiency syndrome (AIDS) may require prolonged therapy for treatment of a persistent bronchopleural fistula, and treatment by standard methods often fails. This pilot study was done to test the effectiveness of aggressive surgical therapy for definitive treatment of persistent bronchopleural fistula in patients with AIDS. Between March 1989 and September 1991, 44 patients with AIDS were treated for spontaneous pneumothorax with closed tube thoracostomy; 14 of these patients had development of persistent bronchopleural fistula for more than 10 days, and 2 patients had subsequent bronchopleural fistula on the opposite side. Operative therapy in 14 patients included 15 thoracotomies and one sternotomy. The bronchopleural fistula was closed directly with suture or staples in 15 procedures and resected by lobectomy in 1 patient. All 14 patients received adjuvant parietal pleurectomy. Operative mortality was 7% (1 of 14 patients). The fistula was closed in all survivors and 13 patients were discharged between 7 and 28 days postoperatively. Pathologic examination confirmed Pneumocystis carinii in 13 patients with a high incidence of diffuse involvement and subpleural necrosis, further demonstrating the need for pleurectomy. These data suggest that in selected patients bronchopleural fistulas associated with AIDS can be effectively controlled by surgical closure combined with pleurectomy.