DITPA (3,5-Diiodothyropropionic Acid), a thyroid hormone analog to treat heart failure: phase II trial veterans affairs cooperative study.

BACKGROUND: In animal studies and a pilot trial in patients with congestive heart failure, the thyroid hormone analog 3,5 diiodothyropropionic acid (DITPA) had beneficial hemodynamic effects. METHODS AND RESULTS: This was a phase II multicenter, randomized, placebo-controlled, double-blind trial of New York Heart Association class II to IV congestive heart failure patients randomized (2:1) to DITPA or placebo and treated for 6 months. The study enrolled 86 patients (n=57 to DITPA, n=29 to placebo). The primary objective was to assess the effect of DITPA on a composite congestive heart failure end point that classifies patients as improved, worsened, or unchanged based on symptom changes and morbidity/mortality. DITPA was poorly tolerated, which obscured the interpretation of congestive heart failure-specific effects. Fatigue and gastrointestinal complaints, in particular, were more frequent in the DITPA group. DITPA increased cardiac index (by 18%) and decreased systemic vascular resistance (by 11%), serum cholesterol (-20%), low-density lipoprotein cholesterol (-30%), and body weight (-11 lb). Thyroid-stimulating hormone was suppressed in patients given DITPA, which reflects its thyromimetic effect; however, no symptoms or signs of potential hypothyroidism or thyrotoxicosis were seen. CONCLUSIONS: DITPA improved some hemodynamic and metabolic parameters, but there was no evidence for symptomatic benefit in congestive heart failure.

Secondhand tobacco smoke in children with asthma: sources of and parental perceptions about exposure in children and parental readiness to change.

BACKGROUND: Secondhand smoke triggers childhood asthma. Understanding sources of exposure, parental beliefs about exposure, and readiness to change that exposure are important for designing smoke exposure reduction interventions. METHODS: As part of screening for a clinical trial of a smoke exposure reduction intervention, 519 smoke-exposed children 3 to 12 years old with asthma provided urine specimens for cotinine testing, and their primary caregivers completed questionnaires. RESULTS: The urine cotinine to creatinine ratio (CCR) was lowest if neither the primary caregiver nor day-care provider smoked (mean CCR, 14.0; SD, 14.4), greater if either smoked (mean CCR, 22.2; SD, 21.3; and mean, CCR, 26.3; SD, 22.2, respectively), and greatest if both smoked (mean CCR, 39.6; SD, 27.5; p < 0.01). Parental perception of their child's exposure was weakly associated with the child's CCR (r(2) = 0.11, p < 0.001). Most parents (58.3%) reported that tobacco smoke exposure had small/no negative effect on their child's asthma. Substantial proportions of those for whom a specific exposure reduction action was relevant were classified as contemplating, preparing, or had recently taken action to reduce their child's exposure, including smoking cessation (61.3%), keeping the child out of smoke-exposed places (72.7%), and making the child's home (49.2%) and areas out of the home smoke free (66.9%). CONCLUSIONS: Smoking by the primary caregiver and day-care provider are important sources of exposure for children with asthma. Parental assessment of their child's exposure is associated with biologically confirmed exposure but cannot be relied on to assess that exposure. Although the harm of smoke exposure was frequently underestimated, many parents appeared receptive to considering action to reduce their child's exposure. TRIAL REGISTRATION: (Clinicaltrials.gov). Identifier: NCT00217958.

A multicenter randomized controlled trial of endovascular therapy following imaging evaluation for ischemic stroke (DEFUSE 3).

Rationale Early reperfusion in patients experiencing acute ischemic stroke is effective in patients with large vessel occlusion. No randomized data are available regarding the safety and efficacy of endovascular therapy beyond 6 h from symptom onset. Aim The aim of the study is to demonstrate that, among patients with large vessel anterior circulation occlusion who have a favorable imaging profile on computed tomography perfusion or magnetic resonance imaging, endovascular therapy with a Food and Drug Administration 510 K-cleared mechanical thrombectomy device reduces the degree of disability three months post stroke. Design The study is a prospective, randomized, multicenter, phase III, adaptive, blinded endpoint, controlled trial. A maximum of 476 patients will be randomized and treated between 6 and 16 h of symptom onset. Procedures Patients undergo imaging with computed tomography perfusion or magnetic resonance diffusion/perfusion, and automated software (RAPID) determines if the Target Mismatch Profile is present. Patients who meet both clinical and imaging selection criteria are randomized 1:1 to endovascular therapy plus medical management or medical management alone. The individual endovascular therapist chooses the specific device (or devices) employed. Study outcomes The primary endpoint is the distribution of scores on the modified Rankin Scale at day 90. The secondary endpoint is the proportion of patients with modified Rankin Scale 0-2 at day 90 (indicating functional independence). Analysis Statistical analysis for the primary endpoint will be conducted using a normal approximation of the Wilcoxon-Mann-Whitney test (the generalized likelihood ratio test).

Effects of 12 months of vagus nerve stimulation in treatment-resistant depression: a naturalistic study.

BACKGROUND: The need for effective, long-term treatment for recurrent or chronic, treatment-resistant depression is well established. METHODS: This naturalistic follow-up describes outpatients with nonpsychotic major depressive (n = 185) or bipolar (I or II) disorder, depressed phase (n = 20) who initially received 10 weeks of active (n = 110) or sham vagus nerve stimulation (VNS) (n = 95). The initial active group received another 9 months, while the initial sham group received 12 months of VNS. Participants received antidepressant treatments and VNS, both of which could be adjusted. RESULTS: The primary analysis (repeated measures linear regression) revealed a significant reduction in 24-item Hamilton Rating Scale for Depression (HRSD(24)) scores (average improvement, .45 points [SE = .05] per month (p < .001). At exit, HRSD(24) response rate was 27.2% (55/202); remission rate (HRSD(24) < or = 9) was 15.8% (32/202). Montgomery Asberg Depression Rating Scale (28.2% [57/202]) and Clinical Global Impression-Improvement (34.0% [68/200]) showed similar response rates. Voice alteration, dyspnea, and neck pain were the most frequently reported adverse events. CONCLUSIONS: These 1-year open trial data found VNS to be well tolerated, suggesting a potential long-term, growing benefit in treatment-resistant depression, albeit in the context of changes in depression treatments. Comparative long-term data are needed to determine whether these benefits can be attributed to VNS.