Acceptability of second-step treatments to depressed outpatients: a STAR*D report

OBJECTIVE: Treatment of major depressive disorder typically entails implementing treatments in a stepwise fashion until a satisfactory outcome is achieved. This study sought to identify factors that affect patients' willingness to accept different second-step treatment approaches. METHOD: Participants in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial who had unsatisfactory outcomes after initial treatment with citalopram were eligible for a randomized second-step treatment trial. An equipoise-stratified design allowed participants to exclude or include specific treatment strategies. Analyses were conducted to identify factors associated with the acceptability of the following second-step treatments: cognitive therapy versus no cognitive therapy, any switch strategy versus any augmentation strategy (including cognitive therapy), and a medication switch strategy only versus a medication augmentation strategy only. RESULTS: Of the 1,439 participants who entered second-step treatment, 1% accepted all treatment strategies, 3% accepted only cognitive therapy, and 26% accepted cognitive therapy (thus, 71% did not accept cognitive therapy). Those with higher educational levels or a family history of a mood disorder were more likely to accept cognitive therapy. Participants in primary care settings and those who experienced a greater side effect burden or a lower reduction in symptom severity with citalopram were more likely to accept a switch strategy as compared with an augmentation strategy. Those with concurrent drug abuse and recurrent major depressive disorder were less likely to accept a switch strategy. CONCLUSIONS: Few participants accepted all treatments. Acceptance of cognitive therapy was primarily associated with sociodemographic characteristics, while acceptance of a treatment switch was associated with the results of the initial treatment.     

Predictors of attrition during initial (citalopram) treatment for depression: a STAR*D report

OBJECTIVE: Premature attrition from treatment may lead to worse outcomes and compromise the integrity of clinical trials in major depressive disorder. The purpose of this study was to identify the pretreatment predictors of attrition during acute treatment with citalopram in a large, "real world" clinical trial. METHOD: A total of 4,041 adult outpatients with nonpsychotic major depressive disorder were enrolled in treatment with citalopram for up to 14 weeks. Attrition was defined as "immediate" (patients who attended a baseline visit only) or "later" (patients who attended at least one postbaseline visit but who dropped out before the 12-week visit). RESULTS: Overall, 26% of enrolled patients dropped out of the acute phase treatment for nonmedical reasons. Of these, 34% dropped out immediately, 59% dropped out by week 12, and 7% dropped out after 12 weeks. Immediate attrition was associated with younger age, less education, and higher perceived mental health functioning. Attrition later in treatment was associated with younger age, less education, and African American race. Experience with more than one episode of depression was associated with less attrition. CONCLUSIONS: In clinical trials and clinical practice, several time points in treatment may provide opportunities to engage and encourage populations at higher risk for attrition and populations with high-risk presentation of illness. Additionally, more aggressive forms of treatment implemented earlier in the treatment process in order to increase the likelihood of more rapid efficacy may reduce dropout rates.     

Effect of on-admission antiplatelet treatment on patients with cerebral hemorrhage

BACKGROUND: Antiplatelet treatment remains the first choice for primary and secondary prevention of vascular diseases; even so, expected benefits may be offset by risk of bleeding, particularly cerebral hemorrhage. The aim of this study was to assess the influence of antiplatelet treatment on clinical outcome at hospital discharge. MATERIALS AND METHODS: Consecutive patients with first-ever stroke due to a primary intraparenchymal hemorrhage were prospectively identified over a 4-year period (2000-2003). Data on hemorrhage location, vascular risk factors, and antiplatelet and anticoagulant treatment were collected. At discharge, outcome was measured using the modified Rankin Scale (disabling stroke > or =3). Patients treated with anticoagulant therapy were excluded from the study. RESULTS: Of 457 consecutive patients with cerebral hemorrhage, 94 (20.5%) had been taking antiplatelet agents. The treated patients (mean age for antiplatelet group 78.9 +/- 9.0 years) were older than the nontreated patients (73.8 +/- 9.4, p = 0.02). In-hospital mortality was 23.4 and 23.1% (p = n.s.) for patients who had been taking antiplatelet agents or no treatment. Poor outcome at discharge was found in 52.1 and 59.7% (p = n.s.), respectively. Univariate analysis showed that age and coma at admission were predictors of disability at discharge, but antiplatelet treatment was not. Additionally, age and coma were shown to be determinants of disability at discharge after multivariate analysis: OR 1.03 per year (95% CI: 1.018-1.049), p < 0.001 and OR 1.68 (95% CI: 1.138-2.503), p = 0.009, respectively. CONCLUSIONS: Hemorrhagic stroke continues to be responsible for a high percentage of disability and death. Furthermore, it was seen here that functional outcome was independent of previous antiplatelet treatment.     

Effect of corpus callosum damage on ipsilateral motor activation in patients with multiple sclerosis: a functional and anatomical study

Functional MRI (fMRI) studies have shown increased activation of ipsilateral motor areas during hand movement in patients with multiple sclerosis (MS). We hypothesized that these changes could be due to disruption of transcallosal inhibitory pathways. We studied 18 patients with relapsing-remitting MS. Conventional T1- and T2-weighted images were acquired and lesion load (LL) measured. Diffusion tensor imaging (DTI) was performed to estimate fractional anisotropy (FA) and mean diffusivity (MD) in the body of the corpus callosum (CC). fMRI was obtained during a right-hand motor task. Patients were studied to evaluate transcallosal inhibition (TCI, latency and duration) and central conduction time (CCT). Eighteen normal subjects were studied with the same techniques. Patients showed increased MD (P < 0.0005) and reduced FA (P < 0.0005) in the body of the CC. Mean latency and duration of TCI were altered in 12 patients and absent in the others. Between-group analysis showed greater activation in patients in bilateral premotor, primary motor (M1), and middle cingulate cortices and in the ipsilateral supplementary motor area, insula, and thalamus. A multivariate analysis between activation patterns, structural MRI, and neurophysiological findings demonstrated positive correlations between T1-LL, MD in the body of CC, and activation of the ipsilateral motor cortex (iM1) in patients. Duration of TCI was negatively correlated with activation in the iM1. Our data suggest that functional changes in iM1 in patients with MS during a motor task partially represents a consequence of loss of transcallosal inhibitory fibers.     

Clinical features of depression in outpatients with and without co-occurring general medical conditions in STAR*D: confirmatory analysis

Background: Concurrent medical comorbidity influences the accurate diagnosis and treatment of major depressive disorder (MDD).Objective: The objective of this study was to validate previous findings from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study using a confirmation analysis in a previously unanalyzed cohort.Design: Baseline cross-sectional case-control study of patients enrolling in a prospective randomized multistage treatment study of nonpsychotic MDD.Setting: Fourteen regional U.S. centers representing 18 primary care and 23 psychiatric practices.Participants: 2541 outpatients with DSM-IV nonpsychotic MDD.Measurements: Sociodemographic status, medical illness ratings, psychiatric status, quality of life, and DSM-IV depression symptom ratings.Results: The prevalence of significant general medical comorbidity in this population was 50.0% (95% CI = 48.1% to 52.0%), consistent with findings reported for the first cohort. Concurrent significant medical comorbidity was associated with older age, lower income, unemployment, limited education, and longer duration of index depressive episode. The group with significant medical comorbidity reported higher rates of somatic symptoms, gastrointestinal symptoms, sympathetic arousal, and leaden paralysis. These results were generally consistent between the 2 cohorts from STAR*D.Conclusions: Major depressive disorder with concurrent general medical conditions is associated with a specific sociodemographic profile and pattern of depressive symptoms. This association has implications for diagnosis and clinical care.     

Increased cx43 and angiogenesis in exercised mouse hearts

Several studies focused on the macroscopic architecture of increased cardiac wall induced by exercise training. Our goal was to evaluate myocardiocyte, interstitial and vascular component, and connexin-43 expression in endurance-trained mouse hearts. Sixty-three 10-week-old male Swiss mice were divided into four sedentary groups (C0, C15, C30 and C45) and three groups exercised respectively for 15 (T15-D; running intensity [RI]: 3.18 m/min; running duration [RD]: 75 min/first week and 150 min/second week), 30 (T30-D; RI: 3.96 m/min; RD: 150 min/third week and 225 min/fourth week) and 45 days (T45-D; RI: 3.96 m/min and 4.8 m/min, respectively for the fifth and sixth week; RD: 300 min) on a treadmill. Morphometric analyses were performed to quantify myocardiocyte size and number, and the capillary and interstitial connective tissue (ICT) area. We assessed the expression of ventricle myosin light chain-II, vimentin and connexin-43 by western blot analyses. Our results showed a hypertrophy of the interventricular septum and left ventricle in T30-D and T45-D mice that was not due to variations in myofibrillar content, myocardiocyte size and number, or ICT quantity but to a significant increase in the capillary area. The microvascular remodeling was associated with vimentin increased expression in ICT cells and connexin-43 upregulation. The first phenomenon might be related to an enhanced request of remodeling and growth factors; the second suggests a new role of connexin-43 in cardiac angiogenesis.     

Wrist and hand ultrasound

With adequate equipment, training, and expertise, ultrasound (US) should be regarded as the first-line imaging modality for the assessment of a wide range of pathological conditions affecting the soft tissues around the wrist and hand. With high-resolution transducers, US allows detection of foreign bodies and a reliable identification of a variety of traumatic lesions affecting tendons, retinacula and annular pulleys, ligaments, vessels, and nerves. In addition, inflammatory arthropathies, infectious disorders, overuse tendinopathies, and degenerative conditions can be diagnosed with this technique. In the wrist, US is able to identify the entrapment of the median, ulnar, and radial nerves. In patients with localized soft tissue swelling, US is able to assess the presence of a space-occupying lesion and to characterize its nature in many cases.