Electromyographic and Joint Kinematic Patterns in Runner\u27s Dystonia.

Runner’s dystonia (RD) is a task-specific focal dystonia of the lower limbs that occurs when running. In this retrospective case series, we present surface electromyography (EMG) and joint kinematic data from thirteen patients with RD who underwent instrumented gait analysis (IGA) at the Functional and Biomechanics Laboratory at the National Institutes of Health. Four cases of RD are described in greater detail to demonstrate the potential utility of EMG with kinematic studies to identify dystonic muscle groups in RD. In these cases, the methodology for muscle selection for botulinum toxin therapy and the therapeutic response is discussed. Lateral heel whip, a proposed novel presentation of lower-limb dystonia, is also described

Global State Measures of the Dentate Gyrus Gene Expression System Predict Antidepressant-Sensitive Behaviors

Background Selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine are the most common form of medication treatment for major depression. However, approximately 50% of depressed patients fail to achieve an effective treatment response. Understanding how gene expression systems respond to treatments may be critical for understanding antidepressant resistance. Methods We take a novel approach to this problem by demonstrating that the gene expression system of the dentate gyrus responds to fluoxetine (FLX), a commonly used antidepressant medication, in a stereotyped-manner involving changes in the expression levels of thousands of genes. The aggregate behavior of this large-scale systemic response was quantified with principal components analysis (PCA) yielding a single quantitative measure of the global gene expression system state. Results Quantitative measures of system state were highly correlated with variability in levels of antidepressant-sensitive behaviors in a mouse model of depression treated with fluoxetine. Analysis of dorsal and ventral dentate samples in the same mice indicated that system state co-varied across these regions despite their reported functional differences. Aggregate measures of gene expression system state were very robust and remained unchanged when different microarray data processing algorithms were used and even when completely different sets of gene expression levels were used for their calculation. Conclusions System state measures provide a robust method to quantify and relate global gene expression system state variability to behavior and treatment. State variability also suggests that the diversity of reported changes in gene expression levels in response to treatments such as fluoxetine may represent different perspectives on unified but noisy global gene expression system state level responses. Studying regulation of gene expression systems at the state level may be useful in guiding new approaches to augmentation of traditional antidepressant treatments

The relationship between depressive symptoms, health service consumption, and prognosis after acute myocardial infarction: a prospective cohort study

<p>Abstract</p> <p>Background</p> <p>The use of cardiovascular health services is greater among patients with depressive symptoms than among patients without. However, the extent to which such associations between depressive symptoms and health service utilization are attributable to variations in comorbidity and prognostic disease severity is unknown. This paper explores the relationship between depressive symptoms, health service cardiovascular consumption, and prognosis following acute myocardial infarction (AMI).</p> <p>Methods</p> <p>The study design was a prospective cohort study with follow-up telephone interviews of 1,941 patients 30 days following AMI discharged from 53 hospitals across Ontario, Canada between December 1999 and February, 2003. Outcome measures were post discharge use of cardiac and non-cardiac health care services. The service utilization outcomes were adjusted for age, sex, income, comorbidity, two validated measures of prognosis (cardiac functional capacity and risk adjustment severity index), cardiac procedures (CABG or PTCA) and drugs prescribed at discharge.</p> <p>Results</p> <p>Depressive symptoms were associated with a 24% (Adjusted RR:1.24; 95% CI:1.19–1.30, P < 0.001), 9% (Adjusted RR:1.09; 95% CI:1.02–1.16, P = 0.007) and 43% (Adjusted RR: 1.43; 95% CI:1.34–1.52, P < 0.001) increase in total, cardiac, and non-cardiac hospitalization days post-AMI respectively, after adjusting for baseline patient and hospital characteristics. Depressive-associated increases in cardiac health service consumption were significantly more pronounced among patients of lower than higher cardiac risk severity. Depressive symptoms were not associated with increased mortality after adjusting for baseline patient characteristics.</p> <p>Conclusion</p> <p>Depressive symptoms are associated with significantly higher cardiac and non-cardiac health service consumption following AMI despite adjustments for comorbidity and prognostic severity. The disproportionately higher cardiac health service consumption among lower-risk AMI depressive patients may suggest that health seeking behaviors are mediated by psychosocial factors more so than by objective measures of cardiovascular risk or necessity.</p

The relationship between depressive symptoms, health service consumption, and prognosis after acute myocardial infarction: a prospective cohort study

<p>Abstract</p> <p>Background</p> <p>The use of cardiovascular health services is greater among patients with depressive symptoms than among patients without. However, the extent to which such associations between depressive symptoms and health service utilization are attributable to variations in comorbidity and prognostic disease severity is unknown. This paper explores the relationship between depressive symptoms, health service cardiovascular consumption, and prognosis following acute myocardial infarction (AMI).</p> <p>Methods</p> <p>The study design was a prospective cohort study with follow-up telephone interviews of 1,941 patients 30 days following AMI discharged from 53 hospitals across Ontario, Canada between December 1999 and February, 2003. Outcome measures were post discharge use of cardiac and non-cardiac health care services. The service utilization outcomes were adjusted for age, sex, income, comorbidity, two validated measures of prognosis (cardiac functional capacity and risk adjustment severity index), cardiac procedures (CABG or PTCA) and drugs prescribed at discharge.</p> <p>Results</p> <p>Depressive symptoms were associated with a 24% (Adjusted RR:1.24; 95% CI:1.19–1.30, P < 0.001), 9% (Adjusted RR:1.09; 95% CI:1.02–1.16, P = 0.007) and 43% (Adjusted RR: 1.43; 95% CI:1.34–1.52, P < 0.001) increase in total, cardiac, and non-cardiac hospitalization days post-AMI respectively, after adjusting for baseline patient and hospital characteristics. Depressive-associated increases in cardiac health service consumption were significantly more pronounced among patients of lower than higher cardiac risk severity. Depressive symptoms were not associated with increased mortality after adjusting for baseline patient characteristics.</p> <p>Conclusion</p> <p>Depressive symptoms are associated with significantly higher cardiac and non-cardiac health service consumption following AMI despite adjustments for comorbidity and prognostic severity. The disproportionately higher cardiac health service consumption among lower-risk AMI depressive patients may suggest that health seeking behaviors are mediated by psychosocial factors more so than by objective measures of cardiovascular risk or necessity.</p

Targeted hepatitis C antibody testing interventions: a systematic review and meta-analysis

Testing for hepatitis C virus (HCV) infection may reduce the risk of liver-related morbidity, by facilitating earlier access to treatment and care. This review investigated the effectiveness of targeted testing interventions on HCV case detection, treatment uptake, and prevention of liver-related morbidity. A literature search identified studies published up to 2013 that compared a targeted HCV testing intervention (targeting individuals or groups at increased risk of HCV) with no targeted intervention, and results were synthesised using meta-analysis. Exposure to a targeted testing intervention, compared to no targeted intervention, was associated with increased cases detected [number of studies (n) = 14; pooled relative risk (RR) 1.7, 95 % CI 1.3, 2.2] and patients commencing therapy (n = 4; RR 3.3, 95 % CI 1.1, 10.0). Practitioner-based interventions increased test uptake and cases detected (n = 12; RR 3.5, 95 % CI 2.5, 4.8; and n = 10; RR 2.2, 95 % CI 1.4, 3.5, respectively), whereas media/information-based interventions were less effective (n = 4; RR 1.5, 95 % CI 0.7, 3.0; and n = 4; RR 1.3, 95 % CI 1.0, 1.6, respectively). This meta-analysis provides for the first time a quantitative assessment of targeted HCV testing interventions, demonstrating that these strategies were effective in diagnosing cases and increasing treatment uptake. Strategies involving practitioner-based interventions yielded the most favourable outcomes. It is recommended that testing should be targeted at and offered to individuals who are part of a population with high HCV prevalence, or who have a history of HCV risk behaviour

Phase II Study of Nivolumab and Salvage Nivolumab/Ipilimumab in Treatment-Naive Patients With Advanced Clear Cell Renal Cell Carcinoma (HCRN GU16-260-Cohort A)

PURPOSE To determine the value of tumor cell programmed death-ligand 1 (PD-L1) expression as a predictive biomarker of nivolumab monotherapy efficacy in treatment-naive patients with clear cell renal cell carcinoma (ccRCC) and the efficacy of salvage nivolumab/ipilimumab in patients with tumors unresponsive to nivolumab monotherapy. METHODS Eligible patients with treatment-naive ccRCC received nivolumab until progressive disease (PD), toxicity, or completing 96 treatment weeks (part A). Patients with PD before or stable disease at 48 weeks could receive salvage nivolumab/ipilimumab (part B). The primary end point was improvement in 1-year progression-free survival in patients with tumor PD-L1 expression > 20% versus 0%. RESULTS One hundred twenty-three patients were enrolled. The objective response rate (ORR) was 34.1% (95% CI, 25.8 to 43.2). ORR by International Metastatic RCC Database Consortium category was favorable-risk 57.1%, intermediate-risk/poor-risk 25.0%, and by sarcomatoid features 36.4%. The ORR was 26.9%, 50.0%, and 75.0% for patients with the tumor PD-L1 expression of 0, 1-20, or > 20%, respectively (trend test P value = .002). The median duration of response was 27.6 (19.3 to not reached) months, with 26 of 42 responders including 17 of 20 with favorable-risk disease remaining progression-free. The 1-year progression-free survival was 34.6% and 75.0% in the PD-L1 = 0% and > 20% categories, respectively (P = .050). Ninety-seven patients with PD or prolonged stable disease were potentially eligible for part B, and 35 were enrolled. The ORR for part B was 11.4%. Grade >= 3 treatment-related adverse events occurred in 35% of patients on nivolumab and 43% of those on salvage nivolumab/ipilimumab. CONCLUSION Nivolumab monotherapy is active in treatment-naive ccRCC. Although efficacy appears to be less than that of nivolumab/ipilimumab in patients with intermediate-risk/poor-risk disease, favorable-risk patients had notable benefit. Efficacy correlated with tumor PD-L1 status. Salvage nivolumab/ipilimumab was frequently not feasible and of limited benefit

Phase II study of nivolumab and salvage nivolumab/ipilimumab in treatment-naïve patients with advanced non-clear cell renal cell carcinoma (HCRN GU16-260-Cohort B)

Background To determine the efficacy and toxicity of nivolumab monotherapy in treatment-naive patients with non-clear cell renal cell carcinoma (nccRCC) and the efficacy of nivolumab/ipilimumab salvage therapy in patients with tumors unresponsive to initial nivolumab monotherapy.Methods Eligible patients with treatment-naive nccRCC received nivolumab until progressive disease (PD), toxicity, or completion of 96 weeks of treatment (Part A). Patients with PD prior to, or stable disease (SD) at 48 weeks (prolonged SD) were potentially eligible to receive salvage nivolumab/ipilimumab (Part B). Patients were required to submit tissue from a metastatic lesion obtained within 12 months prior to study entry and prior to Part B for correlative studies.Results 35 patients with nccRCC were enrolled: 19 (54%) had papillary, 6 (17%) had chromophobe and 10 (29%) had unclassified histology. At median follow-up of 22.9 months, RECIST-defined objective response rate (ORR) was 5 of 35 (14.3% 95% CI 4.8% to 30.3%) (complete response (CR) 2 (5.7%) and partial response (PR) 3 (8.6%)). ORR by histology was: papillary-1/19 (5%); chromophobe-1/6 (17%); and unclassified-3/10 (30%). Nine patients (26%) had tumors with sarcomatoid features with 3 (33%) (2 unclassified and 1 papillary) responding. ORR was 0/18, 3/11 (27%) and 2/6 (33%) for patients with tumor progammed death ligand 1 (PD-L1) expression of = 5% or not measured, respectively. Median progression-free survival was 4.0 (2.7-4.3) months. Two of five responders have progressed. Thirty-two patients had PD or prolonged SD and therefore, were potentially eligible for salvage nivolumab/ipilimumab (Part B), but 15 patients did not enroll due to grade 2-3 toxicity (6) on nivolumab, symptomatic disease progression (5), or other reasons including no biopsy tissue (4). In the 17 Part B patients, there was one PR (6%) (unclassified/non-sarcomatoid). Grade >3 treatment-related adverse events were seen in 7/35 (20%) on nivolumab and 7/17 (41%) on salvage nivolumab/ipilimumab with one patient experiencing sudden death.Conclusions Nivolumab monotherapy has limited activity in treatment-naive nccRCC with most responses (4 of 5) seen in patients with sarcomatoid and/or unclassified tumors. Toxicity is consistent with prior nivolumab studies. Salvage treatment with nivolumab/ipilimumab was provided in half of these patients with minimal activity