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ObjectiveTo demonstrate the safety and effectiveness of responsive stimulation at the seizure focus as an adjunctive therapy to reduce the frequency of seizures in adults with medically intractable partial onset seizures arising from one or two seizure foci.MethodsRandomized multicenter double-blinded controlled trial of responsive focal cortical stimulation (RNS System). Subjects with medically intractable partial onset seizures from one or two foci were implanted, and 1 month postimplant were randomized 1:1 to active or sham stimulation. After the fifth postimplant month, all subjects received responsive stimulation in an open label period (OLP) to complete 2 years of postimplant follow-up.ResultsAll 191 subjects were randomized. The percent change in seizures at the end of the blinded period was -37.9% in the active and -17.3% in the sham stimulation group (p = 0.012, Generalized Estimating Equations). The median percent reduction in seizures in the OLP was 44% at 1 year and 53% at 2 years, which represents a progressive and significant improvement with time (p

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Significance: Intravital cellular calcium imaging has emerged as a powerful tool to investigate how different types of neurons interact at the microcircuit level to produce seizure activity, with newfound potential to understand epilepsy. Although many methods exist to measure seizure-related activity in traditional electrophysiology, few yet exist for calcium imaging. Aim: To demonstrate an automated algorithmic framework to detect seizure-related events using calcium imaging--including the detection of pre-ictal spike events, propagation of the seizure wavefront, and terminal spreading waves for both population- level activity and that of individual cells. Approach: We developed an algorithm for precise recruitment detection of population and individual cells during seizure-associated events, which broadly leverages averaged population activity and high-magnitude slope features to detect single-cell pre-ictal spike and seizure recruitment. We applied this method to data recorded using awake in vivo two-photon calcium imaging during pentylenetetrazol-induced seizures in mice. Results: We demonstrate that our detected recruitment times are concordant with visually identified labels provided by an expert reviewer and are sufficiently accurate to model the spatiotemporal progression of seizure-associated traveling waves. Conclusions: Our algorithm enables accurate cell recruitment detection and will serve as a useful tool for researchers investigating seizure dynamics using calcium imaging. [ABSTRACT FROM AUTHOR]

: Introduction: ACTG A5288 was a strategy trial conducted in diverse populations from multiple continents of people living with HIV (PLWH) failing second‐line protease inhibitor (PI)‐based antiretroviral therapy (ART) from 10 low‐ and middle‐income countries (LMICs). Participants resistant to lopinavir (LPV) and/or multiple nucleotide reverse transcriptase inhibitors started on third‐line regimens that included raltegravir (RAL), darunavir/ritonavir (DRV/r) and/or etravirine (ETR) according to their resistance profiles. At 48 weeks, 87% of these participants achieved HIV‐1 RNA ≤200 copies/ml. We report here long‐term outcomes over 144 weeks. Methods: Study participants were enrolled from 2013 to 2015, prior to the availability of dolutegravir in LMICs. “Extended Follow‐up” of the study started after the last participant enrolled had reached 48 weeks and included participants still on antiretroviral (ARV) regimens containing RAL, DRV/r and/or ETR at that time. RAL, DRV/r and ETR were provided for an additional 96 weeks (giving total follow‐up of ≥144 weeks), with HIV‐1 RNA measured at 48 and 96 weeks and CD4 count at 96 weeks after entry into Extended Follow‐up. Proportion of participants with HIV‐1 RNA ≤200 copies/ml was estimated every 24 weeks, using imputation if necessary to handle the different measurement schedule in Extended Follow‐up; mean CD4 count changes were estimated using loess regression. Results and Discussion: Of 257 participants (38% females), at study entry, median CD4 count was 179 cells/mm[sup.3], and HIV‐1 RNA was 4.6 log[sub.10] copies/ml. Median follow‐up was 168 weeks (IQR: 156–204); 15 (6%) participants were lost to follow‐up and 9 (4%) died. 27/246 (11%), 26/246 (11%) and 13/92 (14%) of participants who started RAL, DRV/r and ETR, respectively, discontinued these drugs; only three due to adverse events. 87%, 86%, 83% and 80% of the participants had HIV‐1 RNA ≤200 copies/ml at weeks 48, 96, 144 and 168 (95% CI at week 168: 74–85%), respectively. Mean increase from study entry in CD4 count at week 168 was 265 cells/mm[sup.3] (95% CI 247–283). Conclusions: Third‐line regimens comprising of RAL, DRV/r and/or ETR were very well tolerated and had high rates of durable virologic suppression among PLWH in LMICs who were failing on second‐line PI‐based ART prior to the availability of dolutegravir., INTRODUCTION Mathematical modelling suggests that by 2030, up to 4.6 million people living with HIV (PLWH) will require second‐line antiretroviral therapy (ART) globally [1]. Studies in Asia and Africa have [...]

The US National Institute of Neurological Disorders and Stroke convened major stakeholders in June 2012 to discuss how to improve the methodological reporting of animal studies in grant applications and publications. The main workshop recommendation is that at a minimum studies should report on sample-size estimation, whether and how animals were randomized, whether investigators were blind to the treatment, and the handling of data. We recognize that achieving a meaningful improvement in the quality of reporting will require a concerted effort by investigators, reviewers, funding agencies and journal editors. Requiring better reporting of animal studies will raise awareness of the importance of rigorous study design to accelerate scientific progress.

BackgroundCooccurring pain, mood disorders, and substance abuse are common in HIV-infected patients. Our objective was to investigate the relationship between pain, alone and in the context of mood disorders and substance abuse, on clinic utilization, antiretroviral therapy adherence, and virologic suppression.MethodsPain, mood disorders, and substance abuse were assessed at the first visit. No-show and urgent visits were measured over a 1-year period. Models were adjusted for age, race, sex, insurance status, CD4(+) T-lymphocyte count, and HIV risk factor.ResultsAmong 1521 participants, 509 (34%) reported pain, 239 (16%) had pain alone, 189 (13%) had pain and a mood disorder, and 30 (2%) had pain and substance abuse. In univariate models, participants with pain, mood disorders, and substance abuse had higher odds of a no-show visit than those without these conditions [odds ratio (OR), 1.4; 95% confidence interval (CI), 1.1-1.8; OR, 1.5; 95% CI, 1.2-1.9; OR, 2.0; 95% CI, 1.4-2.8, respectively]. In the multivariable model, pain increased the odds of a no-show visit only in participants without substance abuse (OR, 1.5; 95% CI, 1.1-1.9) and pain reduced the odds of a no-show visit in participants with substance abuse (OR, 0.5; 95% CI, 0.2-0.9; P for interaction = 0.0022).ConclusionsIn this study, pain increased the odds of no-show visits but only for participants without substance abuse. Because pain, mood disorders, and substance abuse are highly prevalent in HIV-infected patients, our findings have implications for HIV treatment success. Interventions that incorporate pain management may be important for improving health outcomes in patients living with HIV infection.

BackgroundCooccurring pain, mood disorders, and substance abuse are common in HIV-infected patients. Our objective was to investigate the relationship between pain, alone and in the context of mood disorders and substance abuse, on clinic utilization, antiretroviral therapy adherence, and virologic suppression.MethodsPain, mood disorders, and substance abuse were assessed at the first visit. No-show and urgent visits were measured over a 1-year period. Models were adjusted for age, race, sex, insurance status, CD4(+) T-lymphocyte count, and HIV risk factor.ResultsAmong 1521 participants, 509 (34%) reported pain, 239 (16%) had pain alone, 189 (13%) had pain and a mood disorder, and 30 (2%) had pain and substance abuse. In univariate models, participants with pain, mood disorders, and substance abuse had higher odds of a no-show visit than those without these conditions [odds ratio (OR), 1.4; 95% confidence interval (CI), 1.1-1.8; OR, 1.5; 95% CI, 1.2-1.9; OR, 2.0; 95% CI, 1.4-2.8, respectively]. In the multivariable model, pain increased the odds of a no-show visit only in participants without substance abuse (OR, 1.5; 95% CI, 1.1-1.9) and pain reduced the odds of a no-show visit in participants with substance abuse (OR, 0.5; 95% CI, 0.2-0.9; P for interaction = 0.0022).ConclusionsIn this study, pain increased the odds of no-show visits but only for participants without substance abuse. Because pain, mood disorders, and substance abuse are highly prevalent in HIV-infected patients, our findings have implications for HIV treatment success. Interventions that incorporate pain management may be important for improving health outcomes in patients living with HIV infection.