evaluating a novel online depression intervention for persons with epilepsy

Background Depression is common among persons with epilepsy (PwE), affecting roughly one in three individuals, and its presence is associated with personal suffering, impaired quality of life, and worse prognosis. Despite the availability of effective treatments, depression is often overlooked and treated inadequately in PwE, in part because of assumed concerns over drug interactions or proconvulsant effects of antidepressants. Internet- administered psychological interventions might complement antidepressant medication or psychotherapy, and preliminary evidence suggests that they can be effective. However, no trial has yet examined whether an Internet intervention designed to meet the needs of PwE can achieve sustained reductions in depression and related symptoms, such as anxiety, when offered as adjunct to treatment as usual. Methods/Design This randomized controlled trial will include 200 participants with epilepsy and a current depressive disorder, along with currently at least moderately elevated depression (Patient Health Questionnaire (PHQ-9) sum score of at least 10). Patients will be recruited via epilepsy treatment centers and other sources, including Internet forums, newspaper articles, flyers, posters, and media articles or advertisements, in German-speaking countries. Main inclusion criteria are: self-reported diagnosis of epilepsy and a depressive disorder, as assessed with a phone-administered structured diagnostic interview, none or stable antidepressant medication, no current psychotherapy, no other major psychiatric disorder, no acute suicidality. Participants will be randomly assigned to either (1) a care-as-usual/waitlist (CAU/WL) control group, in which they receive CAU and are given access to the Internet intervention after 3 months (that is, a CAU/WL control group), or (2) a treatment group that may also use CAU and in addition immediately receives six-month access to the novel, Internet-administered intervention. The primary outcome measure is the PHQ-9, collected at three months post-baseline; secondary measures include self-reported anxiety, work and social adjustment, epilepsy symptoms (including seizure frequency and severity), medication adherence, potential negative treatment effects and health-related quality of life. Measurements are collected online at pre-treatment (T0), three months (T1), six months (T2), and nine months (T3). Discussion Results of this trial are expected to extend the body of knowledge with regard to effective and efficient treatment options for PwE who experience elevated depression and anxiety. Trial registration ClinicalTrials.gov: NCT02791724. Registered 01 June 2016

Improved upper limb function in non-ambulant children with SMA type 2 and 3 during nusinersen treatment: a prospective 3-years SMArtCARE registry study

Background The development and approval of disease modifying treatments have dramatically changed disease progression in patients with spinal muscular atrophy (SMA). Nusinersen was approved in Europe in 2017 for the treatment of SMA patients irrespective of age and disease severity. Most data on therapeutic efficacy are available for the infantile-onset SMA. For patients with SMA type 2 and type 3, there is still a lack of sufficient evidence and long-term experience for nusinersen treatment. Here, we report data from the SMArtCARE registry of non-ambulant children with SMA type 2 and typen 3 under nusinersen treatment with a follow-up period of up to 38 months. Methods SMArtCARE is a disease-specific registry with data on patients with SMA irrespective of age, treatment regime or disease severity. Data are collected during routine patient visits as real-world outcome data. This analysis included all non-ambulant patients with SMA type 2 or 3 below 18 years of age before initiation of treatment. Primary outcomes were changes in motor function evaluated with the Hammersmith Functional Motor Scale Expanded (HFMSE) and the Revised Upper Limb Module (RULM). Results Data from 256 non-ambulant, pediatric patients with SMA were included in the data analysis. Improvements in motor function were more prominent in upper limb: 32.4% of patients experienced clinically meaningful improvements in RULM and 24.6% in HFMSE. 8.6% of patients gained a new motor milestone, whereas no motor milestones were lost. Only 4.3% of patients showed a clinically meaningful worsening in HFMSE and 1.2% in RULM score. Conclusion Our results demonstrate clinically meaningful improvements or stabilization of disease progression in non-ambulant, pediatric patients with SMA under nusinersen treatment. Changes were most evident in upper limb function and were observed continuously over the follow-up period. Our data confirm clinical trial data, while providing longer follow-up, an increased number of treated patients, and a wider range of age and disease severity

Use of serial changes in biomarkers vs. baseline levels to predict left ventricular remodelling after STEMI

Aims: Cellular communication network factor 1 (CCN1) is an independent predictor of MACE after ACS and elevated levels correlated with infarct size after STEMI. We compared the prognostic accuracy of baseline levels of CCN1, NT-proBNP, hsTnT, and ST2 and changes in levels over time to predict the development of structural and functional alterations typical of LV remodelling. Methods: Serial 3-T cMRI scans were performed to determine LVEF, LVEDV, LVESV, infarct size, and relative infarct size, which were correlated with serial measurements of the four biomarkers. The prognostic significance of these biomarkers was assessed by multiple logistic regression analysis by examining their performance in predicting dichotomized cardiac MRI values 12 months after STEMI based on their median. For each biomarker three models were created using baseline (BL), the Δ value (BL to 6 months), and the two values together as predictors. All models were adjusted for age and renal function. Receiver operator curves were plotted with area under the curve (AUC) to discriminate the prognostic accuracy of individual biomarkers for MRI-based structural or functional changes. Results: A total of 44 predominantly male patients (88.6%) from the ETiCS (Etiology, Titre-Course, and Survival) study were identified at a mean age of 55.5 ± 11.5 (SD) years treated by successful percutaneous coronary intervention (97.7%) at a rate of 95.5% stent implantation within a median pain-to-balloon time of 260 min (IQR 124–591). Biomarkers hsTnT and ST2 were identified as strong predictors (AUC > 0.7) of LVEDV and LVEF. BL measurement to predict LVEF [hsTnT: AUC 0.870 (95% CI: 0.756–0.983), ST2: AUC 0.763 (95% CI: 0.615–0.911)] and the Δ value BL-6M [hsTnT: AUC 0.870 (95% CI: 0.756–0.983), ST2: AUC 0.809 (95% CI: 0.679–0.939)] showed a high prognostic value without a significant difference for the comparison of the BL model vs. the Δ-value model (BL-6M) for hsTnT (P = 1) and ST2 (P = 0.304). The combined model that included baseline and Δ value as predictors was not able to improve the ability to predict LVEF [hsTnT: AUC 0.891 (0.791–0.992), P = 0.444; ST2: AUC 0.778 (0.638–0.918), P = 0.799]. Baseline levels of CCN1 were closely associated with LVEDV at 12 months [AUC 0.708 (95% CI: 0.551–0.865)] and infarct size [AUC 0.703 (95% CI: 0.534–0.872)]. Conclusions: Baseline biomarker levels of hsTnT and ST2 were the strongest predictors of LVEF and LVEDV at 12 months after STEMI. The association of CCN1 with LVEDV and infarct size warrants further study into the underlying pathophysiology of this novel biomarker

Mechanisms of Hg species induced toxicity in cultured human astrocytes : genotoxicity and DNA-damage response

The toxicologically most relevant mercury (Hg) species for human exposure is methylmercury (MeHg). Thiomersal is a common preservative used in some vaccine formulations. The aim of this study is to get further mechanistic insight into the yet not fully understood neurotoxic modes of action of organic Hg species. Mercury species investigated include MeHgCl and thiomersal. Additionally HgCl2 was studied, since in the brain mercuric Hg can be formed by dealkylation of the organic species. As a cellular system astrocytes were used. In vivo astrocytes provide the environment necessary for neuronal function. In the present study, cytotoxic effects of the respective mercuricals increased with rising alkylation level and correlated with their cellular bioavailability. Further experiments revealed for all species at subcytotoxic concentrations no induction of DNA strand breaks, whereas all species massively increased H2O2-induced DNA strand breaks. This co-genotoxic effect is likely due to a disturbance of the cellular DNA damage response. Thus, at nanomolar, sub-cytotoxic concentrations, all three mercury species strongly disturbed poly(ADP-ribosyl)ation, a signalling reaction induced by DNA strand breaks. Interestingly, the molecular mechanism behind this inhibition seems to be different for the species. Since chronic PARP-1 inhibition is also discussed to sacrifice neurogenesis and learning abilities, further experiments on neurons and in vivo studies could be helpful to clarify whether the inhibition of poly(ADP-ribosyl)ation contributes to organic Hg induced neurotoxicity