Takotsubo Cardiomyopathy With Inconspicuous Initial Electrocardiogram: A Potentially Serious Cardiac Pathology Related to Emotional Stress

Introduction: Takotsubo cardiomyopathy (TCM) is frequently associated with emotional or physical stress. Thus, patients with TCM might present primarily at a psychiatric clinic. Appropriate diagnosis and therapy may thus be delayed.Case report: A 43-year-old female patient presented as an emergency to the psychiatric outpatient clinic after experiencing severe work-related bullying. On admission, she complained of acute left thoracic chest pain as well as depressed mood, low energy, anhedonia, generalized anxiety, and sleep difficulties, present for several weeks. The initial electrocardiogram (ECG) was unremarkable; serum troponin levels, however, were markedly elevated. The patient was transferred to the department of cardiology. Via cardiac catheterization and MRI, an acute coronary syndrome was excluded and apical ballooning and left ventricular dysfunction, compatible with TCM, was found.Conclusion: Patients with acute psychopathology, recent emotional or physical stress, and acute cardiothoracic symptoms should receive immediate cardiological investigations. As the ECG may be normal in patients with TCM, concurrent measurement of the troponin serum level is recommended. Psychiatrists should consider TCM in patients who report recent stressful events accompanied by cardiothoracic symptoms

Non-Invasive Brain Stimulation in Conversion (Functional) Weakness and Paralysis: A Systematic Review and Future Perspectives

Conversion (functional) limb weakness or paralysis (FW) can be a debilitating condition, and often causes significant distress or impairment in social, occupational, or other important areas of functioning. Most treatment concepts are multi-disciplinary, containing a behavioral approach combined with a motor learning program. Non-invasive brain stimulation (NIBS) methods, such as electroconvulsive therapy (ECT), and transcranial magnetic stimulation (TMS) have been used in the past few decades to treat FW. In order to identify all published studies that used NIBS methods such as ECT, TMS and transcranial direct current stimulation (tDCS) for treating FW patients a systematic review of the literature was conducted in PubMed and Web of Science. In a second step, narratives were used to retrospectively determine nominal CGI-I (Clinical Global Impression scale–Improvement) scores to describe approximate changes of FW symptoms. We identified two articles (case reports) with ECT used for treatment of FW, five with TMS with a total of 86 patients, and none with tDCS. In 75 out of 86 patients treated with repetitive (r)TMS a nominal CGI-I score could be estimated, showing a satisfactory short-term improvement. Fifty-four out of seventy-five identified patients (72%) had a CGI-I score of 1 (very much improved), 13 (17%) a score of 2 (much improved), 5 (7%) a score of 3 (minimally improved), and 3 (5%) remained unchanged (CGI-I = 4). In no case did patients worsen after rTMS treatment, and no severe adverse effects were reported. At follow-up, symptom improvement was not quantifiable in terms of CGI-I for the majority of the cases. Patients treated with ECT showed a satisfactory short-term response (CGI-I = 2), but deterioration of FW symptoms at follow-up. Despite the predominantly positive results presented in the identified studies and satisfactory levels of efficacy measured with retrospectively calculated nominal CGI-I scores, any assumption of a beneficial effect of NIBS in FW has to be seen with caution, as only few articles could be retrieved and their quality was mostly poor. This article elucidates how NIBS might help in FW and gives recommendations for future study designs using NIBS in this condition

Sham or real—Post hoc estimation of stimulation condition in a randomized transcranial magnetic stimulation trial

Selecting a suitable sham condition within the frame of repetitive transcranial magnetic stimulation (rTMS) treatment trials is a central issue. On the one hand, the ideal sham condition should not have a real stimulation effect; on the other hand, it should not be recognized as sham by patients, particularly when considering that real stimulation conditions come along with rTMS specific side effects. Within the course of a multi-centre trial assessing the antidepressant effects of rTMS, patients were randomized to sham or real stimulation, in both cases using a standard stimulation coil. In one centre, patients (n = 33) were asked about their impression whether they received the sham or the real treatment, and if they would recommend the treatment to others. 29 patients returned the questionnaires and were included into the analysis. From 15 subjects with real stimulation, 11 suggested to have obtained real, and 4 to have obtained sham. From 14 sham stimulated subjects, 9 suggested to have obtained the real condition and 5 to have been sham stimulated. This difference was not significant (p = 0.60, chi square test). In addition, the major part of patients in both stimulation conditions would recommend rTMS to others. In both conditions, real and sham, the majority of subjects believed to have obtained the real condition. This implies suitability of the sham condition used since subjects appeared not to be able to identify the condition. The results imply the feasibility of a valid sham condition with a “real” coil

Psychological distress, fear and coping strategies during the second and third waves of the COVID-19 pandemic in Southern Germany

Background: The COVID-19 pandemic has imposed enormous psychological discomfort and fear across the globe, including Germany. Objectives: To assess the levels of COVID-19 associated psychological distress and fear amongst Southern German population, and to identify their coping strategies. Methods: A cross-sectional survey using an online questionnaire was conducted in healthcare and community settings in the region of Ulm, Southern Germany. Assessment inventories were the Kessler Psychological Distress Scale (K-10), the Brief Resilient Coping Scale (BRCS), and the Fear of COVID-19 Scale (FCV-19S), which were valid and reliable tools. Results: A total of 474 Individuals participated in the study. The mean age was 33.6 years, and 327 (69%) were females. Most participants (n = 381, 80.4%) had high levels of psychological distress, whereas only 5.1% had high levels of fear, and two-thirds of participants showed higher levels of coping. Moderate to very high levels of psychological distress were associated with being female, living alone, distress due to employment changes, experiencing financial impact, having multiple co-morbidities, being a smoker, increased alcohol use over the previous 6 months, contact with COVID-19 cases and healthcare providers for COVID-19-related stress. Individuals who wer

Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation

Sensitivity of Quantitative Signal Detection in Regards to Pharmacological Neuroenhancement

Pharmacological neuroenhancement (PNE) is a form of abuse and has not yet been addressed by methods of pharmacovigilance. In the present study, we tested if quantitative signal detection may be sensitive in regards to PNE. We evaluated the risk of drug abuse and dependence (DAAD) related to substances that are known to be used for PNE and divided this group into agents with (methylphenidate) and without a known abuse potential outside the field of PNE (atomoxetine, modafinil, acetylcholine esterase inhibitors, and memantine). Reporting odds ratios (RORs) were calculated using a case/non-case approach based on global and country-specific drug safety data from the Uppsala Monitoring Centre (UMC). Both control substances (diazepam and lorazepam) and methylphenidate were statistically associated with DAAD in all datasets (except methylphenidate in Italy). Modafinil was associated with DAAD in the total dataset (ROR, 2.7 (95% confidence interval (CI), 2.2–3.3)), Germany (ROR, 4.6 (95% CI, 1.8–11.5)), and the USA (ROR, 2.0 (95% CI, 1.6–2.5)). Atomoxetine was associated with DAAD in the total dataset (ROR, 1.3 (95% CI, 1.2–1.5)) and in the UK (ROR, 3.3 (95% CI, 1.8–6.1)). Apart from memantine, which was associated with DAAD in Germany (ROR, 1.8 (95% CI, 1.0–3.2)), no other antidementia drug was associated with DAAD. Quantitative signal detection is suitable to detect agents with a risk for DAAD. Its sensitivity regarding PNE is limited, although atomoxetine and modafinil, which do not have a known abuse potential outside PNE, and no antidementia drugs, whose use in PNE is presumably low, were associated with DAAD in our analysis

Harmonization of summaries of product characteristics (SmPCs) of drugs with the same active ingredients: an evaluation of SmPCs of the most frequently prescribed active substances

Purpose!#!In aut-idem or generic substitution, discrepancies between summaries of product characteristics (SmPCs) referring to the same active substance (AS) may cause difficulties regarding informed consent and medical liability. The qualitative and quantitative characteristics of such discrepancies are insufficiently studied, impeding harmonization of same-substance SmPCs and compromising safe drug treatment.!##!Methods!#!SmPCs of the one hundred most frequently prescribed ASs in Germany were analyzed for discrepancies in the presentation of indications (Inds) and contraindications (CInds). Inclusion and exclusion criteria of drugs/SmPCs were chosen according to the standards of the aut-idem substitution in Germany.!##!Results!#!According to the study protocol, we identified 1486 drugs, of which 1426 SmPCs could be obtained. 41% respectively 65% of the ASs had same-substance SmPCs that differed from the respective reference SmPC in the number of listed Inds respectively CInds. The number of listed Inds/CInds varied considerably between same-substance SmPCs with maximum ranges in Inds of 7 in amoxicillin, and in CInds of 11 in lisinopril. Many ASs had large proportions (> 50%) of associated same-substance SmPCs that differed from the respective reference SmPC. A considerable proportion of ASs had same-substance SmPCs with formal and content-related differences other than the discrepancy in the number of Inds/CInds.!##!Conclusion!#!This evaluation of same-substance SmPCs shows a clear lack of harmonization of same-substance SmPCs. Considering that generic substitution has become the rule and that physicians usually do not know which drug the patient receives in the pharmacy, these discrepancies raise several questions, that require a separate legal evaluation