Dramatic outcomes in epilepsy: depression, suicide, injuries, and mortality

In this narrative review, we will discuss some of the significant risks and dramatic consequences that are associated with epilepsy: depression, suicide, seizure-related injuries, and mortality, both in adults and in children. Considering the high prevalence of depression among people with epilepsy (PWE), routine and periodic screening of all PWE for early detection and appropriate management of depression is recommended. PWE should be screened for suicidal ideation regularly and when needed, patients should be referred for a psychiatric evaluation and treatment. When starting an antiepileptic drug (AED) or switching from one to another AED, patients should be advised to report to their treating physician any change in their mood and existence of suicidal ideation. The risk of injuries for the general epilepsy population is increased only moderately. The risk is higher in selected populations attending epilepsy clinics and referral centers. This being said, there are PWE that may suffer frequent, severe, and sometimes even life-threatening seizure-related injuries. The most obvious way to reduce risk is to strive for improved seizure control. Finally, PWE have a 2–3 times higher mortality rate than the general population. Deaths in PWE may relate to the underlying cause of epilepsy, to seizures (including sudden unexpected death in epilepsy [SUDEP] and seizure related injuries) and to status epilepticus, as well as to other conditions that do not appear directly related to epilepsy. Improving seizure control and patient education may be the most important measures to reduce epilepsy related mortality in general and SUDEP in particular

Effect of Common Medications on the Expression of SARS-CoV-2 Entry Receptors in Kidney Tissue

Besides the respiratory system, severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) infection was shown to affect other essential organs such as the kidneys. Early kidney involvement during the course of infection was associated with worse outcomes, which could be attributed to the direct SARS-CoV-2 infection of kidney cells. In this study, the effect of commonly used medications on the expression of SARS-CoV-2 receptor, angiotensin-converting enzyme (ACE)2, and TMPRSS2 protein in kidney tissues was evaluated. This was done by in silico analyses of publicly available transcriptomic databases of kidney tissues of rats treated with multiple doses of commonly used medications. Of 59 tested medications, 56% modified ACE2 expression, whereas 24% modified TMPRSS2 expression. ACE2 was increased with only a few of the tested medication groups, namely the renin-angiotensin inhibitors, such as enalapril, antibacterial agents, such as nitrofurantoin, and the proton pump inhibitor, omeprazole. The majority of the other medications decreased ACE2 expression to variable degrees with allopurinol and cisplatin causing the most noticeable downregulation. The expression level of TMPRSS2 was increased with a number of medications, such as diclofenac, furosemide, and dexamethasone, whereas other medications, such as allopurinol, suppressed the expression of this gene. The prolonged exposure to combinations of these medications could regulate the expression of ACE2 and TMPRSS2 in a way that may affect kidney susceptibility to SARS-CoV-2 infection. Data presented here suggest that we should be vigilant about the potential effects of commonly used medications on kidney tissue expression of ACE2 and TMPRSS2

Multiple early introductions of SARS-CoV-2 into a global travel hub in the Middle East

International travel played a significant role in the early global spread of SARS-CoV-2. Understanding transmission patterns from different regions of the world will further inform global dynamics of the pandemic. Using data from Dubai in the United Arab Emirates (UAE), a major international travel hub in the Middle East, we establish SARS-CoV-2 full genome sequences from the index and early COVID-19 patients in the UAE. The genome sequences are analysed in the context of virus introductions, chain of transmissions, and possible links to earlier strains from other regions of the world. Phylogenetic analysis showed multiple spatiotemporal introductions of SARS-CoV-2 into the UAE from Asia, Europe, and the Middle East during the early phase of the pandemic. We also provide evidence for early community-based transmission and catalogue new mutations in SARS-CoV-2 strains in the UAE. Our findings contribute to the understanding of the global transmission network of SARS-CoV-2

The Dawn of Open Access to Phylogenetic Data

The scientific enterprise depends critically on the preservation of and open access to published data. This basic tenet applies acutely to phylogenies (estimates of evolutionary relationships among species). Increasingly, phylogenies are estimated from increasingly large, genome-scale datasets using increasingly complex statistical methods that require increasing levels of expertise and computational investment. Moreover, the resulting phylogenetic data provide an explicit historical perspective that critically informs research in a vast and growing number of scientific disciplines. One such use is the study of changes in rates of lineage diversification (speciation - extinction) through time. As part of a meta-analysis in this area, we sought to collect phylogenetic data (comprising nucleotide sequence alignment and tree files) from 217 studies published in 46 journals over a 13-year period. We document our attempts to procure those data (from online archives and by direct request to corresponding authors), and report results of analyses (using Bayesian logistic regression) to assess the impact of various factors on the success of our efforts. Overall, complete phylogenetic data for ~60% of these studies are effectively lost to science. Our study indicates that phylogenetic data are more likely to be deposited in online archives and/or shared upon request when: (1) the publishing journal has a strong data-sharing policy; (2) the publishing journal has a higher impact factor, and; (3) the data are requested from faculty rather than students. Although the situation appears dire, our analyses suggest that it is far from hopeless: recent initiatives by the scientific community -- including policy changes by journals and funding agencies -- are improving the state of affairs

Does publication bias inflate the apparent efficacy of psychological treatment for major depressive disorder? A systematic review and meta-analysis of US national institutes of health-funded trials

Background The efficacy of antidepressant medication has been shown empirically to be overestimated due to publication bias, but this has only been inferred statistically with regard to psychological treatment for depression. We assessed directly the extent of study publication bias in trials examining the efficacy of psychological treatment for depression. Methods and Findings We identified US National Institutes of Health grants awarded to fund randomized clinical trials comparing psychological treatment to control conditions or other treatments in patients diagnosed with major depressive disorder for the period 1972–2008, and we determined whether those grants led to publications. For studies that were not published, data were requested from investigators and included in the meta-analyses. Thirteen (23.6%) of the 55 funded grants that began trials did not result in publications, and two others never started. Among comparisons to control conditions, adding unpublished studies (Hedges’ g = 0.20; CI95% -0.11~0.51; k = 6) to published studies (g = 0.52; 0.37~0.68; k = 20) reduced the psychotherapy effect size point estimate (g = 0.39; 0.08~0.70) by 25%. Moreover, these findings may overestimate the "true" effect of psychological treatment for depression as outcome reporting bias could not be examined quantitatively. Conclusion The efficacy of psychological interventions for depression has been overestimated in the published literature, just as it has been for pharmacotherapy. Both are efficacious but not to the extent that the published literature would suggest. Funding agencies and journals should archive both original protocols and raw data from treatment trials to allow the detection and correction of outcome reporting bias. Clinicians, guidelines developers, and decision makers should be aware that the published literature overestimates the effects of the predominant treatments for depression

Statin-Associated Muscular and Renal Adverse Events: Data Mining of the Public Version of the FDA Adverse Event Reporting System

OBJECTIVE: Adverse event reports (AERs) submitted to the US Food and Drug Administration (FDA) were reviewed to assess the muscular and renal adverse events induced by the administration of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) and to attempt to determine the rank-order of the association. METHODS: After a revision of arbitrary drug names and the deletion of duplicated submissions, AERs involving pravastatin, simvastatin, atorvastatin, or rosuvastatin were analyzed. Authorized pharmacovigilance tools were used for quantitative detection of signals, i.e., drug-associated adverse events, including the proportional reporting ratio, the reporting odds ratio, the information component given by a Bayesian confidence propagation neural network, and the empirical Bayes geometric mean. Myalgia, rhabdomyolysis and an increase in creatine phosphokinase level were focused on as the muscular adverse events, and acute renal failure, non-acute renal failure, and an increase in blood creatinine level as the renal adverse events. RESULTS: Based on 1,644,220 AERs from 2004 to 2009, signals were detected for 4 statins with respect to myalgia, rhabdomyolysis, and an increase in creatine phosphokinase level, but these signals were stronger for rosuvastatin than pravastatin and atorvastatin. Signals were also detected for acute renal failure, though in the case of atorvastatin, the association was marginal, and furthermore, a signal was not detected for non-acute renal failure or for an increase in blood creatinine level. CONCLUSIONS: Data mining of the FDA's adverse event reporting system, AERS, is useful for examining statin-associated muscular and renal adverse events. The data strongly suggest the necessity of well-organized clinical studies with respect to statin-associated adverse events

Data sharing: not as simple as it seems

In recent years there has been a major change on the part of funders, particularly in North America, so that data sharing is now considered to be the norm rather than the exception. We believe that data sharing is a good idea. However, we also believe that it is inappropriate to prescribe exactly when or how researchers should preserve and share data, since these issues are highly specific to each study, the nature of the data collected, who is requesting it, and what they intend to do with it. The level of ethical concern will vary according to the nature of the information, and the way in which it is collected - analyses of anonymised hospital admission records may carry a quite different ethical burden than analyses of potentially identifiable health information collected directly from the study participants. It is striking that most discussions about data sharing focus almost exclusively on issues of ownership (by the researchers or the funders) and efficiency (on the part of the funders). There is usually little discussion of the ethical issues involved in data sharing, and its implications for the study participants. Obtaining prior informed consent from the participants does not solve this problem, unless the informed consent process makes it completely clear what is being proposed, in which case most study participants would not agree. Thus, the undoubted benefits of data sharing does not remove the obligations and responsibilities that the original investigators hold for the people they invited to participate in the study

Mine, Yours, Ours? Sharing Data on Human Genetic Variation

The achievement of a robust, effective and responsible form of data sharing is currently regarded as a priority for biological and bio-medical research. Empirical evaluations of data sharing may be regarded as an indispensable first step in the identification of critical aspects and the development of strategies aimed at increasing availability of research data for the scientific community as a whole. Research concerning human genetic variation represents a potential forerunner in the establishment of widespread sharing of primary datasets. However, no specific analysis has been conducted to date in order to ascertain whether the sharing of primary datasets is common-practice in this research field. To this aim, we analyzed a total of 543 mitochondrial and Y chromosomal datasets reported in 508 papers indexed in the Pubmed database from 2008 to 2011. A substantial portion of datasets (21.9%) was found to have been withheld, while neither strong editorial policies nor high impact factor proved to be effective in increasing the sharing rate beyond the current figure of 80.5%. Disaggregating datasets for research fields, we could observe a substantially lower sharing in medical than evolutionary and forensic genetics, more evident for whole mtDNA sequences (15.0% vs 99.6%). The low rate of positive responses to e-mail requests sent to corresponding authors of withheld datasets (28.6%) suggests that sharing should be regarded as a prerequisite for final paper acceptance, while making authors deposit their results in open online databases which provide data quality control seems to provide the best-practice standard. Finally, we estimated that 29.8% to 32.9% of total resources are used to generate withheld datasets, implying that an important portion of research funding does not produce shared knowledge. By making the scientific community and the public aware of this important aspect, we may help popularize a more effective culture of data sharing

Increased expression of endothelial lipase in symptomatic and unstable carotid plaques

The aim of this study was to evaluate endothelial lipase (EL) protein expression in advanced human carotid artery plaques (HCAP) with regard to plaque (in)stability and the incidence of symptoms. HCAP were collected from 66 patients undergoing carotid endarterectomy (CEA). The degree of plaque (in)stability was estimated by ultrasound and histology. In HCAP sections, EL expression was determined by immunostaining and the intensity was assessed on a semi-quantitative scale (low: <25%, high: >25% positive cells). Monocytes and macrophages in adjacent HCAP sections were stained with a CD163 specific antibody. High EL staining was more prevalent in histologically unstable plaques (in 33.3% of fibrous plaques, 50% of ulcerated non-complicated plaques and 79.2% of ulcerated complicated plaques; χ2 test, p = 0.004) and in the symptomatic group (70.8 vs. 42.9% in the asymptomatic group; χ2 test, p = 0.028). The majority of EL immunostaining was found in those HCAP regions exhibiting a strong CD163 immunostaining. EL in HCAP might be a marker and/or promoter of plaque instability and HCAP-related symptomatology