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Reporting quality of randomized controlled trials in Restless Legs Syndrome based on the CONSORT statement
Randomized Controlled Trials (RCTs) are the cornerstone of modern medical research and their reporting may not always be optimal. The CONSORT (CONsolidated Standards of Reporting Trials) statement is an evidence-based means of improving and assessing the quality of these trials.
The aim of the present study was to assess the reporting quality of published RCTs on the Restless Legs Syndrome (RLS) based on a checklist stemming from the CONSORT statement.
RCTs involving patients with RLS were searched for into medical electronic databases. Inclusion criteria were English language of publication and the randomization of RLS patients in a minimum of two treatment cohorts of different medicinal orientations. The reporting quality was evaluated by the means of the aforementioned 38-item CONSORT checklist and the articles were divided into three 6-year periods. Descriptive statistics were used to make the comparisons.
Fifty four (54) eligible trials were found, published in 21 different scientific journals. The average CONSORT compliance score was 56.6% (23.68%-84.21%). CONSORT-endorsing journals had a mean CONSORT compliance of 58.47%, whereas non-endorsing journals 50.4%. The median CONSORT compliance for articles published in low (IF7) ranked journals was 52.63%, 56.57% and 59.21% respectively. Throughout the whole 1998-2016 period, 14 items (36.8%) were reported in >75% of the articles.
This study shows that the reporting of RLS-related RCTs is suboptimal, regardless of the time period, the quality of the publishing journal and the endorsing or not of the CONSORT statement
Advancements in the Treatment of Cerebrovascular Complications of Cancer
Purpose of review: To present the new guidelines and therapeutic options regarding cerebrovascular complications of cancer, mainly ischemic stroke, cerebral venous thrombosis (CVT), and leptomeningeal carcinomatosis (LMC).
Recent findings: A temporal trend study (2019) revealed that clinicians are still reluctant to apply thrombolysis to cancer patients, although two new studies (2018) reported no increased mortality. Several clinical trials on direct oral anticoagulants (DOACs) showed their superiority or, at least, non-inferiority compared with low molecular weight heparins in the treatment of venous thromboembolism (VTE) (2018–2019). These trials helped in formulating the new guidelines that are being published and the decisions made for cancer-associated thrombosis (CAT) as a whole. A new DOAC antidote was also officially released (US 2018, Europe 2019). Summary: Thrombolysis is safe in a malignancy setting, thus cancer per se should not be considered a contraindication for thrombolysis. Clinical trials assessing the newest DOACs for cancer-associated arterial thrombosis are scarce; however, based on data from VTE studies, the newest DOACs seem to be safe for CAT in patients that are not in high risk of bleeding or suffering from certain malignancies. The treatment should not be ceased after 6 months, but rather continued as long as the cancer remains active. Decompressive craniectomy should maintain its place in patients with CVST in risk of herniation. Last, the future also holds much promise on the role of novel compounds to be used in LMC
Genetic polymorphisms in amyotrophic lateral sclerosis: Evidence for implication in detoxification pathways of environmental toxicants
Language performance as a prognostic factor for developing alzheimer's clinical syndrome and mild cognitive impairment: results from the population-based HELIAD cohort
Lack of an association between SCFD1 rs10139154 polymorphism and amyotrophic lateral sclerosis
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease. Through a genome‑wide association study (GWAS), the Sec1 family domain‑containing protein 1 (SCFD1) rs10139154 variant at 14q12 has emerged as a risk factor gene for ALS. Moreover, it has been reported to influence the age at onset (AAO) of patients with ALS. The aim of the present study was to assess the association of the SCFD1 rs10139154 polymorphism with the risk of developing ALS. For this purpose, 155 patients with sporadic ALS and 155 healthy controls were genotyped for the SCFD1 rs10139154. The effect of the SCFD1 rs10139154 polymorphism was then examined on the following parameters: i) The risk of developing ALS; ii) the AAO of ALS; iii) the site of ALS onset (patients with bulbar onset ALS vs. healthy controls; and patients with limb onset ALS vs. healthy controls); and iv) the AAO of ALS onset with subgroup analyses based on the site of onset (bulbar and limb, crude and adjusted for sex). The analysis of all the outcomes was performed assuming five genetic models. Crude and adjusted analyses were applied. The threshold for statistical significance was set at 0.05. The results revealed no association between SCFD1 rs10139154 and any of the examined phenotypes in any of the models examined. On the whole, based on the findings of the present study, SCFD1 rs10139154 does not appear to play a determining role in the risk of developing ALS
Unraveling the Possible Routes of SARS-COV-2 Invasion into the Central Nervous System
Purpose of Review: To describe the possible neuroinvasion pathways of Severe Acute Respiratory Syndrome-related Coronavirus-2 (SARS-CoV-2), the virus responsible for the Coronavirus disease-19 (Covid-19) pandemic.
Recent Findings: We present data regarding the family of Coronaviruses (CoVs) and the central nervous system (CNS), and describe parallels between SARS-CoV-2 and other members of the family, which have been investigated in more depth and combine these findings with the recent advancements regarding SARS-CoV-2.
Summary: SARS-CoV-2 like other CoVs is neuroinvasive, neurotropic and neurovirulent. Two main pathways of CNS penetration seem to be the strongest candidates, the hematogenous and the neuronal. Τhe olfactory route in particular appears to play a significant role in neuroinvasion of coronaviruses and SARS-CoV-2, as well. However, existing data suggest that other routes, involving the nasal epithelium in general, lymphatic tissue and the CSF may also play roles in SARS-CoV-2 invasion into the CNS
A Mechanistic and Pathophysiological Approach for Stroke Associated with Drugs of Abuse
Drugs of abuse are associated with stroke, especially in young individuals. The major classes of drugs linked to stroke are cocaine, amphetamines, heroin, morphine, cannabis, and new synthetic cannabinoids, along with androgenic anabolic steroids (AASs). Both ischemic and hemorrhagic stroke have been reported due to drug abuse. Several common mechanisms have been identified, such as arrhythmias and cardioembolism, hypoxia, vascular toxicity, vascular spasm and effects on the thrombotic mechanism, as causes for ischemic stroke. For hemorrhagic stroke, acute hypertension, aneurysm formation/rupture and angiitis-like changes have been implicated. In AAS abuse, the effect of blood pressure is rather substance specific, whereas increased erythropoiesis usually leads to thromboembolism. Transient vasospasm, caused by synthetic cannabinoids, could lead to ischemic stroke. Opiates often cause infective endocarditis, resulting in ischemic stroke and hypereosinophilia accompanied by pyogenic arthritis, provoking hemorrhagic stroke. Genetic variants are linked to increased risk for stroke in cocaine abuse. The fact that case reports on cannabis-induced stroke usually refer to the young population is very alarming
Mental illness through the perspective of undergraduate medical students in Greece: a cross-sectional study at Aristotle University of Thessaloniki
IntroductionNumerous studies reveal that mental health-related stigma, stereotypes, and prejudices negatively affect the patients, jeopardizing their health, prognosis, and social opportunities. Healthcare professionals, who are in the first line of combating mental disease, are expected to play a significant role in drastically changing discriminatory and stigmatizing attitudes toward psychiatric patients and in diminishing the existing healthcare and social disparities. In this study, we aimed to explore and highlight the views of Greek medical students—that is of the future physicians—toward mental illness and people suffering from it.Materials and methodsIt is a cross-sectional, observational study, in which 324 undergraduate students from the most populous Greek medical school of the Aristotle University of Thessaloniki, participated online, during the spring semester of 2022. The tools used were the Opinions about Mental Illness Scale (OMI) that assesses one’s viewpoints about mental illness, the Social Distance Scale (SDS) that captures the desired degree of social distancing from patients with mental disorders, and the Level of Contact Report (LCR-12) that estimates the level of familiarity with them.ResultsParticipants displayed rather positive attitudes regarding the etiology of mental illness, social integration, and discrimination toward psychiatric patients [as evaluated with the respective OMI subscales; Etiology mean score (μ):8.87 ± 4.68, Social Integration (μ):17.79 ± 5.42, Social Discrimination (μ):13.54 ± 11.17], and more clearly favorable opinions concerning the need for social provision or the enactment of restrictive measures [as expressed with the relative OMI subscales; Social Care (μ):22.74 ± 4.56, Social Restriction (μ):13.27 ± 8.98], while claiming to be quite familiar with mental disorders and individuals experiencing them (as assessed with LCR; μ: 8.71 ± 2.16), and relatively willing to interact with them (as measured with SDS; μ:8.95 ± 4.23). Degree of familiarity with mental illness was directly proportional to the desire for contact with patients living with it, while the higher both were, the more improved most of the aforementioned OMI sectors were found to be. Female sex, clinical medical education, previous clinical psychiatric training, and living with or being a person with a mental disorder were the factors that defined a statistically refined profile in many of the aspects above.ConclusionOur findings are in accordance with many prior and recent studies, while showing improved opinions compared to those of previous research in Greek student and healthcare population. They are calling for vigilance, rather than complacency, as well as educational and social interventions, in order to enable current and future healthcare professionals to perform their function to its fullest extent. Implications of our results and further research suggestions are included
Locus for severity implicates CNS resilience in progression of multiple sclerosis
Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) that results in significant neurodegeneration in the majority of those affected and is a common cause of chronic neurological disability in young adults(1,2). Here, to provide insight into the potential mechanisms involved in progression, we conducted a genome-wide association study of the age-related MS severity score in 12,584 cases and replicated our findings in a further 9,805 cases. We identified a significant association with rs10191329 in the DYSF-ZNF638 locus, the risk allele of which is associated with a shortening in the median time to requiring a walking aid of a median of 3.7 years in homozygous carriers and with increased brainstem and cortical pathology in brain tissue. We also identified suggestive association with rs149097173 in the DNM3-PIGC locus and significant heritability enrichment in CNS tissues. Mendelian randomization analyses suggested a potential protective role for higher educational attainment. In contrast to immune-driven susceptibility(3), these findings suggest a key role for CNS resilience and potentially neurocognitive reserve in determining outcome in MS
Study of genetic polymorphisms in patients with focal dystonia
BACKROUND: A few genetic variants are implicated in the development of blepharospasm (BSP). The precise role of the rs6265 on the brain-derived neurotrophic factor (BDNF) gene on BSP remains controversial. Also, the genetic variant rs75392628 in the Triggering Receptor Expressed on Myeloid cells 2 (TREM2) has been previously associated with essential tremor and Parkinson's disease.OBJECTIVE: Evaluation of the effect of rs6265 and of rs75392628 on BSP.METHODS: 206 patients with BSP and 206 healthy controls were recruited and genotyped for the rs6265 and for the rs75392628. We also performed a meta-analysis for the rs6265, by pooling our results with those from previous studies.RESULTS: A significant effect of rs6265 on the risk of BSP was found in the dominant model of inheritance [Odds Ratio, OR (95% confidence interval, C.I.): 1.52 (1.01-2.29), p=0.044]. Mutational load analysis of rs6265 in the risk of BSP using the ORG, revealed that higher load of the “A” allele of rs6265 denotes higher probability of a subject to develop BSP (ORG 1.48 95%CI 1.00-2.19). Finally, pooled results from the meta-analysis revealed that the rs6265 is associated with an increased risk of BSP in the dominant model [OR: 1.26; 95%CI: 1.02-1.55, pz=0.03]. Also, higher load of the “A” allele of rs6265 denotes higher probability of a subject to develop BSP (ORG 1.26 95%CI 1.04-1.53). There were no T alleles of rs75392628 in our sample, therefore no further analysis was possible for the particular genetic variant.CONCLUSIONS: The present study provides additional evidence to the existing knowledge concerning the contribution of the rs6265 BDNF on the risk of developing BSP. While the pathophysiology and genetic susceptibility in BSP and focal dystonia are only partially understood, it seems that BDNF and rs6265 may constitute one essential risk factor that is heavily involved. Based on our results for the rs75392628 of TREM2, there are no indications that it is a possible risk factor in the BSP.ΥΠΟΒΑΘΡΟ: Γενετικές παραλλαγές εμπλέκονται στην ανάπτυξη του βλεφαρόσπασμου. Ο ακριβής ρόλος του πολυμορφισμού rs6265 στο γονίδιο του brain-derived neurotrophic factor (BDNF) στον βλεφαρόσπασμο παραμένει αμφιλεγόμενος. Επίσης η γενετική παραλλαγή rs75392628 στο Triggering Receptor Expressed on Myeloid cells 2 (TREM2), έχει συσχετισθεί με ιδιοπαθή τρόμο και νόσο του Πάρκινσον.ΣΚΟΠΟΣ: Η αξιολόγηση της επίδρασης του rs6265 και του rs75392628 στον βλεφαρόσπασμο.ΜΕΘΟΔΟΙ: 206 ασθενείς με βλεφαρόσπασμο και 206 υγιείς μάρτυρες συγκεντρώθηκαν και γονοτυπήθηκαν για τον rs6265 και τον rs75392628. Επίσης, πραγματοποιήσαμε μια μέτα-ανάλυση για τον rs6265, αναλύοντας τα αποτελέσματά της συγκεκριμένης μελέτης με αυτά από προηγούμενες μελέτες.ΑΠΟΤΕΛΕΣΜΑΤΑ: Στο dominant μοντέλο κληρονομικότητας βρέθηκε σημαντική επίδραση του rs6265 στον κίνδυνο εμφάνισης βλεφαρόσπασμου [Odds Ratio, OR (95% confidence interval, C.I.): 1,52 (1,01-2,29), p=0,044]. Η ανάλυση χρησιμοποιώντας το ORG, έδειξε ότι υψηλότερο φορτίο του αλληλόμορφου "Α" του rs6265 υποδηλώνει μεγαλύτερη πιθανότητα ενός ατόμου να αναπτύξει βλεφαρόσπασμο (ORG 1,48 95%CI 1,00-2,19). Τέλος, τα αποτελέσματα από τη μέτα-ανάλυση αποκάλυψαν ότι ο rs6265 σχετίζεται με αυξημένο κίνδυνο βλεφαρόσπασμου στο dominant μοντέλο [OR: 1,26; 95% CI: 1,02-1,55, pz = 0,03]. Επίσης, υψηλότερο φορτίο του αλληλόμορφου "Α" του rs6265 υποδηλώνει μεγαλύτερη πιθανότητα ενός υποκειμένου να αναπτύξει βλεφαρόσπασμο (ORG 1,26 95% CI 1,04-1,53). Δεν ανιχνεύθηκε κανένα αλληλόμορφο Τ του rs75392628 στο δείγμα μας, επομένως δεν ήταν δυνατή περαιτέρω ανάλυση για τη συγκεκριμένη γενετική παραλλαγή.ΣΥΜΠΕΡΑΣΜΑΤΑ: Η παρούσα μελέτη παρέχει πρόσθετες αποδείξεις στις υπάρχουσες γνώσεις σχετικά με τη συμβολή του rs6265 BDNF στον κίνδυνο ανάπτυξης του βλεφαρόσπασμου. Ενώ η παθοφυσιολογία και η γενετική του βλεφαρόσπασμου και της εστιακής δυστονίας είναι εν μέρει μόνο γνωστές, φαίνεται ότι το BDNF γονίδιο και ο rs6265 μπορεί να αποτελούν έναν βασικό παράγοντα κινδύνου που εμπλέκονται σε μεγάλο βαθμό. Με βάση τα αποτελέσματα μας για τον rs75392628 του TREM2, δεν έχουμε ενδείξεις ότι αποτελεί παράγοντα κινδύνου στο βλεφαρόσπασμο
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