Expression Profile of miRs in Mesial Temporal Lobe Epilepsy: Systematic Review

Temporal lobe epilepsy (TLE) is one of the most common forms of focal epilepsy in children and adults. TLE is characterized by variable onset and seizures. Moreover, this form of epilepsy is often resistant to pharmacotherapy. The search for new mechanisms for the development of TLE may provide us with a key to the development of new diagnostic methods and a personalized approach to the treatment. In recent years, the role of non-coding ribonucleic acids (RNA) has been actively studied, among which microRNA (miR) is of the greatest interest. (1) Background: The purpose of the systematic review is to analyze the studies carried out on the role of miRs in the development of mesial TLE (mTLE) and update the existing knowledge about the biomarkers of this disease. (2) Methods: The search for publications was carried out in the databases PubMed, Springer, Web of Science, Clinicalkeys, Scopus, OxfordPress, Cochrane. The search was carried out using keywords and combinations. We analyzed publications for 2016‒2021, including original studies in an animal model of TLE and with the participation of patients with TLE, thematic and systemic reviews, and Cochrane reviews. (3) Results: this thematic review showed that miR‒155, miR‒153, miR‒361‒5p, miR‒4668‒5p, miR‒8071, miR‒197‒5p, miR‒145, miR‒181, miR‒199a, miR‒1183, miR‒129‒2‒3p, miR‒143‒3p (upregulation), miR–134, miR‒0067835, and miR‒153 (downregulation) can be considered as biomarkers of mTLE. However, the roles of miR‒146a, miR‒142, miR‒106b, and miR‒223 are questionable and need further study. (4) Conclusion: In the future, it will be possible to consider previously studied miRs, which have high specificity and sensitivity in mTLE, as prognostic biomarkers (predictors) of the risk of developing this disease in patients with potentially epileptogenic structural damage to the mesial regions of the temporal lobe of the brain (congenital disorders of the neuronal migration and neurogenesis, brain injury, neuro-inflammation, tumor, impaired blood supply, neurodegeneration, etc.).

Usefulness of Cochrane Reviews in Clinical Guideline Development—A Survey of 585 Recommendations

The Danish Health Authority develops clinical practice guidelines to support clinical decision-making based on the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system and prioritizes using Cochrane reviews. The objective of this study was to explore the usefulness of Cochrane reviews as a source of evidence in the development of clinical recommendations. Evidence-based recommendations in guidelines published by the Danish Health Authority between 2014 and 2021 were reviewed. For each recommendation, it was noted if and how Cochrane reviews were utilized. In total, 374 evidence-based recommendations and 211 expert consensus recommendations were published between 2014 and 2021. Of the 374 evidence-based recommendations, 106 included evidence from Cochrane reviews. In 28 recommendations, all critical and important outcomes included evidence from Cochrane reviews. In 36 recommendations, a minimum of all critical outcomes included evidence from Cochrane reviews, but not all important outcomes. In 33 recommendations, some but not all critical outcomes included evidence from Cochrane reviews. Finally, in nine recommendations, some of the important outcomes included evidence from Cochrane reviews. In almost one-third of the evidence-based recommendations, Cochrane reviews were used to inform clinical recommendations. This evaluation should inform future evaluations of Cochrane review uptake in clinical practice guidelines concerning outcomes important for clinical decision-making.

Psychotherapie nach einem Suizidversuch – Evidenzlage und Bewertung

ZusammenfassungSuizidversuche gelten als einer der wichtigsten Risikofaktoren für Suizide. Vor diesem Hintergrund wurden in den letzten Jahren diverse Psychotherapieangebote für Personen nach einem Suizidversuch entwickelt und untersucht. Im Rahmen dieses Artikels wird der aktuelle Stand der Effektivitätsforschung zusammengefasst, es werden Beispiele für erfolgreiche suizidfokussierte Psychotherapieprogramme gegeben und der gegenwärtige Forschungs- und Wissensstand wird kritisch reflektiert. Die Ergebnisse von 2 aktuellen Cochrane-Reviews zur Psychotherapie nach selbstverletzendem Verhalten im Kindes‑, Jugend- und Erwachsenenalter sowie Befunde aus 14 weiteren Metaanalysen zur psychologischen Suizidprävention, die in den vergangenen 5 Jahren publiziert wurden, werden überblicksartig dargestellt.Die kognitive Verhaltenstherapie (KVT) und die dialektisch-behaviorale Therapie (DBT) haben sich als effektiv erwiesen. Insgesamt sind die gemittelten Effektstärken jedoch von geringer Größe und diverse methodische Probleme verunmöglichen weitreichende Schlussfolgerungen. Grundsätzlich kommt der suizidspezifischen Psychotherapie in der individuumszentrierten Suizidprävention besondere Bedeutung zu; die empirische Fundierung und Dissemination entsprechender Programme sind jedoch noch unzureichend.

Inequity in smoking cessation clinical trials testing pharmacotherapies: exclusion of smokers with mental health disorders

ObjectivesPeople suffering from mental health disorder (MHDs) are often under-represented in clinical research though the reasons for their exclusion are rarely recorded. As they have higher rates of smoking and nicotine dependence, it is crucial that they are adequately represented in clinical trials of established pharmacotherapy interventions for smoking cessation. This review aims to examine the practice of excluding smokers with MHDs and reasons for such exclusion in clinical trials evaluating pharmacotherapy treatments for smoking cessation.Data sourceThe Cochrane database of systematic reviews was searched until September 2020 for reviews on smoking cessation using pharmacotherapies.Study selectionRandomised controlled trials (RCTs) within the selected Cochrane reviews were included.Data extractionConducted by one author and independently verified by three authors.Data synthesisWe included 279 RCTs from 13 Cochrane reviews. Of all studies, 51 (18.3%) explicitly excluded participants with any MHDs, 152 (54.5%) conditionally excluded based on certain MHD criteria and 76 (27.2%) provided insufficient information to ascertain either inclusion or exclusion. Studies of antidepressant medications used for smoking cessation were found to be 3.33 times more likely (95% CI 1.38 to 8.01, p=0.007) to conditionally exclude smokers with MHDs than explicitly exclude compared with studies of nicotine replacement therapy.ConclusionSmokers with MHDs are not sufficiently represented in RCTs examining the safety and effectiveness of smoking cessation medications. Greater access to clinical trial participation needs to be facilitated for this group to better address access to appropriate pharmacotherapeutic interventions in this vulnerable population.

A review of Cochrane reviews on pharmacological treatment for attention deficit hyperactivity disorder

ABSTRACT. Attention deficit hyperactivity disorder (ADHD) is one of the most frequent childhood psychiatric problems. Objective: The objective of this study was to identify, synthesize the results, and critically evaluate all Cochrane systematic reviews (SRs) on the pharmacological interventions for children and adolescents (up to age 18) diagnosed with ADHD. Methods: The search was performed in the Cochrane Database of Systematic Reviews (via Wiley) in July 2020. Results: The search strategy resulted in four SRs of high methodological quality, analyzing 51 randomized clinical trials (9,013 participants). Compared to placebo, treatment with tricyclic antidepressants (TCAs) (desipramine), amphetamine, and methylphenidate showed improvement in symptoms such as difficulty concentrating, impulsivity, and hyperactivity in the short term (up to 6 months). There was an increase in the occurrence of adverse events, such as reduced appetite, difficulty sleeping, and abdominal pain. Insufficient evidence was found to support the effects of supplementation with polyunsaturated fatty acids. Conclusions: The use of TCAs, amphetamine, and methylphenidate in children and adolescents with ADHD seems to present positive effects and higher rates of minor adverse events when compared to placebo.

Empirical evaluation of fundamental principles of evidence-based medicine: a meta-epidemiological study

Rationale, aims and objectives 39 Evidence-based medicine (EBM) holds that estimates of effects of health interventions based on 40 high-certainty evidence (CoE) are expected to change less frequently than the effects generated 41 in low CoE studies. However, this foundational principle of EBM has never been empirically 42 tested. 43 Methods 44 We reviewed all systematic reviews and meta-analyses in Cochrane Database of Systematic 45 Reviews from January 2016 through May 2021 (n=3,323). We identified 414(207x2) and 384 46 (192x2) pairs of original and updated Cochrane reviews that assessed CoE and pooled 47 treatment effect estimates. We appraised CoE using the Grading of Recommendations 48 Assessment, Development and Evaluation (GRADE) method. We assessed the difference in 49 effect sizes between the original versus updated reviews as a function of change in CoE, which 50 we report as a ratio of odds ratio (ROR). We compared ROR generated in the studies that 51 changed CoE from very low/low (VL/L) to moderate/high (M/H) vs. MH/H VL/L. We also 52 assessed the heterogeneity and inconsistency (using the tau and I2 statistic), the change in 53 precision of effect estimates (by calculating the ratio of standard errors) (seR), and the absolute 54 deviation in estimates of treatment effects (aROR). 55 Results 56 57 We found that CoE originally appraised as VL/L had 2.1 (95%CI: 1.19 to 4.12; p=0.0091) times 58 higher odds to be changed in the future studies than M/H CoE. However, the effect size was not 59 different when CoE changed from VL/L M/H vs. M/H VL/L [ROR=1.02 (95%CI: 0.74 to 1.39) 60 vs. 1.02 (95%CI: 0.44 to 2.37); p=1 for the between subgroup differences]. aROR was similar 61 between the subgroups [median (IQR):1.12 (1.07 to 1.57) vs 1.21 (1.12 to 2.43)]. We observed 62 large inconsistency (I 2=99%) and imprecision in treatment effects (seR=1.09). 63 Conclusions 64 We provide the first empirical support for a foundational principle of EBM showing that low65 quality evidence changes more often than high CoE. However, the effect size was not different 66 between studies with low vs high CoE. The finding that the effect size did not differ between low 67 and high CoE indicate urgent need to refine current EBM critical appraisal methods

Problems, complications, and reinterventions in 4893 onlay humeral lateralized reverse shoulder arthroplasties, a systematic review: part II—problems and reinterventions

Background Several modifications to the original Grammont reverse shoulder arthroplasty (RSA) design have been proposed to prevent distinctive issues, such as both glenoid and humeral lateralization. The aim of this systematic review was to determine rates of problems, complications, reoperations, and revisions after onlay lateralized humeral stem RSA, hypothesizing that these are design related. Methods This systematic review was performed in accordance with the PRISMA statement guidelines. A literature search was conducted (1 January 2000 to 14 April 2020) using PubMed, Cochrane Reviews, Scopus, and Google Scholar, employing several combinations of keywords: “reverse shoulder arthroplasty,” “reverse shoulder prosthesis,” “inverse shoulder arthroplasty,” “inverse shoulder prosthesis,” “problems,” “complications,” “results,” “outcomes,” “reoperation,” and “revision.” Results Thirty-one studies with 4893 RSA met inclusion criteria. The 892 postoperative problems and 296 postoperative complications represented overall problem and complication rates of 22.7% and 7.5%, respectively. Forty-one reoperations and 63 revisions resulted, with overall reoperation and revision rates of 1.7% and 2.6%, respectively. Conclusions Problem, complication, and reintervention rates proved acceptable when implanting a high humeral lateralization stem RSA. The most frequent problem was scapular notching (12.6%), and the most common postoperative complication was scapular stress fracture (1.8%). An overall humeral complication rate of 1.9% was identified, whereas no humeral fractures or stem loosening were reported with short stems. Infections (1.3%) were the most common reason for component revision, followed by instability (0.8%). Level of evidence Systematic review IV.