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

USE OF FLUNARIZINE AS A PREVENTIVE FOR VESTIBULAR MIGRAINE CRISES IN COMPARISON WITH OTHER DRUGS: SYSTEMATIC LITERATURE REVIEW

INTRODUCTION: Vestibular migraine is the main cause of episodic vertigo and the second most common cause of dizziness in adults. Treatment for vestibular migraine encompasses the prevention of crises and the control of acute symptoms. Flunarizine works by preventing the contraction of labyrinthine vessels and altering blood flow, thus preventing symptoms. Due to the high prevalence of the disease, its negative impacts on individual health and increased expenditure on public health, preventive pharmacological and non-pharmacological treatment must be implemented early. PURPOSE: To evaluate the efficacy of Flunarizine as a preventive for migraine and vestibular crises compared to other preventive drugs. MATERIAL AND METHODS: Scientific articles were searched in the databases using the terms (vestibular migraine OR migrainous vertigo) AND (flunarizine) AND (prophylaxis). Subsequently, a systematic literature review and meta-analysis was performed, including 3 randomized clinical trials comparing flunarizine and other preventive drugs in terms of efficacy and safety for preventing migraine vertigo attacks. The studies were analyzed using a ROB table, analysis using the GRADE method and meta-analysis. RESULTS: Qualitatively, the analysis showed that flunariniza was positive for decreasing the frequency of vertigo in cases of vestibular migraine, with a moderate degree of evidence, a relative risk of 0.34 and a confidence interval of 0.15 to 0.76. CONCLUSIONS: There are few studies available in the scientific literature on the use of flunarizine in vestibular migraine, many of which are heterogeneous among themselves, mainly in the way of evaluating and monitoring patients, carried out mainly through subjective methods. The meta-analysis showed a positive result for flunarizine as a preventive drug for the studied population. Furthermore, in all the studies analyzed, no serious side effects resulting from the use of the medication were reported, which makes it safe for patients to use. Flunarizine is a good drug for the prevention of vestibular migraine, especially in reducing the number of attacks, with a good level of evidence.

Should ascorbic acid be a primary therapy for sepsis in prehospital settings?

Background: Prehospital emergency medical services (EMS) are believed to be responsible for the initial treatment of 68 000 septic patients annually in the UK, 88% of whom have severely low ascorbic acid levels, which can lead to organ dysfunction, increasing the likelihood of mortality. Objective: This review aims to determine if early therapeutic use of ascorbic acid (vitamin C) could reduce the deterioration of septic patients and therefore overall mortality. Method: A literature review was conducted using the mySearch, PubMed and Cochrane Library databases. Each was systematically searched for human studies that addressed the use of ascorbic acid as a primary method of treatment during varying stages of sepsis and whether it reduced associated mortality. Studies not published in English or that were more the 5 years old at the time were excluded. The quality of evidence in the remaining articles were appraised using the GRADE method and further assessed for quality with an adjusted Downs and Black scoring tool. Results: Nineteen articles were found, three of which met the inclusion criteria. All addressed the use of ascorbic acid as a therapy in the treatment of sepsis; none were conducted in a prehospital setting. Conclusion: Intravenous ascorbic acid appears to be a safe and effective therapy in treating septic patients, with the potential to reduce mortality rates if given prophylactically. However, a series of clinical trials would need to be conducted to measure the extent of any improvement and therefore clinical value in the prehospital environment.

Pre-emptive epidural analgesia for acute and chronic post-thoracotomy pain in adults: a systematic review and meta-analysis

Background and objectivesEpidural analgesia is the gold standard for post-thoracotomy pain management and can be started before or after surgical incision. This systematic review and meta-analysis investigated whether pre-emptive epidural analgesia before thoracotomy incision reduces acute and chronic post-thoracotomy pain in adults compared with epidural analgesia after incision.MethodsWe searched databases including MEDLINE, Embase, and CENTRAL for randomized controlled trials comparing epidural analgesia initiated before (pre-emptive group) and after (control group) thoracotomy incision in adults. The primary outcomes were the pain intensity during rest and coughing within 72 hours after surgery and the incidence of pain 1 to 6 months after surgery. Data were combined with random-effects meta-analyses. We rated the quality of evidence as high, moderate, low, and very low using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) method.ResultsWe included 19 trials with 1062 participants involving 529 in the pre-emptive group and 533 in the control group. The pain intensity was significantly lower at rest within 72 hours after surgery (19 studies, n=1062) and during coughing within 48 hours after surgery (11 studies, n=638), and the incidence of pain was significantly lower 1 to 6 months after surgery (6 studies, n=276) in the pre-emptive group than in the control group. The quality of evidence was moderate or low in the primary outcomes.ConclusionsOur review provides low-quality evidence that pre-emptive epidural analgesia reduces the intensity of acute pain and the incidence of chronic pain after thoracotomy in adults.Protocol registration numberCRD42019131620.

International and National Approaches to the Conducting of Iodine Thyroid Blocking in the Accident of a Nuclear Reactor

Purpose: Carry out a comparative analysis of the criteria and practices of conduct Iodine thyroid blocking (ITB) in various countries from the standpoint of WHO publication (2017) “Iodine thyroid blocking. Guidelines for use in planning for and responding to radiological and nuclear emergencies” (WHO Guidelines) and national Rules and requirements 2.6.1.2523-09 (NRB-99/2009) and other documents, including facility and territorial Emergency plans and instructions contained therein. Results: The WHO Guidelines, prepared using the GRADE method, determine the conditional recommendation in favor of conduct ITB in the event of a release of radioactive iodine: “During a radiation or nuclear emergency, the provision of ITB for people who are at risk of exposure to radioactive iodine should be implemented as urgent protective action as part of a justified and optimized protection strategy”. In the WHO Guidelines, such a recommendation is recognized as qualitatively low, and the strength of this recommendation is conditional, due to insufficient data on the use of stable iodine drugs. However, after studying the implementation of this protective measure, it was determined that the benefits of the intervention outweigh the disadvantages and associated costs. The article contains a selective discussion and opinion of the authors on a number of key issues of organization and conduct ITB. Conclusion: A comparative analysis revealed the similarities and differences between foreign and national practices of conduct ITB. The convergence of positions is necessary and aimed at harmonizing national and international criteria and practices. To date, there is no federal level document in the Russian regulatory framework that regulates the planning, organization and conduct of ITB in relation to people who are not associated with work at radiation hazardous facilities and do not live on territories served by the FMBA of Russia. Based on this, a range of priority important issues that need to be addressed has been identified.

Remdesivir use in patients with coronavirus COVID-19 disease: a systematic review and meta-analysis of the Chinese Lancet trial with the NIH trial

BackgroundCoronavirus disease 2019 (COVID-19), caused by the novel coronavirus SARS-CoV-2, has led to significant global mortality and morbidity. Until now, no treatment has proven to be effective in COVID-19. To explore whether the use of remdesivir, initially an experimental broad-spectrum antiviral, is effective in the treatment of hospitalized patients with COVID-19, we conducted a systematic review and meta-analysis of randomized, placebo-controlled trials investigating its use.MethodsA rapid search of the MEDLINE and EMBASE medical databases was conducted for randomized controlled trials. A systematic approach was used to screen, abstract, and critically appraise the studies. Grading of Recommendations Assessment, Development, and Evaluation (GRADE) method was applied to rate the certainty and quality of the evidence reported per study.ResultsTwo RCTs studies were identified (n=1,299). A fixed-effects meta-analysis revealed reductions in mortality (RR=0.69, 0.49 to 0.99), time to clinical improvement (3.95 less days, from 3.86 days less to 4.05 less days), serious adverse events (RR=0.77, 0.63 to 0.94) and all adverse events (RR=0.87, 0.79 to 0.96).ConclusionIn this rapid systematic review, we present pooled evidence from the 2 included RCT studies that reveal that remdesivir has a modest yet significant reduction in mortality and significantly improves the time to recovery, as well as significantly reduced risk in adverse events and serious adverse events. It is more than likely that as an antiviral, remdesivir is not sufficient on its own and may be suitable in combination with other antivirals or treatments such as convalescent plasma. Research is ongoing to clarify and contextual these promising findings.

Perinatal palliative care: a dedicated care pathway

ObjectiveEnsure access to perinatal palliative care (PnPC) to all eligible fetuses/infants/parents.DesignDuring 12 meetings in 2016, a multidisciplinary work-group (WG) performed literature review (Grading of Recommendations, Assessment, Development and Evaluation (GRADE) method was applied), including the ethical and legal references, in order to propose shared care pathway.SettingMaternal-Infant Department of Padua’s University Hospital.PatientsPnPC eligible population has been divided into three main groups: extremely preterm newborns (first group), newborns with prenatal/postnatal diagnosis of life-limiting and/or life-threatening disease and poor prognosis (second group) and newborns for whom a shift to PnPC is appropriate after the initial intensive care (third group).InterventionsThe multidisciplinary WG has shared care pathway for these three groups and defined roles and responsibilities.Main outcome measuresPrenatal and postnatal management, symptom’s treatment, end-of-life care.ResultsThe best care setting and the best practice for PnPC have been defined, as well as the indications for family support, corpse management and postmortem counselling, as well suggestion for conflicts’ mediation.ConclusionsPnPC represents an emerging field within the paediatric palliative care and calls for the development of dedicated shared pathways, in order to ensure accessibility and quality of care to this specific population of newborns.