Explore the vast range of titles available.

Background A broad range of disease-modifying therapies (DMTs) for relapsing–remitting multiple sclerosis (RRMS) is available. However, the efficacy and safety of traditional DMTs compared with the recently developed DMTs remain unclear. Objective Therefore, we have synthesised available evidence of clinical outcomes for DMTs in adults with RRMS. Methods PubMed, Scopus and a manual search were performed. Bayesian network meta-analyses of randomised clinical trials assessing DMTs as monotherapies were conducted. SUCRA and GRADE were used to rank therapies and to assess quality of general evidence, respectively. Results Thirty-three studies were included in the meta-analyses. The most effective therapies for the outcome of annualised relapse rate were alemtuzumab (96% probability), natalizumab (96%) and ocrelizumab (85%), compared with all other therapies (hazard ratio versus placebo, 0.31, 0.31 and 0.37, respectively; p  < 0.05 for all comparisons) (high-quality evidence). However, no significant differences among these three therapies were found. Discontinuation due to adverse events revealed similarity across all therapies, except for alemtuzumab, which showed less discontinuation when compared with interferon-1a intramuscular (relative risk 0.37; p  < 0.05). Conclusion High-quality evidence shows that alemtuzumab, natalizumab and ocrelizumab present the highest efficacy among DMTs, and other meta-analyses are required regarding adverse events frequency, to better understand the safety of therapies. Based on efficacy profile, guidelines should consider a three-category classification (i.e. high, intermediate and low efficacy).

ObjectiveWe assessed the extent of lag times in the publication and indexing of network meta-analyses (NMAs).Study designThis was a survey of published NMAs on drug interventions.SettingNMAs indexed in PubMed (searches updated in May 2020).Primary and secondary outcome measuresLag times were measured as the time between the last systematic search and the article submission, acceptance, online publication, indexing and Medical Subject Headings (MeSH) allocation dates. Time-to-event analyses were performed considering independent variables (geographical origin, Journal Impact Factor, Scopus CiteScore, open access status) (SPSS V.24, R/RStudio).ResultsWe included 1245 NMAs. The median time from last search to article submission was 6.8 months (204 days (IQR 95–381)), and to publication was 11.6 months. Only 5% of authors updated their search after first submission. There is a very slightly decreasing historical trend of acceptance (rho=−0.087; p=0.010), online publication (rho=−0.080; p=0.008) and indexing (rho=−0.080; p=0.007) lag times. Journal Impact Factor influenced the MeSH allocation process, but not the other lag times. The comparison between open access versus subscription journals confirmed meaningless differences in acceptance, online publication and indexing lag times.ConclusionEfforts by authors to update their search before submission are needed to reduce evidence production time. Peer reviewers and editors should ensure authors’ compliance with NMA standards. The accuracy of these findings depends on the accuracy of the metadata used; as we evaluated only NMA on drug interventions, results may not be generalisable to all types of studies.

Oral anticoagulants are the treatment of choice for diverse types of coagulation disorders. Warfarin is widely used by the Brazilian population, possibly due to its lower cost than other oral anticoagulants. However, it has a high risk of serious adverse effects if used incorrectly. The Anticoagulation Knowledge Tool (AKT) can assess a patient's knowledge about her/his oral anticoagulant therapy and can assist health professionals in identifying patients with difficulties in adherence. This study aimed to translate, culturally adapt, and validate the AKT into Brazilian Portuguese. After a standard forward-backward procedure to translate the AKT into Brazilian Portuguese (AKT-Br), a version of the instrument was applied in three groups (patients, pharmacists, and the general population). The reliability of the AKT-Br was tested using an internal consistency measure and test-retest. The validity of the instrument was confirmed with data from the contrasted groups. All statistical analyses were performed with RStudio. The median scores obtained with the AKT-Br were 29.0, 17.0, and 7.5 for pharmacists, patients, and the general population, respectively (maximum score of 35 points). There was moderate internal consistency for the instrument and test-retest reliability was satisfactory. Analysis of variance for validity of the groups revealed a significant relationship between the total score and the evaluated groups. The ATK-Br is a reliable and valid tool to assess knowledge about oral anticoagulants. AKT-Br can be used in clinical practice as an auxiliary tool to improve patient care through personalised educational interventions.

Background and Objective Migraine is a neurological disorder characterized by episodes of moderate-to-severe headache. The emergence of drugs derived from monoclonal antibodies specific for the calcitonin gene has brought forth a therapeutic option for patients in whom the traditional treatments have failed. This study aimed to evaluate the clinical effectiveness of calcitonin gene-related peptide antibodies in the prevention of migraine through a systematic review and meta-analysis of observational cohort studies. Methods A literature search for evidence was performed in electronic databases for observational studies that evaluated adult patients with migraine receiving calcitonin gene-related peptide receptor antagonists (e.g. erenumab, fremanezumab, galcanezumab and eptinezumab) and reported effectiveness outcomes (mean reduction in monthly migraine/headache days, and proportion of patients with 50% or greater reduction in migraine/headache days). Results During the screening process, 47 records were included for data extraction and qualitative and quantitative analyses. The overall rate of patients with a reduction of at least 50% of mean monthly migraine days was 54% (95% CI 49–59%), and overall mean monthly migraine reduction was about 7.7 days (95% CI 8.4–7.0 days). Regarding the outcome ≥ 50% reduction in mean monthly headache reduction, the overall rate of patients with a reduction of at least 50% was 57% (95% CI 48–64%), and the overall mean monthly headache reduction was approximately 8.8 days (95% CI 10.1–7.5 days). Subgroup analyses considering the drug treatment used and type of migraine were consistent with previous results. Conclusions The use of calcitonin gene-related peptide antibodies in real-world studies to prevent migraine demonstrates promising effectiveness outcomes, in agreement with those reported in previously published randomized clinical trial reports.

Burkitt lymphoma/leukemia (BL/L) is an aggressive oncohematological disease. This study evaluated the population-based prognosis and survival on BL/L as well as if BL/L behaved as a risk factor for the development of second primary cancers (SPCs) and if other first tumors behaved as risk factors for the occurrence of BL/L as an SPC. A retrospective cohort using the Surveillance, Epidemiology and End Results (SEER) Program (2008–2016) was performed. Kaplan–Meier, time-dependent covariate Cox regression and Poisson regression models were conducted. Overall, 3094 patients were included (median, 45 years; IQR, 22–62). The estimated overall survival was 65.4 months (95% CI, 63.6–67.3). Significantly more deaths occurred for older patients, black race, disease at an advanced stage, patients without chemotherapy/surgery and patients who underwent radiotherapy. Hodgkin lymphomas (nodal) (RR, 7.6 (3.9–15.0; p < 0.001)), Kaposi sarcomas (34.0 (16.8–68.9; p < 0.001)), liver tumors (3.4 (1.2–9.3; p = 0.020)) and trachea, mediastinum and other respiratory cancers (15.8 (2.2–113.9; p = 0.006)) behaved as risk factors for the occurrence of BL/L as an SPC. BL/L was a risk factor for the occurrence of SPCs as acute myeloid leukemias (4.6 (2.1–10.4; p < 0.001)), Hodgkin lymphomas (extranodal) (74.3 (10.0–549.8; p < 0.001)) and Kaposi sarcomas (35.1 (12.1–101.4; p < 0.001)). These results may assist the development of diagnostic and clinical recommendations for BL/L.

PurposeTo quantitatively assess the benefit–risk ratio on the efficacy and safety of all phosphodiesterase type 5 inhibitors (PDE5i) in men with erectile dysfunction.MethodsA systematic review with network meta-analysis, surface under the cumulative ranking analysis and stochastic multicriteria acceptability analyses were performed. Searches were conducted in Pubmed, Scopus, Web of Science without limits for time-frame or language. Randomized controlled trials evaluating the efficacy or safety of any PDE5i compared to a placebo or to other PDE5i in males with erectile disfunction were included.ResultsOverall, 184 articles representing 179 randomized controlled trials (50,620 patients) were included. All PDE5i were significantly more efficient than placebo. Sildenafil 25 mg was statistically superior to all interventions in enhancing IIEF (with a 98% probability of being the most effective treatment), followed by sildenafil 50 mg (80% of probability). Taladafil 10 mg and 20 mg also presented good profiles (73% and 76%, respectively). Avanafil and lodenafil were less effective interventions. Mirodenafil 150 mg was the treatment that caused more adverse events, especially flushing and headaches. Sildenafil 100 mg was more related to visual disorders, while vardenafil and udenafil were more prone to cause nasal congestion.ConclusionSildenafil at low doses and tadalafil should be the first therapeutic options. Avanafil, lodenafil and mirodenafil use are hardly justified given the lack of expressive efficacy or high rates of adverse events.

PurposeAcromegaly is a rare disease that results in the enlargement of body extremities and in organomegaly. Treatments include surgery, drugs, and radiotherapy, which are all onerous. Therefore, well-conducted cost-analyses are crucial in the decision-making process.MethodsA systematic review of cost-effectiveness studies on acromegaly therapies was performed following PRISMA and Cochrane recommendations. The search for records was conducted in PubMed, Scopus, and Web of Science (May 2018). The quality of the included studies was assessed using the Joana Briggs Institute Tool.ResultsFrom initial 547 records, 16 studies were included in the review. The studies could present more than one economic evaluation, and encompassed cost-effectiveness (n = 13), cost-utility (n = 5), and cost-consequence (n = 1) analyses. All studies were model-based and evaluated only direct medical costs. Eleven records did not mention discounting and only 10 performed sensitivity analyses. The characteristic of the studies, the cost-effectiveness results and the studies’ conclusions are described and commented upon. The main limitation of the studies was discussed and aspects to improve in future studies were pointed out.ConclusionsCost-effectiveness studies on acromegaly have been performed in several scenarios, evaluating different phases of treatment. However, the studies present limitations and, overall, were considered of moderate quality. Further economic models should be developed following health economics guidelines recommendations, and must improve transparency.

Background and Objectives Second-generation direct-acting antivirals (DAAs) have recently arisen as more effective and safer treatments for chronic hepatitis C. These drugs can be combined into treatments without interferon (IFN), and are therefore called IFN-free therapies. Objective The objective of this study systematic review was to evaluate the efficacy of IFN-free therapies for the treatment of chronic hepatitis C, and thus increase the clinical evidence for these therapies. Methods A systematic review was conducted in accordance with Cochrane Collaboration recommendations. A search was performed in six different electronic databases using ‘clinical trials’, ‘hepatitis C’ and ‘interferon-free’ as the main descriptors, and studies that conformed to the inclusion criteria had their data extracted, including study information, baseline characteristics, and efficacy outcomes (sustained virologic response, rapid virologic response, and virologic failure). Results Sixty-four randomized clinical trials including 15 different therapies were included in a total of 15,731 patients infected with the hepatitis C virus, mostly with genotype 1, and mainly treated for 12 or 24 weeks. The sustained virologic response rate after 12 weeks of treatment was approximately 89%, while the virologic failure rate was below 5%. Conclusions Second-generation DAAs presented several advantages: virologic response values higher than the average achieved by previous IFN-based therapies, reduced treatment duration, and the possibility of different combinations of therapies to meet patient needs. Thus, IFN-free therapies appear to be valuable alternatives for the treatment of chronic hepatitis C.

PurposeAlthough randomized controlled trials (RCTs) are the gold standard for the assessment of clinical outcomes, long-term extension trials (LTEs) and observational cohorts may help generate evidence. Our goal was to compare the discontinuation rates of abatacept, rituximab, and tocilizumab in rheumatoid arthritis (RA) reported in different study designs.MethodsA systematic review was conducted with searches in PubMed, Scopus, and the Cochrane Library, plus a manual search, for RCTs, LTEs, and observational cohorts reporting discontinuation rates by any of three causes (all-cause, inefficacy, adverse events). Meta-analyses with sensitivity analyses and meta-regressions were conducted.ResultsOf the 111 studies included, 74 were RCTs (n = 55) or LTEs (n = 17) reporting data on abatacept (n = 33), rituximab (n = 10), and tocilizumab (n = 31) and 37 were observational cohort studies (abatacept = 11, rituximab = 8, tocilizumab = 18). The follow-up duration did not differ among the study designs. Discontinuation rates were similar among the drugs but varied among the study designs. Discontinuation rates were significantly higher in cohort studies than those in interventional studies for the three drugs. Sensitivity analyses could not identify patient characteristics associated with these differences. Meta-regression analyses demonstrated no correlation between study follow-up duration and discontinuation rates.ConclusionsThe discontinuation rates reported for non-anti-TNF drugs varied relative to the study design in which they were investigated. Regulatory agencies, price-setting entities, and evidence-gathering researchers should consider the effect of the real-life environment in their decisions and conclusions.

ObjectivePresent a gnathodynamometer design that increases patient comfort, precision, and/or ease for the operator during bite force tests.Materials and methodsA bite tip capable of pivoting 180° was tested on senior dental students in a double-blind trial. The tests were performed in teeth 11 and 16 with the bite tip on the long axis of the clamp and at an angle of 90° to the clamp. The sample was composed of 24 students, 13 males and 11 females, randomly divided into two groups: the operator group (OP), which was composed of 12 students, 7 males and 5 females, and the test group (TI), which was composed of 12 students, 6 males and 6 females. The operator and participants were asked to evaluate comfort and precision/ease in positioning the bite tip by attributing scores from 0 (total discomfort) to 10 (total comfort) during the test.ResultsNo difference was noted in tooth 11 (P > 0.05). In tooth 16, there was a statistically significant improvement (P < 0.01) for the participants tested and the operator using the pivoting bite tip.ConclusionsThe pivoting bite tip showed no difference in the comfort of the participants and operator precision when testing incisors; however, the tip showed a difference for both conditions in the molar region. The gnathodynamometer geometry showed good results in participant comfort and operator precision when used in bite force tests of the incisors and molars. Further investigations are needed to confirm whether these improvements influence the mean value and maximum bite force measurement.Clinical relevance Bite force measurement is a method for obtaining important data to check the functional conditions of the stomatognathic system. With the aging of the world population, it has become important to check the quality of life during aging. The pivoting bite tip improves the comfort and precision of bite tests for the participants tested and for the operator, respectively.