Efficacy of transcranial direct current stimulation in patients with dysphagia after stroke: a systematic review.

BACKGROUND: Swallowing is a complex function that can be disrupted after stroke. Transcranial Direct Current Stimulation (tDCS) is a non-invasive brain stimulation therapy that recently has been tested to treat stroke-related dysphagia. METHODS: The authors performed a search in the literature to review the described evidence of the use of tDCS in dysphagia after stroke. Three electronic databases were searched. The risk of bias evaluation was carried out through the RoB-2 tool. The Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) framework was also implemented. RESULTS: Of 265 articles, only nine studies were included in this review. The most common location of the tDCS stimulation was the unaffected hemisphere (44%). Regarding the outcome measure, the Dysphagia Outcome and Severity Scale (DOSS) was the most commonly used (55%). However, due to the high heterogeneity of the protocols, and considering the differences between the types of stroke, the authors opted not to perform a metanalysis. Instead, a systematic review with a thorough analysis of each individual study and the impact of the differences to the outcomes was preferred. CONCLUSIONS: The final considerations are that even though the majority of studies described benefits from tDCS in post-stroke dysphagia, as they present too many methodological differences, it is not possible to compare them. In addition, many articles included patients with less than 6 months after stroke, which is an important bias as the swallowing function can be recovered spontaneously within this period, turning the certainty of the evidence really low.

Heterogenous relapse and efficacy endpoint definitions for neuromyelitis optica spectrum disorder studies: A systematic review.

BACKGROUND: Over the last years, multiple studies have been dedicated to evaluate the efficacy of different treatment options for Neuromyelitis Optica Spectrum Disorder (NMOSD). However, there is a wide variety of endpoints employed across these studies. Our goal is to conduct a systematic review describing the endpoints utilized in studies related to NMOSD. METHODS: Medline, Embase, and Cochrane were searched from inception to May 2023, to identify studies analyzing treatment options in patients with NMOSD. We collected data on baseline study characteristics and all efficacy outcomes available. RESULTS: We included 127 studies and identified approximately 40 different efficacy endpoints, categorized into 1) relapse, 2) disability, 3) visual acuity, and 4) surrogate outcomes. Most studies were retrospective (54.3 %) and aimed at attack prevention (81.4 %). The most common relapse-related outcomes were annualized relapse rate (73.2 %), followed by relapse rate (50.4 %), and relapse-free rate (36.2 %). The relapse definition also varied widely among studies, with only 73 (57.4 %) studies explicitly addressing the definition used. The most common disability outcome was the Expanded Disability Scale (97.6 %), followed by the Modified Rankin Scale (7.9 %). Visual Acuity Score was employed in 14.2 % of studies, followed by Visual Evoked Potentials (6.3 %). Imaging was the most common surrogate (20.5 %), followed by the fraction of B cells (18.1 %). CONCLUSION: Publications were heterogeneous in measuring efficacy, with different use of endpoints and relapse definitions. Standardization across studies would improve data analysis and application in clinical practice.

Anticoagulation strategy for patients presenting with ischemic strokes while using a direct oral anticoagulant: A systematic review and meta-analysis.

BACKGROUND: While direct-acting oral anticoagulants (DOACs) have established efficacy in reducing the risk of ischemic stroke, they still leave a residual risk of stroke, which may be greater in practice (0.7-2.3%) than in controlled clinical trial settings. This meta-analysis examines four therapeutic approaches following a stroke in patients already on DOACs: continuing with the same DOAC, changing to a different DOAC, increasing the current DOAC dosage, or switching to a vitamin K antagonist (VKA), such as warfarin. METHODS: Systematic review of literature from the MEDLINE, Embase, and Cochrane databases, was conducted in line with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The analysis focused on six studies with varied patient demographics, examining as outcomes as recurrent ischemic stroke, intracranial hemorrhage, other bleeding events, and mortality. RESULTS: Six studies comprising 12,159 patients were included, all of them were observational. Patients who remained on their initial DOAC regimen had a lower risk of experiencing ischemic strokes (risk ratio (RR) 0.55; 95% confidence interval (CI) 0.43-0.70; p < 0.001; I2 = 0%), intracranial hemorrhage (RR 0.37; 95% CI 0.25-0.55; p < 0.001; I2 = 0%), and hemorrhagic events (RR 0.44; 95% CI 0.30-0.63; p < 0.001; I2 = 6%) compared to those who were switched to warfarin, with an increase in mortality rates (hazard ratio (HR) 1.85; 95% CI 1.06-3.24; p = 0.03; I2 = 84%). In contrast, neither changing to a different DOAC nor adjusting the dose proved to be more effective than the original regimen. CONCLUSION: Post-stroke adjustments to anticoagulation therapy-whether altering the drug or its dosage-do not yield additional benefits. In addition, the results suggest that warfarin may be less effective than DOACs for preventing stroke recurrence, bleeding complications, and death in this patient population.

Long-Term Safety and Effectiveness of Erenumab in Patients with Migraine: A Systematic Review and Single-Arm Meta-analysis.

BACKGROUND AND OBJECTIVE: Several studies on use of erenumab for migraine treatment have been published over recent years. However, its long-term safety and effectiveness have not been consistently established in the literature yet. We aimed to perform a qualitative and quantitative analysis of the long-term safety and effectiveness of erenumab for the treatment of migraine headaches. METHODS: Long-term follow-up was defined as ≥ 1 year. PubMed, Embase and Cochrane Library were systematically searched from inception to 14 June 2022 for studies meeting the inclusion criteria. Risk of bias was assessed using the Newcastle-Ottawa Scale. RESULTS: Fourteen studies, comprising 3574 patients, were included. The total follow-up period ranged from 48 to 268 weeks (i.e., 1 year to 5.6 years). Pooled estimate rates for all adverse events (AEs) were 63% (95% CI 46-78); for serious AEs, 3% (95% CI 1-7); and for AEs leading to discontinuation of erenumab, 3% (95% CI 2-5). Reduction in monthly migraine days (MMDs) was -6.98 (95% CI -8.90 to -5.05) and in migraine-specific medication days (MSMDs) was - 6.09 (95% CI - 9.43 to - 2.75). More than half (57%; 95% CI 51-63) and around one-third (35%; 95% CI 28-42) of patients presented with reductions of ≥ 50% and ≥ 75% in MMDs, respectively. Headache Impact Test-6 (HIT-6) score was decreased by -9.68 points (95% CI - 12.03 to - 7.34). Nine studies were considered of poor methodological quality and five of fair quality. CONCLUSIONS: Erenumab has a favorable safety profile, with a low incidence of serious AEs, and sustained efficacy over ≥1 year of follow-up in the treatment of migraine.

Dual orexin receptor antagonists for the treatment of insomnia: systematic review and network meta-analysis.

BACKGROUND: Several randomized clinical trials (RCTs) have shown that dual orexin receptor antagonists (DORAs) are effective in the treatment of chronic insomnia. However, the superiority of one particular DORA over the others remains unclear. OBJECTIVE: To perform a network meta-analysis to evaluate the efficacy of different DORAs in patients with chronic insomnia. METHODS: The Medline, Embase, and Cochrane Central databases were searched for RCTs that compared DORA with placebo in patients ≥ 18 years of age with a diagnosis of insomnia disorder. We pooled outcomes for wake time after sleep onset (WASO), latency to persistent sleep (LPS), total sleep time (TST), and adverse events (AEs). RESULTS: We included 10 RCTs with 7,806 patients, 4,849 of whom received DORAs as the intervention. Overall, we found that DORAs were associated with the improvement of all analyzed efficacy outcomes. Concerning TST, an apparent dose-dependent pattern was noticed, with higher doses relating to a longer TST. Lemborexant 10mg provided the largest reduction in WASO (at month 1) in minutes (standardized mean difference [SMD] = -25.40; 95% confidence interval [95%CI] = -40.02--10.78), followed by suvorexant 20/15mg (SMD = -25.29; 95%CI = -36.42--14.15), which also appeared to provide the largest decrease in long-term WASO (SMD = -23.70; 95%CI = -35.89--11.51). The most frequent AEs were somnolence, nasopharyngitis, and headache, with rates of up to 14.8%. CONCLUSION: Our results suggest that DORAs are associated with greater efficacy when compared with placebo in the treatment of insomnia, a complex 24-hour sleep disorder. Additionally, dosing might play an important role in the management of chronic insomnia.

ANTECEDENTES: Inúmeros ensaios clínicos randomizados (ECRs) têm demonstrado que os antagonistas duais do receptor de orexina (dual orexin receptor antagonists, DORAs, em inglês) são eficazes no tratamento da insônia. Contudo, restam dúvidas quanto à superioridade de um DORA com relação aos outros. OBJETIVO: Realizar uma meta-análise em rede para avaliar a eficácia de diferentes DORAs em pacientes com insônia. MéTODOS: Foram feitas buscas nas bases de dados Medline, Embase e Cochrane Central por ECRs que comparassem DORAs e placebo em pacientes ≥ 18 anos de idade com diagnóstico de insônia. Os seguintes desfechos foram selecionados: tempo desperto após o início do sono (wake time after sleep onset, WASO, em inglês), latência para o sono persistente (latency to persistent sleep, LPS, em inglês), tempo total de sono (total sleep time, TST, em inglês), e efeitos adversos (EAs). RESULTADOS: Incluímos 10 ensaios clínicos com 7,806 pacientes, 4,849 dos quais receberam DORAs como intervenção. Os DORAs foram associados à melhoria de todos os desfechos de eficácia analisados. Em relação ao TST, um aparente padrão de dependência da dose foi identificado, com doses maiores se associando a um maior TST. Lemborexant 10 mg proporcionou a maior redução em WASO (no primeiro mês) em minutos (diferença padronizada das médias [standardized mean difference, [SMD], em inglês) = -25.40; intervalo de confiança de 95% [IC95%] = -40.02­-10.78), seguido de suvorexant 20/15mg (SMD = -25.29; IC95% = -36.42­-14.15), o qual também proporcionou a maior diminuição em WASO no longo prazo (SMD = -23.70; IC95% = -35.89­-11.51). Os EAs mais frequentes foram sonolência, nasofaringite e cefaleia, com taxas de até 14.8%. CONCLUSãO: Nossos resultados sugerem que os DORAs estão associados a uma maior eficácia quando comparados com placebo no tratamento da insônia, um complexo transtorno do sono de 24 horas. Além disso, a dosagem pode desempenhar um papel importante no manejo da insônia crônica.

Development and adaptations of the Graded Prognostic Assessment (GPA) scale: a systematic review.

The Graded Prognostic Assessment (GPA) score has the best accuracy among prognostic scales for patients with brain metastases (BM). A wide range of GPA-derived scales have been established to different types of primary tumor BM. However, there is a high variability between them, and their characteristics have not been described altogether yet. We aim to summarize the features of the existent GPA-derived scales and to compare their predictor factors and their uses in clinical setting. Medline was searched from inception until January 2023 to identify studies related to the development, update, or validation of GPA. The initial search yielded 1,083 results. 16 original studies and 16 validation studies were included, comprising a total of 33,348 patients. 13 different scales were assessed, including: GPA, Diagnosis-Specific GPA, Extracranial Score, Lung-molGPA, Updated Renal GPA, Updated Gastrointestinal GPA, Modified Breast GPA, Integrated Melanoma GPA, Melanoma Mol GPA, Sarcoma GPA, Hepatocellular Carcinoma GPA, Colorectal Cancer GPA, and Uterine Cancer GPA. The most prevalent prognostic predictors were age, Karnofsky Performance Status, number of BM, and presence or absence of extracranial metastases. Treatment modalities consisted of whole brain radiation therapy, stereotactic radiosurgery, surgery, cranial radiotherapy, gamma knife radiosurgery, and BRAF inhibitor therapy. Median survival rates with no treatment and with a specific treatment ranged from 6.1 weeks to 33 months and from 3.1 to 21 months, respectively. Original GPA and GPA-derived scales are valid prognostic tools, but with heterogeneous survival results when compared to each other. More studies are needed to improve scientific evidence of these scales.

Prophylactic antiseizure drugs for spontaneous intracerebral hemorrhage: An updated systematic review and meta-analysis.

BACKGROUND: There is concern that recommendations on prophylactic antiseizure drugs (PASDs) for patients with spontaneous intracerebral hemorrhage (sICH) are biased by studies using older drugs and no electrographic monitoring. AIMS: We performed a systematic review and meta-analysis to determine whether PASDs in patients with sICH reduced seizure occurrence and improved functional outcomes. We included analyses of newer trials, newer antiseizure drugs, and effectiveness in patients with consistent electrographic monitoring. METHODS: Medline, Embase, and Cochrane were searched from inception until 12 August 2022, to identify studies with patients with sICH treated with PASDs, regardless of study design. The studied outcomes were functional status and occurrence of seizures. RESULTS: Fourteen studies were included, including 6742 patients. Risk of bias was low overall. There was no effect of PASD on seizure occurrence overall (odds ratio (OR) 0.73, 95% confidence interval (CI) 0.47-1.15), but they were associated with reduced occurrence in studies with electrographic monitoring (OR 0.36, 95% CI 0.18-0.70). There was no effect of PASDs on functional outcomes (OR 1.15; 95% CI 0.91-1.47) or mortality (OR 0.85, 95% CI 0.65-1.11). CONCLUSION: Prophylactic antiseizure medications after sICH reduce seizures in studies with electroencephalogram monitoring in high-risk patients. However, this benefit did not reflect in the improvement of functional outcomes, even in studies with newer, less toxic, antiseizure drugs.

Dual orexin receptor antagonists for the treatment of insomnia: systematic review and network meta-analysis / Antagonistas duais do receptor de orexina para o tratamento da insônia: revisão sistemática e metanálise em rede

Abstract Background Several randomized clinical trials (RCTs) have shown that dual orexin receptor antagonists (DORAs) are effective in the treatment of chronic insomnia. However, the superiority of one particular DORA over the others remains unclear. Objective To perform a network meta-analysis to evaluate the efficacy of different DORAs in patients with chronic insomnia. Methods The Medline, Embase, and Cochrane Central databases were searched for RCTs that compared DORA with placebo in patients ≥ 18 years of age with a diagnosis of insomnia disorder. We pooled outcomes for wake time after sleep onset (WASO), latency to persistent sleep (LPS), total sleep time (TST), and adverse events (AEs). Results We included 10 RCTs with 7,806 patients, 4,849 of whom received DORAs as the intervention. Overall, we found that DORAs were associated with the improvement of all analyzed efficacy outcomes. Concerning TST, an apparent dose-dependent pattern was noticed, with higherdoses relating to a longerTST. Lemborexant 10mg provided the largest reduction in WASO (at month 1) in minutes (standardized mean difference [SMD] = −25.40; 95% confidence interval [95%CI] = −40.02- −10.78), followed by suvorexant 20/15mg (SMD = −25.29; 95%CI = −36.42- −14.15), which also appeared to provide the largest decrease in long-term WASO (SMD = −23.70; 95%CI = −35.89- −11.51). The most frequent AEs were somnolence, nasopharyngitis, and headache, with rates of up to 14.8%. Conclusion Our results suggest that DORAs are associated with greater efficacy when compared with placebo in the treatment of insomnia, a complex 24-hour sleep disorder. Additionally, dosing might play an important role in the management of chronic insomnia.

Resumo Antecedentes Inúmeros ensaios clínicos randomizados (ECRs) têm demonstrado que os antagonistas duais do receptor de orexina (dual orexin receptor antagonists, DORAs, em inglês) são eficazes no tratamento da insônia. Contudo, restam dúvidas quanto à superioridade de um DORA com relação aos outros. Objetivo Realizar uma meta-análise em rede para avaliar a eficácia de diferentes DORAs em pacientes com insônia. Métodos Foram feitas buscas nas bases de dados Medline, Embase e Cochrane Central por ECRs que comparassem DORAs e placebo em pacientes ≥ 18 anos de idade com diagnóstico de insônia. Os seguintes desfechos foram selecionados: tempo desperto após o início do sono (wake time after sleep onset, WASO, em inglês), latência para o sono persistente (latency to persistent sleep, LPS, em inglês), tempo total de sono (total sleep time, TST, em inglês), e efeitos adversos (EAs). Resultados Incluímos 10 ensaios clínicos com 7,806 pacientes, 4,849 dos quais receberam DORAs como intervenção. Os DORAs foram associados à melhoria de todos os desfechos de eficácia analisados. Em relação ao TST, um aparente padrão de dependência da dose foi identificado, com doses maiores se associando a um maior TST. Lemborexant 10 mg proporcionou a maior redução em WASO (no primeiro mês) em minutos (diferença padronizada das médias [standardized mean difference, [SMD], em inglês) = −25.40; intervalo de confiança de 95% [IC95%] = −40.02- −10.78), seguido de suvorexant 20/15mg (SMD = −25.29; IC95% = −36.42- −14.15), o qual também proporcionou a maior diminuição em WASO no longo prazo (SMD = −23.70; IC95% = −35.89- −11.51). Os EAs mais frequentes foram sonolência, nasofaringite e cefaleia, com taxas de até 14.8%. Conclusão Nossos resultados sugerem que os DORAs estão associados a uma maior eficácia quando comparados com placebo no tratamento da insónia, um complexo transtorno do sono de 24 horas. Além disso, a dosagem pode desempenhar um papel importante no manejo da insónia crônica.