Endovascular thrombectomy with or without intravenous alteplase in acute stroke: a systematic review and meta-analysis of randomized clinical trials

Journal of Neurology - This study investigated clinical outcomes after direct endovascular thrombectomy (EVT) compared to bridging therapy (EVT with prior intravenous alteplase) in acute stroke...     

Non-invasive neuromodulation in the acute treatment of migraine: a systematic review and meta-analysis of randomized controlled trials

Neurological Sciences - A systematic review and meta-analysis was performed to determine the efficacy of non-invasive neuromodulation modalities for the treatment of acute migraine. Although...     

Stent retriever thrombectomy for acute ischemic stroke: A systematic review and meta-analysis of randomized controlled trials,including THRACE

Background and purpose

Endovascular thrombectomy has become the reference therapy for patients with large vessel occlusion (LVO). However, no meta-analysis including the THRACE Trial has yet been reported. Thus, the present review assessed the outcomes of stent retriever thrombectomy added to medical care compared with medical care alone in LVO patients.

Second-generation antipsychotic agents in the treatment of acute mania: a systematic review and meta-analysis of randomized controlled trials

CONTEXT: Recommendations of treatment guidelines concerning the use of second-generation antipsychotic (SGA) agents for acute mania vary substantially across committees or working groups. Meta-analyses addressing the use of SGAs in the treatment of acute mania are lacking. OBJECTIVE: To conduct a meta-analysis of the efficacy and safety of SGAs in the treatment of acute mania. DATA SOURCES: Randomized controlled trials comparing SGAs with placebo, first-generation antipsychotic drugs, or mood stabilizers (MSs) in the treatment of acute mania were searched for in the PsiTri and MEDLINE databases (last search: May 2006). STUDY SELECTION: The abstracts, titles, and index terms of studies were searched using the following key words: aripiprazole, amisulpride, clozapine, olanzapine, quetiapine, risperidone, ziprasidone, and zotepine in conjunction with mania, manic, and bipolar. DATA EXTRACTION: Data on efficacy, global dropout, dropout due to adverse events, dropout due to inefficacy, weight gain, rate of somnolence, and extrapyramidal symptoms were extracted and combined in a meta-analysis. DATA SYNTHESIS: A total of 24 studies with 6187 patients were included. The SGAs were significantly more efficacious than placebo. The analysis demonstrated that adding antipsychotic agents to MS treatment was significantly more effective than treatment with MSs alone. The SGAs displayed efficacy comparable with that of MSs. Some SGAs seemed to induce more extrapyramidal symptoms than placebo. The SGAs were also associated with higher rates of somnolence than placebo. CONCLUSION: Currently available data suggest that combining SGAs and MSs is the most efficacious treatment of acute mania.     

Valerian for insomnia: a systematic review of randomized clinical trials

Objective: To systematically review the evidence for the effects of the herb valerian (Valeriana officinalis) on insomnia, based on randomized, placebo-controlled, double-blind trials.Background: Valerian has long been advocated and used for promoting sleep but until quite recently evidence was solely anecdotal. However, during the last two decades a number of clinical trials have been conducted.Materials and methods: Systematic literature searches were performed to locate randomized, placebo-controlled, double-blind trials measuring the effect of valerian monopreparations on sleep in human participants. Data were extracted in a standardized manner and methodological quality was assessed by the Jadad score.Results: Nine trials were located meeting the selection criteria. The findings of the studies were contradictory and there was great inconsistency between trials in terms of patients, experimental design and procedures and methodological quality.Conclusion: The evidence for valerian as a treatment for insomnia is inconclusive. There is a need for rigorous trials to determine its efficacy.     

Lithium for schizophrenia revisited: a systematic review and meta-analysis of randomized controlled trials

BACKGROUND: Clinicians frequently use lithium to augment antipsychotic medication in schizophrenia. Therefore, we undertook a systematic review and meta-analysis of the use of lithium in the treatment of schizophrenia. DATA SOURCES AND STUDY SELECTION: Randomized controlled trials examining lithium (as a sole or an adjunctive compound) in participants with schizophrenia or related disorders were searched in the register of the Cochrane Schizophrenia Group. No language restrictions were applied. The Boolean phrase [lithium* or lithicarb or eskalith or lithobid or lithane or cibalith-s or quilonum or hypnorex] was used to locate articles. The search strategy initially identified 90 references. The authors of the included studies were contacted to obtain original patient data. The data were combined in a meta-analysis. The main outcome parameters were the number of patients with a clinically significant response and the number of patients leaving the studies early. RESULTS: The meta-analysis includes 20 studies (N = 611). The evidence shows that lithium as a sole agent is ineffective in the treatment of schizophrenia. Eleven trials examined the augmentation of antipsychotics with lithium. More patients who received lithium augmentation than those who received antipsychotics alone were classified as responders. However, the superiority was not consistent across different response thresholds, and when patients with prominent affective symptoms were excluded from the analysis, the advantage of lithium augmentation was not significant (p =.07). Significantly more patients taking lithium left the trials early, suggesting a lower acceptability of lithium augmentation compared with that of taking antipsychotics alone. CONCLUSION: Despite some evidence in favor of lithium augmentation, the overall results are inconclusive. A large trial of lithium augmentation of antipsychotic medications will be required in order to detect a benefit of small effect size in patients with schizophrenia who lack affective symptoms.     

Yoga for anxiety: A systematic review and meta-analysis of randomized controlled trials

Yoga has become a popular approach to improve emotional health. The aim of this review was to systematically assess and meta-analyze the effectiveness and safety of yoga for anxiety. Medline/PubMed, Scopus, the Cochrane Library, PsycINFO, and IndMED were searched through October 2016 for randomized controlled trials (RCTs) of yoga for individuals with anxiety disorders or elevated levels of anxiety. The primary outcomes were anxiety and remission rates, and secondary outcomes were depression, quality of life, and safety. Risk of bias was assessed using the Cochrane tool. Eight RCTs with 319 participants (mean age: 30.0–38.5 years) were included. Risk of selection bias was unclear for most RCTs. Meta-analyses revealed evidence for small short-term effects of yoga on anxiety compared to no treatment (standardized mean difference [SMD] = −0.43; 95% confidence interval [CI] = −0.74, −0.11; P = .008), and large effects compared to active comparators (SMD = −0.86; 95% CI = −1.56, −0.15; P = .02). Small effects on depression were found compared to no treatment (SMD = −0.35; 95% CI = −0.66, −0.04; P = .03). Effects were robust against potential methodological bias. No effects were found for patients with anxiety disorders diagnosed by Diagnostic and Statistical Manual criteria, only for patients diagnosed by other methods, and for individuals with elevated levels of anxiety without a formal diagnosis. Only three RCTs reported safety-related data but these indicated that yoga was not associated with increased injuries. In conclusion, yoga might be an effective and safe intervention for individuals with elevated levels of anxiety. There was inconclusive evidence for effects of yoga in anxiety disorders. More high-quality studies are needed and are warranted given these preliminary findings and plausible mechanisms of action.     

Updated clinical evidence of Chinese herbal medicine for insomnia: a systematic review and meta-analysis of randomized controlled trials

This systematic review is to evaluate the efficacy and safety of Chinese herbal medicine (CHM) for people with insomnia. Randomized controlled trials (RCTs) investigating oral CHM alone or in combination with conventional therapies for primary insomnia were identified by searching English and Chinese publications and databases of clinical trial registration. Risk of bias was assessed according to the Cochrane Handbook 5.1. Meta-analysis was conducted using RevMan 5.2.4. Seventy-nine trials (7886 participants) were finally included in the review, and 76 were included in the meta-analysis. Twenty-seven trials reported the methods of random sequence generation, and five of them used the allocation concealment. Blinding of participants and personnel were used in 10 studies. The main meta-analysis showed that CHM alone was more effective than placebo by reducing scores of Pittsburgh Sleep Quality Index (mean difference, MD: −3.06, 95% confidence interval, CI: −5.14 to −0.98, I² = 97%) and benzodiazepine drugs (BZDs) (MD: −1.94, 95% CI: −2.45 to −1.43, I² = 96%). The effect was also seen when CHM was combined with BZDs compared with placebo plus BZDs (MD: −1.88, 95% CI: −2.78 to −0.97, I² = 0%) or cognitive and behavioral therapy (MD: −3.80, 95% CI: −4.91 to −2.68, I² = 68%) alone. There was no significant difference between CHM and placebo regarding the frequency of adverse events (relative risk, RR: 1.65, 95% CI: 0.67–4.10, I² = 0). Overall, oral CHM used as a monotherapy or as an adjunct to conventional therapies appears safe, and it may improve subjective sleep in people with insomnia. However, the typical effect of CHM for insomnia cannot be determined due to heterogeneity. Further study focusing on individual CHM formula for insomnia is needed. The development of a comparable placebo is also needed to improve the successful blinding in RCTs.     

Closure of patent foramen ovale for cryptogenic stroke patients: an updated systematic review and meta-analysis of randomized trials

Objective

This systematic review and meta-analysis was performed to investigate the efficacy and safety of transcatheter device closure (TDC) plus anti-thrombotic drugs over medical management alone for patients with cryptogenic stroke and patent foramen oval.

Methods

PubMed, Embase and Cochrane Library database were searched for randomized controlled clinical trials (RCTs). The primary endpoint is the composite of stroke and transient ischemic attack. The secondary endpoints are all-cause mortality, total serious adverse events, atrial fibrillation and bleeding.

Results

Five RCTs with a total of 3440 participants were included. TDC significantly decreased the risk of primary endpoint when compared to medical therapy alone (RR 0.54, 95% CI 0.43–0.69). Further subgroup analyses showed that patients with male gender and with substantial shunt size of foramen ovale significantly benefited from TDC as compared to those with female gender and with no substantial shunt size of foramen oval separately. Moreover, TDC was superior to medical therapy with anti-platelet drug alone (not with anti-coagulation). On the other hand, the incidence of atrial fibrillation was higher in TDC group (RR 4.49, 95% CI 2.02–9.97), with the risk of other adverse events equivalent between the two groups.

Conclusions

TDC plus anti-thrombotic drugs is superior than medical therapy alone for secondary prevention of stroke, especially for those with male gender and with substantial shunt size of foramen ovale. Though it may increase the risk of postoperative atrial fibrillation, it would not bring higher risk of all-cause mortality, total adverse events and bleeding.

     

Dehydroepiandrosterone for depressive symptoms: A systematic review and meta-analysis of randomized controlled trials

Depression is a mental disorder that affects millions of people around the world. However, depressive symptoms can be seen in other psychiatric and medical conditions. Here, we investigate the effect of DHEA treatment on depressive symptoms in individuals with depression and/or other clinical conditions in which depressive symptoms are present. An electronic search was performed until October 2019, with no restrictions on language or year of publication in the following databases: Medline, EMBASE, LILACS, and Cochrane Library. Randomized controlled trials comparing DHEA versus placebo were included if the depressive symptoms were assessed. Fifteen studies with 853 female and male individuals were included in this review. To conduct the meta-analysis, data were extracted from 14 studies. In comparison with placebo, DHEA improved depressive symptoms (standardized mean difference [SMD] −0.28, 95% (CI) −0.45 to −0.11, p =.001, 12 studies, 742 individuals (375 in the experimental group and 367 in the placebo group), I² = 24%), very low quality of evidence, 2 of 14 studies reporting this outcome were removed in a sensitivity analysis as they were strongly influencing heterogeneity between studies. No hormonal changes that indicated any risk to the participants' health were seen. Side effects observed were uncommon, mild, and transient, but commonly related to androgyny. In conclusion, DHEA was associated with a beneficial effect on depressive symptoms compared to placebo. However, these results should be viewed with caution, since the quality of evidence for this outcome was considered very low according to the GRADE criteria.     

Constraint-induced movement therapy in treatment of acute and sub-acute stroke: a meta-analysis of 16 randomized controlled trials

OBJECTIVE: The aim of this meta-analysis was to evaluate the clinical efficacy of constraint-induced movement therapy in acute and sub-acute stroke.DATA SOURCES: The key words were stroke, cerebrovascular accident, constraint-induced therapy, forced use, and randomized controlled trial. The databases, including China National Knowledge Infrastructure, Wan Fang, Weipu Information Resources System, Chinese Biomedical Literature Database, Pub Med, Medline, Embase, the Cochrane Central Register of Controlled Trials, and the Cochrane Database of Systematic Reviews, were searched for studies on randomized controlled trials for treating acute or sub-acute stroke published before March 2016. DATA SELECTION: We retrieved relevant randomized controlled trials that compared constraint-induced movement therapy in treatment of acute or sub-acute stroke with traditional rehabilitation therapy(traditional occupational therapy). Patients were older than 18 years, had disease courses less than 6 months, and were evaluated with at least one upper extremity function scale. Study quality was evaluated, and data that met the criteria were extracted. Stata 11.0 software was used for the meta-analysis. OUTCOME MEASURES: Fugl-Meyer motor assessment of the arm, the action research-arm test, a motor activity log for amount of use and quality of movement, the Wolf motor function test, and a modified Barthel index.RESULTS: A total of 16 prospective randomized controlled trials(379 patients in the constraint-induced movement-therapy group and 359 in the control group) met inclusion criteria. Analysis showed significant mean differences in favor of constraint-induced movement therapy for the Fugl–Meyer motor assessment of the arm(weighted mean difference(WMD) = 10.822; 95% confidence intervals(95% CI): 7.419–14.226), the action research-arm test(WMD = 10.718; 95% CI: 5.704–15.733), the motor activity log for amount of use and quality of movement(WMD = 0.812; 95% CI: 0.331–1.293) and the modified Barthel index(WMD = 10.706; 95% CI: 4.417–16.966). CONCLUSION: Constraint-induced movement therapy may be more beneficial than traditional rehabilitation therapy for improving upper limb function after acute or sub-acute stroke.     

Effect of homocysteine lowering treatment on cognitive function: a systematic review and meta-analysis of randomized controlled trials

Elevated total plasma homocysteine has been linked to the development of cognitive impairment and dementia in later life and this can be reliably lowered by the daily supplementation of vitamin B6, B12, and folic acid. We performed a systematic review and meta-analysis of 19 English language randomized, placebo-controlled trials of homocysteine lowering B-vitamin supplementation of individuals with and without cognitive impairment at the time of study entry. We standardized scores to facilitate comparison between studies and to enable us to complete a meta-analysis of randomized trials. In addition, we stratified our analyses according to the folate status of the country of origin. B-vitamin supplementation did not show an improvement in cognitive function for individuals with (SMD = 0.10, 95%CI -0.08 to 0.28) or without (SMD = -0.03, 95%CI -0.1 to 0.04) significant cognitive impairment. This was irrespective of study duration (SMD = 0.05, 95%CI -0.10 to 0.20 and SMD = 0, 95%CI -0.08 to 0.08), study size (SMD = 0.05, 95%CI -0.09 to 0.19 and SMD = -0.02, 95%CI -0.10 to 0.05), and whether participants came from countries with low folate status (SMD = 0.14, 95%CI -0.12 to 0.40 and SMD = -0.10, 95%CI -0.23 to 0.04). Supplementation of vitamins B12, B6, and folic acid alone or in combination does not appear to improve cognitive function in individuals with or without existing cognitive impairment. It remains to be established if prolonged treatment with B-vitamins can reduce the risk of dementia in later life.     

Pharmacological interventions for acute bipolar mania: a systematic review of randomized placebo-controlled trials

OBJECTIVES: We conducted a systematic review and meta-analysis of randomized, placebo-controlled trials in acute bipolar mania to summarize available data on drug treatment of mania. METHODS: We included trials of medications licensed in the USA or UK for the treatment of any phase of bipolar disorder. Outcomes investigated were changes in mania scores, attrition, extrapyramidal effects and weight change. Data were combined through meta-analyses. RESULTS: We included 13 studies (involving 3,089 subjects) and identified 2 studies for each of the following medications: carbamazepine, haloperidol, lithium, olanzapine, quetiapine, risperidone, valproate semisodium and aripiprazole. All drugs showed significant benefit compared with placebo for reduction in mania scores. Compared with placebo, for all antipsychotics pooled, response to treatment (> or =50% reduction in Young Mania Rating Scale scores) was increased more than 1.7 times [relative risk (RR) = 1.74, 95% confidence interval (CI) = 1.54, 1.96]; for all mood stabilizers pooled, response to treatment was doubled (RR 2.01, 95% CI = 1.66, 2.43). Overall withdrawals were 34% fewer (24-43%) with antipsychotics, and 26% fewer (10-39%) with mood stabilizers. However, for carbamazepine, aripiprazole and lithium an increase in risk of withdrawal could not be excluded. Small but significant increases in extrapyramidal side effects occurred with risperidone and aripiprazole. CONCLUSIONS: Antipsychotics and mood stabilizers are significantly more effective than placebo for the treatment of acute mania. Their effect sizes are similar. Small differences between effect sizes may be due to differences in the patients included in the studies or to chance. Carbamazepine and lithium may be more poorly tolerated, and antipsychotics cause more extrapyramidal side effects.     

Low-molecular-weight heparins and heparinoids in acute ischemic stroke : a meta-analysis of randomized controlled trials

BACKGROUND AND PURPOSE: Low-molecular-weight heparins and heparinoids (LMWHs) are superior to unfractionated heparin in the prevention and treatment of venous thromboembolism and acute coronary syndromes. We performed a systematic review of randomized controlled trials (RCTs) to examine the safety and efficacy of LMWH in acute ischemic stroke. METHODS: Randomized, controlled, and nonconfounded trials of LMWH in acute ischemic stroke were identified from the Cochrane Library (version 2, 1999), previous systematic reviews, and a review of publication quality relating to acute stroke trials. The authors each independently extracted data by treatment group and assessed trial quality using Cochrane Collaboration criteria. RESULTS: Eleven completed RCTs involving 3048 patients were identified; data were available from 10 of these. Four trials explicitly excluded patients with presumed cardioembolic stroke. Treatment with LMWH was associated with significant reductions in prospectively identified deep vein thrombosis (OR 0.27, 95% CI 0.08 to 0.96) and symptomatic pulmonary embolism (OR 0.34, 95% CI 0.17 to 0.69) and with increased major extracranial hemorrhage (OR 2.17, 95% 1.10 to 4.28). Nonsignificant increases in end-of-treatment (OR 1.20, 95% CI 0.86 to 1.69) and end-of-trial (OR 1.05, 95% CI 0.83 to 1.32) case fatality and symptomatic intracranial hemorrhage (OR 1.77, 95% CI 0. 95 to 3.31) were observed. End-of-trial death and disability was nonsignificantly reduced (OR 0.87, 95% CI 0.72 to 1.06). CONCLUSIONS: ++LMWHs reduce venous thromboembolic events in patients with acute ischemic stroke and increase the risk of extracranial bleeding. A nonsignificant reduction in combined death and disability and nonsignificant increases in case fatality and symptomatic intracranial hemorrhage were also observed. On the basis of the current evidence, LMWH should not be used in the routine management of patients with ischemic stroke.