The effects and side effects of laquinimod for the treatment of multiple sclerosis patients: a systematic review and meta-analysis of clinical trials

Objective--To determine if hydroxychloroquine (HCQ) reduces the incidence of new illness, hospitalization or death among outpatients at risk for or infected with SARS-CoV-2 (COVID-19). Design--Systematic review and meta-analysis of randomized clinical trials. Data sources--Search of MEDLINE, EMBASE, PubMed, medRxiv, PROSPERO, and the Cochrane Central Register of Controlled Trials. Also review of reference lists from recent meta-analyses. Study selection--Randomized clinical trials in which participants were treated with HCQ or placebo/standard-of-care for pre-exposure prophylaxis, post-exposure prophylaxis, or outpatient therapy for COVID-19. Methods--Two investigators independently extracted data on trial design and outcomes. Medication side effects and adverse reactions were also assessed. The primary outcome was COVID-19 hospitalization or death. When unavailable, new COVID-19 infection was used. We calculated random effects meta-analysis according to the method of DerSimonian and Laird. Heterogeneity between the studies was evaluated by calculation of Cochran Q and I2 parameters. An Egger funnel plot was drawn to investigate publication bias. We also calculated the fixed effects meta-analysis summary of the five studies. All calculations were done in Excel, and results were considered to be statistically significant at a two-sided threshold of P=.05. Results--Five randomized controlled clinical trials enrolling 5,577 patients were included. HCQ was associated with a 24% reduction in COVID-19 infection, hospitalization or death, P=.025 (RR, 0.76 [95% CI, 0.59 to 0.97]). No serious adverse cardiac events were reported. The most common side effects were gastrointestinal. Conclusion--Hydroxychloroquine use in outpatients reduces the incidence of the composite outcome of COVID-19 infection, hospitalization, and death. Serious adverse events were not reported and cardiac arrhythmia was rare. Systematic review registration--This review was not registered.

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Interferon-beta injection in multiple sclerosis patients is related to the induction of headache and flu-like pain symptoms: a systematic review and meta-analysis of randomised controlled trials

Current Neuropharmacology ◽

10.2174/1570159x19666211101142115 ◽

2021 ◽

Vol 19 ◽

Author(s):

Leonardo Gomes Pereira ◽

Gabriela Trevisan ◽

Patrícia Rodrigues ◽

Fernanda Tibolla Viero ◽

Julia Maria Frare ◽

...

Keyword(s):

Multiple Sclerosis ◽

Systematic Review ◽

Adverse Effects ◽

Randomised Controlled Trials ◽

Meta Analysis ◽

Controlled Trials ◽

First Choice ◽

Pain Symptoms ◽

Randomised Controlled ◽

Multiple Sclerosis Patients

: Multiple sclerosis (MS) is a chronic neurodegenerative, inflammatory and autoimmune disease characterised by the demyelination of the central nervous system. One of the main approaches to treating MS is the use of disease-modifying therapies (DMTs). Among the DMTs are interferons (IFNs), which are cytokines responsible for controlling the activity of the immune system, exerting immunomodulatory, antiviral, and antiproliferative activities. IFN-beta (IFN-β) is the first-choice drug used to treat relapsing-remitting MS. However, the administration of IFN-β causes numerous painful adverse effects, resulting in lower adherence to the treatment. Therefore, this study aimed to investigate the headache and flu-like pain symptoms observed after IFNβ injection in MS patients using a systematic review and meta-analysis of randomised controlled trials. The search of research databases identified 2370 articles. Nine articles were included (three involving IFNβ-1b and six involving IFNβ-1a). All studies included in the meta-analysis had a low risk of bias. Headache and flu-like pain symptoms frequency increased in MS patients treated with IFN-β. Thus, the adverse effects of headache and flu-like pain symptoms appear to be linked to IFN-β treatment in MS. The protocol of the study was registered in the Prospective International Registry of Systematic Reviews.

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Functional lesional neurosurgery for tremor: a systematic review and meta-analysis

Journal of Neurology Neurosurgery & Psychiatry ◽

10.1136/jnnp-2017-316302 ◽

2018 ◽

Vol 89 (7) ◽

pp. 717-726 ◽

Cited By ~ 7

Author(s):

Sebastian R Schreglmann ◽

Joachim K Krauss ◽

Jin Woo Chang ◽

Kailash P Bhatia ◽

Georg Kägi

Keyword(s):

Multiple Sclerosis ◽

Systematic Review ◽

Radiofrequency Ablation ◽

Side Effects ◽

Focused Ultrasound ◽

Meta Analysis ◽

Consistency Effect ◽

Rubral Tremor ◽

Ventral Intermediate Nucleus ◽

Mri Guided

BackgroundThis work evaluates the consistency, effect size and incidence of persistent side effects of lesional neurosurgical interventions in the treatment of tremor due to Parkinson’s disease (PD), essential tremor (ET), multiple sclerosis (MS) and midbrain lesions.MethodsSystematic review and meta-analysis according to PRISMA-P guidelines. Random effects meta-analysis of standardised mean difference based on a peer-reviewed protocol (PROSPERO no. CRD42016048049).ResultsFrom 1249 abstracts screened, 86 peer-reviewed studies reporting 102 cohorts homogeneous for tremor aetiology, surgical target and technique were included.Effect on PD tremor was better when targeted at the ventral intermediate nucleus (V.im.) by radiofrequency ablation (RF) (Hedge’s g: −4.15;) over V.im. by Gamma Knife (GK) (−2.2), subthalamic nucleus (STN) by RF (−1.12) and globus pallidus internus (GPi) by RF (−0.89). For ET MRI-guided focused ultrasound (MRIgFUS) ablation of the cerebellothalamic tract (CTT) (−2.35) and V.im. (−2.08) showed similar mean tremor reductions to V.im. ablation by RF (−2.42) or GK (−2.13). In MS V.im. ablation by GK (−1.96) and RF (−1.63) were similarly effective.Mean rates of persistent side effects after unilateral lesions in PD were 12.8% (RF V.im.), 13.6% (RF STN), 9.2% (RF GPi), 0.7% (GK V.im.) and 7.0% (MRIgFUS V.im.). For ET, rates were 9.3% (RF V.im.), 1.8% (GK V.im.), 18.7% (MRIgFUS V.im.) and 0.0% (MRIgFUS CTT), for MS 37.7% (RF V.im.) and for rubral tremor 30.3% (RF V.im.).ConclusionThis meta-analysis quantifies safety, consistency and efficacy of lesional neurosurgical interventions for tremor by target, technique and aetiology.

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Prolonging the duration of single-shot intrathecal labour analgesia with morphine: A systematic review

Scandinavian Journal of Pain ◽

10.1016/j.sjpain.2016.06.010 ◽

2016 ◽

Vol 13 (1) ◽

pp. 36-42 ◽

Cited By ~ 4

Author(s):

Hadeel Al-Kazwini ◽

Irene Sandven ◽

Vegard Dahl ◽

Leiv Arne Rosseland

Keyword(s):

Systematic Review ◽

Clinical Trials ◽

Side Effects ◽

Pain Relief ◽

Beneficial Effect ◽

Intrathecal Morphine ◽

Meta Analysis ◽

Labour Analgesia ◽

Single Shot ◽

Standardized Mean Difference

AbstractBackground and aimsSingle-shot spinal with bupivacaine plus fentanyl or sufentanil is commonly used as analgesia during labour, but the short duration limits the clinical feasibility. Different drugs have been added to prolong the analgesic duration. The additional effect of intra-thecal morphine has been studied during labour pain as well as after surgery. We assessed whether adding morphine to intra-thecal bupivacaine + fentanyl or sufentanil prolongs pain relief during labour.MethodsMeta-analysis of placebo-controlled randomized clinical trials of analgesia prolongation after single-shot intrathecal morphine ≤250µg during labour when given in combination with bupivacaine + fentanyl or sufentanil. After identifying 461 references, 24 eligible studies were evaluated after excluding duplicate publications, case reports, studies of analgesia after caesarean delivery, and epidural labour analgesia. Mean duration in minutes was the primary outcome measure and was included in the calculation of the standardized mean difference. Duration was defined as the time between a single shot spinal until patient request of rescue analgesia. All reported side effects were registered. Results of individual trials were combined using a random effect model. Cochrane tool was used to assess risk of bias.ResultsFive randomized placebo-controlled clinical trials (286 patients) were included in the metaanalysis. A dose of 50–250µg intrathecal morphine prolonged labour analgesia by a mean of 60.6 min (range 3–155 min). Adding morphine demonstrated a medium beneficial effect as we found a pooled effect of standardized mean difference = 0.57 (95% CI: –0.10 to 1.24) with high heterogeneity (I2 =88.1%). However, the beneficial effect was statistically non-significant (z =1.66, p = 0.096). The lower-bias trials showed a small statistically non-significant beneficial effect with lower heterogeneity. In influential analysis, that excluded one study at a time from the meta-analysis, the effect size appears unstable and the results indicate no robustness of effect. Omitting the study with highest effects size reduces the pooled effect markedly and that study suffers from inadequate concealment of treatment allocation and blinding. Trial quality was generally low, and there were too few trials to explore sources of heterogeneity in meta-regression and stratified analyses. In general, performing meta-analyses on a small number of trials are possible and may be helpful if one is aware of the limitations. As few as one more placebo-controlled trial would increase the reliability greatly.ConclusionsEvidence from this systematic review suggests a possible beneficial prolonging effect of adding morphine to spinal analgesia with bupivacaine + fentanyl or +sufentanil during labour. The study quality was low and heterogeneity high. No severe side effects were reported. More adequately-powered randomized trials with low bias are needed to determine the benefits and harms of adding morphine to spinal local anaesthetic analgesia during labour.ImplicationsEpidural analgesia is documented as the most effective method for providing pain relief during labour, but from a global perspective most women in labour have no access to epidural analgesia. Adding morphine to single shot spinal injection of low dose bupivacaine, fentanyl or sufentanil may be efficacious but needs to be investigated.

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