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Journal of Clinical Neuromuscular... Dec 2023Isaac syndrome (IS) is a condition characterized by peripheral nerve hyperexcitability caused by voltage-gated potassium channel (VGKC)-complex antibodies. Muscle...
OBJECTIVES
Isaac syndrome (IS) is a condition characterized by peripheral nerve hyperexcitability caused by voltage-gated potassium channel (VGKC)-complex antibodies. Muscle twitching, stiffness, hypertrophy, and dysautonomic characteristics, such as hyperhidrosis, are common manifestations. The syndrome can be autoimmune or paraneoplastic, with thymoma being a common cause of paraneoplastic IS. Furthermore, this condition could be handed down from one generation to another. However, there is limited information regarding outcomes, relapses, associated syndromes, associated malignancies (other than thymoma), and treatment options. Despite its rarity, there remains a need for effective management strategies for patients with IS. To address this gap, we conducted a systematic review to summarize the most common and effective treatments of IS in immunomodulatory agents and symptomatic medications, as well as to describe outcomes, relapses, and associated malignancies. Altogether, this review serves to guide clinical practice recommendations for IS and highlight areas for further research.
METHODS
We used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocol to conduct a systematic review of cases reposted through the PubMed and Google Scholar databases. The terms "Isaac Syndrome" and "Acquired Neuromyotonia" were used. The Joanna Briggs Institute's critical appraisal tool was used to evaluate the quality of the included studies.
RESULTS
We identified 61 case reports and 4 case series, comprising a total of 70 patients with IS (mean age at onset: 42.5 ± 18 years, and 69% were males). Fourteen cases reported relapses. Thymoma was the most common malignancy associated with IS, followed by lymphoma. Among various serum antibodies, voltage-gated potassium channel-complex antibodies were the most reported antibodies elevated in IS (reported in 38 patients and elevated in 21 patients [55.2%]), followed by acetylcholine ganglionic receptor antibodies, which were reported in 30% of patients (n = 21) and were elevated in 5 cases. The most common electromyography findings were myokymic discharges (n = 22), followed by fasciculations (n = 21) and neuromyotonia (n = 19). For treatment, combining anticonvulsants such as carbamazepine with immunotherapy therapy showed the best results in controlling the symptoms. Among immunotherapy therapies, the combination of plasma exchange plus intravenous high-dose steroids achieved the best results in the acute treatment of IS ([n = 6], with improvement noted in 83.3% [n = 5] of cases). Among the symptomatic treatments with anticonvulsants, carbamazepine was the most efficacious anticonvulsant in treatment of IS, with an average effective dosing of 480 mg/day (carbamazepine was used in 32.3% of acute treatment strategies [n = 23], with improvement noted in 73.9% [n = 17] of cases).
CONCLUSIONS
IS a rare neuromuscular syndrome that tends to affect middle-aged men. These patients should be screened for thymoma and other malignancies such as lymphomas. The management of IS symptoms can be challenging, but based on our review, the combination of multiple immunosuppressives such as IV steroids and plasmapheresis with anticonvulsants such as carbamazepine seems to achieve the best results.
Topics: Male; Middle Aged; Humans; Female; Isaacs Syndrome; Thymoma; Anticonvulsants; Thymus Neoplasms; Autoantibodies; Potassium Channels, Voltage-Gated; Carbamazepine; Receptors, Cholinergic; Steroids; Recurrence
PubMed: 37962197
DOI: 10.1097/CND.0000000000000460 -
The Cochrane Database of Systematic... Oct 2023Newborn infants are more prone to seizures than older children and adults. The neuronal injury caused by seizures in neonates often results in long-term... (Review)
Review
BACKGROUND
Newborn infants are more prone to seizures than older children and adults. The neuronal injury caused by seizures in neonates often results in long-term neurodevelopmental sequelae. There are several options for anti-seizure medications (ASMs) in neonates. However, the ideal choice of first-, second- and third-line ASM is still unclear. Further, many other aspects of seizure management such as whether ASMs should be initiated for only-electrographic seizures and how long to continue the ASM once seizure control is achieved are elusive.
OBJECTIVES
1. To assess whether any ASM is more or less effective than an alternative ASM (both ASMs used as first-, second- or third-line treatment) in achieving seizure control and improving neurodevelopmental outcomes in neonates with seizures. We analysed EEG-confirmed seizures and clinically-diagnosed seizures separately. 2. To assess maintenance therapy with ASM versus no maintenance therapy after achieving seizure control. We analysed EEG-confirmed seizures and clinically-diagnosed seizures separately. 3. To assess treatment of both clinical and electrographic seizures versus treatment of clinical seizures alone in neonates.
SEARCH METHODS
We searched MEDLINE, Embase, CENTRAL, Epistemonikos and three databases in May 2022 and June 2023. These searches were not limited other than by study design to trials.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) that included neonates with EEG-confirmed or clinically diagnosed seizures and compared (1) any ASM versus an alternative ASM, (2) maintenance therapy with ASM versus no maintenance therapy, and (3) treatment of clinical or EEG seizures versus treatment of clinical seizures alone.
DATA COLLECTION AND ANALYSIS
Two review authors assessed trial eligibility, risk of bias and independently extracted data. We analysed treatment effects in individual trials and reported risk ratio (RR) for dichotomous data, and mean difference (MD) for continuous data, with respective 95% confidence interval (CI). We used GRADE to assess the certainty of evidence.
MAIN RESULTS
We included 18 trials (1342 infants) in this review. Phenobarbital versus levetiracetam as first-line ASM in EEG-confirmed neonatal seizures (one trial) Phenobarbital is probably more effective than levetiracetam in achieving seizure control after first loading dose (RR 2.32, 95% CI 1.63 to 3.30; 106 participants; moderate-certainty evidence), and after maximal loading dose (RR 2.83, 95% CI 1.78 to 4.50; 106 participants; moderate-certainty evidence). However, we are uncertain about the effect of phenobarbital when compared to levetiracetam on mortality before discharge (RR 0.30, 95% CI 0.04 to 2.52; 106 participants; very low-certainty evidence), requirement of mechanical ventilation (RR 1.21, 95% CI 0.76 to 1.91; 106 participants; very low-certainty evidence), sedation/drowsiness (RR 1.74, 95% CI 0.68 to 4.44; 106 participants; very low-certainty evidence) and epilepsy post-discharge (RR 0.92, 95% CI 0.48 to 1.76; 106 participants; very low-certainty evidence). The trial did not report on mortality or neurodevelopmental disability at 18 to 24 months. Phenobarbital versus phenytoin as first-line ASM in EEG-confirmed neonatal seizures (one trial) We are uncertain about the effect of phenobarbital versus phenytoin on achieving seizure control after maximal loading dose of ASM (RR 0.97, 95% CI 0.54 to 1.72; 59 participants; very low-certainty evidence). The trial did not report on mortality or neurodevelopmental disability at 18 to 24 months. Maintenance therapy with ASM versus no maintenance therapy in clinically diagnosed neonatal seizures (two trials) We are uncertain about the effect of short-term maintenance therapy with ASM versus no maintenance therapy during the hospital stay (but discontinued before discharge) on the risk of repeat seizures before hospital discharge (RR 0.76, 95% CI 0.56 to 1.01; 373 participants; very low-certainty evidence). Maintenance therapy with ASM compared to no maintenance therapy may have little or no effect on mortality before discharge (RR 0.69, 95% CI 0.39 to 1.22; 373 participants; low-certainty evidence), mortality at 18 to 24 months (RR 0.94, 95% CI 0.34 to 2.61; 111 participants; low-certainty evidence), neurodevelopmental disability at 18 to 24 months (RR 0.89, 95% CI 0.13 to 6.12; 108 participants; low-certainty evidence) and epilepsy post-discharge (RR 3.18, 95% CI 0.69 to 14.72; 126 participants; low-certainty evidence). Treatment of both clinical and electrographic seizures versus treatment of clinical seizures alone in neonates (two trials) Treatment of both clinical and electrographic seizures when compared to treating clinical seizures alone may have little or no effect on seizure burden during hospitalisation (MD -1871.16, 95% CI -4525.05 to 782.73; 68 participants; low-certainty evidence), mortality before discharge (RR 0.59, 95% CI 0.28 to 1.27; 68 participants; low-certainty evidence) and epilepsy post-discharge (RR 0.75, 95% CI 0.12 to 4.73; 35 participants; low-certainty evidence). The trials did not report on mortality or neurodevelopmental disability at 18 to 24 months. We report data from the most important comparisons here; readers are directed to Results and Summary of Findings tables for all comparisons.
AUTHORS' CONCLUSIONS
Phenobarbital as a first-line ASM is probably more effective than levetiracetam in achieving seizure control after the first loading dose and after the maximal loading dose of ASM (moderate-certainty evidence). Phenobarbital + bumetanide may have little or no difference in achieving seizure control when compared to phenobarbital alone (low-certainty evidence). Limited data and very low-certainty evidence preclude us from drawing any reasonable conclusion on the effect of using one ASM versus another on other short- and long-term outcomes. In neonates who achieve seizure control after the first loading dose of phenobarbital, maintenance therapy compared to no maintenance ASM may have little or no effect on all-cause mortality before discharge, mortality by 18 to 24 months, neurodevelopmental disability by 18 to 24 months and epilepsy post-discharge (low-certainty evidence). In neonates with hypoxic-ischaemic encephalopathy, treatment of both clinical and electrographic seizures when compared to treating clinical seizures alone may have little or no effect on seizure burden during hospitalisation, all-cause mortality before discharge and epilepsy post-discharge (low-certainty evidence). All findings of this review apply only to term and late preterm neonates. We need well-designed RCTs for each of the three objectives of this review to improve the precision of the results. These RCTs should use EEG to diagnose seizures and should be adequately powered to assess long-term neurodevelopmental outcomes. We need separate RCTs evaluating the choice of ASM in preterm infants.
Topics: Infant; Child; Infant, Newborn; Adult; Humans; Adolescent; Phenytoin; Levetiracetam; Epilepsy; Phenobarbital; Seizures
PubMed: 37873971
DOI: 10.1002/14651858.CD014967.pub2 -
JAMA Network Open Aug 2023Patients undergoing spine surgery often experience severe pain. The optimal dosage of pregabalin and gabapentin for pain control and safety in these patients has not... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Patients undergoing spine surgery often experience severe pain. The optimal dosage of pregabalin and gabapentin for pain control and safety in these patients has not been well established.
OBJECTIVE
To evaluate the associations of pain, opioid consumption, and adverse events with different dosages of pregabalin and gabapentin in patients undergoing spine surgery.
DATA SOURCES
PubMed/MEDLINE, Embase, Web of Science, Cochrane library, and Scopus databases were searched for articles until August 7, 2021.
STUDY SELECTION
Randomized clinical trials conducted among patients who received pregabalin or gabapentin while undergoing spine surgery were included.
DATA EXTRACTION AND SYNTHESIS
Two investigators independently performed data extraction following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) reporting guideline. The network meta-analysis was conducted from August 2022 to February 2023 using a random-effects model.
MAIN OUTCOMES AND MEASURES
The primary outcome was pain intensity measured using the Visual Analog Scale (VAS), and secondary outcomes included opioid consumption and adverse events.
RESULTS
Twenty-seven randomized clinical trials with 1861 patients (median age, 45.99 years [range, 20.00-70.00 years]; 759 women [40.8%]) were included in the systematic review and network meta-analysis. Compared with placebo, the VAS pain score was lowest with gabapentin 900 mg per day, followed by gabapentin 1200 mg per day, gabapentin 600 mg per day, gabapentin 300 mg per day, pregabalin 300 mg per day, pregabalin 150 mg per day, and pregabalin 75 mg per day. Additionally, gabapentin 900 mg per day was found to be associated with the lowest opioid consumption among all dosages of gabapentin and pregabalin, with a mean difference of -22.07% (95% CI, -33.22% to -10.92%) for the surface under the cumulative ranking curve compared with placebo. There was no statistically significant difference in adverse events (nausea, vomiting, and dizziness) among all treatments. No substantial inconsistency between direct and indirect evidence was detected for all outcomes.
CONCLUSIONS AND RELEVANCE
These findings suggest that gabapentin 900 mg per day before spine surgery is associated with the lowest VAS pain score among all dosages. In addition, no differences in adverse events were noted among all treatments.
Topics: Humans; Female; Middle Aged; Gabapentin; Pregabalin; Analgesics; Analgesics, Opioid; Network Meta-Analysis; Pain, Postoperative
PubMed: 37556139
DOI: 10.1001/jamanetworkopen.2023.28121 -
Seizure Nov 2023Despite many new ASM, the rate of patients with drug-resistant epilepsy (DRE) has not changed. Cenobamate (CNB) is a novel ASM for the treatment of focal-onset seizures... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Despite many new ASM, the rate of patients with drug-resistant epilepsy (DRE) has not changed. Cenobamate (CNB) is a novel ASM for the treatment of focal-onset seizures in adults with high seizure freedom rates in randomized controlled trials (RCT). Although CNB appears to be effective, it is not commonly prescribed to patients with DRE, resulting in a lack of "real-world data".
METHODS
To evaluate the real-world effect of CNB and to assess the generalizability of RCT data, a systematic review and meta-analysis was conducted. Pooled proportions were calculated using a random intercept logistic regression model.
RESULTS
The analysis included seven studies with a total of 229 patients with DRE, 77.3 % of whom were adults and 91.5 % had focal-onset seizures. Seizure reduction >50 % was achieved in 68 % of patients [54.54; 79.07], with seizure freedom in 16.2 % [8.38; 28.97]. There was no difference between pediatric and adult patients. CNB was discontinued in 10 % [6.74; 14.6] of patients, mostly due to lack of efficacy (39 %) or adverse effects (AE, 43 %). AE, observed in 57.3 % [39.7; 73.2] of patients, included fatigue and vertigo. A comparison of the rates calculated in this meta-analysis to the active arm of equivalent RCTs revealed no significant difference.
CONCLUSION
CNB achieves a good treatment response in patients with DRE in real-world settings, like the effect reported in RCTs. The high heterogeneity between studies calls for studies focusing on specific DRE subpopulations.
Topics: Adult; Child; Humans; Anticonvulsants; Carbamates; Drug Resistant Epilepsy; Seizures; Treatment Outcome
PubMed: 37713961
DOI: 10.1016/j.seizure.2023.09.006 -
BMJ Sexual & Reproductive Health Apr 2024To identify and appraise current national and international clinical menopause guidance documents, and to extract and compare the recommendations of the most robust...
OBJECTIVE AND RATIONALE
To identify and appraise current national and international clinical menopause guidance documents, and to extract and compare the recommendations of the most robust examples.
DESIGN
Systematic review.
DATA SOURCES
Ovid MEDLINE, EMBASE, PsycINFO and Web of Science ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Practice guidance documents for menopause published from 2015 until 20 July 2023. Quality was assessed by the Appraisal of Guidelines for Research and Evaluation II (AGREE II) instrument.
RESULTS
Twenty-six guidance papers were identified. Of these, five clinical practice guidelines (CPGs) and one non-hormonal therapy position statement met AGREE II criteria of being at least of moderate quality. The five CPGs listed symptoms associated with the perimenopause and menopause to be vasomotor symptoms (VMS), disturbed sleep, musculoskeletal pain, decreased sexual function or desire, and mood disturbance (low mood, mood changes or depressive symptoms). Acknowledged potential long-term menopause consequences were urogenital atrophy, and increased risks of cardiovascular disease and osteoporosis. VMS and menopause-associated mood disturbance were the only consistent indications for systemic menopausal hormone therapy (MHT). Some CPGs supported MHT to prevent or treat osteoporosis, but specific guidance was lacking. None recommended MHT for cognitive symptoms or prevention of other chronic disease. Perimenopause-specific recommendations were scant. A neurokinin 3B antagonist, selective serotonin/norepinephrine (noradrenaline) reuptake inhibitors and gabapentin were recommended non-hormonal medications for VMS, and cognitive behavioural therapy and hypnosis were consistently considered as being of potential benefit.
DISCUSSION
The highest quality CPGs consistently recommended MHT for VMS and menopause-associated mood disturbance, whereas clinical depression or cognitive symptoms, and cardiometabolic disease and dementia prevention were not treatment indications. Further research is needed to inform clinical recommendations for symptomatic perimenopausal women.
Topics: Female; Humans; Hot Flashes; Menopause; Gabapentin; Osteoporosis
PubMed: 38336466
DOI: 10.1136/bmjsrh-2023-202099 -
Epilepsia Open Apr 2024Antiseizure medications (ASMs) constitute the principal of treatment for patients with epilepsy, where long-term treatment is usually necessary. The purpose of this... (Review)
Review
Antiseizure medications (ASMs) constitute the principal of treatment for patients with epilepsy, where long-term treatment is usually necessary. The purpose of this systematic review is to provide practical and useful information regarding various aspects of the interactions between ASMs and foods and drinks. MEDLINE and ScienceDirect, from the inception to July 15, 2023, were searched for related publications. In both electronic databases, the following search strategy was applied, and the following keywords were used (in title/abstract): "food OR drink" AND "antiepileptic OR antiseizure." The primary search yielded 738 studies. After implementing our inclusion and exclusion criteria, we could identify 19 studies on the issue of interest for our endeavor. Four studies were identified in the recheck process and not by the primary search. All studies provided low level of evidence. Interactions between foods and ASMs are a common phenomenon. Many factors may play a role for such an interaction to come to play; these include drug properties, administration route, and administration schedule, among others. Drugs-foods (-drinks) interactions may change the drug exposure or plasma levels of drugs (e.g., grapefruit juice increases carbamazepine concentrations and the bioavailability of cannabidiol is increased 4-5 folds with concomitant intake of fat-rich food); this may require dosage adjustments. Interactions between ASMs and foods and drinks may be important. This should be taken seriously into consideration when consulting patients and their caregivers about ASMs. Future well-designed investigations should explore the specific interactions between foods (and drinks) and ASMs to clarify whether they are clinically important. PLAIN LANGUAGE SUMMARY: Interactions between antiseizure medications and foods and drinks may be important. This should be taken into consideration in patients with epilepsy.
Topics: Humans; Anticonvulsants; Biological Availability; Benzodiazepines; Food; Epilepsy
PubMed: 38345419
DOI: 10.1002/epi4.12918 -
CNS Drugs Nov 2023In Parkinson's disease, safinamide and zonisamide are novel monoamine oxidase-B inhibitors with a dual mechanism of action involving the inhibition of sodium and calcium... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND OBJECTIVE
In Parkinson's disease, safinamide and zonisamide are novel monoamine oxidase-B inhibitors with a dual mechanism of action involving the inhibition of sodium and calcium channels and the subsequent release of glutamate. The aim of this systematic review and meta-analysis was to examine the efficacy and safety of both drugs compared with placebo on motor symptoms, cognitive function, and quality of life in patients with Parkinson's disease.
METHODS
We searched MEDLINE, EMBASE, Cochrane Central, Scopus, PsycINFO, and trials registries up to March 2023 for randomized controlled trials of adults with Parkinson's disease administered either safinamide or zonisamide and published in English. We excluded single-arm trials or if neither the efficacy nor safety outcomes of interest were reported. Primary outcomes were the change from baseline in Unified Parkinson's Disease Rating Scale section III (UPDRS-III) and serious adverse events. Secondary outcomes included a change from baseline in OFF-time, Parkinson's Disease Questionnaire 39 to evaluate quality of life, and Mini-Mental State Examination for cognitive function assessment. The meta-analysis was conducted using Review Manager 5.4.1. Random-effect models were used to calculate the pooled mean differences (MDs) and risk ratios with 95% confidence intervals (CIs). Subgroup analyses by medication, doses, Parkinson's disease stage, and risk of bias were conducted. We assessed the risk of bias using the Cochrane's risk of bias tool. Sensitivity analysis was conducted, and publication bias were evaluated. This meta-analysis was not externally funded, and the protocol is available on the Open Science Framework Registration ( https://doi.org/10.17605/OSF.IO/AMNP5 ).
RESULTS
Of 3570 screened citations, 16 trials met inclusion criteria (4314 patients with Parkinson's disease). Ten safinamide trials were conducted in several countries. Six zonisamide trials were included, five of which were conducted in Japan and one in India. UPDRS Part III scores were significantly lower with both monoamine oxidase-B inhibitors than with placebo (MD = - 2.18; 95% CI - 2.88 to - 1.49; I =63%; n = 14 studies). A subgroup analysis showed a significant improvement in UPDRS-III in safinamide (MD = - 2.10; 95% CI - 3.09 to - 1.11; I = 71%; n = 8 studies) and zonisamide (MD = - 2.31; 95% CI - 3.35 to - 1.27; I = 52%; n = 6 studies) compared with placebo. Monoamine oxidase-B inhibitors significantly decreased OFF-time compared with placebo. No significant differences in cognitive function (Mini-Mental State Examination), whereas an improvement in quality of life (Parkinson's Disease Questionnaire 39 scores) was observed. There was no significant difference in incidence rates of serious adverse events among all examined doses of zonisamide and safinamide compared with placebo. Two trials were reported as a high risk of bias and sensitivity analyses confirmed the primary analysis results.
CONCLUSIONS
Evidence suggests that novel monoamine oxidase-B inhibitors not only improve motor symptoms but also enhance patients' quality of life. The meta-analysis showed that both medications have a similar safety profile to placebo with regard to serious adverse events. The overall findings emphasize the effectiveness of safinamide and zonisamide in the treatment of Parkinson's disease as adjunct therapy. Further long-term studies examining the impact of these medications on motor and non-motor symptoms are necessary.
Topics: Adult; Humans; Parkinson Disease; Zonisamide; Quality of Life; Randomized Controlled Trials as Topic; Dopamine Agents; Monoamine Oxidase
PubMed: 37973769
DOI: 10.1007/s40263-023-01048-x -
Journal of Perinatology : Official... Sep 2023To evaluate the effect of antenatal magnesium sulfate (MgSO) on mortality and morbidity outcomes related to the gastrointestinal system (GI) in preterm infants. (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
To evaluate the effect of antenatal magnesium sulfate (MgSO) on mortality and morbidity outcomes related to the gastrointestinal system (GI) in preterm infants.
METHODS
Data sources: A systematic literature search was conducted in November 2022. PubMed, CINAHL Plus with Full Text (EBSCOhost), Embase (Elsevier), and CENTRAL (Ovid) were searched. There were 6695 references. After deduplication, 4332 remained. Ninety-nine full-text articles were assessed and forty four articles were included in the final analysis.
STUDY ELIGIBILITY CRITERIA
Randomized or quasi-randomized clinical trials and observational studies that evaluated at least one of the pre-specified outcomes were included. Preterm infants whose mothers were given antenatal MgSO were included and whose mothers did not receive antenatal MgSO were the comparators. The main outcomes and measures were: Necrotizing enterocolitis (NEC) (stage ≥ 2), surgical NEC, spontaneous intestinal perforation (SIP), feeding intolerance, time to reach full feeds, and GI-associated mortality.
STUDY APPRAISAL AND SYNTHESIS METHODS
A random-effects model meta-analysis was performed to yield pooled OR and its 95% CI for each outcome due to expected heterogeneity in the studies. The analysis for each predefined outcome was performed separately for adjusted and unadjusted comparisons. All included studies were assessed for methodological quality. The risk of bias was assessed using elements of the Cochrane Collaboration's tool 2.0 and the Newcastle-Ottawa Scale for randomized controlled trials (RCTs) and non-randomized studies (NRS), respectively. The study findings were reported as per PRISMA guidelines.
RESULTS
A total of thirty-eight NRS and six RCTs involving 51,466 preterm infants were included in the final analysis. There were no increased odds of stage ≥2 NEC, (NRS : n = 45,524, OR: 0.95; 95% CI: 0.84-1.08, I- 5% & RCT's: n = 5205 OR: 1.00; 95% CI: 0.89-1.12, I- 0%), SIP (n = 34,186, OR: 1.22, 95% CI: 0.94-1.58, I-30%), feeding intolerance (n = 414, OR: 1.06, 95% CI: 0.64-1.76, I-12%) in infants exposed to antenatal MgSO. On the contrary, the incidence of surgical NEC was significantly lower in MgSO exposure infants (n = 29,506 OR:0.74; 95% CI: 0.62-0.90, ARR: 0.47%). Studies assessing the effect on GI-related mortality were limited to make any conceivable conclusion. The certainty of evidence (CoE) for all outcomes was adjudged as 'very low' as per GRADE.
CONCLUSION
Antenatal magnesium sulfate did not increase the incidence of gastrointestinal-related morbidities or mortality in preterm infants. With the current evidence concerns, regarding the adverse effects of MgSO administration leading to NEC/SIP or GI-related mortality in preterm infants should not be a hurdle in its routine use in antenatal mothers.
Topics: Infant; Infant, Newborn; Humans; Magnesium Sulfate; Infant, Premature; Enterocolitis, Necrotizing; Infant, Premature, Diseases; Incidence
PubMed: 37391507
DOI: 10.1038/s41372-023-01710-8 -
CNS Drugs Jan 2024Studies have suggested that levetiracetam may help improve cognitive function in patients with epilepsy. Recently, its efficacy in improving cognitive function was... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Studies have suggested that levetiracetam may help improve cognitive function in patients with epilepsy. Recently, its efficacy in improving cognitive function was reported in patients with amnestic mild cognitive impairment, schizophrenia, and Alzheimer's disease. However, the specific cognitive domains affected and the degree of evidence supporting these effects remain unclear. This systematic review and meta-analysis aimed to explore the effects of levetiracetam on different cognitive domains.
METHODS
This meta-analysis was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. We defined our inclusion criteria for the systematic review as: (1) randomized placebo-controlled trials (RCTs) involving human subjects, (2) double-blinded RCTs, and (3) RCTs evaluating the quantitative differences in cognitive function between levetiracetam and placebo. We excluded: (1) non-RCT studies, (2) open-label studies, and (3) RCTs lacking cognitive assessments for either intervention. Two authors independently searched electronic databases, including PubMed, Embase, Cochrane CENTRAL, and ClinicalTrials.gov, from inception until 2 July 2023. The methodological quality of the included studies was assessed using the Cochrane risk of bias tool. Meta-analytic techniques were applied to examine the impact of levetiracetam on cognitive domain tests, with Hedges' g facilitating the comparison with placebo. The domains analyzed comprised multi-domain, executive function, processing speed, working memory, verbal memory/learning (verbal ML), visuospatial memory/learning (visuospatial ML), and language. We used odds ratios to compare the incidence of treatment-emergent adverse events between the groups, including somnolence, fatigue, dizziness, headache, irritability, and cognitive adverse events.
RESULTS
A random-effects model was utilized to perform a meta-analysis of 16 RCTs including 545 participants. Compared with a placebo, levetiracetam was associated with improved executive function [Hedges'g = - 0.390, 95% confidence interval (CI) = - 0.609 to - 0.172, p < 0.001, I = 24.0%]. Subgroup analysis showed that levetiracetam outperformed placebo in patients without epilepsy (Hedges' g = - 0.419, 95% CI = - 0.647 to - 0.191, p < 0.001, I = 26.2%). Meanwhile, low-dose levetiracetam showed a moderate favorable effect over placebo (Hedges' g = -0.544, 95% CI = - 1.085 to - 0.003, p = 0.049, I = 65.3%). In patients without epilepsy, low-dose levetiracetam was associated with improved executive function (Hedges'g = - 0.544, 95% CI = - 1.085 to - 0.003, p = 0.049, I = 65.3%). Concurrently, levetiracetam was associated with more frequent somnolence than a placebo (odds ratio = 4.654, 95% CI = 1.533 to 14.124, p = 0.007, I = 32.9%). Potential publication bias was observed in the executive function domain.
CONCLUSIONS
This exploratory study suggests that levetiracetam might improve executive function in specific populations. However, the diversity in study populations and potential publication bias warrant caution.
Topics: Humans; Cognition; Cognitive Dysfunction; Epilepsy; Levetiracetam; Randomized Controlled Trials as Topic; Sleepiness
PubMed: 38102532
DOI: 10.1007/s40263-023-01058-9 -
The Journal of Headache and Pain Oct 2023Topiramate is a repurposed first-line treatment for migraine prophylaxis. The aim of this systematic review and meta-analysis is to critically re-appraise the existing... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Topiramate is a repurposed first-line treatment for migraine prophylaxis. The aim of this systematic review and meta-analysis is to critically re-appraise the existing evidence supporting the efficacy and tolerability of topiramate.
METHODS
A systematic search in MEDLINE, EMBASE, Cochrane CENTRAL, and ClinicalTrials.gov was performed for trials of pharmacological treatment in migraine prophylaxis as of August 13, 2022, following the Preferred Reporting Items for Systematic Reviews (PRISMA). Randomized controlled trials in adult patients that used topiramate for the prophylactic treatment of migraine, with placebo as active comparator, were included. Two reviewers independently screened the retrieved studies and extracted all data. Outcomes of interest were the 50% responder rates, the reduction in monthly migraine days, and adverse events leading to treatment discontinuation. Results were pooled and meta-analyzed, with sensitivity analysis based on the risk of bias of the studies, the monthly migraine days at baseline, and the previous use of other prophylactic treatments. Certainty evidence was judged according to the GRADE framework.
RESULTS
Eight out of 10,826 studies fulfilled the inclusion/exclusion criteria, accounting for 2,610 randomized patients. Six studies included patients with episodic migraine and two with chronic migraine. Topiramate dose ranged from 50 to 200 mg/day, and all studies included a placebo arm. There was a high certainty that topiramate: 1) increased the proportion of patients who achieved a 50% responder rate in monthly migraine days, compared to placebo [relative risk: 1.61 (95% confidence interval (CI): 1.29-2.01); absolute risk difference: 168 more per 1,000 (95% CI: 80 to 278 more)]; 2) was associated with 0.99 (95% CI: 1.41-0.58) fewer migraine days than placebo; 3) and had a higher proportion of patients with adverse events leading to treatment discontinuation [absolute risk difference 80 patients more per 1,000 (95% CI: 20 to 140 more patients)].
CONCLUSIONS
There is high-quality evidence of the efficacy of topiramate in the prophylaxis of migraine, albeit its use poses a risk of adverse events that may lead to treatment discontinuation, with a negative effect on patient satisfaction and adherence to care.
Topics: Adult; Humans; Topiramate; Migraine Disorders; Headache; Patient Satisfaction; Transcription Factors
PubMed: 37814223
DOI: 10.1186/s10194-023-01671-5