Efficacy of nonvenous medications for acute convulsive seizures: A network meta-analysis.
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ABSTRACT: Objective
This is a network meta-analysis of nonvenous drugs used in randomized controlled trials (RCTs) for treatment of acute convulsive seizures and convulsive status epilepticus.Methods
Literature was searched according to Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines for RCTs examining treatment of acute convulsive seizures or status epilepticus with at least one of the study arms being a nonvenous medication. After demographic and outcome data extraction, a Bayesian network meta-analysis was performed and efficacy results were summarized using treatment effects and their credible intervals (CrI). We also calculated the probability of each route-drug combination being the most clinically effective for a given outcome, and provided their Bayesian hierarchical ranking.Results
This meta-analysis of 16 studies found that intramuscular midazolam (IM-MDZ) is superior to other nonvenous medications regarding time to seizure termination after administration (2.145 minutes, 95% CrI 1.308-3.489), time to seizure cessation after arrival in the hospital (3.841 minutes, 95% CrI 2.697-5.416), and time to initiate treatment (0.779 minutes, 95% CrI 0.495-1.221). Additionally, intranasal midazolam (IN-MDZ) was adjudged most efficacious for seizure cessation within 10 minutes of administration (90.4% of participants, 95% CrI 79.4%-96.9%), and persistent seizure cessation for ≥1 hour (78.5% of participants, 95% CrI 59.5%-92.1%). Paucity of RCTs produced evidence gaps resulting in small networks, routes/drugs included in some networks but not others, and some trials not being connected to any network.Conclusions
Despite the evidence gaps, IM-MDZ and IN-MDZ exhibit the best efficacy data for the nonvenous treatment of acute convulsive seizures or status epilepticus.
SUBMITTER: Arya R
PROVIDER: S-EPMC4662705 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundThere is little published evidence on how pack size impacts on health system costs. In the UK, children and adolescents aged 10 to < 18 years with prolonged acute convulsive seizures (PACS) occurring in the community setting are usually managed by the administration of buccal midazolam: Epistatus® or Buccolam®. These two preparations have markedly differing cost structures, being sold at different prices and presented as single units versus 4-packs, respectively. Consequently, the cost-per-PACS and overall budget impact of the two products cannot be simply inferred but is instead dependent on the likelihood of use. Also relevant to its likelihood of use is midazolam's status as a controlled substance under the Misuse of Drugs Act.Objective and methodsThe purpose of this economic analysis was to present the cost implications of single-unit versus multi-pack prescribing of a rescue medication based on likelihood of use. There is little published evidence to inform the likelihood of a midazolam dose being used once prescribed. A Delphi survey was conducted with physicians (n = 5), nurses (n = 11) and pharmacists (n = 24) from the community and hospital healthcare settings in the UK to explore the frequency distribution of prolonged seizures in the general epileptic population per 6-month period, along with common patterns of prescribing. This informed a model of the budgetary impact of single-unit (Epistatus®) versus 4-pack (Buccolam®) prescribing.ResultsRespondents cited both 'wastage' and 'dispensing more than is likely to be used of a controlled drug' as poor clinical practice, which suggests that prescribing in multiples of four should be reserved for patients who are likely to experience PACS at a higher frequency. The Delphi survey and subsequent regression analysis found that PACS frequency distribution follows an exponential drop, with over half (55%) of patients experiencing zero to one prolonged seizure(s) per 6-month period. Despite this, the majority (70%) of low PACS frequency patients are prescribed buccal midazolam in multiples of four by their treating physician. When looking at overall budgetary impact, the strategy of prescribing single-unit Epistatus® versus 4-pack Buccolam® is cost saving in low PACS frequency patients who do not require multiple units (referred to as spare loading), at - £15.33 per patient per 6 months. If spare loading is universally applied to all patients irrespective of seizure frequency, the mean incremental cost of single unit Epistatus® instead of 4-pack Buccolam® equates to £51.23 per patient per 6 months. If spare loading is reserved for higher PACS frequency patients (two or more per 6 months), the universal prescribing of single-unit Epistatus® versus 4-pack Buccolam® would result in a mean incremental cost of £17.82 per patient per 6 months.ConclusionsThe availability of single-unit Epistatus® allows for greater flexibility in prescribing. Physicians should attempt to categorise patients according to past PACS frequency with low PACS patients being prescribed single unit Epistatus® (with/without spare loading) and 4-pack Buccolam® reserved for patients in whom a high volume of usage is anticipated.
| S-EPMC7018870 | biostudies-literature
Project description: Not available
| S-EPMC10915785 | biostudies-literature
Project description:ObjectiveSeveral antiseizure medications (ASMs) have been approved for the treatment of focal epilepsy. However, there is a paucity of evidence on direct comparison of ASMs. We evaluated the comparative efficacy and safety of all approved add-on ASMs for the treatment of focal epilepsy using network meta-analysis.MethodsData through extensive literature search was retrieved from PubMed, Embase, Cochrane, and ClinicalTrial.gov databases using predefined search terms from inception through March 2023. PRISMA reporting guidelines (CRD42023403450) were followed in this study. Efficacy outcomes assessed were ≥50%, ≥75%, and 100% responder rates. Patient retention rate and safety outcomes such as overall treatment-emergent adverse events (TEAEs) and individual TEAEs were assessed. "Gemtc" 4.0.4 package was used to perform Bayesian analysis. Outcomes are reported as relative risks (RRs) and 95% confidence interval (CI).ResultsLiterature search retrieved 5807 studies of which, 75 studies were included in the analysis. All ASMs showed significantly higher ≥50% responder rate compared with placebo. Except the ≥75% seizure frequency reduction for zonisamide (2.23; 95% CI: 1.00-5.70) and 100% for rufinamide (2.03; 95% CI: 0.54-11.00), all other interventions showed significantly higher ≥75% and 100% responder rates compared with placebo. Among treatments, significantly higher 100% responder rate was observed with cenobamate compared to eslicarbazepine (10.71; 95% CI: 1.56-323.9) and zonisamide (10.63; 95% CI: 1.37-261.2). All ASMs showed a lower patient retention rate compared to placebo, with the least significant value observed for oxcarbazepine (0.77; 95% CI: 0.7-0.84). Levetiracetam showed a lower risk of incidence (1.0; 95%CI: 0.94-1.1; SUCRA: 0.885067) for overall TEAE compared with other medications.SignificanceAll approved ASMs were effective as add-on treatment for focal epilepsy. Of the ASMs included, cenobamate had the greatest likelihood of allowing patients to attain seizure freedom.Plain language summaryThis article compares the efficacy and safety of antiseizure medications (ASMs) currently available to neurologists in the treatment of epileptic patients. Several newer generation ASMs that have been developed may be as effective or better than the older medications. We included 75 studies in the analysis. In comparison, all drugs improved ≥50%, ≥75% and 100% responder rates compared to control, except for Zonisamide and Rufinamide in the ≥75% and 100% responder rate categories. Retention of patients undergoing treatment was lower in drugs than placebo. All drugs were tolerated, the levetiracetam showed the best tolerability. Cenobamate more likely help completely to reduce seizures.
| S-EPMC11296132 | biostudies-literature
Project description:Purpose: In this study, we intended to compare and rank the efficacy and acceptability of antiseizure medications (ASMs) for adjunctive treatment of children with drug-resistant focal-onset seizures. Method: We conducted a computerized search of PubMed, EMBASE, Cochrane Library, Web of Science, and Google Scholar to identify eligible randomized controlled trials (RCTs) published before 31 May 2022. We included studies evaluating the efficacy and tolerability of antiseizure medications for children with drug-resistant focal-onset seizures. The efficacy and safety were reported in terms of responder and dropout rate along with serious adverse events, the outcomes were ranked with the surface under the cumulative ranking curve (SUCRA). Results: A total of 14 studies (16 trials) with 2,464 patients were included, involving 10 active antiseizure medications. For the primary endpoint of at least 50% reduction in focal-onset seizures, the surface under the cumulative ranking curve ranking suggested that lamotrigine and levetiracetam were more effective as compared with other antiseizure medications; moreover, levetiracetam had the highest probability of rank first for achieving seizure freedom. Concerning tolerability, oxcarbazepine and eslicarbazepine acetate were associated with higher dropout rates relative to other antiseizure medications and placebo, and topiramate was associated with higher occurrence of side effects. No significant differences were found between active antiseizure medications concerning dropout for side effects. Conclusion: According to the surface under the cumulative ranking curve ranking, lamotrigine, levetiracetam, and oxcarbazepine were more efficacious than other active antiseizure medications in terms of responder rate. Concerning tolerability, oxcarbazepine was more likely to lead to dropout and topiramate was associated with higher occurrence of side effects.
| S-EPMC9800847 | biostudies-literature
Project description:BackgroundThe use of immune nutrients in the treatment of severe pancreatitis remains controversial. No study has yet compared the effects of different immune nutrients on patients with severe acute pancreatitis. This study aimed to compare the effects of different immune nutrients in treating severe acute pancreatitis through a network meta-analysis.MethodsPubMed, Embase, Cochrane Library, Web of Science, and Scopus were used to search randomized controlled trials from the inception to July 2023. Information was collected from patients with severe acute pancreatitis and their intervention methods, which included the administration of glutamine, omega-3 polyunsaturated fatty acids, arginine, and nucleotides. The evaluated outcomes included mortality, infection, the length of the hospital stay (LOH), the length of intensive care unit stay (LOI), and C-reactive protein (CRP). Risk ratio (95% confidence interval [CI]) and mean difference (MD) (95% CI) were calculated using a network meta-analysis random-effects model. The ranking between interventions was calculated using the surface under the cumulative ranking curve. The Cochrane Risk of Bias tool 2 was used to assess the risk of bias. The sources of heterogeneity were assessed using sensitivity analysis and network meta-regression. The credibility of the evidence was assessed using grading of recommendations assessment, development, and evaluation.ResultsNineteen studies with 1035 patients were included in this network meta-analysis. Parenteral glutamine was more effective in reducing mortality, infection, LOH, and LOI, as well as in the downregulation of CRP compared to the control. Risk ratio (95%CI) or MD (95%CI) were 0.38 (0.16, 0.90), 0.35 (0.14, 0.90), -3.32 (-4.90, -1.75), -2.53 (-4.46, -0.61), and -17.78 (-28.77, -6.78), respectively. Parenteral omega-3 polyunsaturated fatty acids was more effective in reducing LOH and LOI, as well as in the downregulation of CRP. MD (95%CI) were -6.77 (-11.40, -2.14), -5.19 (-7.80, -2.57), and -26.20 (-39.71, -12.68), respectively. Immune nutrients in the other groups did not exert any effect compared to the control regarding all the outcomes. Parenteral glutamine ranked best in reducing infections. Parenteral omega-3 polyunsaturated fatty acids ranked best in reducing mortality, LOH, and LOI, as well as in the downregulation of CRP.ConclusionSome immune nutrients were beneficial for patients with severe acute pancreatitis. Parenteral administration could be better than enteral administration.
| S-EPMC10615524 | biostudies-literature
Project description:Background: The mainstream medications for rheumatoid arthritis (RA) include conventional disease-modifying antirheumatic drugs (cDMARDs), which mostly are methotrexate (MTX), and biologic agents such as adalimumab (ADA), certolizumab (CZP), etanercept (ETN), golimumab (GOL), infliximab (IFX), and tocilizumab (TCZ). This network meta-analysis was aimed at evaluating the efficacy and safety of the medications above and interventions combining cDMARDs and biologic agents for patients with RA. Methods: PubMed, EMBASE, Cochrane Library, and ClinicalTrials.gov were searched systematically for eligible randomized controlled trials (RCTs). Outcomes concerning efficacy and safety were evaluated utilizing odds ratios (ORs) and 95% credible intervals (CrI). The outcomes of efficacy would be evaluated through remission and American College of Rheumatology (ACR) scores. The surface under the cumulative ranking curve (SUCRA) was calculated to rank each treatment on each index. Results: A total of 20 RCTs with 9,047 patients were included, and the efficacy and safety of the concerning interventions for RA were evaluated. Compared with cDMARDs alone, TCZ+MTX, ETN+MTX, IFX+MTX, TCZ, and ADA+MTX showed significant statistical advantage on ACR20, ACR50, and ACR70. Apart from that, as for remission, TCZ+MTX, IFX+MTX, TCZ, and CZP+MTX performed better compared to cDMARDs alone. The SUCRA ranking also indicated that TCZ+MTX was the intervention with best ranking in the entire four efficacy indexes followed by ETX+MTX and IFX+MTX. However, there was no obvious difference among these medications compared with cDMARDs when it comes to safety, which need more specific studies on that. Conclusion: TCZ+MTX was potentially the most recommended combination of medications for RA due to its good performance in all outcomes of efficacy. ETX+MTX and IFX+MTX, which also performed well, could be introduced as alternative treatments. However, considering the adverse events, the treatments concerning should be introduced with caution.
| S-EPMC5871709 | biostudies-literature
Project description:BackgroundCatecholamines, especially norepinephrine, are the most frequently used vasopressors for treating patients with septic shock. During the recent decades, terlipressin, vasopressin V1A agonist, and even Ca2+ sensitizer were increasingly used by physicians. The aim of this study is to compare the efficacy of such different kinds of vasoactive medications on mortality among patients with septic shock.MethodsRelevant randomized controlled trials were identified by searching PubMed, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials updated to February 22, 2018. A network meta-analysis was performed to evaluate the effect of different types of vasoactive medications. The primary outcome was 28-day mortality. Intensive care unit (ICU) mortality, hospital and ICU length of stay (LOS), and adverse events were also assessed.ResultsA total of 43 trials with 5767 patients assessing 17 treatment modalities were included. Treatments ranking based on surface under the cumulative ranking curve values from largest to smallest were NE/DB 85.9%, TP 75.1%, NE/EP 74.6%, PI 74.1%, EP 72.5%, VP 66.1%, NE 59.8%, PE 53.0%, DA 42.1%, DX 38.2%, SP 27.0%, PA 24.3%, EX 22.8%, LE 21.5%, and DB 13.3% for 28-day mortality. Treatments ranking for ICU mortality were TP/NE 86.4%, TP 80.3%, TP/DB/NE 65.7%, VP/NE 62.8%, NE 57.4%, VP 56.5%, PE 48.4%, DA 33.0%, PA 27.5%, LE 22.1%, and DB 9.9%. The incidence of myocardial infarction was reported with NE/EP 3.33% (n = 1 of 30), followed by EP 3.11% (n = 5 of 161), and then VP 3.10% (n = 19 of 613), NE 3.03% (n = 43 of 1417), DA 2.21% (n = 19 of 858), NE/DB 2.01% (n = 4 of 199), LE 1.16% (n = 3 of 258), and PA 0.39% (n = 1 of 257). The incidence of arrhythmia was reported with DA 26.01% (n = 258 of 992), followed by EP 22.98% (n = 37 of 161), and then NE/DB 20.60% (n = 41 of 199), NE/EP 20.0% (n = 6 of 30), NE 8.33% (n = 127 of 1525), LE 5.81% (n = 15 of 258), PA 2.33% (n = 6 of 257), and VP 1.67% (n = 10 of 600).ConclusionsThe use of norepinephrine plus dobutamine was associated with lower 28-day mortality for septic shock, especially among patients with lower cardiac output.
| S-EPMC6518735 | biostudies-literature
Project description:Background: A network meta-analysis (NMA) of the current recommended drugs for the treatment of acute heart failure (AHF), was performed to compare the relative efficacy. Methods: We used PubMed, EMBASE, Cochrane Clinical Trials Register, and Web of Science systems to search studies of randomized controlled trials (RCT) for the treatment of AHF recommended by the guidelines and expert consensus until 1 December 2020. The primary outcome was all-cause mortality within 30 days. The secondary outcomes included 30-days all-cause rehospitalization, rates of HF-related rehospitalization, rates of adverse events, and rates of serious adverse events. A Bayesian NMA based on random effects model was performed. Results: After screening 14,888 citations, 23 RCTs (17,097 patients) were included, focusing on nesiritide, placebo, serelaxin, rhANP, omecamtiv mecarbil, tezosentan, KW-3902, conivaptan, tolvaptan, TRV027, chlorothiazide, metolazone, ularitide, relaxin, and rolofylline. Omecamtiv mecarbil had significantly lower all-cause mortality rates than the placebo (odds ratio 0.04, 0.01–0.22), rhANP (odds ratio 0.03, 0–0.40), serelaxin (odds ratio 0.05, 0.01–0.38), tezosentan (odds ratio 0.04, 0–0.22), tolvaptan (odds ratio 0.04, 0.01–0.30), and TRV027 (odds ratio 0.03, 0–0.36). No drug was superior to the other drugs for the secondary outcomes and safety outcomes. Conclusion: No drug was superior to the other drugs for the secondary outcomes and safety outcomes. Current drugs for AHF show similar efficacy and safety.
| S-EPMC9537610 | biostudies-literature
Project description:BackgroundWhile clinical trial evidence has firmly established the efficacy of several atypical antipsychotics (AAPs) for treating bipolar depression, no randomized controlled trials (RCT's) comparing AAPs have been conducted. This Bayesian network meta-analysis (NMA) compared the relative efficacy and tolerability of AAP monotherapy in adults with bipolar depression.MethodsEfficacy measures included change in Montgomery Åsberg Depression Rating Scale (MADRS), Clinical Global Improvement - Bipolar Disorder (CGI-BP), response, and remission. Multiple tolerability outcomes were examined. Results from random effects models were reported as difference in change from baseline for continuous variables or odds ratios for dichotomous variables. Treatments were ranked using the surface under the curve cumulative ranking probabilities. Number needed to treat (NNT) and harm (NNH) were calculated.ResultsEighteen RCT's met inclusion criteria of the systematic literature review. On change in MADRS, lurasidone (- 4.71 [95% Crl - 6.98, - 2.41]), quetiapine (- 4.80 [- 5.93, - 3.72]), olanzapine (- 4.57 [- 5.92, - 3.20]), and cariprazine (- 2.29 [- 3.47, - 1.09]) were more efficacious than placebo. Lurasidone was associated with a significantly greater odds of response (≥50% improvement in MADRS) compared to cariprazine (1.78 [95% Crl 1.08, 2.77]), aripiprazole (2.38 [1.38, 3.85]), and ziprasidone (2.47 [1.41, 3.98]), but was similar to olanzapine (1.68 [0.99,2.65]) and quetiapine (1.25 [0.78, 1.90]). For change in CGI-BP-S-overall score, lurasidone was significantly better than cariprazine (- 0.38 [95% Crl - 0.66,-0.10]) and ziprasidone (- 0.58 [- 0.91,-0.26]), but similar to quetiapine (- 0.08 [- 0.36, 0.19])and olanzapine (- 0.04 [- 1.41, 1.46]). Lurasidone (0.34 kg [95% Crl - 0.22, 0.89]) and aripiprazole (0.20 kg [- 0.59, 1.00]) had a similar weight change compared to placebo, but olanzapine (2.88 kg [2.40, 3.36]), quetiapine (1.17 kg [0.84, 1.49]), and cariprazine (0.65 kg [0.34, 0.96]) were associated with greater weight gain. The NNT for response was the lowest for lurasidone (NNT = 5) followed by quetiapine (NNT = 6), olanzapine (NNT = 10) and cariprazine (NNT = 12).ConclusionsIn this NMA in adults with bipolar depression, which evaluated change in depressive symptoms (assessed by MADRS) across short-term trials, the largest improvement versus placebo was observed for lurasidone, olanzapine and quetiapine with cariprazine, showing a smaller treatment effect. Aripiprazole and ziprasidone were ineffective for the treatment of bipolar depression. Improvement in CGI-BP-S score for lurasidone was larger than cariprazine and ziprasidone but similar to quetiapine and olanzapine. Based on short term studies lurasidone and aripiprazole had similar weight gain compared to placebo.
| S-EPMC8112003 | biostudies-literature
Project description:BackgroundConventional meta-analyses and randomized controlled trials have shown inconsistent results regarding the efficacy of immunosuppressants for pediatric steroid-resistant nephrotic syndrome (SRNS).ObjectiveTo conduct a network meta-analysis aimed at evaluating the efficacy and safety of available immunosuppressive agents in pediatric patients with SRNS.Study methodsMEDLINE, the Cochrane Central Register of Controlled Trials, and EMBASE were searched on January 2017. Data from randomized controlled trials (RCTs) were included. The main outcomes analyzed were efficacy [number/portion with complete remission (CR), number/portion with partial remission (PR), and total number/portion in remission (TR)] and safety [adverse secondary event (ASE) rates].ResultsA meta-analysis of 18 RCTs showed that tacrolimus was more efficacious for achieving CR than intravenous (i.v.) cyclophosphamide, mycophenolate mofetil (MMF), oral cyclophosphamide, leflunomide, chlorambucil, azathioprine, and plaebo/nontreatment (P/NT), and more efficacious than i.v. cyclophosphamide, oral cyclophosphamide, and P/NT in terms of TR outcomes. Cyclosporin was associated with a greater CR rate than i.v. cyclophosphamide, MMF, oral cyclophosphamide, chlorambucil, azathioprine, or P/NT, and associated with a greater TR rate than i.v. cyclophosphamide, oral cyclophosphamide, or P/NT. MMF was found to be more efficacious than i.v. cyclophosphamide and oral cyclophosphamide in terms of TR.ConclusionsTacrolimus and cyclosporine may be preferred initial treatments for children with SRNS. MMF may be another option for this patient population. Further studies of the efficacy and safety of these three drugs in children with SRNS should be pursued.
| S-EPMC5641191 | biostudies-literature