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PM & R : the Journal of Injury,... Apr 2024The purpose of this systematic review was to ascertain guideline-recommended pharmaceutical approaches to lumbosacral radicular symptoms, assess the quality of the... (Review)
Review
OBJECTIVE
The purpose of this systematic review was to ascertain guideline-recommended pharmaceutical approaches to lumbosacral radicular symptoms, assess the quality of the clinical practice guidelines (CPGs) with the Appraisal of Guidelines for Research and Evaluation II (AGREE II) tool, and qualitatively synthesize the guideline recommendations.
LITERATURE SURVEY
Literature searches were performed in PubMed, Cochrane Database of Systematic Reviews, Index to Chiropractic Literature, Allied and Complementary Medicine Database (AMED), Cumulative Index for Nursing and Allied Health Literature (CINAHL), and Physiotherapy Evidence Database (PEDro). We included guidelines published between January 1, 2017, and January 9, 2022, written in the English language, related to radiculopathy, sciatica, and/or low back pain with leg pain, and that provided recommendations on oral medication.
METHODOLOGY
The review was performed in accordance with Preferred Reporting Items for Systemic Reviews and Meta-Analyses (PRISMA) and the protocol was pre-registered with the International Prospective Register of Systematic Reviews (PROSPERO). Eligibility screening, full-text review, extraction of information pertaining to pharmacological management, and synthesis of results were performed independently by two authors and a third investigator was recruited to arbitrate any disagreements. The AGREE II tool was administered by four authors to appraise CPG quality.
SYNTHESIS
After screening 413 citations and assessing 37 full-text articles, 11 CPGs met the inclusion criteria. They represented seven countries (Belgium, Canada, England, France, Japan, Korea, and United States) and three continents (Asia, Europe, and North America), as well as the Global Spine Care Initiative aimed at a worldwide presence. The mean overall AGREE II score was 87.1% (standard deviation [SD] 12.6%), generally reflecting high-quality CPGs. The highest domain mean score was for Clarity of Presentation (96.7%, SD 4.4%), and the lowest was Applicability (75.6%, SD 22.8%). Five classes of medications were recommended by at least one CPG: anticonvulsants, antidepressants, oral corticosteroids, nonsteroidal anti-inflammatory drugs (NSAIDs), and opioids.
CONCLUSIONS
The most common medication class recommended by the CPGs for lumbar radiculopathy was antidepressants. No CPGs recommended prescribing acetaminophen, benzodiazepines, muscle relaxants, or antibiotics. There was very little agreement between the CPGs, and all the medication classes had at least one CPG recommended against its use. Three guidelines reviewed did not recommend any medications due to lack of supporting literature, and instead recommended nonpharmacologic therapy.
PubMed: 38629664
DOI: 10.1002/pmrj.13142 -
Expert Opinion on Drug Metabolism &... May 2024Antiseizure medication (ASM) add-on to clozapine may be efficient to target clozapine-resistant mood or psychotic symptoms or clozapine-related adverse drug reactions...
INTRODUCTION
Antiseizure medication (ASM) add-on to clozapine may be efficient to target clozapine-resistant mood or psychotic symptoms or clozapine-related adverse drug reactions (ADR) such as seizures. We aimed to synthesize the information relevant for clinical practice on the risks and benefits of clozapine-ASM co-prescription.
AREAS COVERED
Articles were identified with MEDLINE, Web of Sciences and PsycINFO search from inception through October 2023. The review was restricted to ASM with mood-stabilizing properties or with potential efficacy for resistant psychotic symptoms (valproate (VPA), lamotrigine, topiramate, carbamazepine, oxcarbazepine).
EXPERT OPINION
VPA add-on to clozapine is associated with a high risk of serious ADR (myocarditis, neutropenia, pneumonia) mostly explained by complex time-dependent drug-drug interactions. The initial inhibitory effects on clozapine metabolism require slow titration to avoid immuno-allergic reactions. After the titration period, VPA has mainly inductive effects on clozapine metabolism that are more marked in smokers requiring therapeutic drug monitoring. Lamotrigine and topiramate add-on may be recommended as the first-line treatment for clozapine-related seizures, but there is limited evidence regarding the efficacy of this strategy for clozapine-resistant psychotic symptoms. Carbamazepine should not be co-prescribed with clozapine because of its potential for agranulocytosis and for inducing clozapine metabolism.
Topics: Humans; Anticonvulsants; Antipsychotic Agents; Clozapine; Drug Interactions; Drug Monitoring; Drug Therapy, Combination; Psychotic Disorders; Seizures
PubMed: 38613254
DOI: 10.1080/17425255.2024.2343020 -
Clinical practice guidelines on the management of status epilepticus in adults: A systematic review.Epilepsia Jun 2024Status epilepticus (SE) is the second most common neurological emergency in adults. Despite improvements in the management of acute neurological conditions over the last... (Review)
Review
OBJECTIVE
Status epilepticus (SE) is the second most common neurological emergency in adults. Despite improvements in the management of acute neurological conditions over the last decade, mortality is still durably high. Because a gap has emerged between SE management based on clinical practice guidelines (CPGs) and actual clinical practice, we conducted a systematic review of CPGs, assessing their quality, outlining commonalities and discrepancies in recommendations, and highlighting research gaps.
METHODS
We searched the PubMed and EMBASE databases and other gray literature sources (nine among guideline registries, evidence-based medicine databases, point-of-care tools; seven websites of governmental organizations and international neurologic societies) in December 2021 (updated in November 2023). The units of analysis were CPGs that included recommendations on the diagnostic and/or therapeutic management of SE in adults. The quality of the CPGs was assessed using the AGREE II tool.
RESULTS
Fifteen CPGs were included. The "Applicability" domain was assigned the lowest median score of 10%. The domains "Stakeholder Involvement", "Rigor of Development," and "Editorial Independence" were as well generally underrated. Recommendations on general and diagnostic management and on organizational interventions were fragmented and scattered. Recommendations on pre-hospital and hospital treatment of early-onset and refractory SE were broadly agreed, whereas there was less agreement on the treatment model and medications for established SE and super-refractory SE.
SIGNIFICANCE
The CPGs for the management of SE developed in recent years are flawed by several methodological issues and discrepancies in the coverage of important topics. The gap between CPG-based management of SE and actual clinical practice may be due in part to the inherent limitations of the CPGs produced so far.
Topics: Humans; Status Epilepticus; Practice Guidelines as Topic; Adult; Anticonvulsants; Disease Management
PubMed: 38606469
DOI: 10.1111/epi.17982 -
Expert Opinion on Pharmacotherapy Apr 2024Ganaxolone has exhibited potential in managing seizures for epilepsy. This systematic review and meta-analysis aim to assess both the safety and efficacy of Ganaxolone... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Ganaxolone has exhibited potential in managing seizures for epilepsy. This systematic review and meta-analysis aim to assess both the safety and efficacy of Ganaxolone for refractory epilepsy.
METHODS
A thorough search of electronic databases was conducted to identify relevant randomized controlled trials involving patients with drug-resistant focal epilepsy and CDKL5 deficiency disorder. Efficacy and safety outcomes were extracted from the selected studies. Cochrane Review Manager was utilized for data synthesis and analysis, with risk ratios and mean differences calculated to evaluate the efficacy and safety profile of Ganaxolone.
RESULTS
The meta-analysis included a total of five randomized controlled trials. Ganaxolone exhibited significant efficacy in reducing seizure frequency by at least 50% from baseline [RR 0.90 (95% CI: 0.83, 0.98), = 0.02]. However, the results did not reach significance for reducing 28-day seizure frequency [Mean Difference -1.45 (95% CI: -3.39, 0.49), = 0.14]. Ganaxolone exhibited a positive safety profile, with no statistically significant occurrence of adverse events [RR 1.30 (95% CI: 0.93, 1.83), = 0.12] and adverse events leading to discontinuation of the study drug [RR 1.01 (95% CI: 0.42, 2.39), = 0.99] compared to placebo.
CONCLUSION
Ganaxolone presents itself as a viable therapeutic option for refractory epilepsy, showing efficacy in reducing seizure frequency and exhibited a favorable safety profile.
PROSPERO REGISTRATION NUMBER
CRD42023434883.
Topics: Humans; Anticonvulsants; Randomized Controlled Trials as Topic; Drug Resistant Epilepsy; Pregnanolone; Epilepsy; Treatment Outcome
PubMed: 38606458
DOI: 10.1080/14656566.2024.2342413 -
Epilepsy Research May 2024Nonadherence to antiepileptic drugs (AEDs) is a prevalent issue in India, contributing to suboptimal seizure control, higher morbidity and mortality, increased... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Nonadherence to antiepileptic drugs (AEDs) is a prevalent issue in India, contributing to suboptimal seizure control, higher morbidity and mortality, increased hospitalization rates, and a substantial effect on the overall quality of life for individuals with epilepsy.
OBJECTIVES
This study aimed to measure the prevalence of medication adherence among individuals with epilepsy in India and to identify factors associated with nonadherence.
METHODS
Following PRISMA guidelines, we searched PubMed, Scopus, Embase, and Google Scholar for studies on AED adherence in India. Quality assessment employed Newcastle Ottawa Scale adapted for cross-sectional studies. Pooled prevalence was ascertained using a random-effects model in R software (version 4.2.2), with a 95% confidence interval. Heterogeneity was estimated with the I statistic, and publication bias was appraised via a funnel plot. Subgroup analyses, based on study region and adherence measurement tool, were done to investigate heterogeneity.
RESULTS
Nine cross-sectional studies with 1772 participants were analyzed. The pooled prevalence of adherence to AEDs in India stood at 49.9% (95% CI: 39.8%-60.1%). Subgroup analyses showed comparable adherence rates in the South (50.9%) and North (46.5%) regions of India. However, adherence rates varied substantially based on the measurement tool: Morisky Medication Adherence Scale-4 (MMAS-4) reported 71.3%, MMAS-8 indicated 45.9%, and Morisky Green Levine (MGL) adherence scale exhibited 42.0%. Factors contributing to non-adherence to antiepileptic therapies involved poor socioeconomic status, lower education levels, polytherapy, drug-related side effects, and substance abuse.
CONCLUSIONS
Almost half of persons with epilepsy in India were non-adherent to their AEDs. This underscores the importance for healthcare professionals to pay greater attention to improving the adherence rate to AEDs within the healthcare service.
Topics: Humans; Anticonvulsants; Epilepsy; India; Medication Adherence; Cross-Sectional Studies
PubMed: 38603915
DOI: 10.1016/j.eplepsyres.2024.107358 -
PloS One 2024Juvenile Myoclonic Epilepsy (JME) is a prevalent form of epileptic disorder, specifically categorized within the realm of Genetic Generalized Epilepsy (GGE). Its... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Juvenile Myoclonic Epilepsy (JME) is a prevalent form of epileptic disorder, specifically categorized within the realm of Genetic Generalized Epilepsy (GGE). Its hallmark features encompass unprovoked bilateral myoclonus and tonic-clonic seizures that manifest during adolescence. While most JME patients respond favorably to anti-seizure medication (ASM), a subset experiences refractory JME, a condition where seizures persist despite rigorous ASM treatment, often termed "Drug-Resistant Epilepsy" (DRE). This systematic review and meta-analysis aims to determine the prevalence of refractory JME, and further to identify socio-demographic, electrophysiological and clinical risk factors associated with its occurrence. Pinpointing these factors is crucial as it offers the potential to predict ASM responsiveness, enabling early interventions and tailored care strategies for patients.
MATERIAL AND METHODS
The systematic review and meta-analysis followed the Cochrane Handbook and adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The study evaluated outcomes post ASM treatment in JME cohorts by searching papers published up to September 2023 in PubMed/MEDLINE, Scopus, and Google Scholar databases. Predefined inclusion criteria were met by 25 eligible studies, forming the basis for analysis.
RESULTS
A total of 22 potential risk factors for refractory JME were documented. Notably, robust risk factors for treatment resistance included Psychiatric Disorder (Odds Ratio (OR), 3.42 [2.54, 4.61] (95% Confidence Inverval (Cl)), Febrile Seizures (OR, 1.83 [1.14, 2.96] (95% Cl)), Alcohol Consumption (OR, 16.86 [1.94, 146.88] (95%Cl)), Aura (OR, 2.15 [1.04, 4.47] (95%Cl)), childhood absence epilepsy (CAE) evolving into JME (OR, 4.54 [1.61, 12.78] (95%CI)), occurrence of three seizure types (OR, 2.96 [1.96, 4.46] (95%CI)), and Focal EEG abnormalities (OR, 1.85 [1.13, 3.01] (95%Cl)). In addition, there were some non-significant risk factors for DRE because of noticeable heterogeneity.
CONCLUSION
In aggregate, over 36% of JME patients demonstrated drug resistance, with seven significant risk factors closely linked to this refractoriness. The interplay between these factors and whether they denote treatment non-response or heightened disease burden remains an open question and more studies would be required to fully examine their influence.
Topics: Adolescent; Humans; Child; Myoclonic Epilepsy, Juvenile; Epilepsy, Absence; Seizures; Drug Resistant Epilepsy; Risk Factors; Electroencephalography; Anticonvulsants
PubMed: 38593118
DOI: 10.1371/journal.pone.0300930 -
JAMA Neurology May 2024Guidelines recommend seizure prophylaxis for early posttraumatic seizures (PTS) after severe traumatic brain injury (TBI). Use of antiseizure medications for early... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Guidelines recommend seizure prophylaxis for early posttraumatic seizures (PTS) after severe traumatic brain injury (TBI). Use of antiseizure medications for early seizure prophylaxis after mild or moderate TBI remains controversial.
OBJECTIVE
To determine the association between seizure prophylaxis and risk reduction for early PTS in mild and moderate TBI.
DATA SOURCES
PubMed, Google Scholar, and Web of Science (January 1, 1991, to April 18, 2023) were systematically searched.
STUDY SELECTION
Observational studies of adult patients presenting to trauma centers in high-income countries with mild (Glasgow Coma Scale [GCS], 13-15) and moderate (GCS, 9-12) TBI comparing rates of early PTS among patients with seizure prophylaxis with those without seizure prophylaxis.
DATA EXTRACTION AND SYNTHESIS
The Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) reporting guidelines were used. Two authors independently reviewed all titles and abstracts, and 3 authors reviewed final studies for inclusion. A meta-analysis was performed using a random-effects model with absolute risk reduction.
MAIN OUTCOME MEASURES
The main outcome was absolute risk reduction of early PTS, defined as seizures within 7 days of initial injury, in patients with mild or moderate TBI receiving seizure prophylaxis in the first week after injury. A secondary analysis was performed in patients with only mild TBI.
RESULTS
A total of 64 full articles were reviewed after screening; 8 studies (including 5637 patients) were included for the mild and moderate TBI analysis, and 5 studies (including 3803 patients) were included for the mild TBI analysis. The absolute risk reduction of seizure prophylaxis for early PTS in mild to moderate TBI (GCS, 9-15) was 0.6% (95% CI, 0.1%-1.2%; P = .02). The absolute risk reduction for mild TBI alone was similar 0.6% (95% CI, 0.01%-1.2%; P = .04). The number needed to treat to prevent 1 seizure was 167 patients.
CONCLUSION AND RELEVANCE
Seizure prophylaxis after mild and moderate TBI was associated with a small but statistically significant reduced risk of early posttraumatic seizures after mild and moderate TBI. The small absolute risk reduction and low prevalence of early seizures should be weighed against potential acute risks of antiseizure medications as well as the risk of inappropriate continuation beyond 7 days.
Topics: Humans; Brain Injuries, Traumatic; Anticonvulsants; Seizures
PubMed: 38587858
DOI: 10.1001/jamaneurol.2024.0689 -
Lancet (London, England) Apr 2024Pharmacotherapy provides an option for adults with overweight and obesity to reduce their bodyweight if lifestyle modifications fail. We summarised the latest evidence... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Pharmacotherapy provides an option for adults with overweight and obesity to reduce their bodyweight if lifestyle modifications fail. We summarised the latest evidence for the benefits and harms of weight-lowering drugs.
METHODS
This systematic review and network meta-analysis included searches of PubMed, Embase, and Cochrane Library (CENTRAL) from inception to March 23, 2021, for randomised controlled trials of weight-lowering drugs in adults with overweight and obesity. We performed frequentist random-effect network meta-analyses to summarise the evidence and applied the Grading of Recommendations Assessment, Development, and Evaluation frameworks to rate the certainty of evidence, calculate the absolute effects, categorise interventions, and present the findings. The study was registered with PROSPERO, CRD 42021245678.
FINDINGS
14 605 citations were identified by our search, of which 132 eligible trials enrolled 48 209 participants. All drugs lowered bodyweight compared with lifestyle modification alone; all subsequent numbers refer to comparisons with lifestyle modification. High to moderate certainty evidence established phentermine-topiramate as the most effective in lowering weight (odds ratio [OR] of ≥5% weight reduction 8·02, 95% CI 5·24 to 12·27; mean difference [MD] of percentage bodyweight change -7·98, 95% CI -9·27 to -6·69) followed by GLP-1 receptor agonists (OR 6·33, 95% CI 5·00 to 8·00; MD -5·79, 95% CI -6·34 to -5·25). Naltrexone-bupropion (OR 2·69, 95% CI 2·10 to 3·44), phentermine-topiramate (2·40, 1·68 to 3·44), GLP-1 receptor agonists (2·22, 1·74 to 2·84), and orlistat (1·71, 1·42 to 2·05) were associated with increased adverse events leading to drug discontinuation. In a post-hoc analysis, semaglutide, a GLP-1 receptor agonist, showed substantially larger benefits than other drugs with a similar risk of adverse events as other drugs for both likelihood of weight loss of 5% or more (OR 9·82, 95% CI 7·09 to 13·61) and percentage bodyweight change (MD -11·40, 95% CI -12·51 to -10·29).
INTERPRETATION
In adults with overweight and obesity, phentermine-topiramate and GLP-1 receptor agonists proved the best drugs in reducing weight; of the GLP-1 agonists, semaglutide might be the most effective.
FUNDING
1.3.5 Project for Disciplines of Excellence, West China Hospital, Sichuan University.
Topics: Adult; Humans; Overweight; Network Meta-Analysis; Topiramate; Obesity; Weight Loss; Phentermine; Randomized Controlled Trials as Topic
PubMed: 38582569
DOI: 10.1016/S0140-6736(24)00351-9 -
Lupus Jun 2024Drug-induced lupus erythematosus (DILE) is the development of lupus-like syndrome following a drug exposure. DILE has been reported less frequently among children than... (Review)
Review
BACKGROUND
Drug-induced lupus erythematosus (DILE) is the development of lupus-like syndrome following a drug exposure. DILE has been reported less frequently among children than adults.
METHODS
In this study, we present four children with DILE and similar published cases through a systematic literature review.
RESULTS
We report four children (three girls and one boy) who developed DILE associated with the use of topiramate, doxycycline, etanercept, and ethosuximide. Three of them were positive for anti-histone antibodies. In all patients, the drug was discontinued and symptoms resolved completely. The literature review revealed 48 articles describing 61 children with DILE. In the evaluation of 65 patients (our 4 patients and 61 patients from the literature), the most frequently reported drugs associated with DILE were ethosuximide ( = 13) and minocycline ( = 12). Fever ( = 33), arthralgia ( = 31), rash ( = 30), and arthritis ( = 29) were the most common clinical manifestations. Antinuclear antibody (ANA) was positive in 93.5% of patients and anti-histone antibodies were detected in 72.2% of the patients. As for treatment, the responsible drug was discontinued in all patients, and corticosteroids were initiated in 53.3%. Improvement was achieved in 92.0% of patients.
CONCLUSION
For children presenting with SLE features, proper drug history is crucial since DILE may be more frequent than anticipated. An association of the relevant drug with the symptoms, and resolution of symptoms on drug withdrawal provides evidence for the diagnosis of DILE.
Topics: Humans; Female; Male; Child; Lupus Erythematosus, Systemic; Topiramate; Doxycycline; Ethosuximide; Adolescent; Etanercept; Minocycline; Antibodies, Antinuclear; Child, Preschool
PubMed: 38580326
DOI: 10.1177/09612033241245078 -
Cureus Mar 2024Mental health problems among children and adolescents are a significant global public health concern, with a prevalence of approximately 10-20%. Psychotropic... (Review)
Review
Mental health problems among children and adolescents are a significant global public health concern, with a prevalence of approximately 10-20%. Psychotropic medications, including stimulants, antipsychotics, antidepressants, and mood stabilizers, have been proven effective in treating various psychiatric disorders among children and adolescents. Despite the common use of these medications, they have various side effects and complications. This systematic review aimed to assess the trends and prevalence of psychotropic medication use among children and adolescents from 2013 to 2023. A comprehensive literature search was conducted in PubMed, Web of Science, Ovid, Scopus, and Cochrane databases using relevant keywords. Two independent researchers screened the studies for inclusion and exclusion criteria. Data were extracted using a Microsoft Excel spreadsheet (Microsoft Corporation, Redmond, WA), including information on study characteristics, participant demographics, psychiatric disorders, and psychotropic medications. The risk of bias assessment was performed using the ROBINS-I (Risk of Bias in Non-randomized Studies of Interventions) tool for non-randomized studies of interventions (NRSI) and Risk of Bias 2 (ROB2) for the randomized clinical trial. Data synthesis was conducted through a qualitative interpretation of the findings. A total of 52 papers were identified through the search, with 37 remaining after duplicate removal. After applying the inclusion and exclusion criteria, nine articles were considered suitable for the systematic review. A total of 9,034,109 patients suffered from several psychiatric diseases, such as autism, major depressive disorder, Down syndrome, attention-deficit/hyperactivity disorder, adjustment disorder, anxiety, bipolar disorder, conduct disorder, depression, personality disorder, psychotic disorder, tic disorder, pervasive developmental disorder, and disruptive behavior disorder. Stimulants showed a consistent prevalence rate over the years. Antidepressants, including selective serotonin reuptake inhibitors, have demonstrated variations over the years, with a substantial increase in 2015, followed by a decrease in subsequent years. In addition, antipsychotics, including atypical antipsychotics, have varied over the years; however, their use increased in 2023. Anticonvulsants and anxiolytics were also utilized, albeit at lower prevalence rates. This systematic review provides an overview of the trends and prevalence of psychotropic medication use among children and adolescents from 2013 to 2023. The prevalence of antipsychotic prescribing has shown fluctuations among different countries over the years, with a decline in recent years but a slight increase in 2023. Further research is warranted to explore the factors influencing these trends and to assess the long-term effectiveness and safety of psychotropic medications in children and adolescents.
PubMed: 38571846
DOI: 10.7759/cureus.55452