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BMC Complementary Medicine and Therapies Jun 2021Elevated lipid profiles and impaired glucose homeostasis are risk factors for several cardiovascular diseases (CVDs), which, subsequently, represent a leading cause of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Elevated lipid profiles and impaired glucose homeostasis are risk factors for several cardiovascular diseases (CVDs), which, subsequently, represent a leading cause of early mortality, worldwide. The aim of the current study was to conduct a systematic review and meta-analysis of the effect of apple cider vinegar (ACV) on lipid profiles and glycemic parameters in adults.
METHODS
A systematic search was conducted in electronic databases, including Medline, Scopus, Cochrane Library, and Web of Knowledge, from database inception to January 2020. All clinical trials which investigated the effect of ACV on lipid profiles and glycemic indicators were included. Studies were excluded if ACV was used in combination with other interventions or when the duration of intervention was < 2 weeks. To account for between-study heterogeneity, we performed meta-analysis using a random-effects model.
RESULTS
Overall, nine studies, including 10 study arms, were included in this meta-analysis. We found that ACV consumption significantly decreased serum total cholesterol (- 6.06 mg/dL; 95% CI: - 10.95, - 1.17; I: 39%), fasting plasma glucose (- 7.97 mg/dL; 95% CI: - 13.74, - 2.21; I: 75%), and HbA1C concentrations (- 0.50; 95% CI: - 0.90, - 0.09; I: 91%). No significant effect of ACV consumption was found on serum LDL-C, HDL-C, fasting insulin concentrations, or HOMA-IR. The stratified analysis revealed a significant reduction of serum TC and TG in a subgroup of patients with type 2 diabetes, those who took ≤15 mL/day of ACV, and those who consumed ACV for > 8-weeks, respectively. Furthermore, ACV consumption significantly decreased FPG levels in a subgroup of studies that administered ACV for > 8-weeks. Further, ACV intake appeared to elicit an increase in FPG and HDL-C concentrations in apparently healthy participants.
CONCLUSION
We found a significant favorable effect of ACV consumption on FPG and blood lipid levels.
Topics: Acetic Acid; Blood Glucose; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Insulin; Malus; Randomized Controlled Trials as Topic
PubMed: 34187442
DOI: 10.1186/s12906-021-03351-w -
The Cochrane Database of Systematic... May 2020Acne is an inflammatory disorder with a high global burden. It is common in adolescents and primarily affects sebaceous gland-rich areas. The clinical benefit of the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Acne is an inflammatory disorder with a high global burden. It is common in adolescents and primarily affects sebaceous gland-rich areas. The clinical benefit of the topical acne treatments azelaic acid, salicylic acid, nicotinamide, sulphur, zinc, and alpha-hydroxy acid is unclear.
OBJECTIVES
To assess the effects of topical treatments (azelaic acid, salicylic acid, nicotinamide, zinc, alpha-hydroxy acid, and sulphur) for acne.
SEARCH METHODS
We searched the following databases up to May 2019: the Cochrane Skin Group Specialised Register, CENTRAL, MEDLINE, Embase, and LILACS. We also searched five trials registers.
SELECTION CRITERIA
Clinical randomised controlled trials of the six topical treatments compared with other topical treatments, placebo, or no treatment in people with acne.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane. Key outcomes included participants' global self-assessment of acne improvement (PGA), withdrawal for any reason, minor adverse events (assessed as total number of participants who experienced at least one minor adverse event), and quality of life.
MAIN RESULTS
We included 49 trials (3880 reported participants) set in clinics, hospitals, research centres, and university settings in Europe, Asia, and the USA. The vast majority of participants had mild to moderate acne, were aged between 12 to 30 years (range: 10 to 45 years), and were female. Treatment lasted over eight weeks in 59% of the studies. Study duration ranged from three months to three years. We assessed 26 studies as being at high risk of bias in at least one domain, but most domains were at low or unclear risk of bias. We grouped outcome assessment into short-term (less than or equal to 4 weeks), medium-term (from 5 to 8 weeks), and long-term treatment (more than 8 weeks). The following results were measured at the end of treatment, which was mainly long-term for the PGA outcome and mixed length (medium-term mainly) for minor adverse events. Azelaic acid In terms of treatment response (PGA), azelaic acid is probably less effective than benzoyl peroxide (risk ratio (RR) 0.82, 95% confidence interval (CI) 0.72 to 0.95; 1 study, 351 participants), but there is probably little or no difference when comparing azelaic acid to tretinoin (RR 0.94, 95% CI 0.78 to 1.14; 1 study, 289 participants) (both moderate-quality evidence). There may be little or no difference in PGA when comparing azelaic acid to clindamycin (RR 1.13, 95% CI 0.92 to 1.38; 1 study, 229 participants; low-quality evidence), but we are uncertain whether there is a difference between azelaic acid and adapalene (1 study, 55 participants; very low-quality evidence). Low-quality evidence indicates there may be no differences in rates of withdrawal for any reason when comparing azelaic acid with benzoyl peroxide (RR 0.88, 95% CI 0.60 to 1.29; 1 study, 351 participants), clindamycin (RR 1.30, 95% CI 0.48 to 3.56; 2 studies, 329 participants), or tretinoin (RR 0.66, 95% CI 0.29 to 1.47; 2 studies, 309 participants), but we are uncertain whether there is a difference between azelaic acid and adapalene (1 study, 55 participants; very low-quality evidence). In terms of total minor adverse events, we are uncertain if there is a difference between azelaic acid compared to adapalene (1 study; 55 participants) or benzoyl peroxide (1 study, 30 participants) (both very low-quality evidence). There may be no difference when comparing azelaic acid to clindamycin (RR 1.50, 95% CI 0.67 to 3.35; 1 study, 100 participants; low-quality evidence). Total minor adverse events were not reported in the comparison of azelaic acid versus tretinoin, but individual application site reactions were reported, such as scaling. Salicylic acid For PGA, there may be little or no difference between salicylic acid and tretinoin (RR 1.00, 95% CI 0.92 to 1.09; 1 study, 46 participants; low-quality evidence); we are not certain whether there is a difference between salicylic acid and pyruvic acid (1 study, 86 participants; very low-quality evidence); and PGA was not measured in the comparison of salicylic acid versus benzoyl peroxide. There may be no difference between groups in withdrawals when comparing salicylic acid and pyruvic acid (RR 0.89, 95% CI 0.53 to 1.50; 1 study, 86 participants); when salicylic acid was compared to tretinoin, neither group had withdrawals (both based on low-quality evidence (2 studies, 74 participants)). We are uncertain whether there is a difference in withdrawals between salicylic acid and benzoyl peroxide (1 study, 41 participants; very low-quality evidence). For total minor adverse events, we are uncertain if there is any difference between salicylic acid and benzoyl peroxide (1 study, 41 participants) or tretinoin (2 studies, 74 participants) (both very low-quality evidence). This outcome was not reported for salicylic acid versus pyruvic acid, but individual application site reactions were reported, such as scaling and redness. Nicotinamide Four studies evaluated nicotinamide against clindamycin or erythromycin, but none measured PGA. Low-quality evidence showed there may be no difference in withdrawals between nicotinamide and clindamycin (RR 1.12, 95% CI 0.49 to 2.60; 3 studies, 216 participants) or erythromycin (RR 1.40, 95% CI 0.46 to 4.22; 1 study, 158 participants), or in total minor adverse events between nicotinamide and clindamycin (RR 1.20, 95% CI 0.73 to 1.99; 3 studies, 216 participants; low-quality evidence). Total minor adverse events were not reported in the nicotinamide versus erythromycin comparison. Alpha-hydroxy (fruit) acid There may be no difference in PGA when comparing glycolic acid peel to salicylic-mandelic acid peel (RR 1.06, 95% CI 0.88 to 1.26; 1 study, 40 participants; low-quality evidence), and we are uncertain if there is a difference in total minor adverse events due to very low-quality evidence (1 study, 44 participants). Neither group had withdrawals (2 studies, 84 participants; low-quality evidence).
AUTHORS' CONCLUSIONS
Compared to benzoyl peroxide, azelaic acid probably leads to a worse treatment response, measured using PGA. When compared to tretinoin, azelaic acid probably makes little or no difference to treatment response. For other comparisons and outcomes the quality of evidence was low or very low. Risk of bias and imprecision limit our confidence in the evidence. We encourage the comparison of more methodologically robust head-to-head trials against commonly used active drugs.
Topics: Acne Vulgaris; Adapalene; Adolescent; Adult; Anti-Bacterial Agents; Benzoyl Peroxide; Bias; Child; Clindamycin; Dermatologic Agents; Dicarboxylic Acids; Erythromycin; Female; Glycolates; Humans; Keratolytic Agents; Male; Mandelic Acids; Niacinamide; Patient Dropouts; Pyruvic Acid; Quality of Life; Salicylic Acid; Sulfur; Tretinoin; Young Adult; Zinc
PubMed: 32356369
DOI: 10.1002/14651858.CD011368.pub2 -
Clinical Journal of the American... Dec 2016Vancomycin has been in use for more than half a century, but whether it is truly nephrotoxic and to what extent are still highly controversial. The objective of this... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND OBJECTIVES
Vancomycin has been in use for more than half a century, but whether it is truly nephrotoxic and to what extent are still highly controversial. The objective of this study was to determine the risk of AKI attributable to intravenous vancomycin.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS
We conducted a systematic review of randomized, controlled trials and cohort studies that compared patients treated with intravenous vancomycin with a control group of patients given a comparator nonglycopeptide antibiotic and in which kidney function or kidney injury outcomes were reported. PubMed and Cochrane Library were searched from 1990 to September of 2015. Two reviewers extracted data and assessed study risk of bias, and one reviewer adjudicated the assessments. A meta-analysis was conducted on seven randomized, controlled trials (total of 4033 patients).
RESULTS
Moderate quality evidence suggested that vancomycin treatment is associated with a higher risk of AKI, with a relative risk of 2.45 (95% confidence interval, 1.69 to 3.55). The risk of kidney injury was similar in patients treated for skin and soft tissue infections compared with those treated for nosocomial pneumonia and other complicated infections. There was an uncertain risk of reporting bias, because kidney function was not a prespecified outcome in any of the trials. The preponderance of evidence was judged to be indirect, because the majority of studies compared vancomycin specifically with linezolid.
CONCLUSIONS
Our findings suggest that there is a measurable risk of AKI associated with vancomycin, but the strength of the evidence is moderate. A randomized, controlled trial designed to study kidney function as an outcome would be needed to draw unequivocal conclusions.
Topics: Acute Kidney Injury; Administration, Intravenous; Anti-Bacterial Agents; Humans; Linezolid; Risk Factors; Vancomycin
PubMed: 27895134
DOI: 10.2215/CJN.05920616 -
The Cochrane Database of Systematic... Jun 2016Management of rotator cuff disease may include use of electrotherapy modalities (also known as electrophysical agents), which aim to reduce pain and improve function via... (Review)
Review
BACKGROUND
Management of rotator cuff disease may include use of electrotherapy modalities (also known as electrophysical agents), which aim to reduce pain and improve function via an increase in energy (electrical, sound, light, or thermal) into the body. Examples include therapeutic ultrasound, low-level laser therapy (LLLT), transcutaneous electrical nerve stimulation (TENS), and pulsed electromagnetic field therapy (PEMF). These modalities are usually delivered as components of a physical therapy intervention. This review is one of a series of reviews that form an update of the Cochrane review, 'Physiotherapy interventions for shoulder pain'.
OBJECTIVES
To synthesise available evidence regarding the benefits and harms of electrotherapy modalities for the treatment of people with rotator cuff disease.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2015, Issue 3), Ovid MEDLINE (January 1966 to March 2015), Ovid EMBASE (January 1980 to March 2015), CINAHL Plus (EBSCOhost, January 1937 to March 2015), ClinicalTrials.gov and the WHO ICTRP clinical trials registries up to March 2015, unrestricted by language, and reviewed the reference lists of review articles and retrieved trials, to identify potentially relevant trials.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) and quasi-randomised trials, including adults with rotator cuff disease (e.g. subacromial impingement syndrome, rotator cuff tendinitis, calcific tendinitis), and comparing any electrotherapy modality with placebo, no intervention, a different electrotherapy modality or any other intervention (e.g. glucocorticoid injection). Trials investigating whether electrotherapy modalities were more effective than placebo or no treatment, or were an effective addition to another physical therapy intervention (e.g. manual therapy or exercise) were the main comparisons of interest. Main outcomes of interest were overall pain, function, pain on motion, patient-reported global assessment of treatment success, quality of life and the number of participants experiencing adverse events.
DATA COLLECTION AND ANALYSIS
Two review authors independently selected trials for inclusion, extracted the data, performed a risk of bias assessment and assessed the quality of the body of evidence for the main outcomes using the GRADE approach.
MAIN RESULTS
We included 47 trials (2388 participants). Most trials (n = 43) included participants with rotator cuff disease without calcification (four trials included people with calcific tendinitis). Sixteen (34%) trials investigated the effect of an electrotherapy modality delivered in isolation. Only 23% were rated at low risk of allocation bias, and 49% were rated at low risk of both performance and detection bias (for self-reported outcomes). The trials were heterogeneous in terms of population, intervention and comparator, so none of the data could be combined in a meta-analysis.In one trial (61 participants; low quality evidence), pulsed therapeutic ultrasound (three to five times a week for six weeks) was compared with placebo (inactive ultrasound therapy) for calcific tendinitis. At six weeks, the mean reduction in overall pain with placebo was -6.3 points on a 52-point scale, and -14.9 points with ultrasound (MD -8.60 points, 95% CI -13.48 to -3.72 points; absolute risk difference 17%, 7% to 26% more). Mean improvement in function with placebo was 3.7 points on a 100-point scale, and 17.8 points with ultrasound (mean difference (MD) 14.10 points, 95% confidence interval (CI) 5.39 to 22.81 points; absolute risk difference 14%, 5% to 23% more). Ninety-one per cent (29/32) of participants reported treatment success with ultrasound compared with 52% (15/29) of participants receiving placebo (risk ratio (RR) 1.75, 95% CI 1.21 to 2.53; absolute risk difference 39%, 18% to 60% more). Mean improvement in quality of life with placebo was 0.40 points on a 10-point scale, and 2.60 points with ultrasound (MD 2.20 points, 95% CI 0.91 points to 3.49 points; absolute risk difference 22%, 9% to 35% more). Between-group differences were not important at nine months. No participant reported adverse events.Therapeutic ultrasound produced no clinically important additional benefits when combined with other physical therapy interventions (eight clinically heterogeneous trials, low quality evidence). We are uncertain whether there are differences in patient-important outcomes between ultrasound and other active interventions (manual therapy, acupuncture, glucocorticoid injection, glucocorticoid injection plus oral tolmetin sodium, or exercise) because the quality of evidence is very low. Two placebo-controlled trials reported results favouring LLLT up to three weeks (low quality evidence), however combining LLLT with other physical therapy interventions produced few additional benefits (10 clinically heterogeneous trials, low quality evidence). We are uncertain whether transcutaneous electrical nerve stimulation (TENS) is more or less effective than glucocorticoid injection with respect to pain, function, global treatment success and active range of motion because of the very low quality evidence from a single trial. In other single, small trials, no clinically important benefits of pulsed electromagnetic field therapy (PEMF), microcurrent electrical stimulation (MENS), acetic acid iontophoresis and microwave diathermy were observed (low or very low quality evidence).No adverse events of therapeutic ultrasound, LLLT, TENS or microwave diathermy were reported by any participants. Adverse events were not measured in any trials investigating the effects of PEMF, MENS or acetic acid iontophoresis.
AUTHORS' CONCLUSIONS
Based on low quality evidence, therapeutic ultrasound may have short-term benefits over placebo in people with calcific tendinitis, and LLLT may have short-term benefits over placebo in people with rotator cuff disease. Further high quality placebo-controlled trials are needed to confirm these results. In contrast, based on low quality evidence, PEMF may not provide clinically relevant benefits over placebo, and therapeutic ultrasound, LLLT and PEMF may not provide additional benefits when combined with other physical therapy interventions. We are uncertain whether TENS is superior to placebo, and whether any electrotherapy modality provides benefits over other active interventions (e.g. glucocorticoid injection) because of the very low quality of the evidence. Practitioners should communicate the uncertainty of these effects and consider other approaches or combinations of treatment. Further trials of electrotherapy modalities for rotator cuff disease should be based upon a strong rationale and consideration of whether or not they would alter the conclusions of this review.
Topics: Adult; Diathermy; Electric Stimulation Therapy; Humans; Magnetic Field Therapy; Middle Aged; Muscular Diseases; Randomized Controlled Trials as Topic; Rotator Cuff; Shoulder Pain; Transcutaneous Electric Nerve Stimulation; Ultrasonic Therapy
PubMed: 27283591
DOI: 10.1002/14651858.CD012225 -
Clinical Microbiology and Infection :... Jan 2022Outcomes of treatment of tuberculosis patients with regimens including pretomanid have not yet been systematically reviewed. (Review)
Review
BACKGROUND
Outcomes of treatment of tuberculosis patients with regimens including pretomanid have not yet been systematically reviewed.
OBJECTIVES
To appraise existing evidence on efficacy and safety of pretomanid in tuberculosis.
DATA SOURCES
Pubmed, clinicaltrials.gov. and Cochrane library.
STUDY ELIGIBILITY CRITERIA
Quantitative studies presenting original data on clinical efficacy or safety of pretomanid.
PARTICIPANTS
Patients with tuberculosis.
INTERVENTIONS
Treatment with pretomanid or pretomanid-containing regimens in minimum one study group.
METHODS
Two authors independently extracted data and assessed risk of bias. Data on efficacy (early bactericidal activity, bactericidal activity, end-of-treatment outcomes and acquired resistance) and safety were summarized in tables. Mean differences in efficacy outcomes between regimens across studies were calculated.
RESULTS
Eight studies were included; four randomized controlled trials on 2-week early bactericidal activity in rifampicin-susceptible tuberculosis, three trials with randomized rifampicin-susceptible tuberculosis arms and a single rifampicin-resistant tuberculosis arm (two on 8-week bactericidal activity, one on end-of-treatment outcomes), one single-arm trial with end-of-treatment outcomes in highly resistant tuberculosis. Activity of pretomanid-moxifloxacin-pyrazinamide was superior to standard treatment on daily change in colony-forming units at days 0-2, 0-56 and 7-56 and time to culture conversion in rifampicin-susceptible tuberculosis (hazard ratio: 1.7; 95% CI 1.1-2.7), but not at end of treatment in one study. This study was stopped due to serious hepatotoxic adverse events, including three deaths, in 4% (95% CI 2-8) patients on pretomanid-moxifloxacin-pyrazinamide and none in controls. In patients with uncomplicated rifampicin-resistant tuberculosis on pretomanid-moxifloxacin-pyrazinamide treatment, 91% (95% CI 59-100) had favourable end-of-treatment outcomes. In patients with highly resistant tuberculosis, 90% (95% CI 83-95) on pretomanid-bedaquiline-linezolid had favourable outcomes six months after treatment, but linezolid-related toxicity was frequent. No acquired resistance to pretomanid was reported.
CONCLUSIONS
Evidence suggests an important role for pretomanid in rifampicin-resistant and highly resistant tuberculosis. Trials comparing pretomanid to existing core and companion drugs are needed to further define that role.
Topics: Antitubercular Agents; Humans; Linezolid; Moxifloxacin; Nitroimidazoles; Pyrazinamide; Randomized Controlled Trials as Topic; Rifampin; Tuberculosis; Tuberculosis, Multidrug-Resistant
PubMed: 34400340
DOI: 10.1016/j.cmi.2021.08.007 -
Journal of Global Antimicrobial... Mar 2021American Thoracic Society/Infectious Diseases Society of America (ATS/IDSA) guidelines suggest that linezolid (LZD) is preferred over vancomycin (VCM) for treating... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
American Thoracic Society/Infectious Diseases Society of America (ATS/IDSA) guidelines suggest that linezolid (LZD) is preferred over vancomycin (VCM) for treating methicillin-resistant Staphylococcus aureus (MRSA) pneumonia. We conducted a systematic review and comparative meta-analysis to compare VCM and LZD efficacy against proven MRSA pneumonia.
METHODS
We searched EMBASE, CINAHL, Cochrane Central Register of Controlled Trials (CENTRAL), and PubMed up to November 2019. The outcomes of the meta-analysis were mortality, clinical cure, microbiological evaluation, and adverse events.
RESULTS
Seven randomized controlled trials (RCTs) with a total of 1239 patients and eight retrospective cohort or case-control studies (CSs) with a total 6125 patients were identified. Clinical cure and microbiological eradication rates were significantly increased in patients treated with LZD in RCTs (clinical cure: risk ratio (RR) = 0.81, 95% confidential interval (CI) = 0.71-0.92; microbiological eradication: RR = 0.71, 95% CI = 0.62-0.81) and CSs (clinical cure: odds ratio (OR) = 0.35, 95% CI = 0.18-0.69). However, mortality was comparable between patients treated with VCM and LZD in RCTs (RR = 1.08, 95% CI = 0.88-1.32) and CSs (OR = 1.20, 95% CI = 0.94-1.53). Likewise, there was no significant difference in adverse events between VCM and LZD in CSs (thrombocytopenia: OR = 0.95, 95% CI = 0.50-1.82; nephrotoxicity: OR = 1.72, 95% CI = 0.85-3.45).
CONCLUSIONS
According to our meta-analysis of RCTs and CSs conducted worldwide, we found robust evidence to corroborate the IDSA guidelines for the treatment of proven MRSA pneumonia.
Topics: Acetamides; Anti-Bacterial Agents; Humans; Linezolid; Methicillin-Resistant Staphylococcus aureus; Oxazolidinones; Pneumonia; Randomized Controlled Trials as Topic; Vancomycin
PubMed: 33401013
DOI: 10.1016/j.jgar.2020.12.009 -
Seizure Nov 2022Multiple interventions have been studied for benzodiazepine-resistant status epilepticus (SE) in children and adults. This review aimed to summarize the available... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Multiple interventions have been studied for benzodiazepine-resistant status epilepticus (SE) in children and adults. This review aimed to summarize the available evidence and provide estimates of comparative effectiveness and ranking of treatment effects.
METHODS
All randomized controlled trials studying patients (>1 month of age) with benzodiazepine-resistant SE were included. Outcomes including seizure cessation within 60 min, seizure freedom for 24 h, death, respiratory depression warranting intubation and cardiovascular instability were studied. Conventional and network meta-analyses (NMA) were done.
RESULTS
Seventeen studies were included (16 in NMA). Phenobarbital and high-dose levetiracetam were significantly superior to phenytoin with respect to seizure cessation within 60 min. Network ranking demonstrated that phenobarbital had the highest probability of being the best among the studied interventions followed by high-dose levetiracetam and high-dose valproate. Network meta-analysis was limited by predominant indirect evidence and high heterogeneity.On pairwise comparisons, phenobarbital was found to be associated with a higher risk of need for intubation and cardiovascular instability. Levetiracetam had a better safety profile than fosphenytoin.
CONCLUSIONS
Based on low quality evidence, phenobarbital appears to be the most effective agent for seizure cessation within 60 min of administration in patients with benzodiazepine resistant status epilepticus. High-dose levetiracetam, high-dose valproate and fosphenytoin are probably equally effective. Choice of medication may be guided by effectiveness, safety concerns, availability, cost and systemic co-morbidities.
Topics: Adult; Child; Humans; Anticonvulsants; Benzodiazepines; Levetiracetam; Network Meta-Analysis; Phenobarbital; Phenytoin; Seizures; Status Epilepticus; Valproic Acid; Drug Resistance; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 36209676
DOI: 10.1016/j.seizure.2022.09.017 -
Epilepsy & Behavior : E&B May 2021To understand the currently available post-marketing real-world evidence of the incidences of and discontinuations due to the BAEs of irritability, anger, and aggression... (Review)
Review
PURPOSE
To understand the currently available post-marketing real-world evidence of the incidences of and discontinuations due to the BAEs of irritability, anger, and aggression in people with epilepsy (PWE) treated with the anti-seizure medications (ASMs) brivaracetam (BRV), levetiracetam (LEV), perampanel (PER), and topiramate (TPM), as well as behavioral adverse events (BAEs) in PWE switching from LEV to BRV.
METHODS
A systematic review of published literature using the Cochrane Library, PubMed/MEDLINE, and Embase was performed to identify retrospective and prospective observational studies reporting the incidence of irritability, anger, or aggression with BRV, LEV, PER, or TPM in PWE. The incidences of these BAEs and the rates of discontinuation due to each were categorized by ASM, and where possible, weighted means were calculated but not statistically assessed. Behavioral and psychiatric adverse events in PWE switching from LEV to BRV were summarized descriptively.
RESULTS
A total of 1500 records were identified in the searches. Of these, 44 published articles reporting 42 studies met the study criteria and were included in the data synthesis, 7 studies were identified in the clinical trial database, and 5 studies included PWE switching from LEV to BRV. Studies included a variety of methods, study populations, and definitions of BAEs. While a wide range of results was reported across studies, weighted mean incidences were 5.6% for BRV, 9.9% for LEV, 12.3% for PER, and 3.1% for TPM for irritability; 3.3%* for BRV, 2.5% for LEV, 2.0% for PER, and 0.2%* for TPM for anger; and 2.5% for BRV, 2.6% for LEV, 4.4% for PER, and 0.5%* for TPM for aggression. Weighted mean discontinuation rates were 0.8%* for BRV, 3.4% for LEV, 3.0% for PER, and 2.2% for TPM for irritability and 0.8%* for BRV, 2.4% for LEV, 9.2% for PER, and 1.2%* for TPM for aggression. There were no discontinuations for anger. Switching from LEV to BRV led to improvement in BAEs in 33.3% to 83.0% of patients (weighted mean, 66.6%). *Denotes only 1 study.
CONCLUSIONS
This systematic review characterizes the incidences of irritability, anger, and aggression with BRV, LEV, PER, and TPM, and it provides robust real-world evidence demonstrating that switching from LEV to BRV may improve BAEs. While additional data remain valuable due to differences in methodology (which make comparisons difficult), these results improve understanding of the real-world incidences of discontinuations due to these BAEs in clinical practice and can aid in discussions and treatment decision-making with PWE.
Topics: Anticonvulsants; Humans; Levetiracetam; Nitriles; Observational Studies as Topic; Pyridones; Pyrrolidinones; Retrospective Studies; Topiramate; Treatment Outcome
PubMed: 33839453
DOI: 10.1016/j.yebeh.2021.107939 -
The Lancet. Respiratory Medicine Apr 2020Treatment of multidrug-resistant tuberculosis requires long-term therapy with a combination of multiple second-line drugs. These drugs are associated with numerous... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Treatment of multidrug-resistant tuberculosis requires long-term therapy with a combination of multiple second-line drugs. These drugs are associated with numerous adverse events that can cause severe morbidity, such as deafness, and in some instances can lead to death. Our aim was to estimate the absolute and relative frequency of adverse events associated with different tuberculosis drugs to provide useful information for clinicians and tuberculosis programmes in selecting optimal treatment regimens.
METHODS
We did a meta-analysis using individual-level patient data that were obtained from studies that reported adverse events that resulted in permanent discontinuation of anti-tuberculosis medications. We used a database created for our previous meta-analysis of multidrug-resistant tuberculosis treatment and outcomes, for which we did a systematic review of literature published between Jan 1, 2009, and Aug 31, 2015 (updated April 15, 2016), and requested individual patient-level information from authors. We also considered for this analysis studies contributing patient-level data in response to a public call made by WHO in 2018. Meta-analysis for proportions and arm-based network meta-analysis were done to estimate the incidence of adverse events for each tuberculosis drug.
FINDINGS
58 studies were identified, including 50 studies from the updated individual patient data meta-analysis for multidrug-resistant tuberculosis treatment. 35 of these studies, with 9178 patients, were included in our analysis. Using meta-analysis of proportions, drugs with low risks of adverse event occurrence leading to permanent discontinuation included levofloxacin (1·3% [95% CI 0·3-5·0]), moxifloxacin (2·9% [1·6-5·0]), bedaquiline (1·7% [0·7-4·2]), and clofazimine (1·6% [0·5-5·3]). Relatively high incidence of adverse events leading to permanent discontinuation was seen with three second-line injectable drugs (amikacin: 10·2% [6·3-16·0]; kanamycin: 7·5% [4·6-11·9]; capreomycin: 8·2% [6·3-10·7]), aminosalicylic acid (11·6% [7·1-18·3]), and linezolid (14·1% [9·9-19·6]). Risk of bias in selection of studies was judged to be low because there were no important differences between included and excluded studies. Variability between studies was significant for most outcomes analysed.
INTERPRETATION
Fluoroquinolones, clofazimine, and bedaquiline had the lowest incidence of adverse events leading to permanent drug discontinuation, whereas second-line injectable drugs, aminosalicylic acid, and linezolid had the highest incidence. These results suggest that close monitoring of adverse events is important for patients being treated for multidrug-resistant tuberculosis. Our results also underscore the urgent need for safer and better-tolerated drugs to reduce morbidity from treatment itself for patients with multidrug-resistant tuberculosis.
FUNDING
Canadian Institutes of Health Research, Centers for Disease Control and Prevention (USA), American Thoracic Society, European Respiratory Society, and Infectious Diseases Society of America.
Topics: Adult; Aminosalicylic Acid; Antitubercular Agents; Canada; Clofazimine; Diarylquinolines; Drug-Related Side Effects and Adverse Reactions; Female; Fluoroquinolones; Humans; Incidence; Linezolid; Male; Mycobacterium tuberculosis; Tuberculosis, Multidrug-Resistant; Tuberculosis, Pulmonary
PubMed: 32192585
DOI: 10.1016/S2213-2600(20)30047-3 -
Journal of Neurology Oct 2023To compare the efficacy and safety of antiseizure medications (ASMs), both as monotherapies and adjunctive therapies, for idiopathic generalized epilepsies (IGEs) and... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
To compare the efficacy and safety of antiseizure medications (ASMs), both as monotherapies and adjunctive therapies, for idiopathic generalized epilepsies (IGEs) and related entities.
METHODS
Two reviewers independently searched PubMed, Embase, and the Cochrane Library for relevant randomized controlled trials from December 2022 to February 2023. Studies on the efficacy and safety of ASM monotherapies or adjunctive therapies for IGEs and related entities-including juvenile myoclonic epilepsy, childhood absence epilepsy (CAE), juvenile absence epilepsy, or generalized tonic-clonic seizures alone (GTCA)-were included. Efficacy outcomes were the proportions of patients remaining seizure free for 1, 3, 6, and 12 months; safety outcomes were the proportions of any treatment-emergent adverse event (TEAE) and TEAEs leading to discontinuation. Network meta-analyses were performed in a random-effects model to obtain odds ratios and 95% confidence intervals. Rankings of ASMs were based on the surface under the cumulative ranking curve (SUCRA). This study is registered with PROSPERO (No. CRD42022372358).
RESULTS
Twenty-eight randomized controlled trials containing 4282 patients were included. As monotherapies, all ASMs were more effective than placebo, and valproate and ethosuximide were significantly better than lamotrigine. According to the SUCRA for efficacy, ethosuximide ranked first for CAE, whereas valproate ranked first for other types of IGEs. As adjunctive therapies, topiramate ranked best for GTCA as well as overall for IGEs, while levetiracetam ranked best for myoclonic seizures. For safety, perampanel ranked best (measured by any TEAE).
CONCLUSIONS
All of the studied ASMs were more effective than placebo. Valproate monotherapy ranked best overall for IGEs, whereas ethosuximide ranked best for CAE. Adjunctive topiramate and levetiracetam were most effective for GTCA and myoclonic seizures, respectively. Furthermore, perampanel had the best tolerability.
Topics: Humans; Child; Valproic Acid; Topiramate; Network Meta-Analysis; Levetiracetam; Ethosuximide; Anticonvulsants; Epilepsy, Generalized; Seizures; Randomized Controlled Trials as Topic
PubMed: 37378757
DOI: 10.1007/s00415-023-11834-8