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Obesity Reviews : An Official Journal... Nov 2021Anti-obesity medications (AOMs) are efficacious and well tolerated in randomized controlled trials, but findings may not be generalizable to routine clinical practice.... (Review)
Review
Anti-obesity medications (AOMs) are efficacious and well tolerated in randomized controlled trials, but findings may not be generalizable to routine clinical practice. This systematic literature review aimed to identify real-world (RW) evidence for AOMs to treat adults ( ≥ 18 years) with obesity or overweight (BMI ≥ 27 kg/m ). Searches conducted in MEDLINE, Embase, Health Technology Assessment (HTA) Database, National Health Service (NHS) Economic Evaluation Database, and Cochrane Central Register of Controlled Trials for studies of relevant FDA-approved AOMs yielded 41 publications. Weight loss (WL) was consistently observed, with 14% to 58.6% of patients achieving ≥ 5% WL on orlistat, phentermine/topiramate, naltrexone/bupropion, phentermine, or liraglutide in studies of 3-6 months' duration where this was measured. When cardiometabolic risk factors were assessed, AOMs reduced or had no impact on blood pressure, lipids, or glycemia. RW data on the impact of AOMs on existing obesity-related comorbidities and mortality were generally lacking. AOMs were associated with various adverse events, but these were of mild to moderate severity and no unexpected safety signals were reported. A pattern of poor adherence and persistence with AOMs was observed across studies. Overall, the review confirmed the effectiveness of AOMs in RW settings but demonstrated large gaps in the evidence base.
Topics: Adult; Anti-Obesity Agents; Humans; Orlistat; Phentermine; State Medicine; Weight Loss
PubMed: 34423889
DOI: 10.1111/obr.13326 -
Current Neuropharmacology 2022Despite increasing worldwide incidence of Parkinson's disease, the therapy is still suboptimal due to the diversified clinical manifestations, lack of sufficient...
BACKGROUND
Despite increasing worldwide incidence of Parkinson's disease, the therapy is still suboptimal due to the diversified clinical manifestations, lack of sufficient treatment, the poor adherence in advanced patients, and varied response. Proper intake of medications regarding food and managing drug-food interactions may optimize Parkinson's disease treatment.
OBJECTIVES
We investigated potential effects that food, beverages, and dietary supplements may have on the pharmacokinetics and pharmacodynamics of drugs used by parkinsonian patients; identified the most probable interactions; and shaped recommendations for the optimal intake of drugs regarding food.
METHODS
We performed a systematic review in adherence to PRISMA guidelines, and included a total of 81 studies in the qualitative synthesis.
RESULTS AND CONCLUSION
We found evidence for levodopa positive interaction with coffee, fiber and vitamin C, as well as for the potential beneficial impact of low-fat and protein redistribution diet. Contrastingly, high-protein diet and ferrous sulfate supplements can negatively affect levodopa pharmacokinetics and effectiveness. For other drugs, the data of food impact are scarce. Based on the available limited evidence, all dopamine agonists (bromocriptine, cabergoline, ropinirole), tolcapone, rasagiline, selegiline in tablets, safinamide, amantadine and pimavanserin can be taken with or without a meal. Opicapone and orally disintegrating selegiline tablets should be administered on an empty stomach. Of monoamine oxidase B inhibitors, safinamide is the least susceptible for interaction with the tyramine-rich food, whereas selegiline and rasagiline may lose selectivity to monoamine oxidase B when administered in supratherapeutic doses. The level of presented evidence is low due to the poor studies design, their insufficient actuality, and missing data.
Topics: Antiparkinson Agents; Dietary Supplements; Humans; Levodopa; Monoamine Oxidase; Monoamine Oxidase Inhibitors; Parkinson Disease; Selegiline
PubMed: 34784871
DOI: 10.2174/1570159X19666211116142806 -
Drugs Oct 2023Dravet syndrome (DS) is a severe developmental and epileptic encephalopathy characterized by drug-resistant, lifelong seizures. The management of seizures in DS has... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Dravet syndrome (DS) is a severe developmental and epileptic encephalopathy characterized by drug-resistant, lifelong seizures. The management of seizures in DS has changed in recent years with the approval of new antiseizure medications (ASMs).
OBJECTIVE
The aim of this study was to estimate the comparative efficacy and tolerability of the ASMs for the treatment of seizures associated with DS using a network meta-analysis (NMA).
METHODS
Studies were identified by conducting a systematic search (week 4, January 2023) of the MEDLINE (accessed by PubMed), EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), and US National Institutes of Health Clinical Trials Registry ( http://www.
CLINICALTRIALS
gov ) databases. Any randomized, controlled, double- or single-blinded, parallel-group study comparing at least one ASM therapy against placebo, another ASM, or a different dose of the same ASM in participants with a diagnosis of DS was identified. The efficacy outcomes were the proportions of participants with ≥ 50% (seizure response) and 100% reduction (seizure freedom) in baseline convulsive seizure frequency during the maintenance period. The tolerability outcomes included the proportions of patients who withdrew from treatment for any reason and who experienced at least one adverse event (AE). Effect sizes were estimated by network meta-analyses within a frequentist framework.
RESULTS
Eight placebo-controlled trials were included, and the active add-on treatments were stiripentol (n = 2), pharmaceutical-grade cannabidiol (n = 3), fenfluramine hydrochloride (n = 2), and soticlestat (n = 1). The studies recruited 680 participants, of whom 409 were randomized to active treatments (stiripentol = 33, pharmaceutical-grade cannabidiol = 228, fenfluramine hydrochloride = 122, and soticlestat = 26) and 271 to placebo. Pharmaceutical-grade cannabidiol was associated with a lower rate of seizure response than fenfluramine hydrochloride (odds ratio [OR] 0.20, 95% confidence interval [CI] 0.07-0.54), and stiripentol was associated with a higher seizure response rate than pharmaceutical-grade cannabidiol (OR 14.07, 95% CI 2.57-76.87). No statistically significant differences emerged across the different ASMs for the seizure freedom outcome. Stiripentol was associated with a lower probability of drug discontinuation for any reason than pharmaceutical-grade cannabidiol (OR 0.45, 95% CI 0.04-5.69), and pharmaceutical-grade cannabidiol was associated with a lower proportion of participants experiencing any AE than fenfluramine hydrochloride (OR 0.22, 95% CI 0.06-0.78). Stiripentol had a higher risk of AE occurrence than pharmaceutical-grade cannabidiol (OR 75.72, 95% CI 3.59-1598.58). The study found high-quality evidence of efficacy and tolerability of the four ASMs in the treatment of convulsive seizures in DS.
CONCLUSIONS
There exists first-class evidence that documents the efficacy and tolerability of stiripentol, pharmaceutical-grade cannabidiol, fenfluramine hydrochloride, and soticlestat for the treatment of seizures associated with DS, and allows discussion about the expected outcomes regarding seizure frequency reduction and tolerability profiles.
Topics: Humans; Anticonvulsants; Cannabidiol; Network Meta-Analysis; Randomized Controlled Trials as Topic; Seizures; Epilepsies, Myoclonic; Fenfluramine; Pharmaceutical Preparations
PubMed: 37695433
DOI: 10.1007/s40265-023-01936-y -
JAMA Network Open Mar 2024Antipsychotic-induced akathisia (AIA) occurs in 14% to 35% of patients treated with antipsychotics and is associated with increased suicide and decreased adherence in... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Antipsychotic-induced akathisia (AIA) occurs in 14% to 35% of patients treated with antipsychotics and is associated with increased suicide and decreased adherence in patients with schizophrenia. However, no comprehensive review and network meta-analysis has been conducted to compare the efficacy of treatments for AIA.
OBJECTIVE
To compare the efficacy associated with AIA treatments.
DATA SOURCES
Three databases (MEDLINE, Web of Science, and Google Scholar) were systematically searched by multiple researchers for double-blind randomized clinical trials (RCTs) comparing active drugs for the treatment of AIA with placebo or another treatment between May 30 and June 18, 2023.
STUDY SELECTION
Selected studies were RCTs that compared adjunctive drugs for AIA vs placebo or adjunctive treatment in patients treated with antipsychotics fulfilling the criteria for akathisia, RCTs with sample size of 10 patients or more, only trials in which no additional drugs were administered during the study, and RCTs that used a validated akathisia score. Trials with missing data for the main outcome (akathisia score at the end points) were excluded.
DATA EXTRACTION AND SYNTHESIS
Data extraction and synthesis were performed, estimating standardized mean differences (SMDs) through pairwise and network meta-analysis with a random-effects model. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline was followed.
MAIN OUTCOMES AND MEASURES
The primary outcome was the severity of akathisia measured by a validated scale at the last available end point.
RESULTS
Fifteen trials involving 492 participants compared 10 treatments with placebo. Mirtazapine (15 mg/d for ≥5 days; SMD, -1.20; 95% CI, -1.83 to -0.58), biperiden (6 mg/d for ≥14 days; SMD, -1.01; 95% CI, -1.69 to -0.34), vitamin B6 (600-1200 mg/d for ≥5 days; SMD, -0.92; 95% CI, -1.57 to -0.26), trazodone (50 mg/d for ≥5 days; SMD, -0.84; 95% CI, -1.54 to -0.14), mianserin (15 mg/d for ≥5 days; SMD, -0.81; 95% CI, -1.44 to -0.19), and propranolol (20 mg/d for ≥6 days; SMD, -0.78; 95% CI, -1.35 to -0.22) were associated with greater efficacy than placebo, with low to moderate heterogeneity (I2 = 34.6%; 95% CI, 0.0%-71.1%). Cyproheptadine, clonazepam, zolmitriptan, and valproate did not yield significant effects. Eight trials were rated as having low risk of bias; 2, moderate risk; and 5, high risk. Sensitivity analyses generally confirmed the results for all drugs except for cyproheptadine and propranolol. No association between effect sizes and psychotic severity was found.
CONCLUSIONS AND RELEVANCE
In this systematic review and network meta-analysis, mirtazapine, biperiden, and vitamin B6 were associated with the greatest efficacy for AIA, with vitamin B6 having the best efficacy and tolerance profile. Trazodone, mianserin, and propranolol appeared as effective alternatives with slightly less favorable efficacy and tolerance profiles. These findings should assist prescribers in selecting an appropriate medication for treating AIA.
Topics: Humans; Antipsychotic Agents; Biperiden; Cyproheptadine; Gallopamil; Mianserin; Mirtazapine; Network Meta-Analysis; Propranolol; Randomized Controlled Trials as Topic; Trazodone; Vitamin B 6; Akathisia, Drug-Induced
PubMed: 38451521
DOI: 10.1001/jamanetworkopen.2024.1527 -
Advances in Therapy Nov 2022Few randomised controlled trials (RCTs) have directly compared long-acting muscarinic antagonist/long-acting β-agonist (LAMA/LABA) dual maintenance therapies for... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Few randomised controlled trials (RCTs) have directly compared long-acting muscarinic antagonist/long-acting β-agonist (LAMA/LABA) dual maintenance therapies for patients with chronic obstructive pulmonary disease (COPD). This systematic literature review and network meta-analysis (NMA) compared the efficacy of umeclidinium/vilanterol (UMEC/VI) versus other dual and mono-bronchodilator therapies in symptomatic patients with COPD.
METHODS
A systematic literature review (October 2015-November 2020) was performed to identify RCTs ≥ 8 weeks long in adult patients with COPD that compared LAMA/LABA combinations against any long-acting bronchodilator-containing dual therapy or monotherapy. Data extracted on changes from baseline in trough forced expiratory volume in 1 s (FEV), St George's Respiratory Questionnaire (SGRQ) total score, Transitional Dyspnoea Index (TDI) focal score, rescue medication use and moderate/severe exacerbation rate were analysed using an NMA in a frequentist framework. The primary comparison was at 24 weeks. Fixed effects model results are presented.
RESULTS
The NMA included 69 full-length publications (including 10 GSK clinical study reports) reporting 49 studies. At 24 weeks, UMEC/VI provided statistically significant greater improvements in FEV versus all dual therapy and monotherapy comparators. UMEC/VI provided similar improvements in SGRQ total score compared with all other LAMA/LABAs, and significantly greater improvements versus UMEC 125 μg, glycopyrronium 50 μg, glycopyrronium 18 μg, tiotropium 18 μg and salmeterol 50 μg. UMEC/VI also provided significantly better outcomes versus some comparators for TDI focal score, rescue medication use, annualised moderate/severe exacerbation rate, and time to first moderate/severe exacerbation.
CONCLUSION
UMEC/VI provided generally better outcomes compared with LAMA or LABA monotherapies, and consistent improvements in lung function (measured by change from baseline in trough FEV at 24 weeks) versus dual therapies. Treatment with UMEC/VI may improve outcomes for symptomatic patients with COPD compared with alternative maintenance treatments.
Topics: Administration, Inhalation; Adrenergic beta-2 Receptor Agonists; Adult; Benzyl Alcohols; Bronchodilator Agents; Chlorobenzenes; Drug Combinations; Dyspnea; Forced Expiratory Volume; Glycopyrrolate; Humans; Muscarinic Antagonists; Network Meta-Analysis; Pulmonary Disease, Chronic Obstructive; Quinuclidines; Salmeterol Xinafoate; Tiotropium Bromide; Treatment Outcome
PubMed: 35857184
DOI: 10.1007/s12325-022-02234-x -
Epileptic Disorders : International... Dec 2022We carried out a systematic review of published information on transfer of antiseizure medications (ASMs) into breastmilk, ASM serum concentrations in breastfed infants,...
We carried out a systematic review of published information on transfer of antiseizure medications (ASMs) into breastmilk, ASM serum concentrations in breastfed infants, and the wellbeing of infants breastfed by mothers on ASM treatment. Information was extracted from 85 relevant articles. No data on ASM levels in breastmilk or in breastfed infants was identified for cannabidiol, cenobamate, clobazam, eslicarbazepine-acetate, everolimus, felbamate, fenfluramine, retigabine, rufinamide, stiripentol, tiagabine, and vigabatrin. For ASMs, with available information on levels in breastfed infants, very low concentrations (in the order of 10% or less of maternal serum concentrations) were reported for carbamazepine, gabapentin, levetiracetam, oxcarbazepine, phenytoin, valproate, and clonazepam. Slightly higher levels (up to approximately 30% of maternal serum concentrations) have been observed with lamotrigine and topiramate, and in single case reports for brivaracetam, lacosamide, and perampanel. High infant levels (30% up to 100% of maternal serum concentrations) have been reported with ethosuximide, phenobarbital and zonisamide. Adverse infant effects during breastfeeding by mothers on ASMs appear to be rare regardless of the type of ASM, but systematic study is limited. Prospective long-term follow-up studies of developmental outcomes among children who have been breastfed by mothers taking ASMs are sparse and have mainly involved children whose mothers were taking carbamazepine, lamotrigine, levetiracetam, phenytoin or valproate as monotherapy while breastfeeding. Although these studies have not indicated poorer outcome among breastfed children compared with those who were not breastfed, further data on long-term outcomes are needed to draw firm conclusions. It is concluded that breastfeeding should in general be encouraged in women taking ASMs, given the well-established benefits of breastfeeding with regard to both short- and long-term infant health in the general population. Counselling needs to be individualized including information on the current knowledge regarding the woman's specific ASM treatment.
Topics: Breast Feeding; Cannabidiol; Carbamazepine; Child; Clobazam; Clonazepam; Epilepsy; Ethosuximide; Everolimus; Felbamate; Female; Fenfluramine; Gabapentin; Humans; Infant; Lacosamide; Lamotrigine; Levetiracetam; Oxcarbazepine; Phenobarbital; Phenytoin; Prospective Studies; Tiagabine; Topiramate; Valproic Acid; Vigabatrin; Zonisamide
PubMed: 36193017
DOI: 10.1684/epd.2022.1492 -
The Cochrane Database of Systematic... Jul 2020Maternal hypotension is the most frequent complication of spinal anaesthesia for caesarean section. It can be associated with nausea or vomiting and may pose serious... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Maternal hypotension is the most frequent complication of spinal anaesthesia for caesarean section. It can be associated with nausea or vomiting and may pose serious risks to the mother (unconsciousness, pulmonary aspiration) and baby (hypoxia, acidosis, neurological injury).
OBJECTIVES
To assess the effects of prophylactic interventions for hypotension following spinal anaesthesia for caesarean section.
SEARCH METHODS
We searched Cochrane Pregnancy and Childbirth's Trials Register (9 August 2016) and reference lists of retrieved studies.
SELECTION CRITERIA
Randomised controlled trials, including full texts and abstracts, comparing interventions to prevent hypotension with placebo or alternative treatment in women having spinal anaesthesia for caesarean section. We excluded studies if hypotension was not an outcome measure.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed study quality and extracted data from eligible studies. We report 'Summary of findings' tables using GRADE.
MAIN RESULTS
We included 125 studies involving 9469 women. Interventions were to prevent maternal hypotension following spinal anaesthesia only, and we excluded any interventions considered active treatment. All the included studies reported the review's primary outcome. Across 49 comparisons, we identified three intervention groups: intravenous fluids, pharmacological interventions, and physical interventions. Authors reported no serious adverse effects with any of the interventions investigated. Most trials reported hypotension requiring intervention and Apgar score of less than 8 at five minutes as the only outcomes. None of the trials included in the comparisons we describe reported admission to neonatal intensive care unit. Crystalloid versus control (no fluids) Fewer women experienced hypotension in the crystalloid group compared with no fluids (average risk ratio (RR) 0.84, 95% confidence interval (CI) 0.72 to 0.98; 370 women; 5 studies; low-quality evidence). There was no clear difference between groups in numbers of women with nausea and vomiting (average RR 0.19, 95% CI 0.01 to 3.91; 1 study; 69 women; very low-quality evidence). No baby had an Apgar score of less than 8 at five minutes in either group (60 babies, low-quality evidence). Colloid versus crystalloid Fewer women experienced hypotension in the colloid group compared with the crystalloid group (average RR 0.69, 95% CI 0.58 to 0.81; 2009 women; 27 studies; very low-quality evidence). There were no clear differences between groups for maternal hypertension requiring intervention (average RR 0.64, 95% CI 0.09 to 4.46, 3 studies, 327 women; very low-quality evidence), maternal bradycardia requiring intervention (average RR 0.98, 95% CI 0.54 to 1.78, 5 studies, 413 women; very low-quality evidence), nausea and/or vomiting (average RR 0.89, 95% CI 0.66 to 1.19, 14 studies, 1058 women, I² = 29%; very low-quality evidence), neonatal acidosis (average RR 0.83, 95% CI 0.15 to 4.52, 6 studies, 678 babies; very low-quality evidence), or Apgar score of less than 8 at five minutes (average RR 0.24, 95% CI 0.03 to 2.05, 10 studies, 730 babies; very low-quality evidence). Ephedrine versus phenylephrine There were no clear differences between ephedrine and phenylephrine groups for preventing maternal hypotension (average RR 0.92, 95% CI 0.71 to 1.18; 401 women; 8 studies; very low-quality evidence) or hypertension (average RR 1.72, 95% CI 0.71 to 4.16, 2 studies, 118 women, low-quality evidence). Rates of bradycardia were lower in the ephedrine group (average RR 0.37, 95% CI 0.21 to 0.64, 5 studies, 304 women, low-quality evidence). There was no clear difference in the number of women with nausea and/or vomiting (average RR 0.76, 95% CI 0.39 to 1.49, 4 studies, 204 women, I² = 37%, very low-quality evidence), or babies with neonatal acidosis (average RR 0.89, 95% CI 0.07 to 12.00, 3 studies, 175 babies, low-quality evidence). No baby had an Apgar score of less than 8 at five minutes in either group (321 babies; low-quality evidence). Ondansetron versus control Ondansetron administration was more effective than control (placebo saline) for preventing hypotension requiring treatment (average RR 0.67, 95% CI 0.54 to 0.83; 740 women, 8 studies, low-quality evidence), bradycardia requiring treatment (average RR 0.49, 95% CI 0.28 to 0.87; 740 women, 8 studies, low-quality evidence), and nausea and/or vomiting (average RR 0.35, 95% CI 0.24 to 0.51; 653 women, 7 studies, low-quality evidence). There was no clear difference between the groups in rates of neonatal acidosis (average RR 0.48, 95% CI 0.05 to 5.09; 134 babies; 2 studies, low-quality evidence) or Apgar scores of less than 8 at five minutes (284 babies, low-quality evidence). Lower limb compression versus control Lower limb compression was more effective than control for preventing hypotension (average RR 0.61, 95% CI 0.47 to 0.78, 11 studies, 705 women, I² = 65%, very low-quality evidence). There was no clear difference between the groups in rates of bradycardia (RR 0.63, 95% CI 0.11 to 3.56, 1 study, 74 women, very low-quality evidence) or nausea and/or vomiting (average RR 0.42, 95% CI 0.14 to 1.27, 4 studies, 276 women, I² = 32%, very-low quality evidence). No baby had an Apgar score of less than 8 at five minutes in either group (130 babies, very low-quality evidence). Walking versus lying There was no clear difference between the groups for women with hypotension requiring treatment (RR 0.71, 95% CI 0.41 to 1.21, 1 study, 37 women, very low-quality evidence). Many included studies reported little to no information that would allow an assessment of their risk of bias, limiting our ability to draw meaningful conclusions. GRADE assessments of the quality of evidence ranged from very low to low. We downgraded evidence for limitations in study design, imprecision, and indirectness; most studies assessed only women scheduled for elective caesarean sections. External validity also needs consideration. Readers should question the use of colloids in this context given the serious potential side effects such as allergy and renal failure associated with their administration.
AUTHORS' CONCLUSIONS
While interventions such as crystalloids, colloids, ephedrine, phenylephrine, ondansetron, or lower leg compression can reduce the incidence of hypotension, none have been shown to eliminate the need to treat maternal hypotension in some women. We cannot draw any conclusions regarding rare adverse effects associated with use of the interventions (for example colloids) due to the relatively small numbers of women studied.
Topics: Anesthesia, Obstetrical; Anesthesia, Spinal; Antiemetics; Cesarean Section; Colloids; Crystalloid Solutions; Ephedrine; Female; Humans; Hypotension; Intraoperative Complications; Isotonic Solutions; Ondansetron; Phenylephrine; Postoperative Nausea and Vomiting; Pregnancy; Randomized Controlled Trials as Topic; Vasoconstrictor Agents; Walking
PubMed: 32619039
DOI: 10.1002/14651858.CD002251.pub4 -
European Journal of Clinical... Dec 2020To investigate the comparative effectiveness of dopamine agonists and monoamine oxidase type-B (MAO-B) inhibitors available for treatment of Parkinson's disease. (Comparative Study)
Comparative Study Meta-Analysis
PURPOSE
To investigate the comparative effectiveness of dopamine agonists and monoamine oxidase type-B (MAO-B) inhibitors available for treatment of Parkinson's disease.
METHODS
We performed a systematic literature search identifying randomized controlled trials investigating 4 dopamine agonists (cabergoline, pramipexole, ropinirole, rotigotine) and 3 MAO-B inhibitors (selegiline, rasagiline, safinamide) for Parkinson's disease. We extracted and pooled data from included clinical trials in a joint model allowing both direct and indirect comparison of the seven drugs. We considered dopamine agonists and MAO-B inhibitors given as monotherapy or in combination with levodopa. Selected endpoints were change in the Unified Parkinson's Disease Rating Scale (UPDRS) score, serious adverse events and withdrawals. We estimated the relative effectiveness of each dopamine agonist and MAO-B inhibitor versus comparator drug.
RESULTS
Altogether, 79 publications were included in the analysis. We found all the investigated drugs to be effective compared with placebo when given as monotherapy except safinamide. When considering combination treatment, the estimated relative effects of selegiline, pramipexole, ropinirole, rotigotine, cabergoline, rasagiline and safinamide were 2.316 (1.819, 2.951), 2.091 (1.889, 2.317), 2.037 (1.804, 2.294), 1.912 (1.716, 2.129), 1.664 (1.113, 2.418), 1.584 (1.379, 1.820) and 1.179 (1.031, 1.352), respectively, compared with joint placebo and levodopa treatment.
CONCLUSIONS
Dopamine agonists were found to be effective as treatment for Parkinson's disease, both when given as monotherapy and in combination with levodopa. Selegiline and rasagiline were also found to be effective for treating Parkinson's disease, and selegiline was the best option in combination with levodopa among all the drugs investigated.
Topics: Dopamine Agonists; Drug Therapy, Combination; Humans; Indans; Levodopa; Monoamine Oxidase Inhibitors; Parkinson Disease; Randomized Controlled Trials as Topic; Selegiline; Treatment Outcome
PubMed: 32710141
DOI: 10.1007/s00228-020-02961-6 -
The Cochrane Database of Systematic... Apr 2023Attention deficit hyperactivity disorder (ADHD) is a major problem in children and adolescents, characterised by age-inappropriate levels of inattention, hyperactivity,... (Review)
Review
BACKGROUND
Attention deficit hyperactivity disorder (ADHD) is a major problem in children and adolescents, characterised by age-inappropriate levels of inattention, hyperactivity, and impulsivity, and is associated with long-term social, academic, and mental health problems. The stimulant medications methylphenidate and amphetamine are the most frequently used treatments for ADHD, but these are not always effective and can be associated with side effects. Clinical and biochemical evidence suggests that deficiencies of polyunsaturated fatty acids (PUFA) could be related to ADHD. Research has shown that children and adolescents with ADHD have significantly lower plasma and blood concentrations of PUFA and, in particular, lower levels of omega-3 PUFA. These findings suggest that PUFA supplementation may reduce the attention and behaviour problems associated with ADHD. This review is an update of a previously published Cochrane Review. Overall, there was little evidence that PUFA supplementation improved symptoms of ADHD in children and adolescents.
OBJECTIVES
To compare the efficacy of PUFA to other forms of treatment or placebo in treating the symptoms of ADHD in children and adolescents.
SEARCH METHODS
We searched 13 databases and two trials registers up to October 2021. We also checked the reference lists of relevant studies and reviews for additional references.
SELECTION CRITERIA
We included randomised and quasi-randomised controlled trials that compared PUFA with placebo or PUFA plus alternative therapy (medication, behavioural therapy, or psychotherapy) with the same alternative therapy alone in children and adolescents (aged 18 years and under) diagnosed with ADHD.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methods. Our primary outcome was severity or improvement of ADHD symptoms. Our secondary outcomes were severity or incidence of behavioural problems; quality of life; severity or incidence of depressive symptoms; severity or incidence of anxiety symptoms; side effects; loss to follow-up; and cost. We used GRADE to assess the certainty of evidence for each outcome.
MAIN RESULTS
We included 37 trials with more than 2374 participants, of which 24 trials were new to this update. Five trials (seven reports) used a cross-over design, while the remaining 32 trials (52 reports) used a parallel design. Seven trials were conducted in Iran, four each in the USA and Israel, and two each in Australia, Canada, New Zealand, Sweden, and the UK. Single studies were conducted in Brazil, France, Germany, India, Italy, Japan, Mexico, the Netherlands, Singapore, Spain, Sri Lanka, and Taiwan. Of the 36 trials that compared a PUFA to placebo, 19 used an omega-3 PUFA, six used a combined omega-3/omega-6 supplement, and two used an omega-6 PUFA. The nine remaining trials were included in the comparison of PUFA to placebo, but also had the same co-intervention in the PUFA and placebo groups. Of these, four trials compared a combination of omega-3 PUFA plus methylphenidate to methylphenidate. One trial each compared omega-3 PUFA plus atomoxetine to atomoxetine; omega-3 PUFA plus physical training to physical training; and an omega-3 or omega-6 supplement plus methylphenidate to methylphenidate; and two trials compared omega-3 PUFA plus dietary supplement to dietary supplement. Supplements were given for a period of between two weeks and six months. Although we found low-certainty evidence that PUFA compared to placebo may improve ADHD symptoms in the medium term (risk ratio (RR) 1.95, 95% confidence interval (CI) 1.47 to 2.60; 3 studies, 191 participants), there was high-certainty evidence that PUFA had no effect on parent-rated total ADHD symptoms compared to placebo in the medium term (standardised mean difference (SMD) -0.08, 95% CI -0.24 to 0.07; 16 studies, 1166 participants). There was also high-certainty evidence that parent-rated inattention (medium-term: SMD -0.01, 95% CI -0.20 to 0.17; 12 studies, 960 participants) and hyperactivity/impulsivity (medium-term: SMD 0.09, 95% CI -0.04 to 0.23; 10 studies, 869 participants) scores were no different compared to placebo. There was moderate-certainty evidence that overall side effects likely did not differ between PUFA and placebo groups (RR 1.02, 95% CI 0.69 to 1.52; 8 studies, 591 participants). There was also moderate-certainty evidence that medium-term loss to follow-up was likely similar between groups (RR 1.03, 95% CI 0.77 to 1.37; 13 studies, 1121 participants).
AUTHORS' CONCLUSIONS
Although we found low-certainty evidence that children and adolescents receiving PUFA may be more likely to improve compared to those receiving placebo, there was high-certainty evidence that PUFA had no effect on total parent-rated ADHD symptoms. There was also high-certainty evidence that inattention and hyperactivity/impulsivity did not differ between PUFA and placebo groups. We found moderate-certainty evidence that overall side effects likely did not differ between PUFA and placebo groups. There was also moderate-certainty evidence that follow-up was similar between groups. It is important that future research addresses the current weaknesses in this area, which include small sample sizes, variability of selection criteria, variability of the type and dosage of supplementation, and short follow-up times.
Topics: Child; Humans; Adolescent; Attention Deficit Disorder with Hyperactivity; Atomoxetine Hydrochloride; Quality of Life; Fatty Acids, Unsaturated; Methylphenidate; Fatty Acids, Omega-3; Amphetamine
PubMed: 37058600
DOI: 10.1002/14651858.CD007986.pub3 -
The Cochrane Database of Systematic... Nov 2020Cardiogenic shock (CS) and low cardiac output syndrome (LCOS) are potentially life-threatening complications of acute myocardial infarction (AMI), heart failure (HF) or... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Cardiogenic shock (CS) and low cardiac output syndrome (LCOS) are potentially life-threatening complications of acute myocardial infarction (AMI), heart failure (HF) or cardiac surgery. While there is solid evidence for the treatment of other cardiovascular diseases of acute onset, treatment strategies in haemodynamic instability due to CS and LCOS remains less robustly supported by the given scientific literature. Therefore, we have analysed the current body of evidence for the treatment of CS or LCOS with inotropic and/or vasodilating agents. This is the second update of a Cochrane review originally published in 2014.
OBJECTIVES
Assessment of efficacy and safety of cardiac care with positive inotropic agents and vasodilator agents in CS or LCOS due to AMI, HF or after cardiac surgery.
SEARCH METHODS
We conducted a search in CENTRAL, MEDLINE, Embase and CPCI-S Web of Science in October 2019. We also searched four registers of ongoing trials and scanned reference lists and contacted experts in the field to obtain further information. No language restrictions were applied.
SELECTION CRITERIA
Randomised controlled trials (RCTs) enrolling patients with AMI, HF or cardiac surgery complicated by CS or LCOS.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures according to Cochrane standards.
MAIN RESULTS
We identified 19 eligible studies including 2385 individuals (mean or median age range 56 to 73 years) and three ongoing studies. We categorised studies into 11 comparisons, all against standard cardiac care and additional other drugs or placebo. These comparisons investigated the efficacy of levosimendan versus dobutamine, enoximone or placebo; enoximone versus dobutamine, piroximone or epinephrine-nitroglycerine; epinephrine versus norepinephrine or norepinephrine-dobutamine; dopexamine versus dopamine; milrinone versus dobutamine and dopamine-milrinone versus dopamine-dobutamine. All trials were published in peer-reviewed journals, and analyses were done by the intention-to-treat (ITT) principle. Eighteen of 19 trials were small with only a few included participants. An acknowledgement of funding by the pharmaceutical industry or missing conflict of interest statements occurred in nine of 19 trials. In general, confidence in the results of analysed studies was reduced due to relevant study limitations (risk of bias), imprecision or indirectness. Domains of concern, which showed a high risk in more than 50% of included studies, encompassed performance bias (blinding of participants and personnel) and bias affecting the quality of evidence on adverse events. All comparisons revealed uncertainty on the effect of inotropic/vasodilating drugs on all-cause mortality with a low to very low quality of evidence. In detail, the findings were: levosimendan versus dobutamine (short-term mortality: RR 0.60, 95% CI 0.36 to 1.03; participants = 1701; low-quality evidence; long-term mortality: RR 0.84, 95% CI 0.63 to 1.13; participants = 1591; low-quality evidence); levosimendan versus placebo (short-term mortality: no data available; long-term mortality: RR 0.55, 95% CI 0.16 to 1.90; participants = 55; very low-quality evidence); levosimendan versus enoximone (short-term mortality: RR 0.50, 0.22 to 1.14; participants = 32; very low-quality evidence; long-term mortality: no data available); epinephrine versus norepinephrine-dobutamine (short-term mortality: RR 1.25; 95% CI 0.41 to 3.77; participants = 30; very low-quality evidence; long-term mortality: no data available); dopexamine versus dopamine (short-term mortality: no deaths in either intervention arm; participants = 70; very low-quality evidence; long-term mortality: no data available); enoximone versus dobutamine (short-term mortality RR 0.21; 95% CI 0.01 to 4.11; participants = 27; very low-quality evidence; long-term mortality: no data available); epinephrine versus norepinephrine (short-term mortality: RR 1.81, 0.89 to 3.68; participants = 57; very low-quality evidence; long-term mortality: no data available); and dopamine-milrinone versus dopamine-dobutamine (short-term mortality: RR 1.0, 95% CI 0.34 to 2.93; participants = 20; very low-quality evidence; long-term mortality: no data available). No information regarding all-cause mortality were available for the comparisons milrinone versus dobutamine, enoximone versus piroximone and enoximone versus epinephrine-nitroglycerine.
AUTHORS' CONCLUSIONS
At present, there are no convincing data supporting any specific inotropic or vasodilating therapy to reduce mortality in haemodynamically unstable patients with CS or LCOS. Considering the limited evidence derived from the present data due to a high risk of bias and imprecision, it should be emphasised that there is an unmet need for large-scale, well-designed randomised trials on this topic to close the gap between daily practice in critical care of cardiovascular patients and the available evidence. In light of the uncertainties in the field, partially due to the underlying methodological flaws in existing studies, future RCTs should be carefully designed to potentially overcome given limitations and ultimately define the role of inotropic agents and vasodilator strategies in CS and LCOS.
Topics: Aged; Cardiac Output, Low; Cardiotonic Agents; Cause of Death; Dobutamine; Enoximone; Epinephrine; Humans; Hydrazones; Middle Aged; Myocardial Infarction; Nitric Oxide; Placebos; Pyridazines; Randomized Controlled Trials as Topic; Shock, Cardiogenic; Simendan; Vasodilator Agents
PubMed: 33152122
DOI: 10.1002/14651858.CD009669.pub4