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Advances in Therapy Jan 2023Short-acting β-agonist (SABA) reliever overuse is common in asthma, despite availability of inhaled corticosteroid (ICS)-based maintenance therapies, and may be... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Short-acting β-agonist (SABA) reliever overuse is common in asthma, despite availability of inhaled corticosteroid (ICS)-based maintenance therapies, and may be associated with increased risk of adverse events (AEs). This systematic literature review (SLR) and meta-analysis aimed to investigate the safety and tolerability of SABA reliever monotherapy for adults and adolescents with asthma, through analysis of randomized controlled trials (RCTs) and real-world evidence.
METHODS
An SLR of English-language publications between January 1996 and December 2021 included RCTs and observational studies of patients aged ≥ 12 years treated with inhaled SABA reliever monotherapy (fixed dose or as needed) for ≥ 4 weeks. Studies of terbutaline and fenoterol were excluded. Meta-analysis feasibility was dependent on cross-trial data comparability. A random-effects model estimated rates of mortality, serious AEs (SAEs), and discontinuation due to AEs (DAEs) for as-needed and fixed-dose SABA treatment groups. ICS monotherapy and SABA therapy were compared using a fixed-effects model.
RESULTS
Forty-two studies were identified by the SLR for assessment of feasibility. Final meta-analysis included 24 RCTs. Too few observational studies (n = 2) were available for inclusion in the meta-analysis. One death unrelated to treatment was reported in each of the ICS, ICS + LABA, and fixed-dose SABA groups. No other treatment-related deaths were reported. SAE and DAE rates were < 4%. DAEs were reported more frequently in the SABA treatment groups than with ICS, potentially owing to worsening asthma symptoms being classified as an AE. SAE risk was comparable between SABA and ICS treatments.
CONCLUSIONS
Meta-analysis of data from RCTs showed that deaths were rare with SABA reliever monotherapy, and rates of SAEs and DAEs were comparable between SABA reliever and ICS treatment groups. When used appropriately within prescribed limits as reliever therapy, SABA does not contribute to excess rates of mortality, SAEs, or DAEs.
Topics: Adult; Adolescent; Humans; Ethanolamines; Asthma; Terbutaline; Adrenal Cortex Hormones; Drug Therapy, Combination; Administration, Inhalation; Anti-Asthmatic Agents
PubMed: 36348141
DOI: 10.1007/s12325-022-02356-2 -
Drug Safety Mar 2021Antidepressant use during the first trimester is reported in 4-8% of pregnancies. The use of some selective serotonin reuptake inhibitors during the first trimester has... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Antidepressant use during the first trimester is reported in 4-8% of pregnancies. The use of some selective serotonin reuptake inhibitors during the first trimester has been identified as increasing the odds for congenital heart defects; however, little is known about the safety of non-selective serotonin reuptake inhibitor antidepressants.
OBJECTIVE
The objective of this study was to assess the odds of congenital heart defects associated with the use of antidepressants during the first trimester of pregnancy, and to update the literature as newer studies have been published since the latest systematic literature review and meta-analysis.
METHODS
PubMed and Embase were searched till 3 June, 2020. Study quality was assessed, and study details were extracted. Meta-analyses were performed using RevMan 5.4, which assessed: (1) any antidepressant usage; (2) classes of antidepressants; and (3) individual antidepressants.
RESULTS
Twenty studies were identified, encompassing 5,337,223 pregnancies. The odds ratio for maternal use of any antidepressant during the first trimester of pregnancy and the presence of congenital heart defects from the random effects meta-analysis was 1.28 (95% confidence interval [CI] 1.17-1.41). Significant odds ratios of 1.69 (95% CI 1.37-2.10) and 1.25 (95% CI 1.15-1.37) were reported for serotonin norepinephrine reuptake inhibitors and selective serotonin reuptake inhibitors, respectively. A non-statistically significant odds ratio of 1.02 (95% CI 0.82-1.25) was reported for the tricyclic antidepressants. Analyses of individual SSRIs produced significant odds ratios of 1.57 (95% CI 1.25-1.97), 1.36 (95% CI 1.08-1.72), and 1.29 (95% CI 1.14-1.45) for paroxetine, fluoxetine, and sertraline, respectively. The norepinephrine-dopamine-reuptake inhibitor bupropion also produced a significant odds ratio of 1.23 (95% CI 1.01-1.49).
CONCLUSIONS
The selective serotonin reuptake inhibitor and serotonin norepinephrine reuptake inhibitor classes of antidepressants pose a greater risk for causing congenital heart defects than the tricyclic antidepressants. However, this risk for individual antidepressants within each class varies, and information regarding some antidepressants is still lacking.
Topics: Antidepressive Agents; Antidepressive Agents, Tricyclic; Female; Heart Defects, Congenital; Humans; Norepinephrine; Pregnancy; Serotonin; Selective Serotonin Reuptake Inhibitors
PubMed: 33354752
DOI: 10.1007/s40264-020-01027-x -
CNS Drugs Sep 2023Although one of the major presentations of vestibular migraine is dizziness with/without unsteady gait, it is still classified as one of the migraine categories.... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Although one of the major presentations of vestibular migraine is dizziness with/without unsteady gait, it is still classified as one of the migraine categories. However, in contrast to ordinary migraine, vestibular migraine patients have distinct characteristics, and the detailed treatment strategy for vestibular migraine is different and more challenging than ordinary migraine treatment. Currently, there is no conclusive evidence regarding its management, including vestibular migraine prophylaxis.
AIM
The objective of this current network meta-analysis (NMA) was to compare the efficacy and acceptability of individual treatment strategies in patients with vestibular migraine.
METHODS
The PubMed, Embase, ScienceDirect, ProQuest, Web of Science, ClinicalKey, Cochrane Central, and ClinicalTrials.gov databases were systematically searched for randomized controlled trials (RCTs), with a final literature search date of 30 December 2022. Patients diagnosed with vestibular migraine were included. The PICO of the current study included (1) patients with vestibular migraine; (2) intervention: any active pharmacologic or non-pharmacologic intervention; (3) comparator: placebo-control, active control, or waiting list; and (4) outcome: changes in migraine frequency or severity. This NMA of RCTs of vestibular migraine treatment was conducted using a frequentist model. We arranged inconsistency and similarity tests to re-examine the assumption of NMA, and also conducted a subgroup analysis focusing on RCTs of pharmacological treatment for vestibular migraine management. The primary outcome was changes in the frequency of vestibular migraines, while the secondary outcomes were changes in vestibular migraine severity and acceptability. Acceptability was set as the dropout rate, which was defined as the participant leaving the study before the end of the trial for any reason. Two authors independently evaluated the risk of bias for each domain using the Cochrane risk-of-bias tool.
RESULTS
Seven randomized controlled trials (N = 828, mean age 37.6 years, 78.4% female) and seven active regimens were included. We determined that only valproic acid (standardized mean difference [SMD] -1.61, 95% confidence interval [CI] -2.69, -0.54), propranolol (SMD -1.36, 95% CI -2.55, -0.17), and venlafaxine (SMD -1.25, 95% CI -2.32, -0.18) were significantly associated with better improvement in vestibular migraine frequency than the placebo/control groups. Furthermore, among all the investigated pharmacologic/non-pharmacologic treatments, valproic acid yielded the greatest decrease in vestibular migraine frequency among all the interventions. In addition, most pharmacologic/non-pharmacologic treatments were associated with similar acceptability (i.e. dropout rate) as those of the placebo/control groups.
CONCLUSIONS
The current study provides evidence that only valproic acid, propranolol, and venlafaxine might be associated with beneficial efficacy in vestibular migraine treatment.
TRIAL REGISTRATION
CRD42023388343.
Topics: Adult; Female; Humans; Male; Migraine Disorders; Network Meta-Analysis; Propranolol; Valproic Acid; Venlafaxine Hydrochloride
PubMed: 37676473
DOI: 10.1007/s40263-023-01037-0 -
Nutrients Jul 2017Studies implicate choline and betaine metabolite trimethylamine N-oxide (TMAO) in cardiovascular disease (CVD). We conducted a systematic review and random-effects... (Meta-Analysis)
Meta-Analysis Review
Studies implicate choline and betaine metabolite trimethylamine N-oxide (TMAO) in cardiovascular disease (CVD). We conducted a systematic review and random-effects meta-analysis to quantify a summary estimated effect of dietary choline and betaine on hard CVD outcomes (incidence and mortality). Eligible studies were prospective studies in adults with comprehensive diet assessment and follow-up for hard CVD endpoints. We identified six studies that met our criteria, comprising 18,076 incident CVD events, 5343 CVD deaths, and 184,010 total participants. In random effects meta-analysis, incident CVD was not associated with choline (relative risk (RR): 1.00; 95% CI: 0.98, 1.02) or betaine (RR: 0.99; 95% CI: 0.98, 1.01) intake. Results did not vary by study outcome (incident coronary heart disease, stroke, total CVD) and there was no evidence for heterogeneity among studies. Only two studies provided data on phosphatidylcholine and CVD mortality. Random effects meta-analysis did not support an association between choline and CVD mortality (RR: 1.09, 95% CI: 0.89, 1.35), but one study supported a positive association and there was significant heterogeneity (² = 84%, -value < 0.001). Our findings do not support an association between dietary choline/betaine with incident CVD, but call for further research into choline and CVD mortality.
Topics: Adult; Aged; Betaine; Cardiovascular Diseases; Choline; Diet; Female; Humans; Male; Middle Aged; Prospective Studies; Risk; Risk Factors
PubMed: 28686188
DOI: 10.3390/nu9070711 -
Cardiovascular Drugs and Therapy Oct 2022To determine the effect of major antihypertensive classes on erectile function (EF) in patients with or at high risk of cardiovascular disease. (Meta-Analysis)
Meta-Analysis
PURPOSE
To determine the effect of major antihypertensive classes on erectile function (EF) in patients with or at high risk of cardiovascular disease.
METHODS
We performed a systematic review and frequentist network meta-analysis of randomized controlled trials assessing the effect of angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, β-blockers, calcium channel blockers, and thiazide diuretics on EF compared to each other and to placebo (PROSPERO: CRD42020189529). Similarly, we performed a network meta-analysis to explore the effect of different β-blockers on erectile function (nebivolol, other vasodilating and non-vasodilating β-blockers, placebo). Records were identified through search of PubMed, Cochrane Library, and Scopus databases and sources of grey literature until September 2020.
RESULTS
We included 25 studies (7784 patients) in the qualitative and 16 studies in the quantitative synthesis. The risk of bias was concerning or high in the majority of studies, and inconsistency was also high. No significant differences in EF were demonstrated in the pairwise comparisons between major antihypertensive classes. Similarly, when placebo was set as the reference treatment group, no treatment strategy yielded significant effects on EF. In the β-blockers analysis, nebivolol contributed a beneficial effect on EF only when compared to non-vasodilatory β-blockers (OR 2.92, 95%CI 1.3-6.5) and not when compared to placebo (OR 2.87, 95%CI 0.75-11.04) or to other vasodilatory β-blockers (OR 2.15, 95%CI 0.6-7.77).
CONCLUSION
All antihypertensive medication classes seem to exert neutral or insignificant effects on EF. Further high-quality studies are needed to better explore the effects of antihypertensive medication on EF.
Topics: Adrenergic beta-Antagonists; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Calcium Channel Blockers; Diuretics; Erectile Dysfunction; Humans; Hypertension; Male; Nebivolol; Network Meta-Analysis; Sodium Chloride Symporter Inhibitors
PubMed: 33945044
DOI: 10.1007/s10557-021-07197-9 -
The Cochrane Database of Systematic... May 2016Transient tachypnea of the newborn is characterized by tachypnea and signs of respiratory distress. Transient tachypnea typically appears within the first two hours of... (Review)
Review
BACKGROUND
Transient tachypnea of the newborn is characterized by tachypnea and signs of respiratory distress. Transient tachypnea typically appears within the first two hours of life in term and late preterm newborns. Although transient tachypnea of the newborn is usually a self limited condition, it is associated with wheezing syndromes in late childhood. The rationale for the use of epinephrine (adrenaline) for transient tachypnea of the newborn is based on studies showing that β-agonists can accelerate the rate of alveolar fluid clearance.
OBJECTIVES
To assess whether epinephrine compared to placebo, no treatment or any other drugs (excluding salbutamol) is effective and safe in the treatment of transient tachypnea of the newborn in infants born at 34 weeks' gestational age or more.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL, 2016, Issue 3), MEDLINE (1996 to March 2016), EMBASE (1980 to March 2016) and CINAHL (1982 to March 2016). We applied no language restrictions. We searched the abstracts of the major congresses in the field (Perinatal Society of Australia and New Zealand and Pediatric Academic Societies) from 2000 to 2015.
SELECTION CRITERIA
Randomized controlled trials, quasi-randomized controlled trials and cluster trials comparing epinephrine versus placebo or no treatment or any other drugs administered to infants born at 34 weeks' gestational age or more and less than three days of age with transient tachypnea of the newborn.
DATA COLLECTION AND ANALYSIS
For the included trial, two review authors independently extracted data (e.g. number of participants, birth weight, gestational age, duration of oxygen therapy (hours), need for continuous positive airway pressure and need for mechanical ventilation, duration of mechanical ventilation, etc.) and assessed the risk of bias (e.g. adequacy of randomization, blinding, completeness of follow-up). The primary outcomes considered in this review were duration of oxygen therapy (hours), need for continuous positive airway pressure and need for mechanical ventilation.
MAIN RESULTS
One trial, which included 20 infants, met the inclusion criteria of this review. Study authors administered three doses of nebulized 2.25% racemic epinephrine or placebo. We found no differences between the two group in the duration of supplemental oxygen therapy (mean difference (MD) -6.60, 95% confidence interval (CI) -54.80 to 41.60 hours) and need for mechanical ventilation (risk ratio (RR) 0.67, 95% CI 0.08 to 5.88; risk difference (RD) -0.07, 95% CI -0.46 to 0.32). Among secondary outcomes, we found no differences in terms of initiation of oral feeding. The quality of the evidence was limited due to the imprecision of the estimates.
AUTHORS' CONCLUSIONS
At present there is insufficient evidence to determine the efficacy and safety of epinephrine in the management of transient tachypnea of the newborn.
Topics: Adrenergic beta-Agonists; Epinephrine; Humans; Infant, Newborn; Oxygen Inhalation Therapy; Randomized Controlled Trials as Topic; Respiration, Artificial; Transient Tachypnea of the Newborn
PubMed: 27211231
DOI: 10.1002/14651858.CD011877.pub2 -
Shock (Augusta, Ga.) Nov 2023Background: Vasopressor plays a crucial role in septic shock. However, the time for vasopressor initiation remains controversial. We conducted a systematic review and... (Meta-Analysis)
Meta-Analysis
Background: Vasopressor plays a crucial role in septic shock. However, the time for vasopressor initiation remains controversial. We conducted a systematic review and meta-analysis to explore its initiation timing for septic shock patients. Methods: PubMed, Cochrane Library, Embase, and Web of Sciences were searched from inception to July 12, 2023, for relevant studies. Primary outcome was short-term mortality. Meta-analysis was performed using Stata 15.0. Results: Twenty-three studies were assessed, including 2 randomized controlled trials and 21 cohort studies. The early group resulted in lower short-term mortality than the late group (OR [95% CI] = 0.775 [0.673 to 0.893], P = 0.000, I2 = 67.8%). The significance existed in the norepinephrine and vasopressin in subgroup analysis. No significant difference was considered in the association between each hour's vasopressor delay and mortality (OR [95% CI] = 1.02 [0.99 to 1.051], P = 0.195, I2 = 57.5%). The early group had an earlier achievement of target MAP ( P < 0.001), shorter vasopressor use duration ( P < 0.001), lower serum lactate level at 24 h ( P = 0.003), lower incidence of kidney injury ( P = 0.001), renal replacement therapy use ( P = 0.022), and longer ventilation-free days to 28 days ( P < 0.001). Conclusions: Early initiation of vasopressor (1-6 h within septic shock onset) would be more beneficial to septic shock patients. The conclusion needs to be further validated by more well-designed randomized controlled trials.
Topics: Humans; Shock, Septic; Vasoconstrictor Agents; Norepinephrine; Cohort Studies; Renal Replacement Therapy
PubMed: 37695641
DOI: 10.1097/SHK.0000000000002214 -
Biology Direct Oct 2023The social impact of glaucoma is worth of note: primary open-angle glaucoma (POAG) is one of the leading causes of irreversible blindness worldwide, affecting some 68.56... (Meta-Analysis)
Meta-Analysis Review
The social impact of glaucoma is worth of note: primary open-angle glaucoma (POAG) is one of the leading causes of irreversible blindness worldwide, affecting some 68.56 million people with overall prevalence of 2.4%. Since one of the main risk factors for the development of POAG is the increase of intraocular pressure (IOP) causing retinal ganglion cells death, the medical treatment of POAG consists in the use of drugs endowed with neuroprotective effect and able to reduce IOP. These drugs include beta-blockers, prostaglandin analogues, carbonic anhydrase inhibitors, alpha or cholinergic agonists and rho kinase inhibitors. However, not all the patients respond to the same extent to the therapy in terms of efficacy and safety. Genetics and genome wide association studies have highlighted the occurrence of mutations and polymorphisms influencing the predisposition to develop POAG and its phenotype, as well as affecting the response to pharmacological treatment. The present systematic review and meta-analysis aims at identifying genetic variants and at verifying whether these can influence the responsiveness of patients to therapy for efficacy and safety. It follows the most updated Preferred Reporting Items for Systematic reviews and Meta-Analyses 2020 recommendations. The literature search was conducted consulting the most relevant scientific databases, i.e. PubMed/MEDLINE, Scopus, Web of Science and Public Health Genomics and Precision Health Knowledge Base up to June 14th, 2023. The search retrieved 1026 total records, among which eight met the eligibility criteria for inclusion in the analysis. The results demonstrated that the most investigated pharmacogenetic associations concern latanoprost and timolol, and that efficacy was studied more in depth than safety. Moreover, the heterogeneity of design and paucity of studies prompt further investigation in randomized clinical trials. In fact, adequately powered and designed pharmacogenetic association studies are needed to provide body of evidence with good certainty for a more appropriate use of medical therapy in POAG.PROSPERO registration: CRD42023434867.
Topics: Humans; Glaucoma, Open-Angle; Antihypertensive Agents; Genome-Wide Association Study; Timolol; Genotype
PubMed: 37833756
DOI: 10.1186/s13062-023-00423-4 -
The Cochrane Database of Systematic... Nov 2021Multiple sclerosis (MS) is the most common neurological cause of disability in young adults. Off-label rituximab for MS is used in most countries surveyed by the... (Review)
Review
BACKGROUND
Multiple sclerosis (MS) is the most common neurological cause of disability in young adults. Off-label rituximab for MS is used in most countries surveyed by the International Federation of MS, including high-income countries where on-label disease-modifying treatments (DMTs) are available. OBJECTIVES: To assess beneficial and adverse effects of rituximab as 'first choice' and as 'switching' for adults with MS.
SEARCH METHODS
We searched CENTRAL, MEDLINE, Embase, CINAHL, and trial registers for completed and ongoing studies on 31 January 2021.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) and controlled non-randomised studies of interventions (NRSIs) comparing rituximab with placebo or another DMT for adults with MS.
DATA COLLECTION AND ANALYSIS
We followed standard Cochrane methodology. We used the Cochrane Collaboration's tool for assessing risk of bias. We rated the certainty of evidence using GRADE for: disability worsening, relapse, serious adverse events (SAEs), health-related quality of life (HRQoL), common infections, cancer, and mortality. We conducted separate analyses for rituximab as 'first choice' or as 'switching', relapsing or progressive MS, comparison versus placebo or another DMT, and RCTs or NRSIs.
MAIN RESULTS
We included 15 studies (5 RCTs, 10 NRSIs) with 16,429 participants of whom 13,143 were relapsing MS and 3286 progressive MS. The studies were one to two years long and compared rituximab as 'first choice' with placebo (1 RCT) or other DMTs (1 NRSI), rituximab as 'switching' against placebo (2 RCTs) or other DMTs (2 RCTs, 9 NRSIs). The studies were conducted worldwide; most originated from high-income countries, six from the Swedish MS register. Pharmaceutical companies funded two studies. We identified 14 ongoing studies. Rituximab as 'first choice' for relapsing MS Rituximab versus placebo: no studies met eligibility criteria for this comparison. Rituximab versus other DMTs: one NRSI compared rituximab with interferon beta or glatiramer acetate, dimethyl fumarate, natalizumab, or fingolimod in active relapsing MS at 24 months' follow-up. Rituximab likely results in a large reduction in relapses compared with interferon beta or glatiramer acetate (hazard ratio (HR) 0.14, 95% confidence interval (CI) 0.05 to 0.39; 335 participants; moderate-certainty evidence). Rituximab may reduce relapses compared with dimethyl fumarate (HR 0.29, 95% CI 0.08 to 1.00; 206 participants; low-certainty evidence) and natalizumab (HR 0.24, 95% CI 0.06 to 1.00; 170 participants; low-certainty evidence). It may make little or no difference on relapse compared with fingolimod (HR 0.26, 95% CI 0.04 to 1.69; 137 participants; very low-certainty evidence). The study reported no deaths over 24 months. The study did not measure disability worsening, SAEs, HRQoL, and common infections. Rituximab as 'first choice' for progressive MS One RCT compared rituximab with placebo in primary progressive MS at 24 months' follow-up. Rituximab likely results in little to no difference in the number of participants who have disability worsening compared with placebo (odds ratio (OR) 0.71, 95% CI 0.45 to 1.11; 439 participants; moderate-certainty evidence). Rituximab may result in little to no difference in recurrence of relapses (OR 0.60, 95% CI 0.18 to 1.99; 439 participants; low-certainty evidence), SAEs (OR 1.25, 95% CI 0.71 to 2.20; 439 participants; low-certainty evidence), common infections (OR 1.14, 95% CI 0.75 to 1.73; 439 participants; low-certainty evidence), cancer (OR 0.50, 95% CI 0.07 to 3.59; 439 participants; low-certainty evidence), and mortality (OR 0.25, 95% CI 0.02 to 2.77; 439 participants; low-certainty evidence). The study did not measure HRQoL. Rituximab versus other DMTs: no studies met eligibility criteria for this comparison. Rituximab as 'switching' for relapsing MS One RCT compared rituximab with placebo in relapsing MS at 12 months' follow-up. Rituximab may decrease recurrence of relapses compared with placebo (OR 0.38, 95% CI 0.16 to 0.93; 104 participants; low-certainty evidence). The data did not confirm or exclude a beneficial or detrimental effect of rituximab relative to placebo on SAEs (OR 0.90, 95% CI 0.28 to 2.92; 104 participants; very low-certainty evidence), common infections (OR 0.91, 95% CI 0.37 to 2.24; 104 participants; very low-certainty evidence), cancer (OR 1.55, 95% CI 0.06 to 39.15; 104 participants; very low-certainty evidence), and mortality (OR 1.55, 95% CI 0.06 to 39.15; 104 participants; very low-certainty evidence). The study did not measure disability worsening and HRQoL. Five NRSIs compared rituximab with other DMTs in relapsing MS at 24 months' follow-up. The data did not confirm or exclude a beneficial or detrimental effect of rituximab relative to interferon beta or glatiramer acetate on disability worsening (HR 0.86, 95% CI 0.52 to 1.42; 1 NRSI, 853 participants; very low-certainty evidence). Rituximab likely results in a large reduction in relapses compared with interferon beta or glatiramer acetate (HR 0.18, 95% CI 0.07 to 0.49; 1 NRSI, 1383 participants; moderate-certainty evidence); and fingolimod (HR 0.08, 95% CI 0.02 to 0.32; 1 NRSI, 256 participants; moderate-certainty evidence). The data did not confirm or exclude a beneficial or detrimental effect of rituximab relative to natalizumab on relapses (HR 1.0, 95% CI 0.2 to 5.0; 1 NRSI, 153 participants; very low-certainty evidence). Rituximab likely increases slightly common infections compared with interferon beta or glatiramer acetate (OR 1.71, 95% CI 1.11 to 2.62; 1 NRSI, 5477 participants; moderate-certainty evidence); and compared with natalizumab (OR 1.58, 95% CI 1.08 to 2.32; 2 NRSIs, 5001 participants; moderate-certainty evidence). Rituximab may increase slightly common infections compared with fingolimod (OR 1.26, 95% CI 0.90 to 1.77; 3 NRSIs, 5187 participants; low-certainty evidence). It may make little or no difference compared with ocrelizumab (OR 0.02, 95% CI 0.00 to 0.40; 1 NRSI, 472 participants; very low-certainty evidence). The data did not confirm or exclude a beneficial or detrimental effect of rituximab on mortality compared with fingolimod (OR 5.59, 95% CI 0.22 to 139.89; 1 NRSI, 136 participants; very low-certainty evidence) and natalizumab (OR 6.66, 95% CI 0.27 to 166.58; 1 NRSI, 153 participants; very low-certainty evidence). The included studies did not measure SAEs, HRQoL, and cancer.
AUTHORS' CONCLUSIONS
For preventing relapses in relapsing MS, rituximab as 'first choice' and as 'switching' may compare favourably with a wide range of approved DMTs. A protective effect of rituximab against disability worsening is uncertain. There is limited information to determine the effect of rituximab for progressive MS. The evidence is uncertain about the effect of rituximab on SAEs. They are relatively rare in people with MS, thus difficult to study, and they were not well reported in studies. There is an increased risk of common infections with rituximab, but absolute risk is small. Rituximab is widely used as off-label treatment in people with MS; however, randomised evidence is weak. In the absence of randomised evidence, remaining uncertainties on beneficial and adverse effects of rituximab for MS might be clarified by making real-world data available.
Topics: Fingolimod Hydrochloride; Glatiramer Acetate; Humans; Multiple Sclerosis; Multiple Sclerosis, Chronic Progressive; Rituximab; Young Adult
PubMed: 34748215
DOI: 10.1002/14651858.CD013874.pub2 -
Resuscitation Mar 2021To evaluate the optimal timing and doses of epinephrine for Infants and children suffering in-hospital or out-of-hospital cardiac arrest. (Meta-Analysis)
Meta-Analysis Review
AIM
To evaluate the optimal timing and doses of epinephrine for Infants and children suffering in-hospital or out-of-hospital cardiac arrest.
METHODS
We searched Medline, EMBASE, and Cochrane Controlled Register of Trials (CENTRAL) for human randomized clinical trials and observational studies including comparative cohorts. Two investigators reviewed relevance of studies, extracted the data, conducted meta-analyses and assessed the risk of bias using the GRADE and CLARITY frameworks. Authors of the eligible studies were contacted to obtain additional data. Critically important outcomes included return of spontaneous circulation, survival to hospital discharge and survival with good neurological outcome.
RESULTS
We identified 7 observational studies suitable for meta-analysis and no randomized clinical trials. The overall certainty of evidence was very low. For the critically important outcomes, the earlier administration of epinephrine was favorable for both in-hospital and out-of-hospital cardiac arrest. Because of a limited number of eligible studies and the presence of severe confounding factors, we could not determine the optimal interval of epinephrine administration.
CONCLUSIONS
Earlier administration of the first epinephrine dose could be more favorable in non-shockable pediatric cardiac arrest. The optimal interval for epinephrine administration remains unclear.
Topics: Child; Epinephrine; Humans; Infant; Out-of-Hospital Cardiac Arrest; Patient Discharge
PubMed: 33529645
DOI: 10.1016/j.resuscitation.2021.01.015