Remimazolam versus traditional sedatives for procedural sedation: A systematic review and meta-analysis of efficacy and safety outcomes

Abstract Background Pyrazinamide (PZA) is a key component of current and future regimens for tuberculosis (TB). Inclusion of PZA at higher doses and for longer durations may improve efficacy outcomes but must be balanced against the potential for worse safety outcomes. Methods We will search for randomised and quasi-randomised clinical trials in adult participants with and without the inclusion of PZA in TB treatment regimens in the Cochrane infectious diseases group’s trials register, Cochrane central register of controlled trials (CENTRAL), MEDLINE, EMBASE, LILACS, the metaRegister of Controlled Trials (mRCT) and the World Health Organization (WHO) international clinical trials registry platform. One author will screen abstracts and remove ineligible studies (10% of which will be double-screened by a second author). Two authors will review full texts for inclusion. Safety and efficacy data will be extracted to pre-piloted forms by one author (10% of which will be double-extracted by a second author). The Cochrane risk of bias tool will be used to assess study quality. The study has three objectives: the association of (1) inclusion, (2) dose and (3) duration of PZA with efficacy and safety outcomes. Risk ratios as relative measures of effect for direct comparisons within trials (all objectives) and proportions as absolute measures of effect for indirect comparisons across trials (for objectives 2 and 3) will be calculated. If there is insufficient data for direct comparisons within trials for objective 1, indirect comparisons between trials will be performed. Measures of effect will be pooled, with corresponding 95% confidence intervals and p values. Meta-analysis will be performed using the generalised inverse variance method for fixed effects models (FEM) or the DerSimonian-Laird method for random effects models (REM). For indirect comparisons, meta-regression for absolute measures against dose and duration data will be performed. Heterogeneity will be quantified through the I2-statistic for direct comparisons and the τ2 statistic for indirect comparisons using meta-regression. Discussion The current use of PZA for TB is based on over 60 years of clinical trial data, but this has never been synthesised to guide rationale use in future regimens and clinical trials. Systematic review registration: International Prospective Register of Systematic Reviews (PROSPERO) CRD42019138735

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The best treatment option(s) for adult and elderly patients with chronic primary musculoskeletal pain: a protocol for a systematic review and network meta-analysis

Systematic Reviews ◽

10.1186/s13643-019-1174-6 ◽

2019 ◽

Vol 8 (1) ◽

Cited By ~ 2

Author(s):

Helen Koechlin ◽

Ben Whalley ◽

Nicky J. Welton ◽

Cosima Locher

Keyword(s):

Systematic Review ◽

Musculoskeletal Pain ◽

Emotional Distress ◽

Treatment Option ◽

Functional Disability ◽

Meta Analysis ◽

Risk Of Bias ◽

Control Group ◽

Efficacy And Safety ◽

Safety Outcomes

Abstract Background Chronic primary musculoskeletal pain (CPMP) is one subcategory of the new classification of chronic primary pain for the upcoming ICD-11, defined as chronic pain in the muscles, bones, joints, or tendons that persists or recurs for more than 3 months and is associated with significant emotional distress or functional disability. An array of pharmacological, psychological, physical, complementary, and rehabilitative interventions is available for CPMP, for which previous research has demonstrated varying effect sizes with regard to effectiveness in pain reduction and other main outcomes. This highlights the need for the synthesis of all available evidence. The proposed network meta-analysis will compare all available interventions for CPMP to determine the best treatment option(s) with a focus on efficacy and safety of interventions. Methods We are interested in comparing interventions of the following types: psychological, pharmacological, physical, complementary, and rehabilitative interventions. We will include all randomized controlled trials that compare one intervention with another, or with a control group, in the treatment of CPMP. Primary efficacy outcomes will be pain intensity, emotional distress, and functional disability. Safety outcomes extracted will include proportion of patients with treatment-emergent adverse events, unwanted events, or drop-out rates due to side effects. Published and unpublished trials will be sought through the search of all relevant databases and trial registries. At least two independent reviewers of the team will select the references and extract data independently. We will assess the risk of bias of each individual study using the Cochrane risk of bias assessment tool. We will conduct a network meta-analysis to synthesize all evidence for each outcome. We will fit our model primarily within a Bayesian framework. Discussion CPMP is a disabling condition for which several interventions exist. To our knowledge, this is the first network meta-analysis to systematically compare all available evidence. This is required by national health institutions to inform their decisions about the best available treatment option(s) with regard to efficacy and safety outcomes. Systematic review registration PROSPERO CRD42018096114

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Antihypertensive therapies in moderate or severe aortic stenosis: a systematic review and meta-analysis

BMJ Open ◽

10.1136/bmjopen-2020-036960 ◽

2020 ◽

Vol 10 (10) ◽

pp. e036960

Author(s):

Jonathan Sen ◽

Erin Chung ◽

Christopher Neil ◽

Thomas Marwick

Keyword(s):

Systematic Review ◽

Blood Pressure ◽

Aortic Stenosis ◽

Severe Aortic Stenosis ◽

Meta Analysis ◽

Left Ventricular ◽

Controlled Trials ◽

Cochrane Central Register ◽

Efficacy And Safety ◽

Safety Outcomes

BackgroundHypertension confers a poor prognosis in moderate or severe aortic stenosis (AS), however, antihypertensive therapy (AHT) is often not prescribed due to the perceived deleterious effects of vasodilation and negative inotropes.ObjectiveTo assess the efficacy and safety outcomes of AHT in adults with moderate or severe AS.DesignSystematic review and meta-analysis.Data sourcesThe Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE and grey literature were searched without language restrictions up to 9 September 2019.Study eligibility criteria, appraisal and synthesis methodsTwo independent reviewers performed screening, data extraction and risk of bias assessments from a systematic search of observational studies and randomised controlled trials comparing AHT with a placebo or no AHT in adults with moderate or severe AS for any parameter of efficacy and safety outcomes. Conflicts were resolved by the third reviewer. Meta-analysis with pooled effect sizes using random-effects model, were estimated in R.Main outcome measuresMortality, Left Ventricular (LV) Mass Index, systolic blood pressure, diastolic blood pressure and LV ejection fractionResultsFrom 3025 publications, 31 studies (26 500 patients) were included in the qualitative synthesis and 24 studies in the meta-analysis. AHT was not associated with mortality when all studies were pooled, but heterogeneity was substantial across studies. The effect size of AHT differed according to drug class. Renin–angiotensin–aldosterone system inhibitors (RAASi) were associated with reduced risk of mortality (Pooled HR 0.58, 95% CI 0.43 to 0.80, p=0.006), The differences in changes of haemodynamic or echocardiographic parameters from baseline with and without AHT did not reach statistical significance.ConclusionAHT appears safe, is well tolerated. RAASi were associated with clinical benefit in patients with moderate or severe AS.

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