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Cardiovascular Diabetology Mar 2022We conducted a systematic review and meta-analysis of the cardiovascular, kidney, and safety outcomes of sodium-glucose cotransporter 2 inhibitors (SGLT2i) among... (Meta-Analysis)
Meta-Analysis
BACKGROUND
We conducted a systematic review and meta-analysis of the cardiovascular, kidney, and safety outcomes of sodium-glucose cotransporter 2 inhibitors (SGLT2i) among patients with diabetic kidney disease (DKD).
METHODS
We searched electronic databases for major randomized placebo-controlled clinical trials published up to September 30, 2021 and reporting on cardiovascular and kidney outcomes of SGLT2i in patients with DKD. DKD was defined as chronic kidney disease in individuals with type 2 diabetes. Random-effects meta-analysis models were used to estimate pooled hazard ratios (HR) and 95% confidence intervals (CI) for clinical outcomes including major adverse cardiovascular events (MACE: myocardial infarction [MI], stroke, and cardiovascular death), kidney composite outcomes (a combination of worsening kidney function, end-stage kidney disease, or death from renal or cardiovascular causes), hospitalizations for heart failure (HHF), deaths and safety events (mycotic infections, diabetic ketoacidosis [DKA], volume depletion, amputations, fractures, urinary tract infections [UTI], acute kidney injury [AKI], and hyperkalemia).
RESULTS
A total of 26,106 participants with DKD from 8 large-scale trials were included (median age: 65.2 years, 29.7-41.8% women, 53.2-93.2% White, median follow-up: 2.5 years). SGLT2i were associated with reduced risks of MACE (HR 0.83, 95% CI 0.75-0.93), kidney composite outcomes (HR 0.66, 95% CI 0.58-0.75), HHF (HR 0.62, 95% CI 0.55-0.71), cardiovascular death (HR 0.84, 95% CI 0.74-0.96), MI (HR 0.78, 95% CI 0.67-0.92), stroke (HR 0.76, 95% CI 0.59-0.97), and all-cause death (HR 0.86, 95% CI 0.77-0.96), with no significant heterogeneity detected. Similar results were observed among participants with reduced estimated glomerular filtration rate (eGFR: < 60 mL/min/1.73m). The relative risks (95% CI) for adverse events were 3.89 (1.42-10.62) and 2.50 (1.32-4.72) for mycotic infections in men and women respectively, 3.54 (0.82-15.39) for DKA, and 1.29 (1.13-1.48) for volume depletion.
CONCLUSIONS
Among adults with DKD, SGLT2i were associated with reduced risks of MACE, kidney outcomes, HHF, and death. With a few exceptions of more clear safety signals, we found overall limited data on the associations between SGLT2i and safety outcomes. More research is needed on the safety profile of SGLT2i in this population.
Topics: Adult; Aged; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Diabetic Ketoacidosis; Diabetic Nephropathies; Female; Heart Failure; Humans; Kidney; Male; Myocardial Infarction; Sodium-Glucose Transporter 2 Inhibitors; Stroke
PubMed: 35321742
DOI: 10.1186/s12933-022-01476-x -
The Lancet. Diabetes & Endocrinology Feb 2018Glucagon-like peptide-1 (GLP-1) receptor agonists are effective glucose-lowering drugs. Findings from cardiovascular outcome trials showed cardiovascular safety of GLP-1... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Glucagon-like peptide-1 (GLP-1) receptor agonists are effective glucose-lowering drugs. Findings from cardiovascular outcome trials showed cardiovascular safety of GLP-1 receptor agonists, but results for cardiovascular efficacy were varied. We aimed to examine overall cardiovascular efficacy for lixisenatide, liraglutide, semaglutide, and extended-release exenatide.
METHODS
In this systematic review and meta-analysis, we analysed data from eligible trials that assessed the safety and efficacy of GLP-1 receptor agonists compared with placebo in adult patients (aged 18 years or older) with type 2 diabetes and had a primary outcome including, but not limited to, cardiovascular mortality, non-fatal myocardial infarction, and non-fatal stroke. We searched PubMed and MEDLINE without language restrictions up to Sept 18, 2017, for eligible trials. We did a meta-analysis of available trial data using a random-effects model to calculate overall hazard ratios (HRs) for cardiovascular efficacy outcomes and odds ratios for key safety outcomes.
FINDINGS
Of 12 articles identified in our search and screened for eligibility, four trials of cardiovascular outcomes of GLP-1 receptor agonists were identified: ELIXA (lixisenatide), LEADER (liraglutide), SUSTAIN 6 (semaglutide), and EXSCEL (extended-release exenatide). Compared with placebo, GLP-1 receptor agonist treatment showed a significant 10% relative risk reduction in the three-point major adverse cardiovascular event primary outcome (cardiovascular mortality, non-fatal myocardial infarction, and non-fatal stroke; HR 0·90, 95% CI 0·82-0·99; p=0·033), a 13% RRR in cardiovascular mortality (0·87, 0·79-0·96; p=0·007), and a 12% relative risk reduction in all-cause mortality (0·88, 0·81-0·95; p=0·002), with low-to-moderate between-trial statistical heterogeneity. No significant effect of GLP-1 receptor agonists was identified on fatal and non-fatal myocardial infarction, fatal and non-fatal stroke, hospital admission for unstable angina, or hospital admission for heart failure. Overall, no significant differences were seen in severe hypoglycaemia, pancreatitis, pancreatic cancer, or medullary thyroid cancer reported between GLP-1 receptor agonist treatment and placebo.
INTERPRETATION
Our findings show cardiovascular safety across all GLP-1 receptor agonist cardiovascular outcome trials and suggest that drugs in this class can reduce three-point major adverse cardiovascular events, cardiovascular mortality, and all-cause mortality risk, albeit to varying degrees for individual drugs, without significant safety concerns. GLP-1 receptor agonists have a favourable risk-benefit balance overall, which should allow the choice of drug to be individualised to each patient's needs.
FUNDING
Amylin Pharmaceuticals (AstraZeneca).
Topics: Cardiovascular Diseases; Cardiovascular System; Diabetes Mellitus, Type 2; Glucagon-Like Peptide-1 Receptor; Humans; Hypoglycemic Agents; Prognosis; Survival Rate
PubMed: 29221659
DOI: 10.1016/S2213-8587(17)30412-6 -
The Cochrane Database of Systematic... Nov 2020Stroke is one of the leading causes of disability worldwide. Functional impairment, resulting in poor performance in activities of daily living (ADL) among stroke... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Stroke is one of the leading causes of disability worldwide. Functional impairment, resulting in poor performance in activities of daily living (ADL) among stroke survivors is common. Current rehabilitation approaches have limited effectiveness in improving ADL performance, function, muscle strength, and cognitive abilities (including spatial neglect) after stroke, with improving cognition being the number one research priority in this field. A possible adjunct to stroke rehabilitation might be non-invasive brain stimulation by transcranial direct current stimulation (tDCS) to modulate cortical excitability, and hence to improve these outcomes in people after stroke.
OBJECTIVES
To assess the effects of tDCS on ADL, arm and leg function, muscle strength and cognitive abilities (including spatial neglect), dropouts and adverse events in people after stroke.
SEARCH METHODS
We searched the Cochrane Stroke Group Trials Register, CENTRAL, MEDLINE, Embase and seven other databases in January 2019. In an effort to identify further published, unpublished, and ongoing trials, we also searched trials registers and reference lists, handsearched conference proceedings, and contacted authors and equipment manufacturers.
SELECTION CRITERIA
This is the update of an existing review. In the previous version of this review, we focused on the effects of tDCS on ADL and function. In this update, we broadened our inclusion criteria to compare any kind of active tDCS for improving ADL, function, muscle strength and cognitive abilities (including spatial neglect) versus any kind of placebo or control intervention.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed trial quality and risk of bias, extracted data, and applied GRADE criteria. If necessary, we contacted study authors to ask for additional information. We collected information on dropouts and adverse events from the trial reports.
MAIN RESULTS
We included 67 studies involving a total of 1729 patients after stroke. We also identified 116 ongoing studies. The risk of bias did not differ substantially for different comparisons and outcomes. The majority of participants had ischaemic stroke, with mean age between 43 and 75 years, in the acute, postacute, and chronic phase after stroke, and level of impairment ranged from severe to less severe. Included studies differed in terms of type, location and duration of stimulation, amount of current delivered, electrode size and positioning, as well as type and location of stroke. We found 23 studies with 781 participants examining the effects of tDCS versus sham tDCS (or any other passive intervention) on our primary outcome measure, ADL after stroke. Nineteen studies with 686 participants reported absolute values and showed evidence of effect regarding ADL performance at the end of the intervention period (standardised mean difference (SMD) 0.28, 95% confidence interval (CI) 0.13 to 0.44; random-effects model; moderate-quality evidence). Four studies with 95 participants reported change scores, and showed an effect (SMD 0.48, 95% CI 0.02 to 0.95; moderate-quality evidence). Six studies with 269 participants assessed the effects of tDCS on ADL at the end of follow-up and provided absolute values, and found improved ADL (SMD 0.31, 95% CI 0.01 to 0.62; moderate-quality evidence). One study with 16 participants provided change scores and found no effect (SMD -0.64, 95% CI -1.66 to 0.37; low-quality evidence). However, the results did not persist in a sensitivity analysis that included only trials with proper allocation concealment. Thirty-four trials with a total of 985 participants measured upper extremity function at the end of the intervention period. Twenty-four studies with 792 participants that presented absolute values found no effect in favour of tDCS (SMD 0.17, 95% CI -0.05 to 0.38; moderate-quality evidence). Ten studies with 193 participants that presented change values also found no effect (SMD 0.33, 95% CI -0.12 to 0.79; low-quality evidence). Regarding the effects of tDCS on upper extremity function at the end of follow-up, we identified five studies with a total of 211 participants (absolute values) without an effect (SMD -0.00, 95% CI -0.39 to 0.39; moderate-quality evidence). Three studies with 72 participants presenting change scores found an effect (SMD 1.07; 95% CI 0.04 to 2.11; low-quality evidence). Twelve studies with 258 participants reported outcome data for lower extremity function and 18 studies with 553 participants reported outcome data on muscle strength at the end of the intervention period, but there was no effect (high-quality evidence). Three studies with 156 participants reported outcome data on muscle strength at follow-up, but there was no evidence of an effect (moderate-quality evidence). Two studies with 56 participants found no evidence of effect of tDCS on cognitive abilities (low-quality evidence), but one study with 30 participants found evidence of effect of tDCS for improving spatial neglect (very low-quality evidence). In 47 studies with 1330 participants, the proportions of dropouts and adverse events were comparable between groups (risk ratio (RR) 1.25, 95% CI 0.74 to 2.13; random-effects model; moderate-quality evidence). AUTHORS' CONCLUSIONS: There is evidence of very low to moderate quality on the effectiveness of tDCS versus control (sham intervention or any other intervention) for improving ADL outcomes after stroke. However, the results did not persist in a sensitivity analyses including only trials with proper allocation concealment. Evidence of low to high quality suggests that there is no effect of tDCS on arm function and leg function, muscle strength, and cognitive abilities in people after stroke. Evidence of very low quality suggests that there is an effect on hemispatial neglect. There was moderate-quality evidence that adverse events and numbers of people discontinuing the treatment are not increased. Future studies should particularly engage with patients who may benefit the most from tDCS after stroke, but also should investigate the effects in routine application. Therefore, further large-scale randomised controlled trials with a parallel-group design and sample size estimation for tDCS are needed.
Topics: Activities of Daily Living; Adult; Aged; Bias; Cognition Disorders; Confidence Intervals; Female; Humans; Lower Extremity; Male; Middle Aged; Motor Activity; Muscle Strength; Patient Dropouts; Perceptual Disorders; Randomized Controlled Trials as Topic; Recovery of Function; Stroke Rehabilitation; Transcranial Direct Current Stimulation; Upper Extremity
PubMed: 33175411
DOI: 10.1002/14651858.CD009645.pub4 -
The Cochrane Database of Systematic... Oct 2020Despite the availability of effective drug therapies that reduce low-density lipoprotein (LDL)-cholesterol (LDL-C), cardiovascular disease (CVD) remains an important... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Despite the availability of effective drug therapies that reduce low-density lipoprotein (LDL)-cholesterol (LDL-C), cardiovascular disease (CVD) remains an important cause of mortality and morbidity. Therefore, additional LDL-C reduction may be warranted, especially for people who are unresponsive to, or unable to take, existing LDL-C-reducing therapies. By inhibiting the proprotein convertase subtilisin/kexin type 9 (PCSK9) enzyme, monoclonal antibodies (PCSK9 inhibitors) reduce LDL-C and CVD risk.
OBJECTIVES
Primary To quantify the effects of PCSK9 inhibitors on CVD, all-cause mortality, myocardial infarction, and stroke, compared to placebo or active treatment(s) for primary and secondary prevention. Secondary To quantify the safety of PCSK9 inhibitors, with specific focus on the incidence of influenza, hypertension, type 2 diabetes, and cancer, compared to placebo or active treatment(s) for primary and secondary prevention.
SEARCH METHODS
We identified studies by systematically searching CENTRAL, MEDLINE, Embase, and Web of Science in December 2019. We also searched ClinicalTrials.gov and the International Clinical Trials Registry Platform in August 2020 and screened the reference lists of included studies. This is an update of the review first published in 2017.
SELECTION CRITERIA
All parallel-group and factorial randomised controlled trials (RCTs) with a follow-up of at least 24 weeks were eligible.
DATA COLLECTION AND ANALYSIS
Two review authors independently reviewed and extracted data. Where data were available, we calculated pooled effect estimates. We used GRADE to assess certainty of evidence and in 'Summary of findings' tables.
MAIN RESULTS
We included 24 studies with data on 60,997 participants. Eighteen trials randomised participants to alirocumab and six to evolocumab. All participants received background lipid-lowering treatment or lifestyle counselling. Six alirocumab studies used an active treatment comparison group (the remaining used placebo), compared to three evolocumab active comparison trials. Alirocumab compared with placebo decreased the risk of CVD events, with an absolute risk difference (RD) of -2% (odds ratio (OR) 0.87, 95% confidence interval (CI) 0.80 to 0.94; 10 studies, 23,868 participants; high-certainty evidence), decreased the risk of mortality (RD -1%; OR 0.83, 95% CI 0.72 to 0.96; 12 studies, 24,797 participants; high-certainty evidence), and MI (RD -2%; OR 0.86, 95% CI 0.79 to 0.94; 9 studies, 23,352 participants; high-certainty evidence) and for any stroke (RD 0%; OR 0.73, 95% CI 0.58 to 0.91; 8 studies, 22,835 participants; high-certainty evidence). Compared to active treatment the alirocumab effects, for CVD, the RD was 1% (OR 1.37, 95% CI 0.65 to 2.87; 3 studies, 1379 participants; low-certainty evidence); for mortality, RD was -1% (OR 0.51, 95% CI 0.18 to 1.40; 5 studies, 1333 participants; low-certainty evidence); for MI, RD was 1% (OR 1.45, 95% CI 0.64 to 3.28, 5 studies, 1734 participants; low-certainty evidence); and for any stroke, RD was less than 1% (OR 0.85, 95% CI 0.13 to 5.61; 5 studies, 1734 participants; low-certainty evidence). Compared to placebo the evolocumab, for CVD, the RD was -2% (OR 0.84, 95% CI 0.78 to 0.91; 3 studies, 29,432 participants; high-certainty evidence); for mortality, RD was less than 1% (OR 1.04, 95% CI 0.91 to 1.19; 3 studies, 29,432 participants; high-certainty evidence); for MI, RD was -1% (OR 0.72, 95% CI 0.64 to 0.82; 3 studies, 29,432 participants; high-certainty evidence); and for any stroke RD was less than -1% (OR 0.79, 95% CI 0.65 to 0.94; 2 studies, 28,531 participants; high-certainty evidence). Compared to active treatment, the evolocumab effects, for any CVD event RD was less than -1% (OR 0.66, 95% CI 0.14 to 3.04; 1 study, 218 participants; very low-certainty evidence); for all-cause mortality, the RD was less than 1% (OR 0.43, 95% CI 0.14 to 1.30; 3 studies, 5223 participants; very low-certainty evidence); and for MI, RD was less than 1% (OR 0.66, 95% CI 0.23 to 1.85; 3 studies, 5003 participants; very low-certainty evidence). There were insufficient data on any stroke. AUTHORS' CONCLUSIONS: The evidence for the clinical endpoint effects of evolocumab and alirocumab were graded as high. There is a strong evidence base to prescribe PCSK9 monoclonal antibodies to people who might not be eligible for other lipid-lowering drugs, or to people who cannot meet their lipid goals on more traditional therapies, which was the main patient population of the available trials. The evidence base of PCSK9 inhibitors compared with active treatment is much weaker (low very- to low-certainty evidence) and it is unclear whether evolocumab or alirocumab might be effectively used as replacement therapies. Related, most of the available studies preferentially enrolled people with either established CVD or at a high risk already, and evidence in low- to medium-risk settings is minimal. Finally, there is very limited evidence on any potential safety issues of both evolocumab and alirocumab. While the current evidence synthesis does not reveal any adverse signals, neither does it provide evidence against such signals. This suggests careful consideration of alternative lipid lowering treatments before prescribing PCSK9 inhibitors.
Topics: Antibodies, Monoclonal, Humanized; Anticholesteremic Agents; Cardiovascular Diseases; Cause of Death; Cholesterol, LDL; Cholinergic Antagonists; Ezetimibe; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Middle Aged; Myocardial Infarction; PCSK9 Inhibitors; Primary Prevention; Proprotein Convertase 9; Randomized Controlled Trials as Topic; Secondary Prevention; Stroke; Time Factors
PubMed: 33078867
DOI: 10.1002/14651858.CD011748.pub3 -
Neurology Dec 2013To measure the association of B-type natriuretic peptide (BNP) and N-terminal fragment of BNP (NT-proBNP) with all-cause mortality after stroke, and to evaluate the... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To measure the association of B-type natriuretic peptide (BNP) and N-terminal fragment of BNP (NT-proBNP) with all-cause mortality after stroke, and to evaluate the additional predictive value of BNP/NT-proBNP over clinical information.
METHODS
Suitable studies for meta-analysis were found by searching MEDLINE and EMBASE databases until October 26, 2012. Weighted mean differences measured effect size; meta-regression and publication bias were assessed. Individual participant data were used to estimate effects by logistic regression and to evaluate BNP/NT-proBNP additional predictive value by area under the receiver operating characteristic curves, and integrated discrimination improvement and categorical net reclassification improvement indexes.
RESULTS
Literature-based meta-analysis included 3,498 stroke patients from 16 studies and revealed that BNP/NT-proBNP levels were 255.78 pg/mL (95% confidence interval [CI] 105.10-406.47, p = 0.001) higher in patients who died; publication bias entailed the loss of this association. Individual participant data analysis comprised 2,258 stroke patients. After normalization of the data, patients in the highest quartile had double the risk of death after adjustment for clinical variables (NIH Stroke Scale score, age, sex) (odds ratio 2.30, 95% CI 1.32-4.01 for BNP; and odds ratio 2.63, 95% CI 1.75-3.94 for NT-proBNP). Only NT-proBNP showed a slight added value to clinical prognostic variables, increasing discrimination by 0.028 points (integrated discrimination improvement index; p < 0.001) and reclassifying 8.1% of patients into correct risk mortality categories (net reclassification improvement index; p = 0.003). Neither etiology nor time from onset to death affected the association of BNP/NT-proBNP with mortality.
CONCLUSION
BNPs are associated with poststroke mortality independent of NIH Stroke Scale score, age, and sex. However, their translation to clinical practice seems difficult because BNP/NT-proBNP add only minor predictive value to clinical information.
Topics: Animals; Biomarkers; Humans; Natriuretic Peptide, Brain; Stroke
PubMed: 24186915
DOI: 10.1212/01.wnl.0000436937.32410.32 -
The Cochrane Database of Systematic... Apr 2020Organised inpatient (stroke unit) care is provided by multi-disciplinary teams that manage stroke patients. This can been provided in a ward dedicated to stroke patients... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Organised inpatient (stroke unit) care is provided by multi-disciplinary teams that manage stroke patients. This can been provided in a ward dedicated to stroke patients (stroke ward), with a peripatetic stroke team (mobile stroke team), or within a generic disability service (mixed rehabilitation ward). Team members aim to provide co-ordinated multi-disciplinary care using standard approaches to manage common post-stroke problems.
OBJECTIVES
• To assess the effects of organised inpatient (stroke unit) care compared with an alternative service. • To use a network meta-analysis (NMA) approach to assess different types of organised inpatient (stroke unit) care for people admitted to hospital after a stroke (the standard comparator was care in a general ward). Originally, we conducted this systematic review to clarify: • The characteristic features of organised inpatient (stroke unit) care? • Whether organised inpatient (stroke unit) care provide better patient outcomes than alternative forms of care? • If benefits are apparent across a range of patient groups and across different approaches to delivering organised stroke unit care? Within the current version, we wished to establish whether previous conclusions were altered by the inclusion of new outcome data from recent trials and further analysis via NMA.
SEARCH METHODS
We searched the Cochrane Stroke Group Trials Register (2 April 2019); the Cochrane Central Register of Controlled Trials (CENTRAL; 2019, Issue 4), in the Cochrane Library (searched 2 April 2019); MEDLINE Ovid (1946 to 1 April 2019); Embase Ovid (1974 to 1 April 2019); and the Cumulative Index to Nursing and Allied Health Literature (CINAHL; 1982 to 2 April 2019). In an effort to identify further published, unpublished, and ongoing trials, we searched seven trial registries (2 April 2019). We also performed citation tracking of included studies, checked reference lists of relevant articles, and contacted trialists.
SELECTION CRITERIA
Randomised controlled clinical trials comparing organised inpatient stroke unit care with an alternative service (typically contemporary conventional care), including comparing different types of organised inpatient (stroke unit) care for people with stroke who are admitted to hospital.
DATA COLLECTION AND ANALYSIS
Two review authors assessed eligibility and trial quality. We checked descriptive details and trial data with co-ordinators of the original trials, assessed risk of bias, and applied GRADE. The primary outcome was poor outcome (death or dependency (Rankin score 3 to 5) or requiring institutional care) at the end of scheduled follow-up. Secondary outcomes included death, institutional care, dependency, subjective health status, satisfaction, and length of stay. We used direct (pairwise) comparisons to compare organised inpatient (stroke unit) care with an alternative service. We used an NMA to confirm the relative effects of different approaches.
MAIN RESULTS
We included 29 trials (5902 participants) that compared organised inpatient (stroke unit) care with an alternative service: 20 trials (4127 participants) compared organised (stroke unit) care with a general ward, six trials (982 participants) compared different forms of organised (stroke unit) care, and three trials (793 participants) incorporated more than one comparison. Compared with the alternative service, organised inpatient (stroke unit) care was associated with improved outcomes at the end of scheduled follow-up (median one year): poor outcome (odds ratio (OR) 0.77, 95% confidence interval (CI) 0.69 to 0.87; moderate-quality evidence), death (OR 0.76, 95% CI 0.66 to 0.88; moderate-quality evidence), death or institutional care (OR 0.76, 95% CI 0.67 to 0.85; moderate-quality evidence), and death or dependency (OR 0.75, 95% CI 0.66 to 0.85; moderate-quality evidence). Evidence was of very low quality for subjective health status and was not available for patient satisfaction. Analysis of length of stay was complicated by variations in definition and measurement plus substantial statistical heterogeneity (I² = 85%). There was no indication that organised stroke unit care resulted in a longer hospital stay. Sensitivity analyses indicated that observed benefits remained when the analysis was restricted to securely randomised trials that used unequivocally blinded outcome assessment with a fixed period of follow-up. Outcomes appeared to be independent of patient age, sex, initial stroke severity, stroke type, and duration of follow-up. When calculated as the absolute risk difference for every 100 participants receiving stroke unit care, this equates to two extra survivors, six more living at home, and six more living independently. The analysis of different types of organised (stroke unit) care used both direct pairwise comparisons and NMA. Direct comparison of stroke ward versus general ward: 15 trials (3523 participants) compared care in a stroke ward with care in general wards. Stroke ward care showed a reduction in the odds of a poor outcome at the end of follow-up (OR 0.78, 95% CI 0.68 to 0.91; moderate-quality evidence). Direct comparison of mobile stroke team versus general ward: two trials (438 participants) compared care from a mobile stroke team with care in general wards. Stroke team care may result in little difference in the odds of a poor outcome at the end of follow-up (OR 0.80, 95% CI 0.52 to 1.22; low-quality evidence). Direct comparison of mixed rehabilitation ward versus general ward: six trials (630 participants) compared care in a mixed rehabilitation ward with care in general wards. Mixed rehabilitation ward care showed a reduction in the odds of a poor outcome at the end of follow-up (OR 0.65, 95% CI 0.47 to 0.90; moderate-quality evidence). In a NMA using care in a general ward as the comparator, the odds of a poor outcome were as follows: stroke ward - OR 0.74, 95% CI 0.62 to 0.89, moderate-quality evidence; mobile stroke team - OR 0.88, 95% CI 0.58 to 1.34, low-quality evidence; mixed rehabilitation ward - OR 0.70, 95% CI 0.52 to 0.95, low-quality evidence.
AUTHORS' CONCLUSIONS
We found moderate-quality evidence that stroke patients who receive organised inpatient (stroke unit) care are more likely to be alive, independent, and living at home one year after the stroke. The apparent benefits were independent of patient age, sex, initial stroke severity, or stroke type, and were most obvious in units based in a discrete stroke ward. We observed no systematic increase in the length of inpatient stay, but these findings had considerable uncertainty.
Topics: Hospital Units; Hospitalization; Humans; Length of Stay; Network Meta-Analysis; Outcome Assessment, Health Care; Patient Care Team; Prognosis; Randomized Controlled Trials as Topic; Stroke; Stroke Rehabilitation; Treatment Outcome
PubMed: 32324916
DOI: 10.1002/14651858.CD000197.pub4 -
The Cochrane Database of Systematic... Jun 2020Worldwide, there is an increasing incidence of type 2 diabetes mellitus (T2DM). Metformin is still the recommended first-line glucose-lowering drug for people with T2DM.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Worldwide, there is an increasing incidence of type 2 diabetes mellitus (T2DM). Metformin is still the recommended first-line glucose-lowering drug for people with T2DM. Despite this, the effects of metformin on patient-important outcomes are still not clarified.
OBJECTIVES
To assess the effects of metformin monotherapy in adults with T2DM.
SEARCH METHODS
We based our search on a systematic report from the Agency for Healthcare Research and Quality, and topped-up the search in CENTRAL, MEDLINE, Embase, WHO ICTRP, and ClinicalTrials.gov. Additionally, we searched the reference lists of included trials and systematic reviews, as well as health technology assessment reports and medical agencies. The date of the last search for all databases was 2 December 2019, except Embase (searched up 28 April 2017).
SELECTION CRITERIA
We included randomised controlled trials (RCTs) with at least one year's duration comparing metformin monotherapy with no intervention, behaviour changing interventions or other glucose-lowering drugs in adults with T2DM.
DATA COLLECTION AND ANALYSIS
Two review authors read all abstracts and full-text articles/records, assessed risk of bias, and extracted outcome data independently. We resolved discrepancies by involvement of a third review author. For meta-analyses we used a random-effects model with investigation of risk ratios (RRs) for dichotomous outcomes and mean differences (MDs) for continuous outcomes, using 95% confidence intervals (CIs) for effect estimates. We assessed the overall certainty of the evidence by using the GRADE instrument.
MAIN RESULTS
We included 18 RCTs with multiple study arms (N = 10,680). The percentage of participants finishing the trials was approximately 58% in all groups. Treatment duration ranged from one to 10.7 years. We judged no trials to be at low risk of bias on all 'Risk of bias' domains. The main outcomes of interest were all-cause mortality, serious adverse events (SAEs), health-related quality of life (HRQoL), cardiovascular mortality (CVM), non-fatal myocardial infarction (NFMI), non-fatal stroke (NFS), and end-stage renal disease (ESRD). Two trials compared metformin (N = 370) with insulin (N = 454). Neither trial reported on all-cause mortality, SAE, CVM, NFMI, NFS or ESRD. One trial provided information on HRQoL but did not show a substantial difference between the interventions. Seven trials compared metformin with sulphonylureas. Four trials reported on all-cause mortality: in three trials no participant died, and in the remaining trial 31/1454 participants (2.1%) in the metformin group died compared with 31/1441 participants (2.2%) in the sulphonylurea group (very low-certainty evidence). Three trials reported on SAE: in two trials no SAE occurred (186 participants); in the other trial 331/1454 participants (22.8%) in the metformin group experienced a SAE compared with 308/1441 participants (21.4%) in the sulphonylurea group (very low-certainty evidence). Two trials reported on CVM: in one trial no CVM was observed and in the other trial 4/1441 participants (0.3%) in the metformin group died of cardiovascular reasons compared with 8/1447 participants (0.6%) in the sulphonylurea group (very low-certainty evidence). Three trials reported on NFMI: in two trials no NFMI occurred, and in the other trial 21/1454 participants (1.4%) in the metformin group experienced a NFMI compared with 15/1441 participants (1.0%) in the sulphonylurea group (very low-certainty evidence). One trial reported no NFS occurred (very low-certainty evidence). No trial reported on HRQoL or ESRD. Seven trials compared metformin with thiazolidinediones (very low-certainty evidence for all outcomes). Five trials reported on all-cause mortality: in two trials no participant died; the overall RR was 0.88, 95% CI 0.55 to 1.39; P = 0.57; 5 trials; 4402 participants). Four trials reported on SAE, the RR was 0,95, 95% CI 0.84 to 1.09; P = 0.49; 3208 participants. Four trials reported on CVM, the RR was 0.71, 95% CI 0.21 to 2.39; P = 0.58; 3211 participants. Three trial reported on NFMI: in two trials no NFMI occurred and in one trial 21/1454 participants (1.4%) in the metformin group experienced a NFMI compared with 25/1456 participants (1.7%) in the thiazolidinedione group. One trial reported no NFS occurred. No trial reported on HRQoL or ESRD. Three trials compared metformin with dipeptidyl peptidase-4 inhibitors (one trial each with saxagliptin, sitagliptin, vildagliptin with altogether 1977 participants). There was no substantial difference between the interventions for all-cause mortality, SAE, CVM, NFMI and NFS (very low-certainty evidence for all outcomes). One trial compared metformin with a glucagon-like peptide-1 analogue (very low-certainty evidence for all reported outcomes). There was no substantial difference between the interventions for all-cause mortality, CVM, NFMI and NFS. One or more SAEs were reported in 16/268 (6.0%) of the participants allocated to metformin compared with 35/539 (6.5%) of the participants allocated to a glucagon-like peptide-1 analogue. HRQoL or ESRD were not reported. One trial compared metformin with meglitinide and two trials compared metformin with no intervention. No deaths or SAEs occurred (very low-certainty evidence) no other patient-important outcomes were reported. No trial compared metformin with placebo or a behaviour changing interventions. Four ongoing trials with 5824 participants are likely to report one or more of our outcomes of interest and are estimated to be completed between 2018 and 2024. Furthermore, 24 trials with 2369 participants are awaiting assessment.
AUTHORS' CONCLUSIONS
There is no clear evidence whether metformin monotherapy compared with no intervention, behaviour changing interventions or other glucose-lowering drugs influences patient-important outcomes.
Topics: Adult; Carbamates; Cardiovascular Diseases; Cause of Death; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Glucagon-Like Peptide 1; Humans; Hypoglycemic Agents; Insulin; Metformin; Myocardial Infarction; Piperidines; Quality of Life; Randomized Controlled Trials as Topic; Stroke; Sulfonylurea Compounds
PubMed: 32501595
DOI: 10.1002/14651858.CD012906.pub2 -
European Heart Journal Oct 2019Owing to new evidence from randomized controlled trials (RCTs) in low-risk patients with severe aortic stenosis, we compared the collective safety and efficacy of... (Meta-Analysis)
Meta-Analysis
AIMS
Owing to new evidence from randomized controlled trials (RCTs) in low-risk patients with severe aortic stenosis, we compared the collective safety and efficacy of transcatheter aortic valve implantation (TAVI) vs. surgical aortic valve replacement (SAVR) across the entire spectrum of surgical risk patients.
METHODS AND RESULTS
The meta-analysis is registered with PROSPERO (CRD42016037273). We identified RCTs comparing TAVI with SAVR in patients with severe aortic stenosis reporting at different follow-up periods. We extracted trial, patient, intervention, and outcome characteristics following predefined criteria. The primary outcome was all-cause mortality up to 2 years for the main analysis. Seven trials that randomly assigned 8020 participants to TAVI (4014 patients) and SAVR (4006 patients) were included. The combined mean STS score in the TAVI arm was 9.4%, 5.1%, and 2.0% for high-, intermediate-, and low surgical risk trials, respectively. Transcatheter aortic valve implantation was associated with a significant reduction of all-cause mortality compared to SAVR {hazard ratio [HR] 0.88 [95% confidence interval (CI) 0.78-0.99], P = 0.030}; an effect that was consistent across the entire spectrum of surgical risk (P-for-interaction = 0.410) and irrespective of type of transcatheter heart valve (THV) system (P-for-interaction = 0.674). Transcatheter aortic valve implantation resulted in lower risk of strokes [HR 0.81 (95% CI 0.68-0.98), P = 0.028]. Surgical aortic valve replacement was associated with a lower risk of major vascular complications [HR 1.99 (95% CI 1.34-2.93), P = 0.001] and permanent pacemaker implantations [HR 2.27 (95% CI 1.47-3.64), P < 0.001] compared to TAVI.
CONCLUSION
Compared with SAVR, TAVI is associated with reduction in all-cause mortality and stroke up to 2 years irrespective of baseline surgical risk and type of THV system.
Topics: Aged; Aged, 80 and over; Aortic Valve; Aortic Valve Stenosis; Female; Heart Valve Prosthesis; Heart Valve Prosthesis Implantation; Humans; Male; Postoperative Complications; Transcatheter Aortic Valve Replacement
PubMed: 31329852
DOI: 10.1093/eurheartj/ehz275 -
Toxins Feb 2024This article aims to provide a concise overview of the best available evidence for managing post-stroke spasticity. A modified scoping review, conducted following the... (Review)
Review
This article aims to provide a concise overview of the best available evidence for managing post-stroke spasticity. A modified scoping review, conducted following the PRISMA guidelines and the PRISMA Extension for Scoping Reviews (PRISMA-ScR), involved an intensive search on Medline and PubMed from 1 January 2000 to 31 August 2023. The focus was placed on high-quality (GRADE A) medical, rehabilitation, and surgical interventions. In total, 32 treatments for post-stroke spasticity were identified. Two independent reviewers rigorously assessed studies, extracting data, and evaluating bias using GRADE criteria. Only interventions with GRADE A evidence were considered. The data included the study type, number of trials, participant characteristics, interventions, parameters, controls, outcomes, and limitations. The results revealed eleven treatments supported by GRADE A evidence, comprising 14 studies. Thirteen were systematic reviews and meta-analyses, and one was randomized control trial. The GRADE A treatments included stretching exercises, static stretching with positional orthosis, transcutaneous electrical nerve stimulation, extracorporeal shock wave therapy, peripheral magnetic stimulation, non-invasive brain stimulation, botulinum toxin A injection, dry needling, intrathecal baclofen, whole body vibration, and localized muscle vibration. In conclusion, this modified scoping review highlights the multimodal treatments supported by GRADE A evidence as being effective for improving functional recovery and quality of life in post-stroke spasticity. Further research and exploration of new therapeutic options are encouraged.
Topics: Humans; Quality of Life; Muscle Spasticity; Stroke; Physical Therapy Modalities; Combined Modality Therapy
PubMed: 38393176
DOI: 10.3390/toxins16020098 -
The Cochrane Database of Systematic... Oct 2021Stroke affects millions of people every year and is a leading cause of disability, resulting in significant financial cost and reduction in quality of life.... (Review)
Review
BACKGROUND
Stroke affects millions of people every year and is a leading cause of disability, resulting in significant financial cost and reduction in quality of life. Rehabilitation after stroke aims to reduce disability by facilitating recovery of impairment, activity, or participation. One aspect of stroke rehabilitation that may affect outcomes is the amount of time spent in rehabilitation, including minutes provided, frequency (i.e. days per week of rehabilitation), and duration (i.e. time period over which rehabilitation is provided). Effect of time spent in rehabilitation after stroke has been explored extensively in the literature, but findings are inconsistent. Previous systematic reviews with meta-analyses have included studies that differ not only in the amount provided, but also type of rehabilitation.
OBJECTIVES
To assess the effect of 1. more time spent in the same type of rehabilitation on activity measures in people with stroke; 2. difference in total rehabilitation time (in minutes) on recovery of activity in people with stroke; and 3. rehabilitation schedule on activity in terms of: a. average time (minutes) per week undergoing rehabilitation, b. frequency (number of sessions per week) of rehabilitation, and c. total duration of rehabilitation.
SEARCH METHODS
We searched the Cochrane Stroke Group trials register, CENTRAL, MEDLINE, Embase, eight other databases, and five trials registers to June 2021. We searched reference lists of identified studies, contacted key authors, and undertook reference searching using Web of Science Cited Reference Search.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) of adults with stroke that compared different amounts of time spent, greater than zero, in rehabilitation (any non-pharmacological, non-surgical intervention aimed to improve activity after stroke). Studies varied only in the amount of time in rehabilitation between experimental and control conditions. Primary outcome was activities of daily living (ADLs); secondary outcomes were activity measures of upper and lower limbs, motor impairment measures of upper and lower limbs, and serious adverse events (SAE)/death.
DATA COLLECTION AND ANALYSIS
Two review authors independently screened studies, extracted data, assessed methodological quality using the Cochrane RoB 2 tool, and assessed certainty of the evidence using GRADE. For continuous outcomes using different scales, we calculated pooled standardised mean difference (SMDs) and 95% confidence intervals (CIs). We expressed dichotomous outcomes as risk ratios (RR) with 95% CIs.
MAIN RESULTS
The quantitative synthesis of this review comprised 21 parallel RCTs, involving analysed data from 1412 participants. Time in rehabilitation varied between studies. Minutes provided per week were 90 to 1288. Days per week of rehabilitation were three to seven. Duration of rehabilitation was two weeks to six months. Thirteen studies provided upper limb rehabilitation, five general rehabilitation, two mobilisation training, and one lower limb training. Sixteen studies examined participants in the first six months following stroke; the remaining five included participants more than six months poststroke. Comparison of stroke severity or level of impairment was limited due to variations in measurement. The risk of bias assessment suggests there were issues with the methodological quality of the included studies. There were 76 outcome-level risk of bias assessments: 15 low risk, 37 some concerns, and 24 high risk. When comparing groups that spent more time versus less time in rehabilitation immediately after intervention, we found no difference in rehabilitation for ADL outcomes (SMD 0.13, 95% CI -0.02 to 0.28; P = 0.09; I = 7%; 14 studies, 864 participants; very low-certainty evidence), activity measures of the upper limb (SMD 0.09, 95% CI -0.11 to 0.29; P = 0.36; I = 0%; 12 studies, 426 participants; very low-certainty evidence), and activity measures of the lower limb (SMD 0.25, 95% CI -0.03 to 0.53; P = 0.08; I = 48%; 5 studies, 425 participants; very low-certainty evidence). We found an effect in favour of more time in rehabilitation for motor impairment measures of the upper limb (SMD 0.32, 95% CI 0.06 to 0.58; P = 0.01; I = 10%; 9 studies, 287 participants; low-certainty evidence) and of the lower limb (SMD 0.71, 95% CI 0.15 to 1.28; P = 0.01; 1 study, 51 participants; very low-certainty evidence). There were no intervention-related SAEs. More time in rehabilitation did not affect the risk of SAEs/death (RR 1.20, 95% CI 0.51 to 2.85; P = 0.68; I = 0%; 2 studies, 379 participants; low-certainty evidence), but few studies measured these outcomes. Predefined subgroup analyses comparing studies with a larger difference of total time spent in rehabilitation between intervention groups to studies with a smaller difference found greater improvements for studies with a larger difference. This was statistically significant for ADL outcomes (P = 0.02) and activity measures of the upper limb (P = 0.04), but not for activity measures of the lower limb (P = 0.41) or motor impairment measures of the upper limb (P = 0.06).
AUTHORS' CONCLUSIONS
An increase in time spent in the same type of rehabilitation after stroke results in little to no difference in meaningful activities such as activities of daily living and activities of the upper and lower limb but a small benefit in measures of motor impairment (low- to very low-certainty evidence for all findings). If the increase in time spent in rehabilitation exceeds a threshold, this may lead to improved outcomes. There is currently insufficient evidence to recommend a minimum beneficial daily amount in clinical practice. The findings of this study are limited by a lack of studies with a significant contrast in amount of additional rehabilitation provided between control and intervention groups. Large, well-designed, high-quality RCTs that measure time spent in all rehabilitation activities (not just interventional) and provide a large contrast (minimum of 1000 minutes) in amount of rehabilitation between groups would provide further evidence for effect of time spent in rehabilitation.
Topics: Activities of Daily Living; Adult; Humans; Physical Therapy Modalities; Stroke; Stroke Rehabilitation; Upper Extremity
PubMed: 34695300
DOI: 10.1002/14651858.CD012612.pub2