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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 -
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 -
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 -
Lancet (London, England) May 2020Antiplatelet therapy is recommended among patients with established atherosclerosis. We compared monotherapy with a P2Y inhibitor versus aspirin for secondary prevention. (Comparative Study)
Comparative Study Meta-Analysis
BACKGROUND
Antiplatelet therapy is recommended among patients with established atherosclerosis. We compared monotherapy with a P2Y inhibitor versus aspirin for secondary prevention.
METHODS
In this systematic review and meta-analysis, all randomised trials comparing P2Y inhibitor with aspirin monotherapy for secondary prevention in patients with cerebrovascular, coronary, or peripheral artery disease were evaluated for inclusion. On Dec 18, 2019, we searched PubMed, Embase, BioMedCentral, Google Scholar, and the Cochrane Central Register of Controlled Trials. Additionally, we reviewed references from identified articles and searched abstracts from 2017 to 2019 presented at relevant scientific meetings. Data about year of publication, inclusion and exclusion criteria, sample size, baseline patients' features including the baseline condition determining study inclusion (ie, cerebrovascular, coronary, or peripheral artery disease), P2Y inhibitor type and dosage, aspirin dosage, endpoint definitions, effect estimates, follow-up duration, and percentage of patients lost to follow-up were collected. Odds ratios (ORs) and 95% CIs were used as metric of choice for treatment effects with random-effects models. Co-primary endpoints were myocardial infarction and stroke. Key secondary endpoints were all-cause death and vascular death. Heterogeneity was assessed with the I index. This study is registered with PROSPERO (CRD42018115037).
FINDINGS
A total of nine randomised trials were identified and included in this study, and 42 108 patients randomly allocated to a P2Y inhibitor (n=21 043) or aspirin (n=21 065) were included in our analyses. Patients who received a P2Y inhibitor had a borderline reduction for the risk of myocardial infarction compared with those who received aspirin (OR 0·81 [95% CI 0·66-0·99]; I=10·9%). Risks of stroke (OR 0·93 [0·82-1·06]; I=34·5%), all-cause death (OR 0·98 [0·89-1·08]; I=0%), and vascular death (OR 0·97 [0·86-1·09]; I=0%) did not differ between patients who received a P2Y inhibitor and those who received aspirin. Similarly, the risk of major bleeding (OR 0·90 [0·74-1·10]; I=3·9%) did not differ between patients who received a P2Y inhibitor and those who received aspirin. The number needed to treat to prevent one myocardial infarction with P2Y inhibitor monotherapy was 244 patients. Findings were consistent regardless of the type of P2Y inhibitor used.
INTERPRETATION
Compared with aspirin monotherapy, P2Y inhibitor monotherapy is associated with a risk reduction for myocardial infarction and a comparable risk of stroke in the setting of secondary prevention. The benefit of P2Y inhibitor monotherapy is of debatable clinical relevance, in view of the high number needed to treat to prevent a myocardial infarction and the absence of any effect on all-cause and vascular mortality.
FUNDING
Italian Ministry of Education.
Topics: Aged; Aspirin; Atherosclerosis; Cerebrovascular Disorders; Clopidogrel; Coronary Disease; Female; Hemorrhage; Humans; Male; Middle Aged; Myocardial Infarction; Peripheral Arterial Disease; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Randomized Controlled Trials as Topic; Risk Assessment; Secondary Prevention; Stroke; Ticagrelor; Ticlopidine
PubMed: 32386592
DOI: 10.1016/S0140-6736(20)30315-9 -
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 -
The Cochrane Database of Systematic... Aug 2022Elevated blood pressure, or hypertension, is the leading cause of preventable deaths globally. Diets high in sodium (predominantly sodium chloride) and low in potassium... (Review)
Review
BACKGROUND
Elevated blood pressure, or hypertension, is the leading cause of preventable deaths globally. Diets high in sodium (predominantly sodium chloride) and low in potassium contribute to elevated blood pressure. The WHO recommends decreasing mean population sodium intake through effective and safe strategies to reduce hypertension and its associated disease burden. Incorporating low-sodium salt substitutes (LSSS) into population strategies has increasingly been recognised as a possible sodium reduction strategy, particularly in populations where a substantial proportion of overall sodium intake comes from discretionary salt. The LSSS contain lower concentrations of sodium through its displacement with potassium predominantly, or other minerals. Potassium-containing LSSS can potentially simultaneously decrease sodium intake and increase potassium intake. Benefits of LSSS include their potential blood pressure-lowering effect and relatively low cost. However, there are concerns about potential adverse effects of LSSS, such as hyperkalaemia, particularly in people at risk, for example, those with chronic kidney disease (CKD) or taking medications that impair potassium excretion.
OBJECTIVES
To assess the effects and safety of replacing salt with LSSS to reduce sodium intake on cardiovascular health in adults, pregnant women and children.
SEARCH METHODS
We searched MEDLINE (PubMed), Embase (Ovid), Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science Core Collection (Clarivate Analytics), Cumulative Index to Nursing and Allied Health Literature (CINAHL, EBSCOhost), ClinicalTrials.gov and WHO International Clinical Trials Registry Platform (ICTRP) up to 18 August 2021, and screened reference lists of included trials and relevant systematic reviews. No language or publication restrictions were applied.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) and prospective analytical cohort studies in participants of any age in the general population, from any setting in any country. This included participants with non-communicable diseases and those taking medications that impair potassium excretion. Studies had to compare any type and method of implementation of LSSS with the use of regular salt, or no active intervention, at an individual, household or community level, for any duration.
DATA COLLECTION AND ANALYSIS
Two review authors independently screened titles, abstracts and full-text articles to determine eligibility; and extracted data, assessed risk of bias (RoB) using the Cochrane RoB tool, and assessed the certainty of the evidence using GRADE. We stratified analyses by adults, children (≤ 18 years) and pregnant women. Primary effectiveness outcomes were change in diastolic and systolic blood pressure (DBP and SBP), hypertension and blood pressure control; cardiovascular events and cardiovascular mortality were additionally assessed as primary effectiveness outcomes in adults. Primary safety outcomes were change in blood potassium, hyperkalaemia and hypokalaemia.
MAIN RESULTS
We included 26 RCTs, 16 randomising individual participants and 10 randomising clusters (families, households or villages). A total of 34,961 adult participants and 92 children were randomised to either LSSS or regular salt, with the smallest trial including 10 and the largest including 20,995 participants. No studies in pregnant women were identified. Studies included only participants with hypertension (11/26), normal blood pressure (1/26), pre-hypertension (1/26), or participants with and without hypertension (11/26). This was unknown in the remaining studies. The largest study included only participants with an elevated risk of stroke at baseline. Seven studies included adult participants possibly at risk of hyperkalaemia. All 26 trials specifically excluded participants in whom an increased potassium intake is known to be potentially harmful. The majority of trials were conducted in rural or suburban settings, with more than half (14/26) conducted in low- and middle-income countries. The proportion of sodium chloride replacement in the LSSS interventions varied from approximately 3% to 77%. The majority of trials (23/26) investigated LSSS where potassium-containing salts were used to substitute sodium. In most trials, LSSS implementation was discretionary (22/26). Trial duration ranged from two months to nearly five years. We assessed the overall risk of bias as high in six trials and unclear in 12 trials. LSSS compared to regular salt in adults: LSSS compared to regular salt probably reduce DBP on average (mean difference (MD) -2.43 mmHg, 95% confidence interval (CI) -3.50 to -1.36; 20,830 participants, 19 RCTs, moderate-certainty evidence) and SBP (MD -4.76 mmHg, 95% CI -6.01 to -3.50; 21,414 participants, 20 RCTs, moderate-certainty evidence) slightly. On average, LSSS probably reduce non-fatal stroke (absolute effect (AE) 20 fewer/100,000 person-years, 95% CI -40 to 2; 21,250 participants, 3 RCTs, moderate-certainty evidence), non-fatal acute coronary syndrome (AE 150 fewer/100,000 person-years, 95% CI -250 to -30; 20,995 participants, 1 RCT, moderate-certainty evidence) and cardiovascular mortality (AE 180 fewer/100,000 person-years, 95% CI -310 to 0; 23,200 participants, 3 RCTs, moderate-certainty evidence) slightly, and probably increase blood potassium slightly (MD 0.12 mmol/L, 95% CI 0.07 to 0.18; 784 participants, 6 RCTs, moderate-certainty evidence), compared to regular salt. LSSS may result in little to no difference, on average, in hypertension (AE 17 fewer/1000, 95% CI -58 to 17; 2566 participants, 1 RCT, low-certainty evidence) and hyperkalaemia (AE 4 more/100,000, 95% CI -47 to 121; 22,849 participants, 5 RCTs, moderate-certainty evidence) compared to regular salt. The evidence is very uncertain about the effects of LSSS on blood pressure control, various cardiovascular events, stroke mortality, hypokalaemia, and other adverse events (very-low certainty evidence). LSSS compared to regular salt in children: The evidence is very uncertain about the effects of LSSS on DBP and SBP in children. We found no evidence about the effects of LSSS on hypertension, blood pressure control, blood potassium, hyperkalaemia and hypokalaemia in children.
AUTHORS' CONCLUSIONS
When compared to regular salt, LSSS probably reduce blood pressure, non-fatal cardiovascular events and cardiovascular mortality slightly in adults. However, LSSS also probably increase blood potassium slightly in adults. These small effects may be important when LSSS interventions are implemented at the population level. Evidence is limited for adults without elevated blood pressure, and there is a lack of evidence in pregnant women and people in whom an increased potassium intake is known to be potentially harmful, limiting conclusions on the safety of LSSS in the general population. We also cannot draw firm conclusions about effects of non-discretionary LSSS implementations. The evidence is very uncertain about the effects of LSSS on blood pressure in children.
Topics: Adult; Child; Female; Humans; Hyperkalemia; Hypertension; Hypokalemia; Potassium; Pregnancy; Pregnant Women; Randomized Controlled Trials as Topic; Sodium; Sodium Chloride; Sodium Chloride, Dietary; Stroke
PubMed: 35944931
DOI: 10.1002/14651858.CD015207 -
Basic and Clinical Neuroscience 2021A major cause of injury and the second cause of death worldwide is stroke. Among several infectious agents considered as the risk factor of stroke, some pathogens... (Review)
Review
INTRODUCTION
A major cause of injury and the second cause of death worldwide is stroke. Among several infectious agents considered as the risk factor of stroke, some pathogens demonstrated stronger robust associations with stroke. Proposing an accurate correlation between infectious microorganisms and stroke provides valuable information for early intervention and control of the infections.
METHODS
In this study, we searched the literature using the Web of Science, PMC/Medline via PubMed, and Scopus databases up to July 2018 without time and language restrictions. After quality assessment, 16 articles were included in the study. The whole data extraction process was independently conducted by two reviewers.
RESULTS
Based on the results of the studies, viruses, such as Hepatitis C virus (HCV), Hepatitis B virus (HBV), Human Immunodeficiency Virus (HIV), Herpes Simplex Virus Type-1, 2 (HSV-1, 2), Varicella-Zoster Virus (VZV or Chickenpox), and West Nile virus (WNV) seem to be common causes of ischemic stroke. Moreover, the association of other microbial categories, such as Streptococcus mutans (in bacteria), Toxocara spp. and Toxoplasma gondii (in parasites), and Rhizopus sp. (in fungi) with stroke was reported.
CONCLUSION
Considering the adverse role of the above-mentioned microorganisms, it is necessary to implement some preventive measures for stroke treatment.
PubMed: 35154584
DOI: 10.32598/bcn.2021.1324.2 -
The Cochrane Database of Systematic... May 2020Stroke is caused by the interruption of blood flow to the brain (ischemic stroke) or the rupture of blood vessels within the brain (hemorrhagic stroke) and may lead to... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Stroke is caused by the interruption of blood flow to the brain (ischemic stroke) or the rupture of blood vessels within the brain (hemorrhagic stroke) and may lead to changes in perception, cognition, mood, speech, health-related quality of life, and function, such as difficulty walking and using the arm. Activity limitations (decreased function) of the upper extremity are a common finding for individuals living with stroke. Mental practice (MP) is a training method that uses cognitive rehearsal of activities to improve performance of those activities.
OBJECTIVES
To determine whether MP improves outcomes of upper extremity rehabilitation for individuals living with the effects of stroke. In particular, we sought to (1) determine the effects of MP on upper extremity activity, upper extremity impairment, activities of daily living, health-related quality of life, economic costs, and adverse effects; and (2) explore whether effects differed according to (a) the time post stroke at which MP was delivered, (b) the dose of MP provided, or (c) the type of comparison performed.
SEARCH METHODS
We last searched the Cochrane Stroke Group Trials Register on September 17, 2019. On September 3, 2019, we searched the Cochrane Central Register of Controlled Trials (the Cochrane Library), MEDLINE, Embase, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), PsycINFO, Scopus, Web of Science, the Physiotherapy Evidence Database (PEDro), and REHABDATA. On October 2, 2019, we searched ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform. We reviewed the reference lists of included studies.
SELECTION CRITERIA
We included randomized controlled trials (RCTs) of adult participants with stroke who had deficits in upper extremity function (called upper extremity activity).
DATA COLLECTION AND ANALYSIS
Two review authors screened titles and abstracts of the citations produced by the literature search and excluded obviously irrelevant studies. We obtained the full text of all remaining studies, and both review authors then independently selected trials for inclusion. We combined studies when the review produced a minimum of two trials employing a particular intervention strategy and a common outcome. We considered the primary outcome to be the ability of the arm to be used for appropriate tasks, called upper extremity activity. Secondary outcomes included upper extremity impairment (such as quality of movement, range of motion, tone, presence of synergistic movement), activities of daily living (ADLs), health-related quality of life (HRQL), economic costs, and adverse events. We assessed risk of bias in the included studies and applied GRADE to assess the certainty of the evidence. We completed subgroup analyses for time since stroke, dosage of MP, type of comparison, and type of arm activity outcome measure.
MAIN RESULTS
We included 25 studies involving 676 participants from nine countries. For the comparison of MP in addition to other treatment versus the other treatment, MP in combination with other treatment appears more effective in improving upper extremity activity than the other treatment without MP (standardized mean difference [SMD] 0.66, 95% confidence interval [CI] 0.39 to 0.94; I² = 39%; 15 studies; 397 participants); the GRADE certainty of evidence score was moderate based on risk of bias for the upper extremity activity outcome. For upper extremity impairment, results were as follows: SMD 0.59, 95% CI 0.30 to 0.87; I² = 43%; 15 studies; 397 participants, with a GRADE score of moderate, based on risk of bias. For ADLs, results were as follows: SMD 0.08, 95% CI -0.24 to 0.39; I² = 0%; 4 studies; 157 participants; the GRADE score was low due to risk of bias and small sample size. For the comparison of MP versus conventional treatment, the only outcome with available data to combine (3 studies; 50 participants) was upper extremity impairment (SMD 0.34, 95% CI -0.33 to 1.00; I² = 21%); GRADE for the impairment outcome in this comparison was low due to risk of bias and small sample size. Subgroup analyses of time post stroke, dosage of MP, or comparison type for the MP in combination with other rehabilitation treatment versus the other treatment comparison showed no differences. The secondary outcome of health-related quality of life was reported in only one study, and no study noted the outcomes of economic costs and adverse events.
AUTHORS' CONCLUSIONS
Moderate-certainty evidence shows that MP in addition to other treatment versus the other treatment appears to be beneficial in improving upper extremity activity. Moderate-certainty evidence also shows that MP in addition to other treatment versus the other treatment appears to be beneficial in improving upper extremity impairment after stroke. Low-certainty evidence suggests that ADLs may not be improved with MP in addition to other treatment versus the other treatment. Low-certainty evidence also suggests that MP versus conventional treatment may not improve upper extremity impairment. Further study is required to evaluate effects of MP on time post stroke, the volume of MP required to affect outcomes, and whether improvement is maintained over the long term.
Topics: Arm; Combined Modality Therapy; Female; Humans; Imagination; Male; Paresis; Practice, Psychological; Randomized Controlled Trials as Topic; Recovery of Function; Stroke; Stroke Rehabilitation
PubMed: 32449959
DOI: 10.1002/14651858.CD005950.pub5 -
Circulation Aug 2020To quantify the association between effects of interventions on carotid intima-media thickness (cIMT) progression and their effects on cardiovascular disease (CVD) risk. (Meta-Analysis)
Meta-Analysis
BACKGROUND
To quantify the association between effects of interventions on carotid intima-media thickness (cIMT) progression and their effects on cardiovascular disease (CVD) risk.
METHODS
We systematically collated data from randomized, controlled trials. cIMT was assessed as the mean value at the common-carotid-artery; if unavailable, the maximum value at the common-carotid-artery or other cIMT measures were used. The primary outcome was a combined CVD end point defined as myocardial infarction, stroke, revascularization procedures, or fatal CVD. We estimated intervention effects on cIMT progression and incident CVD for each trial, before relating the 2 using a Bayesian meta-regression approach.
RESULTS
We analyzed data of 119 randomized, controlled trials involving 100 667 patients (mean age 62 years, 42% female). Over an average follow-up of 3.7 years, 12 038 patients developed the combined CVD end point. Across all interventions, each 10 μm/y reduction of cIMT progression resulted in a relative risk for CVD of 0.91 (95% Credible Interval, 0.87-0.94), with an additional relative risk for CVD of 0.92 (0.87-0.97) being achieved independent of cIMT progression. Taken together, we estimated that interventions reducing cIMT progression by 10, 20, 30, or 40 μm/y would yield relative risks of 0.84 (0.75-0.93), 0.76 (0.67-0.85), 0.69 (0.59-0.79), or 0.63 (0.52-0.74), respectively. Results were similar when grouping trials by type of intervention, time of conduct, time to ultrasound follow-up, availability of individual-participant data, primary versus secondary prevention trials, type of cIMT measurement, and proportion of female patients.
CONCLUSIONS
The extent of intervention effects on cIMT progression predicted the degree of CVD risk reduction. This provides a missing link supporting the usefulness of cIMT progression as a surrogate marker for CVD risk in clinical trials.
Topics: Carotid Artery, Common; Carotid Intima-Media Thickness; Female; Heart Disease Risk Factors; Humans; Male; Middle Aged; Myocardial Infarction; Randomized Controlled Trials as Topic; Stroke
PubMed: 32546049
DOI: 10.1161/CIRCULATIONAHA.120.046361