Background: Amplifying endogenous neuroprotective mechanisms is a promising avenue for stroke therapy. One target is mammalian target of rapamycin (mTOR), a serine/threonine kinase regulating cell proliferation, cell survival, protein synthesis and autophagy. Animal studies investigating the effect rapamycin on mTOR inhibition following cerebral ischemia have shown conflicting results. Aim: To conduct a systematic review and meta-analysis evaluating the effectiveness of rapamycin in reducing infarct volume in animal models of ischemic stroke. Summary of review: Our search identified 328 publications. Seventeen publications met inclusion criteria (52 comparisons: 30 reported infarct size, 22 reported neurobehavioral score). Study quality was modest (median 4 out of 9) with no evidence of publication bias. The point estimate for the effect of rapamycin was a 21.6% (95% CI, 7.6%-35.7% p < 0.01) improvement in infarct volume and 30.5% (95% CI 17.2%-43.8%, p < 0.0001) improvement in neuroscores. Effect sizes were greatest in studies using lower doses of rapamycin. Conclusion: Low dose rapamycin treatment may be an effective therapeutic option for stroke. Modest study quality means there is a potential risk of bias. We recommend further high quality preclinical studies on rapamycin in stroke before progressing to clinical trials.
ObjectiveTo evaluate the effectiveness of injection-based therapy in base of thumb osteoarthritis.DesignSystematic review and meta-analysis.Data sourcesMEDLINE and EMBASE via OVID, CINAHL and SPORTDiscus via EBSCO were searched from inception to 22 May 2018.Study selectionRandomised controlled trials (RCTs) and non-RCTs of adults with base of thumb osteoarthritis investigating an injection-based intervention with any comparator/s.Data extraction and analysisData were extracted and checked for accuracy and completeness by pairs of reviewers. Primary outcomes were pain and function. Comparative treatment effects were analysed by random-effects model for short-term and medium-term follow-up.ResultsIn total, 9 RCTs involving 504 patients were identified for inclusion. All compared different injection-based therapies with each other, no studies compared an injection-based therapy with a non-injection-based intervention. Twenty injection-based intervention groups were present within these nine trials, consisting of hyaluronic acid (n=9), corticosteroid (n=7), saline placebo (n=3) and dextrose (n=1). Limited meta-analysis was possible due to the heterogeneity in the injections and outcomes used, as well as incomplete outcome data. Meta-analysis of two RCTs (92 patients) demonstrated reduced Visual Analogue Scale pain on activity with corticosteroid versus hyaluronic acid (mean difference (MD) −1.32, 95% CI −2.23 to −0.41) in the medium term, but no differences in other measures of pain or function in the short term and medium term. Overall, the available evidence does not suggest that any of the commonly used injection therapies are superior to placebo, one another or a non-injection-based comparator.ConclusionCurrent evidence is equivocal regarding the use of injection therapy in base of thumb osteoarthritis, both in terms of which injection-based therapy is the most effective and in terms of whether any injection-based therapy is more effective than other non-injection-based interventions. Given limited understanding of both the short-term and long-term effects, there is a need for a large, methodologically robust RCT investigating the commonly used injection therapies and comparing them with other therapeutic options and placebo.PROSPERO registration numberCRD42018095384.
ObjectiveTo evaluate the prevalence and risk factors of wrist pain.MethodsSystematic review. Data sources: The MEDLINE and EMBASE via OVID, CINAHL and SPORTDiscus via EBSCO databases were searched from database inception to 9th March 2018. Specific criteria were used to define inclusion and exclusion. Data was extracted independently by a pair of reviewers.ResultsIn total 32 cross sectional studies were identified for inclusion (1 with a longitudinal component). The median prevalence of wrist pain in the general population and non-manual workers within the short term (within last week) was 6 and 4.2% within the medium term (> 1 week and within a year). The median prevalence of wrist pain in physically demanding occupations and sports people was 10% within the short term and 24% within the medium term. Non-modifiable factors associated with wrist pain included increased age (1 study in adults and 3 studies in children/adolescents) and female sex (2 studies). Modifiable risk factors included high job physical strain (2 studies), high job psychological strain (1 study), abnormal physeal morphology in children/adolescents (2 studies), high frequency impact tool use (1 study) and effort reward imbalance (1 study).ConclusionsWrist pain is highly prevalent in groups who partake in physically demanding activities from day to day such as manual labourers and sportspeople. It is less prevalent in the general population and non-manual workers, although there is a relative lack of research in the general population.Trial registrationThe review protocol was registered with PROSPERO under the registration number CRD42018090834.Level of Evidence1 (Prognostic study).
Background Timely recognition of the deteriorating inpatient remains challenging. Wearable monitoring systems (WMS) may augment current monitoring practices. However, there are many barriers to implementation in the hospital environment, and evidence describing the clinical impact of WMS on deterioration detection and patient outcome remains unclear. Objective To assess the impact of vital-sign monitoring on detection of deterioration and related clinical outcomes in hospitalised patients using WMS, in comparison with standard care. Methods A systematic search was conducted in August 2020 using MEDLINE, Embase, CINAHL, Cochrane Database of Systematic Reviews, CENTRAL, Health Technology Assessment databases and grey literature. Studies comparing the use of WMS against standard care for deterioration detection and related clinical outcomes in hospitalised patients were included. Deterioration related outcomes (primary) included unplanned intensive care admissions, rapid response team or cardiac arrest activation, total and major complications rate. Other clinical outcomes (secondary) included in-hospital mortality and hospital length of stay. Exploratory outcomes included alerting system parameters and clinical trial registry information. Results Of 8706 citations, 10 studies with different designs met the inclusion criteria, of which 7 were included in the meta-analyses. Overall study quality was moderate. The meta-analysis indicated that the WMS, when compared with standard care, was not associated with significant reductions in intensive care transfers (risk ratio, RR 0.87; 95% confidence interval, CI 0.66–1.15), rapid response or cardiac arrest team activation (RR 0.84; 95% CI 0.69–1.01), total (RR 0.77; 95% CI 0.44–1.32) and major (RR 0.55; 95% CI 0.24–1.30) complications prevalence. There was also no statistically significant association with reduced mortality (RR 0.48; 95% CI 0.18–1.29) and hospital length of stay (mean difference, MD − 0.09; 95% CI − 0.43 to 0.44). Conclusion This systematic review indicates that there is no current evidence that implementation of WMS impacts early deterioration detection and associated clinical outcomes, as differing design/quality of available studies and diversity of outcome measures make it difficult to reach a definite conclusion. Our narrative findings suggested that alarms should be adjusted to minimise false alarms and promote rapid clinical action in response to deterioration. PROSPERO Registration number: CRD42020188633.
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