RANDOMISED TRIALS OF STROKE DUE TO INTRACEREBRAL HAEMORRHAGE: SYSTEMATIC REVIEW OF TRIAL CHARACTERISTICS, RISK OF BIAS, SAMPLE SIZE, AND EFFECT SIZE

Author(s):  
Arina Tamborska
2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
M P Rimmer ◽  
N Black ◽  
S Keay ◽  
S Quenby ◽  
B. H.A Wattar

Abstract Study question What is the effectiveness of IV Intralipid (IVI) in improving pregnancy rates in women undergoing IVF with history of Recurrent implantation failure (RIF) to improve reproductive outcomes. Summary answer The evidence to support the use of IVI at the time of embryo transfer in women with RIF is limited. More RCTs are needed. What is known already: Optimising the implantation process following embryo transfer remains a clinical challenge with 10% of couples undergoing IVF affected by (RIF). Immunotherapy could help to optimise endometrial receptivity and increase the chances for successful conception in women with history of RIF. Intra-venous Intralipid (IVI), a fat-based emulsion of soybean oil, glycerine, phospholipids, egg, and polyunsaturated fatty acids, has been evaluated in several trials as a potential intervention to downregulate the uNK cells and macrophages as well as inhibit the pro-inflammatory mediators including T1 helper cells. Evidence synthesis is needed to evaluate the effectiveness of this intervention. Study design, size, duration We performed this systematic review using a prospectively registered protocol (CRD42019148517) and reported in accordance with the PRISMA guidelines. Participants/materials, setting, methods: We searched MEDLINE, EMBASE and CENTRAL for any randomised trials evaluating the use of IVI at the time of embryo transfer in women undergoing assisted conception until September 2020. We extracted data in duplicate and assessed risk of bias using the Cochrane Risk of Bias tools. We meta-analysed data using a random effect model and reported on dichotomous outcomes using risk ratio (RR) and 95% confidence interval (CI). Main results and the role of chance We included five randomised trials reporting on 843 women with an overall moderate risk of bias. All trials used 20% IVI solution at the time of embryo transfer compared to normal saline infusion or no intervention (routine care). The IVI group had a higher chance of clinical pregnancy (172 vs 119, RR 1.55, 95%CI 1.16–2.07, I2 44.2%) and live birth (132 vs 73, RR 1.83, 95%CI 1.42–2.35, I2 0%) post treatment compared to no intervention. Limitations, reasons for caution Our findings are limited by the small sample size and the variations in treatment protocols and population characteristics. Wider implications of the findings: Our meta-analysis offers an overview on the value of IVI to help women affected by RIF. Given the limitations and the quality of included trials, adopting the use of IVI a-la-carte to couples undergoing IVF remains immature. IVI should not be offered until larger RCTs demonstrate a persistent benefit. Trial registration number CRD42019148517


2015 ◽  
Vol 10 (1) ◽  
pp. 95
Author(s):  
Elizabeth Margaret Stovold

A Review of: Perrier, L., Farrell, A., Ayala, A. P., Lightfoot, D., Kenny, T., Aaronson, E., . . . Weiss, A. ( 2014). Effects of librarian-provided services in healthcare settings: A systematic review. Journal of the American Medical Informatics Association, 21(6), 1118-1124. http://dx.doi.org/10.1136/amiajnl-2014-002825 Abstract Objective – To assess the effects of librarian-provided services, in any healthcare setting, on outcomes important to patients, healthcare providers, and researchers. Design – Systematic review and narrative synthesis. Setting – MEDLINE, CINAHL, ERIC, LISA, and CENTRAL databases; library-related websites, conference proceedings, and reference lists of included studies. Subjects – Twenty-five studies identified through a systematic literature search. Methods – In consultation with the review team, a librarian designed a search to be run in MEDLINE that was peer-reviewed against a published checklist. The team then conducted searches in the five identified databases, adapting the search as appropriate for each database. Authors also checked the websites of library and evidence based healthcare organisations, along with abstracts of relevant conference proceedings, to supplement the electronic search. Two authors screened the literature search results for eligible studies, and reached agreement by consensus. Studies of any librarian-delivered service in a healthcare setting, directed at either patients, clinicians of any type, researchers, or students, along with studies reporting outcomes relevant to clinicians, patients, or researchers, were eligible for inclusion. The authors assessed results initially on the titles and abstracts, and then on the full-text of potentially relevant reports. The data from included studies were then extracted into a piloted data extraction form, and each study was assessed for quality using the Cochrane EPOC risk of bias tool or the Newcastle-Ottawa scale. The results were synthesised narratively. Main Results – The searches retrieved a total of 25 studies that met the inclusion criteria, comprised of 22 primary papers and 3 companion reports. Authors identified 12 randomised trials, 4 controlled before-and-after studies, 3 cohorts, 2 non-randomised trials, and 1 case-control study. They identified three main categories of intervention: librarians teaching search skills; providing literature searching as a service; and a combination of the teaching and provision of search services. The interventions were delivered to a mix of trainees, clinicians, and students. None of the studies examined services delivered directly to patients or to researchers. The quality assessment found most of the studies had a mid- to high-risk of bias due to factors such as lack of random sequence generation, a lack of validated tools for data collection, or a lack of statistical analysis included in the study. Two studies measured patient relevant outcomes and reported that searches provided by librarians to clinicians had a positive impact on the patient’s length of stay in hospital. Five studies examined the effect of librarian provided services on outcomes important to clinicians, such as whether a literature search influenced a clinical decision. There was a trend towards a positive effect, although two studies found no significant difference. The majority of studies investigated the impact of training delivered to trainees and students on their literature search skills. Twelve of these studies found a positive effect of training on the recipients’ search skills, while three found no difference. The secondary outcomes considered by this review were satisfaction with the service (8 studies), relevance of the answers provided by librarians (2), and cost (3). The majority reported good satisfaction, and relevance. A cost benefit was found in 2 of 3 studies that reported this outcome. Conclusion – Authors report a positive effect of training on the literature search skills of trainees and students, and identified a benefit in the small number of studies that examined librarian services to clinicians. Future studies should use validated data collection tools, and further research should be conducted in the area of services provided to clinicians. Research is needed on the effect of librarian-provided services to patients and researchers as no studies meeting the inclusion criteria examining these two groups were identified by the literature search.


2002 ◽  
Vol 180 (5) ◽  
pp. 396-404 ◽  
Author(s):  
David Smith ◽  
Carrie Dempster ◽  
Julie Glanville ◽  
Nick Freemantle ◽  
Ian Anderson

BackgroundIn individual studies and limited meta-analyses venlafaxine has been reported to be more effective than comparator antidepressants, particularly selective serotonin reuptake inhibitors (SSRIs).AimsTo perform a systematic review of all such studies.MethodWe conducted a systematic review of double-blind, randomised trials comparing venlafaxine with alternative antidepressants in the treatment of depression. The primary outcome was the difference in final depression rating scale value, expressed as a standardised effect size. Secondary outcomes were response rate, remission rate and tolerability.ResultsA total of 32 randomised trials were included. Venlafaxine was more effective than other antidepressants (standardised effect size was −0.14, 95% Cl −0.07 to −0.22). A similar significant advantage was found against SSRIs (20 studies) but nottricyclic antidepressants (7 studies).ConclusionsVenlafaxine has greater efficacy than SSRIs although there is uncertainty in comparison with other antidepressants. Further studies are required to determine the clinical importance of this finding.


BMJ Open ◽  
2019 ◽  
Vol 9 (6) ◽  
pp. e024886 ◽  
Author(s):  
Klaus Munkholm ◽  
Asger Sand Paludan-Müller ◽  
Kim Boesen

ObjectivesTo investigate whether the conclusion of a recent systematic review and network meta-analysis (Ciprianiet al) that antidepressants are more efficacious than placebo for adult depression was supported by the evidence.DesignReanalysis of a systematic review, with meta-analyses.Data sources522 trials (116 477 participants) as reported in the systematic review by Ciprianiet aland clinical study reports for 19 of these trials.AnalysisWe used the Cochrane Handbook’s risk of bias tool and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to evaluate the risk of bias and the certainty of evidence, respectively. The impact of several study characteristics and publication status was estimated using pairwise subgroup meta-analyses.ResultsSeveral methodological limitations in the evidence base of antidepressants were either unrecognised or underestimated in the systematic review by Ciprianiet al. The effect size for antidepressants versus placebo on investigator-rated depression symptom scales was higher in trials with a ‘placebo run-in’ study design compared with trials without a placebo run-in design (p=0.05). The effect size of antidepressants was higher in published trials compared with unpublished trials (p<0.0001). The outcome data reported by Ciprianiet aldiffered from the clinical study reports in 12 (63%) of 19 trials. The certainty of the evidence for the placebo-controlled comparisons should be very low according to GRADE due to a high risk of bias, indirectness of the evidence and publication bias. The mean difference between antidepressants and placebo on the 17-item Hamilton depression rating scale (range 0–52 points) was 1.97 points (95% CI 1.74 to 2.21).ConclusionsThe evidence does not support definitive conclusions regarding the benefits of antidepressants for depression in adults. It is unclear whether antidepressants are more efficacious than placebo.


BMJ Open ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. e050519
Author(s):  
Kevin Jenniskens ◽  
Martin C J Bootsma ◽  
Johanna A A G Damen ◽  
Michiel S Oerbekke ◽  
Robin W M Vernooij ◽  
...  

ObjectiveTo systematically review evidence on effectiveness of contact tracing apps (CTAs) for SARS-CoV-2 on epidemiological and clinical outcomes.DesignRapid systematic review.Data sourcesEMBASE (OVID), MEDLINE (PubMed), BioRxiv and MedRxiv were searched up to 28 October 2020.Study selectionStudies, both empirical and model-based, assessing effect of CTAs for SARS-CoV-2 on reproduction number (R), total number of infections, hospitalisation rate, mortality rate, and other epidemiologically and clinically relevant outcomes, were eligible for inclusion.Data extractionEmpirical and model-based studies were critically appraised using separate checklists. Data on type of study (ie, empirical or model-based), sample size, (simulated) time horizon, study population, CTA type (and associated interventions), comparator and outcomes assessed, were extracted. The most important findings were extracted and narratively summarised. Specifically for model-based studies, characteristics and values of important model parameters were collected.Results2140 studies were identified, of which 17 studies (2 empirical, 15 model-based studies) were eligible and included in this review. Both empirical studies were observational (non-randomised) studies and at high risk of bias, most importantly due to risk of confounding. Risk of bias of model-based studies was considered low for 12 out of 15 studies. Most studies demonstrated beneficial effects of CTAs on R, total number of infections and mortality rate. No studies assessed effect on hospitalisation. Effect size was dependent on model parameters values used, but in general, a beneficial effect was observed at CTA adoption rates of 20% or higher.ConclusionsCTAs have the potential to be effective in reducing SARS-CoV-2 related epidemiological and clinical outcomes, though effect size depends on other model parameters (eg, proportion of asymptomatic individuals, or testing delays), and interventions after CTA notification. Methodologically sound comparative empirical studies on effectiveness of CTAs are required to confirm findings from model-based studies.


2020 ◽  
pp. bjgp20X714149
Author(s):  
Tammy Hoffmann ◽  
Ruwani Peiris ◽  
Paul Glasziou ◽  
Gina Cleo ◽  
Christopher Del Mar

Abstract Background: Non-bullous impetigo is typically treated with antibiotics. However, the duration of symptoms without their use is not established which hampers informed decision-making about antibiotic use. Aim: To determine the natural history of non-bullous impetigo. Design and Setting: Systematic review. Method: We searched PubMed up to January 2020 and reference lists of articles identified in the search. Eligible studies involved participants with impetigo in either the placebo group of randomised trials or in single-group prognostic studies not using antibiotics and measured time to resolution or improvement. A modified version of a risk of bias assessment for prognostic studies was used. Outcomes were percentage of participants who, at any timepoint, had: i) symptom resolution, ii) symptom improvement, or iii) failed to improve. Adverse event data were also extracted. Results: Seven randomised trials (557 placebo group participants) were identified. At about 7 days, the percentage of participants classified as resolved ranged from 13% to 74% across the studies, whereas the percentage classified as ‘failure to improve’ ranged from 16% to 41%. The rate of adverse effects was low. Incomplete reporting of some details limited assessment of risk of bias. Conclusions: While some uncertainty around the natural history of non-bullous impetigo remains, symptoms resolve in some patients by about 7 days without using antibiotics, with about one-quarter of patients not improving. Immediate antibiotic use may not be mandatory and discussions with patients should include the expected course of untreated impetigo and careful consideration of the benefits and harms of antibiotic use.


2017 ◽  
Author(s):  
Clarissa F. D. Carneiro ◽  
Thiago C. Moulin ◽  
Malcolm R. Macleod ◽  
Olavo B. Amaral

AbstractProposals to increase research reproducibility frequently call for focusing on effect sizes instead of p values, as well as for increasing the statistical power of experiments. However, it is unclear to what extent these two concepts are indeed taken into account in basic biomedical science. To study this in a real-case scenario, we performed a systematic review of effect sizes and statistical power in studies on learning of rodent fear conditioning, a widely used behavioral task to evaluate memory. Our search criteria yielded 410 experiments comparing control and treated groups in 122 articles. Interventions had a mean effect size of 29.5%, and amnesia caused by memory-impairing interventions was nearly always partial. Mean statistical power to detect the average effect size observed in well-powered experiments with significant differences (37.2%) was 65%, and was lower among studies with non-significant results. Only one article reported a sample size calculation, and our estimated sample size to achieve 80% power considering typical effect sizes and variances (15 animals per group) was reached in only 12.2% of experiments. Actual effect sizes correlated with effect size inferences made by readers on the basis of textual descriptions of results only when findings were non-significant, and neither effect size nor power correlated with study quality indicators, number of citations or impact factor of the publishing journal. In summary, effect sizes and statistical power have a wide distribution in the rodent fear conditioning literature, but do not seem to have a large influence on how results are described or cited. Failure to take these concepts into consideration might limit attempts to improve reproducibility in this field of science.


BMJ ◽  
2020 ◽  
pp. m689 ◽  
Author(s):  
Myura Nagendran ◽  
Yang Chen ◽  
Christopher A Lovejoy ◽  
Anthony C Gordon ◽  
Matthieu Komorowski ◽  
...  

Abstract Objective To systematically examine the design, reporting standards, risk of bias, and claims of studies comparing the performance of diagnostic deep learning algorithms for medical imaging with that of expert clinicians. Design Systematic review. Data sources Medline, Embase, Cochrane Central Register of Controlled Trials, and the World Health Organization trial registry from 2010 to June 2019. Eligibility criteria for selecting studies Randomised trial registrations and non-randomised studies comparing the performance of a deep learning algorithm in medical imaging with a contemporary group of one or more expert clinicians. Medical imaging has seen a growing interest in deep learning research. The main distinguishing feature of convolutional neural networks (CNNs) in deep learning is that when CNNs are fed with raw data, they develop their own representations needed for pattern recognition. The algorithm learns for itself the features of an image that are important for classification rather than being told by humans which features to use. The selected studies aimed to use medical imaging for predicting absolute risk of existing disease or classification into diagnostic groups (eg, disease or non-disease). For example, raw chest radiographs tagged with a label such as pneumothorax or no pneumothorax and the CNN learning which pixel patterns suggest pneumothorax. Review methods Adherence to reporting standards was assessed by using CONSORT (consolidated standards of reporting trials) for randomised studies and TRIPOD (transparent reporting of a multivariable prediction model for individual prognosis or diagnosis) for non-randomised studies. Risk of bias was assessed by using the Cochrane risk of bias tool for randomised studies and PROBAST (prediction model risk of bias assessment tool) for non-randomised studies. Results Only 10 records were found for deep learning randomised clinical trials, two of which have been published (with low risk of bias, except for lack of blinding, and high adherence to reporting standards) and eight are ongoing. Of 81 non-randomised clinical trials identified, only nine were prospective and just six were tested in a real world clinical setting. The median number of experts in the comparator group was only four (interquartile range 2-9). Full access to all datasets and code was severely limited (unavailable in 95% and 93% of studies, respectively). The overall risk of bias was high in 58 of 81 studies and adherence to reporting standards was suboptimal (<50% adherence for 12 of 29 TRIPOD items). 61 of 81 studies stated in their abstract that performance of artificial intelligence was at least comparable to (or better than) that of clinicians. Only 31 of 81 studies (38%) stated that further prospective studies or trials were required. Conclusions Few prospective deep learning studies and randomised trials exist in medical imaging. Most non-randomised trials are not prospective, are at high risk of bias, and deviate from existing reporting standards. Data and code availability are lacking in most studies, and human comparator groups are often small. Future studies should diminish risk of bias, enhance real world clinical relevance, improve reporting and transparency, and appropriately temper conclusions. Study registration PROSPERO CRD42019123605.


2020 ◽  
Vol 70 (699) ◽  
pp. e714-e722
Author(s):  
Tammy Hoffmann ◽  
Ruwani Peiris ◽  
Chris Del Mar ◽  
Gina Cleo ◽  
Paul Glasziou

BackgroundAlthough uncomplicated urinary tract infection (UTI) is commonly treated with antibiotics, the duration of symptoms without their use is not established; this hampers informed decision making about antibiotic use.AimTo determine the natural history of uncomplicated UTI in adults.Design and settingSystematic review.MethodPubMed was searched for articles published until November 2019, along with reference lists of articles identified in the search. Eligible studies were those involving adults with UTIs in either the placebo group of randomised trials or in single-group prognostic studies that did not use antibiotics and measured symptom duration. A modified version of a risk of bias assessment for prognostic studies was used. Outcomes were the percentage of patients who, at any time point, were symptom free, had symptom improvement, or had worsening symptoms (failed to improve). Adverse event data were also extracted.ResultsThree randomised trials (346 placebo group participants) were identified, all of which specified women only in their inclusion criteria. The risk of bias was generally low, but incomplete reporting of some details limited assessment. Over the first 9 days, the percentage of participants who were symptom free or reported improved symptoms was reported as rising to 42%. At 6 weeks, the percentage of such participants was 36%; up to 39% of participants failed to improve by 6 weeks. The rate of adverse effects was low and, in two trials, progression to pyelonephritis was reported in one placebo participant.ConclusionAlthough some uncertainty around the natural history of uncomplicated UTIs remains, some women appear to improve or become symptom free spontaneously, and most improvement occurs in the first 9 days. Other women either failed to improve or became worse over a variable timespan, although the rate of serious complications was low.


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