Meta-analysis using individual participant data (IPD-MA) from randomized controlled trials (RCTs) can strengthen evidence used for decision making and is considered the "gold standard" approach. In ...this study, we present the importance, properties, and main approaches of conducting an IPD-MA. We exemplify the main approaches of conducting an IPD-MA and how these can be used to obtain subgroup effects through estimation of interaction terms. IPD-MA has several benefits over traditional aggregate data (AD) meta-analysis. These include standardization of definitions of outcomes and/or scales, reanalysis of eligible RCTs using the same analysis model across all studies, accounting for missing outcome data, detecting outliers, using participant-level covariates to explore intervention-by-covariate interactions, and tailoring intervention effects to participant characteristics. IPD-MA can be performed in either a 2-stage or 1-stage approach. We exemplify the presented methods using 2 illustrative examples. The first real-life example includes 6 studies assessing sonothrombolysis with or without addition of microspheres against IV thrombolysis alone (i.e., control) in acute ischemic stroke participants with large vessel occlusions. The second real-life example includes 7 studies evaluating the association between blood pressure levels after endovascular thrombectomy and functional improvement of acute ischemic stroke in patients with large vessel occlusion. IPD reviews can be associated with higher quality statistical analysis and may differ from AD reviews. Unlike individual trials that lack power and AD meta-analysis results, which suffer from confounding and aggregation bias, the use of IPD allows us to explore intervention-by-covariate interactions. However, a key limitation of conducting an IPD-MA is retrieval of IPD from original RCTs. Time and resources should be carefully planned before embarking on retrieving IPD.
BACKGROUND AND PURPOSE—Although current guidelines advocate pretreatment with intravenous thrombolysis (IVT) in all eligible patients with acute ischemic stroke with large-vessel occlusion before ...mechanical thrombectomy, there are observational data questioning the efficacy of this approach. One of the main arguments in favor of IVT pretreatment is the potential for tissue-type plasminogen activator–induced successful reperfusion (SR) before the onset of endovascular procedure.
METHODS—We performed a systematic review and meta-analysis of randomized controlled clinical trials and observational cohorts providing rates of SR with IVT in patients with large-vessel occlusion before the initiation of mechanical thrombectomy. We also performed subgroup analyses according to study type (randomized controlled clinical trials versus observational) and according to the inclusion per protocol of patients with tandem (intracranial/extracranial) occlusions.
RESULTS—We identified 13 eligible studies (7 randomized controlled clinical trials and 6 observational cohorts), including 1561 patients with acute ischemic stroke (median National Institutes of Health Stroke Scale score, 17) with large-vessel occlusion. SR following IVT and before mechanical thrombectomy was documented in 11% (95% confidence interval, 7%–16%), with no difference among cohorts derived from randomized controlled clinical trials and observational studies. There was significant heterogeneity across included studies both in the overall analysis and among subgroups (I>84%; P for Cochran Q, <0.001). Higher tissue-type plasminogen activator–induced SR rates were documented in studies reporting the exclusion of tandem occlusions (17%; 95% confidence interval, 11%–23%) compared with the rest (7%; 95% confidence interval, 4%–11%; P for subgroup differences, 0.003).
CONCLUSIONS—Pretreatment with systemic thrombolysis in patients with large-vessel occlusion eligible for mechanical thrombectomy results in SR in 1 of 10 cases, negating the need for additional endovascular reperfusion. Tandem occlusions seem to be the least responsive to IVT pretreatment.
BACKGROUND AND PURPOSE—To date, there is still uncertainty about age and sex differences in access to stroke unit treatment and use of intravenous thrombolysis (IVT), while age and sex differences ...have not been investigated for the new treatment option of mechanical thrombectomy (MT). We, therefore, undertook a complete nationwide analysis of all hospitalized ischemic stroke patients in Germany from 2013 to 2017.
METHODS—We used the nationwide administrative database of the German Federal Statistical Office and investigated access to stroke unit treatment, IVT, MT, and in-hospital mortality. Patients were subdivided into 6 predefined age groups (20–44, 45–59, 60–69, 70–79, 80–89, and >90 years). Pooled overall and age group estimates were calculated using the random-effects model. To evaluate potential sex disparities, we estimated odds ratios (ORs) with 95% CIs.
RESULTS—A total of 1 112 570 patients were hospitalized for first or recurrent ischemic stroke from 2013 to 2017. Overall, stroke unit treatment increased significantly from 66.8% in 2013 to 73.5% in 2017, as did IVT (from 12.4% to 15.9%) and MT (from 2.4% to 5.8%; all P<0.001). Although the difference became smaller over time, patients ≥80 years of age still received significantly less often treatments. Men of all age groups had a significantly higher probability receiving stroke unit treatment (OR, 1.11; 95% CI, 1.09–1.12) and lower in-hospital mortality (OR, 0.91; 95% CI, 0.89–0.93). No disparity was observed in the use of IVT (OR, 1.00; 95% CI, 0.98–1.01), while women of all ages were treated more often with MT (OR, 1.26; 95% CI, 1.22–1.30).
CONCLUSIONS—Access to stroke unit treatment has to be increased in both older patients and women of all ages. While there was no sex difference in IVT use, it is important to further investigate the significantly higher frequency of MT in women with ischemic stroke irrespective of age.
IMPORTANCE: Even with currently available therapies and lifestyle modifications following an ischemic stroke, there remains a substantial residual lifetime risk of stroke recurrence and ...cardiovascular morbidity. This review summarizes emerging novel therapeutic approaches that have demonstrated signals of efficacy for prevention of noncardioembolic stroke from phase II and phase III randomized clinical trials (RCTs) and provides an overview of drug regimens that have had promising results in primary stroke prevention and could be considered for further evaluation. OBSERVATIONS: After a minor acute ischemic stroke or transient ischemic attack, patients bear a high cardiovascular risk that is insufficiently addressed by long-term antiplatelet treatment. The potent combination of low-dose rivaroxaban with aspirin as an antithrombotic option for the secondary prevention in patients with clinical atherosclerosis and a history of previous stroke warrants further study. Two international RCTs are currently evaluating the utility of oral factor XI inhibitors combined with antiplatelets for secondary, noncardioembolic ischemic stroke prevention. Aggressive lipid management with statins has been shown to ameliorate ischemic stroke recurrence and total cardiovascular risk. Proprotein convertase subtilisin/kexin type 9 inhibitors are drug regimens that researchers have suggested confer additional protection against stroke recurrence, while antisense oligonucleotide therapies targeting lipoprotein(a) have been reported to hold great promise as a future therapeutic strategy to decrease the residual cardiovascular risk mediated through lipoprotein(a). Glucagon-like peptide-1 receptor agonists are newer antidiabetic medications, recently highlighted because of their consistently greater benefit on stroke reduction compared with other cardiovascular outcomes. CONCLUSIONS AND RELEVANCE: There are currently several exciting emerging opportunities in secondary stroke prevention, with RCTs investigating novel antithrombotic, hypolipidemic, anti-inflammatory, and antidiabetic agents with novel mechanisms that are likely to reduce the future burden of recurrent stroke.
The association between multiple sclerosis (MS) and inflammatory bowel disease (IBD) has been suggested, apart from their common epidemiological and immunological patterns, also due to observations ...of increased incidence of both IBD among MS patients and MS among IBD patients. We estimated the risk of concurrent IBD and MS comorbidity, using data from all available case–control studies. We calculated the corresponding Risk ratios (RRs) in each included case–control study to express the risk of IBD and MS concurrence at a given population. We performed additional subgroup analyses according to the type of registry from which the data of the cases were exported (IBD or MS registry) and the IBD type (Crohn’s disease, CD or Ulcerative colitis, UC). We included 10 studies, comprising a total of 1,086,430 patients (0.08% of them with concurrent IBD and MS). Pooled RR for IBD/MS comorbitity was 1.54 (95% CI 1.40–1.67; p < 0.0001) with no differences (
p
= 0.91) among IBD and MS registries (RR 1.53, 95% CI 1.36–1.72,
p
< 0.001 for MS comorbidity in IBD patients vs. RR 1.55, 95% CI 1.32–1.81,
p
< 0.001 for IBD comorbidity in MS patients). No difference was also found on the risk of MS comorbidity among patients with CD or UC (RR 1.52, 95% CI 1.34–1.72,
p
< 0.001 vs. RR 1.55, 95% CI 1.38–1.74,
p
< 0.001;
p
for subgroup differences: 0.84). In all analyses no evidence of heterogeneity or publication bias was detected. Both IBD and MS patients seem to have a fifty-percent increased risk of MS or IBD comorbidity, respectively, with no apparent differences between patients with CD or UC.
Abstract Emerging studies highlight high on-treatment of platelet reactivity (HTPR) as a major hindrance to the secondary prevention of cardiovascular ischemic events. The aim of this systematic ...review and meta-analysis is to assess the prevalence of HTPR in patients with ischemic stroke (IS) or transient ischemic attack (TIA) and reveal a possible relation with a higher risk of cerebrovascular event recurrence. Studies were selected if they reported absolute numbers or percentages of HTPR with ASA or clopidogrel in IS/TIA patients at any time point after the cerebrovascular event onset and assessed with any type of platelet function tests. We included 52 full-text studies with a total of 8364 patients. Overall, the pooled prevalence of HTPR was 24% (95%CI: 20–27%). In subgroup analyses, the prevalence of HTPR on ASA was 23% (95%CI: 20–28%), on clopidogrel 27% (95%CI: 22–32%) and on dual antiplatelet treatment (DAPT) 7% (95%CI: 5–10%). The overall analysis of all studies providing data on the risk of IS/TIA recurrence, indicates that the patients with HTPR had a significantly higher risk for IS/TIA recurrence (RR = 1.81, 95%CI: 1.30–2.52; p < 0.001). In conclusion the present study shows a significant lower prevalence of HTPR in DAPT and an increased rate of recurrent cerebrovascular ischemic events in patients presenting HTPR.
Background and purpose
Measurement of the cross‐sectional area (CSA) of cervical nerve roots using ultrasound is useful in the evaluation of inflammatory polyneuropathies, and measurement of CSA of ...the vagal nerve might give information about involvement of the autonomic nervous system. We performed a systematic review and meta‐analysis of published CSA reference values for cervical nerve roots and vagal nerve.
Methods
We included available‐to‐date nerve ultrasound studies on healthy adults and provide meta‐analysis for CSA of the following nerves: cervical nerve roots C5, C6, and C7 as well as vagal nerve in the carotid sheath at the carotid bifurcation level. We report regression and correlation analyses for age, gender, height, weight, and geographic continent.
Results
We included 11 studies with 885 healthy volunteers (mean age = 42.7 years) and 3149 examined nerve sites. Calculated mean pooled CSA of C5 root was 5.6 mm2 (95% confidence interval CI = 4.6–6.7 mm2, n = 911), of C6 root was 8.8 mm2 (95% CI = 7.4–10.3 mm2, n = 909), of C7 root was 9.5 mm2 (95% CI = 8.0–10.9 mm2, n = 909), and of vagal nerve was 2.2 mm2 (95% CI = 1.5–2.9 mm2, n = 420). No heterogeneity was found across studies for any site. Subgroup analysis revealed no significant effects of age, gender, height, weight, and geographic continent on CSA for any of these nerve sites.
Conclusions
We provide the first meta‐analysis on CSA reference values for the cervical nerve roots and the vagal nerve, with no heterogeneity of reported CSA values at all nerve sites. Our data facilitate the goal of an international standardized evaluation protocol.
We provide the first meta‐analysis on cross‐sectional area (CSA) reference values for the cervical nerve roots and the vagal nerve, with no heterogeneity of reported CSA values at all nerve sites. We report regression and correlation analyses for age, gender, height, weight, and geographic continent.
BACKGROUND AND PURPOSE:Accumulating evidence from randomized controlled clinical trials suggests that tenecteplase may represent an effective treatment alternative to alteplase for acute ischemic ...stroke. In the present systematic review and meta-analysis, we sought to compare the efficacy and safety outcomes of intravenous tenecteplase to intravenous alteplase administration for acute ischemic stroke patients with large vessel occlusions (LVOs).
METHODS:We searched MEDLINE (Medical Literature Analysis and Retrieval System Online) and Scopus for published randomized controlled clinical trials providing outcomes of acute ischemic stroke with confirmed LVO receiving intravenous thrombolysis with either tenecteplase at different doses or alteplase at a standard dose of 0.9 mg/kg. The primary outcome was the odds of modified Rankin Scale score of 0 to 2 at 3 months.
RESULTS:We included 4 randomized controlled clinical trials including a total of 433 patients. Patients with confirmed LVO receiving tenecteplase had higher odds of modified Rankin Scale scores of 0 to 2 (odds ratio, 2.06 95% CI, 1.15–3.69), successful recanalization (odds ratio, 3.05 95% CI, 1.73–5.40), and functional improvement defined as 1-point decrease across all modified Rankin Scale grades (common odds ratio, 1.84 95% CI, 1.18–2.87) at 3 months compared with patients with confirmed LVO receiving alteplase. There was little or no heterogeneity between the results provided from included studies regarding the aforementioned outcomes (I≤20%). No difference in the outcomes of early neurological improvement, symptomatic intracranial hemorrhage, any intracranial hemorrhage, and the rates of modified Rankin Scale score 0 to 1 or all-cause mortality at 3 months was detected between patients with LVO receiving intravenous thrombolysis with either tenecteplase or alteplase.
CONCLUSIONS:Acute ischemic stroke patients with LVO receiving intravenous thrombolysis with tenecteplase have significantly better recanalization and clinical outcomes compared with patients receiving intravenous alteplase.
A number of officially approved disease-modifying drugs (DMD) are currently available for the early intervention in patients with relapsing-remitting multiple sclerosis (RRMS). The aim of the present ...study was to systematically evaluate the effect of DMDs on disability progression in RRMS.
We performed a systematic review on MEDLINE and SCOPUS databases to include all available placebo-controlled randomized clinical trials (RCTs) of RRMS patients that reported absolute numbers or percentages of disability progression during each study period. Observational studies, case series, case reports, RCTs without placebo subgroups and studies reporting the use of RRMS therapies that are not still officially approved were excluded. Risk ratios (RRs) were calculated in each study protocol to express the comparison of disability progression in RRMS patients treated with a DMD and those RRMS patients receiving placebo. The mixed-effects model was used to calculate both the pooled point estimate in each subgroup and the overall estimates.
DMDs for RRMS were found to have a significantly lower risk of disability progression compared to placebo (RR = 0.72, 95%CI: 0.66-0.79; p<0.001), with no evidence of heterogeneity or publication bias. In subsequent subgroup analyses, neither dichotomization of DMDs as "first" and "second" line RRMS therapies (RR = 0.72, 95% CI = 0.65-0.80) vs. (RR = 0.72, 95% = 0.57-0.91); p = 0.96 nor the route of administration (injectable or oral) RR = 0.75 (95% CI = 0.64-0.87) vs. RR = 0.74 (95% CI = 0.66-0.83); p = 0.92 had a differential effect on the risk of disability progression. Either considerable (5-20%) or significant (>20%) rates of loss to follow-up were reported in many study protocols, while financial and/or other support from pharmaceutical industries with a clear conflict of interest on the study outcomes was documented in all included studies.
Available DMD are effective in reducing disability progression in patients with RRMS, independently of the route of administration and their classification as "first" or "second" line therapies. Attrition bias needs to be taken into account in the interpretation of these findings.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
BACKGROUND AND PURPOSE—Plasma GFAP (glial fibrillary acidic protein) has recently emerged as a potential biomarker for the differentiation of acute intracerebral hemorrhage (ICH) from acute ischemic ...stroke (AIS). We prospectively assessed the diagnostic accuracy of GFAP in the differential diagnosis of ICH.
METHODS—Consecutive patients presenting to the emergency department within 6 hours from symptom onset were evaluated. All patients underwent extensive diagnostic work-up and were classified according to discharge diagnosis in AIS, ICH, subarachnoid hemorrhage, and stroke mimics. GFAP was also measured in healthy volunteers (controls). Baseline stroke severity was evaluated using National Institutes of Health Stroke Scale. Receiver operating characteristic curve analysis was used to identify the optimal cutoff point for the differentiation between subgroups. Correlation analyses of GFAP plasma concentrations with baseline National Institutes of Health Stroke Scale and onset to sampling time were performed with the nonparametric Spearman rank test and fractional polynomial regression, respectively.
RESULTS—Our study population consisted of 270 individuals (AIS121, ICH34, stroke mimics31, subarachnoid hemorrhage5, controls79). No differences on baseline stroke severity and onset to sampling time were detected between AIS and ICH. Higher median plasma GFAP values were documented in ICH compared with AIS, stroke mimics, and controls (P<0.001). Receiver operating characteristic analysis highlighted a cutoff value of 0.43 ng/mL as the optimal threshold for the differentiation between ICH and AIS (sensitivity91%, specificity97%). No association was detected between plasma GFAP concentrations and baseline stroke severity for both AIS (P=0.515) and ICH (P=0.387). In the fractional polynomial analysis, the association between GFAP concentration and onset to sampling time was best described by a J-shaped curve for AIS and an inverted U-shaped curve for ICH, with a peak at 2 hours.
CONCLUSIONS—Plasma GFAP seems to be a sensitive and specific biomarker for the differentiation of ICH from both AIS and other acute neurological disorders, with the optimal diagnostic yield being present in the second hour from symptom onset.
PDF
