BACKGROUND AND OBJECTIVES: Given the paucity of high-quality safety/efficacy data on acute stroke therapies in patients with premorbid disability, they risk being routinely excluded from such therapies. We examined utilization of endovascular thrombectomy (EVT), associated workflow, and poststroke outcomes among patients with vs without premorbid disability. METHODS: We used national registry data on thrombolysis/EVT for the Czech Republic from 1 January 2016 to 31 December 2020. Premorbid disability was defined as prestroke modified Rankin Scale score (mRS) ≥3. We compared proportions of patients with vs without premorbid disability who received EVT and examined workflow times. We compared ΔmRS-change in mRS from prestroke to 3 months-in patients with vs without premorbid disability, in addition to intracerebral hemorrhage (ICH), mortality, and discharge NIHSS (National Institutes of Health Stroke Scale score), adjusting for age, sex, baseline NIHSS, and comorbidities, and verified using propensity score weighting (PSW) and matching for differences in treatment assignment. We stratified by age group (<65, 65-74, 75-84, ≥85 years) to explore outcome heterogeneity with vs without premorbid disability. RESULTS: Among 22,405 patients with ischemic stroke who received thrombolysis/EVT/both, 1,712 (7.6%) had prestroke mRS ≥ 3. Patients with prestroke disability were less likely to receive EVT vs those without (10.1% vs 20.7%, aOR: 0.30, 95% CI 0.24-0.36). When treated, they had longer door-to-arterial puncture times (median: 75 minutes, IQR: 58-100 vs 54, IQR: 27-77, adjusted difference: 12.5, 95% CI 2.68-22.3). Patients with prestroke disability receiving thrombolysis/EVT/both had worse ΔmRS (adjusted rate ratio, aIRR on PSW: 1.57, 95% CI 1.43-1.72), rates of 3-month mRS 5-6, discharge NIHSS, and mortality (aOR-PSW [mortality]: 2.54, 95% CI 1.92-3.34), while ICH did not significantly differ. 32.1% of patients with prestroke disability receiving thrombolysis/EVT/both successfully returned to prestroke state, but this proportion ranged from 19.6% for those older than 85 years to 66.0% for those younger than 65 years. Regardless of premorbid disability, EVT was associated with better outcomes including lower ΔmRS (aIRR-PSW: 0.87, 95% CI 0.83-0.91) and mortality, with no interaction of treatment effect by premorbid disability status (e.g., mortality pinteraction = 0.73). EVT recipients with premorbid disability did not differ significantly for several outcomes including ΔmRS (aIRR: 0.99, 95% CI 0.84-1.17) but were more likely to have 3-month mRS 5-6 (70.1% vs 39.5% without premorbid disability, aOR: 1.85, 95% CI 1.12-3.04). DISCUSSION: Patients with premorbid disability were less likely to receive EVT, had slower treatment times, and had worse outcomes compared with patients without premorbid disability. However, regardless of premorbid disability, patients fared better with EVT vs medical management and one-third with prestroke disability returned to their prestroke status.

• Publikační typ
• časopisecké články MeSH

INTRODUCTION: Clinical stage 1 (CS1) nonseminomatous (NS) germ cell tumors involve a 30% probability of relapse upon surveillance. Adjuvant chemotherapy with one course of bleomycin, etoposide, and cisplatin (1xBEP) can reduce this risk to <5%. However, 1xBEP results are based solely on five controlled trials from high-volume centers. We analyzed the outcome in a real-life population. PATIENTS AND METHODS: In a multicentric international study, 423 NS CS1 patients receiving 1xBEP were retrospectively evaluated. Median follow-up was 37 (range, 6-89) months. Primary end points were relapse-free and overall survival evaluated after 5 years. We also looked at associations of relapse with clinico-pathological factors using stratified Kaplan-Meier methods and Cox regression models. Treatment modality and outcome of recurrences were analyzed descriptively. RESULTS: The 5-year relapse-free survival rate was 96.2%. Thirteen patients (3.1%; 95% confidence interval, 1.65-5.04%) relapsed after a median time of 13 months, of which 10 were salvaged (77%). Relapses were mostly confined to retroperitoneal nodes. Three patients succumbed, two to disease progression and one to toxicity of chemotherapy. Pathological stage >pT2 was significantly associated with relapse rate. CONCLUSION: The relapse rate of 3.1% found in this population of NS CS1 patients treated with 1xBEP at the routine care level was not inferior to the median rate of 2.3% reported from a meta-analysis of controlled trials. Also, the cure rate of relapses of 77% is consistent with the previously reported rate of 80%. This study clearly shows that the 1xBEP regimen represents a safe treatment for NS CS1 patients.

• Klíčová slova
• bleomycin, cisplatin, embryonal carcinoma, etoposide, germ-cell tumor, local pathological stage, lymphovascular invasion, nonseminoma,
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Infants born extremely preterm are at high risk of dying or suffering from severe brain injuries. Treatment guided by monitoring of cerebral oxygenation may reduce the risk of death and neurologic complications. The SafeBoosC III trial evaluates the effects of treatment guided by cerebral oxygenation monitoring versus treatment as usual. This article describes the detailed statistical analysis plan for the main publication, with the aim to prevent outcome reporting bias and data-driven analyses. METHODS/DESIGN: The SafeBoosC III trial is an investigator-initiated, randomised, multinational, pragmatic phase III trial with a parallel group structure, designed to investigate the benefits and harms of treatment based on cerebral near-infrared spectroscopy monitoring compared with treatment as usual. Randomisation will be 1:1 stratified for neonatal intensive care unit and gestational age (lower gestational age (< 26 weeks) compared to higher gestational age (≥ 26 weeks)). The primary outcome is a composite of death or severe brain injury at 36 weeks postmenstrual age. Primary analysis will be made on the intention-to-treat population for all outcomes, using mixed-model logistic regression adjusting for stratification variables. In the primary analysis, the twin intra-class correlation coefficient will not be considered. However, we will perform sensitivity analyses to address this. Our simulation study suggests that the inclusion of multiple births is unlikely to significantly affect our assessment of intervention effects, and therefore we have chosen the analysis where the twin intra-class correlation coefficient will not be considered as the primary analysis. DISCUSSION: In line with the Declaration of Helsinki and the International Conference on Harmonization Good Clinical Practice guidelines, we have developed and published this statistical analysis plan for the SafeBoosC III trial, prior to any data analysis. TRIAL REGISTRATION: ClinicalTrials.org, NCT03770741. Registered on 10 December 2018.

• Klíčová slova
• Cerebral oximetry, Extremely preterm, Near-infrared spectroscopy, Randomised clinical trial, Statistical analysis plan,
• MeSH
• blízká infračervená spektroskopie přístrojové vybavení   metody   MeSH
• jednotky intenzivní péče o novorozence MeSH
• klinické zkoušky, fáze III jako téma MeSH
• kyslík metabolismus   MeSH
• lidé MeSH
• monitorování fyziologických funkcí přístrojové vybavení   metody   MeSH
• mozek diagnostické zobrazování   metabolismus   patologie   MeSH
• mozková hypoxie diagnóza   epidemiologie   terapie   MeSH
• multicentrické studie jako téma MeSH
• novorozenci extrémně nezralí * MeSH
• novorozenec MeSH
• pragmatické klinické studie jako téma MeSH
• randomizované kontrolované studie jako téma MeSH
• terapie náhlých příhod metody   MeSH
• Check Tag
• lidé MeSH
• novorozenec MeSH
• Publikační typ
• dopisy MeSH
• Názvy látek
• kyslík MeSH