BACKGROUND: The outcomes of several randomized trials on extracorporeal cardiopulmonary resuscitation (ECPR) in patients with refractory out-of-hospital cardiac arrest were examined using frequentist methods, resulting in a dichotomous interpretation of results based on p-values rather than in the probability of clinically relevant treatment effects. To determine such a probability of a clinically relevant ECPR-based treatment effect on neurological outcomes, the authors of these trials performed a Bayesian meta-analysis of the totality of randomized ECPR evidence. METHODS: A systematic search was applied to three electronic databases. Randomized trials that compared ECPR-based treatment with conventional CPR for refractory out-of-hospital cardiac arrest were included. The study was preregistered in INPLASY (INPLASY2023120060). The primary Bayesian hierarchical meta-analysis estimated the difference in 6-month neurologically favorable survival in patients with all rhythms, and a secondary analysis assessed this difference in patients with shockable rhythms (Bayesian hierarchical random-effects model). Primary Bayesian analyses were performed under vague priors. Outcomes were formulated as estimated median relative risks, mean absolute risk differences, and numbers needed to treat with corresponding 95% credible intervals (CrIs). The posterior probabilities of various clinically relevant absolute risk difference thresholds were estimated. RESULTS: Three randomized trials were included in the analysis (ECPR, n = 209 patients; conventional CPR, n = 211 patients). The estimated median relative risk of ECPR for 6-month neurologically favorable survival was 1.47 (95%CrI 0.73-3.32) with a mean absolute risk difference of 8.7% (- 5.0; 42.7%) in patients with all rhythms, and the median relative risk was 1.54 (95%CrI 0.79-3.71) with a mean absolute risk difference of 10.8% (95%CrI - 4.2; 73.9%) in patients with shockable rhythms. The posterior probabilities of an absolute risk difference > 0% and > 5% were 91.0% and 71.1% in patients with all rhythms and 92.4% and 75.8% in patients with shockable rhythms, respectively. CONCLUSION: The current Bayesian meta-analysis found a 71.1% and 75.8% posterior probability of a clinically relevant ECPR-based treatment effect on 6-month neurologically favorable survival in patients with all rhythms and shockable rhythms. These results must be interpreted within the context of the reported credible intervals and varying designs of the randomized trials. REGISTRATION: INPLASY (INPLASY2023120060, December 14th, 2023, https://doi.org/10.37766/inplasy2023.12.0060 ).
- MeSH
- Bayesova věta * MeSH
- kardiopulmonální resuscitace * metody normy MeSH
- lidé MeSH
- mimotělní membránová oxygenace metody MeSH
- randomizované kontrolované studie jako téma metody MeSH
- výsledek terapie MeSH
- zástava srdce mimo nemocnici * terapie mortalita MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- metaanalýza MeSH
- Klíčová slova
- aplikace intralymfatická, studie DIAGNODE-2,
- MeSH
- beta-buňky účinky léků MeSH
- C-peptid fyziologie MeSH
- diabetes mellitus 1. typu * imunologie MeSH
- glutamát dekarboxyláza * terapeutické užití MeSH
- lidé MeSH
- randomizované kontrolované studie jako téma metody MeSH
- vitamin D MeSH
- Check Tag
- lidé MeSH
BACKGROUND: The extent to which differences in results from Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) and Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial (ROCKET) atrial fibrillation (AF)-the landmark trials for the approval of apixaban and rivaroxaban, respectively, for non-valvular AF-were influenced by differences in their protocols is debated. The potential influence of selection criteria on trial results was assessed by emulating these trials in data from the Global Anticoagulant Registry in the Field (GARFIELD)-AF registry. METHODS: Vitamin K antagonist (VKA) and non-vitamin K oral antagonist (NOAC) users from GARFIELD-AF were selected according to eligibility for the original ARISTOTLE or ROCKET AF trials. A propensity score overlap weighted Cox model was used to emulate trial randomisation between treatment groups. Adjusted HRs for stroke or systemic embolism (SE) within 2 years of enrolment were calculated for each NOAC versus VKA. RESULTS: Among patients on apixaban, rivaroxaban and VKA, 2570, 3560 and 8005 were eligible for ARISTOTLE, respectively, and 1612, 2005 and 4368, respectively, for ROCKET AF. When selecting for ARISTOTLE criteria, apixaban users had significantly lower stroke/SE risk versus VKA (HR 0.57; 95% CI 0.34 to 0.94) while no reduction was observed with rivaroxaban (HR 0.98; 95% CI 0.68 to 1.40). When selecting for ROCKET AF criteria, safety and efficacy versus VKA were similar across the NOACs. CONCLUSION: Apixaban and rivaroxaban showed similar results versus VKA in high-risk patients selected according to ROCKET AF criteria, whereas differences emerged when selecting for the more inclusive ARISTOTLE criteria. Our results highlight the importance of trial selection criteria in interpreting trial results and underline the problems faced in comparing treatments across rather than within clinical trials.
- MeSH
- antikoagulancia terapeutické užití MeSH
- aplikace orální MeSH
- cévní mozková příhoda * prevence a kontrola etiologie MeSH
- fibrilace síní * farmakoterapie komplikace MeSH
- hodnocení rizik metody MeSH
- inhibitory faktoru Xa * terapeutické užití aplikace a dávkování MeSH
- lidé MeSH
- pyrazoly * terapeutické užití MeSH
- pyridony * terapeutické užití škodlivé účinky aplikace a dávkování MeSH
- randomizované kontrolované studie jako téma metody MeSH
- registrace MeSH
- rivaroxaban * aplikace a dávkování terapeutické užití MeSH
- rizikové faktory MeSH
- senioři MeSH
- vitamin K antagonisté a inhibitory MeSH
- výběr pacientů * MeSH
- výsledek terapie MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
Cemiplimab, anti-PD-1 protilátka, byl začleněn do 1. linie léčby lokálně pokročilého a generalizovaného nemalobuněčného plicního karcinomu v monoterapii nebo v kombinaci s chemoterapií na základě výsledků klinických studií EMPOWER-Lung 1 a EMPOWER-Lung 3.
Cemiplimab, an anti-PD-1 antibody, was incorporated into the first-line therapy of locally advanced and metastatic non-small cell lung cancer as monotherapy or in combination with chemotherapy based on the results of the EMPOWER-Lung 1 and EMPOWER-Lung 3 clinical trials.
Relugolix je nový antagonista hormonu uvolňujícího gonadotropin (GnRH) s dobrou účinností a příznivou snášenlivostí, který představuje příležitost rozšířit výběr androgen- -deprivační terapie (ADT) pro karcinom prostaty a nabídnout pacientům pohodlí perorálního podání 1x denně. Relugolix má také potenciál zlepšit kardiální bezpečnost ADT.
Relugolix is a novel gonadotropin-releasing hormone (GnRH) antagonist with good efficacy and favourable tolerability, which presents an opportunity to expand the choice of prostate cancer androgen-deprivation therapy (ADT) and offer patients the convenience of a once-daily oral administration. Relugolix has also a potential to improve the cardiac safety of ADT.
BACKGROUND: Vaccine efficacy (VE) assessed in a randomized controlled clinical trial can be affected by demographic, clinical, and other subject-specific characteristics evaluated as baseline covariates. Understanding the effect of covariates on efficacy is key to decisions by vaccine developers and public health authorities. METHODS: This work evaluates the impact of including correlate of protection (CoP) data in logistic regression on its performance in identifying statistically and clinically significant covariates in settings typical for a vaccine phase 3 trial. The proposed approach uses CoP data and covariate data as predictors of clinical outcome (diseased versus non-diseased) and is compared to logistic regression (without CoP data) to relate vaccination status and covariate data to clinical outcome. RESULTS: Clinical trial simulations, in which the true relationship between CoP data and clinical outcome probability is a sigmoid function, show that use of CoP data increases the positive predictive value for detection of a covariate effect. If the true relationship is characterized by a decreasing convex function, use of CoP data does not substantially change positive or negative predictive value. In either scenario, vaccine efficacy is estimated more precisely (i.e., confidence intervals are narrower) in covariate-defined subgroups if CoP data are used, implying that using CoP data increases the ability to determine clinical significance of baseline covariate effects on efficacy. CONCLUSIONS: This study proposes and evaluates a novel approach for assessing baseline demographic covariates potentially affecting VE. Results show that the proposed approach can sensitively and specifically identify potentially important covariates and provides a method for evaluating their likely clinical significance in terms of predicted impact on vaccine efficacy. It shows further that inclusion of CoP data can enable more precise VE estimation, thus enhancing study power and/or efficiency and providing even better information to support health policy and development decisions.
- MeSH
- demografie statistika a číselné údaje MeSH
- klinické zkoušky, fáze III jako téma statistika a číselné údaje metody MeSH
- lidé MeSH
- logistické modely MeSH
- počítačová simulace MeSH
- randomizované kontrolované studie jako téma statistika a číselné údaje metody MeSH
- účinnost vakcíny * statistika a číselné údaje MeSH
- vakcinace statistika a číselné údaje metody MeSH
- vakcíny terapeutické užití MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Pozadí: Tato studie zkoumá dopad tréninkového programu zaměřeného na snižování stresu, deprese a úzkosti na základě všímavosti u zdravotních sester v Maroku. Metody: Účastníci byli vybráni z nemocnice v provincii Tetouan v Maroku. Jednalo se o 80 nemocničních sester, 59 žen a 21 mužů. Byli náhodně rozděleni do intervenční skupiny a kontrolní skupiny, v každé skupině bylo 40 účastníků. Jako psychologická intervence v intervenční skupině byl použit osmitýdenní trénink na všímavost. K posouzení výsledků obou skupin před a po intervenci byla použita škála deprese, úzkosti a stresu a pětiúrovňový dotazník zaměřený na všímavost. Výsledky: Intervenční skupina vykazovala významné rozdíly v průměrném post-testovém skóre od pre-testu v proměnných: deprese (η2 = 0,249; p < 0,001), úzkost = (η2 = 0,282; p < 0,001) a stres = (η2 = 0,396 p < 0,001), stejně jako ve FFMQ (η2 = 0,379; p < 0,001). Podobně čtyřměsíční sledování odhalilo, že všechny proměnné vykazovaly statisticky významné rozdíly se stejnou velikostí účinku (η2 = 1,387; p < 0,001). Závěr: Výcvikový program MBSR je účinná psychoterapeutická intervence založená na důkazech pro léčbu deprese, úzkosti a stresu u nemocničních sester. Doporučují se další hloubkové studie založené na neurovědeckých datech pomocí elektroencefalogramu (EEG) evokovaných mozkových potenciálů.
Background: This study examines the impact of a mindfulness-based stress reduction-training program on depression, anxiety, and stress among nurses in Morocco. Methods: Participants were selected from a hospital in the province of Tetouan, Morocco. They included 80 hospital nurses, 59 women and 21 men. They were randomly assigned to an intervention group and a control group, with 40 participants in each group. An eight-week mindfulness training was used as a psychological intervention in the intervention group. To assess the outcomes of both groups before and after the intervention, a depression, anxiety, and stress scale and a five-facet mindfulness questionnaire were used. Results: In the intervention group, mean post-test scores showed significant differences from pre-test in the depression variable (η2 = 0.249; p < 0.001), Anxiety = (η2 = 0.282; p < 0.001), and Stress = (η2 = 0.396; p < 0.001), as well as in the FFMQ (η2 = 0.379; p < 0.001. Similarly, a 4-month follow-up revealed that all variables showed statistically significant differences, with an equally large effect size (η2 = 1.387; p < 0.001). Conclusion: The MBSR training program is an effective, evidence-based psychotherapeutic intervention for treating depression, anxiety, and stress in hospital nurses. Further in-depth studies based on neuroscientific data using electroencephalogram (EEG) evoked brain potentials are recommended.
- Klíčová slova
- darolutamid, apalutamid, enzalutamid,
- MeSH
- antagonisté androgenních receptorů * farmakologie škodlivé účinky terapeutické užití MeSH
- hodnocení léčiv * metody MeSH
- lidé MeSH
- nádory prostaty rezistentní na kastraci * farmakoterapie MeSH
- randomizované kontrolované studie jako téma metody MeSH
- Check Tag
- lidé MeSH
