Observational analyses for causal inference often rely on real world data collected for purposes other than research. A frequent goal of these observational analyses is to use the data to emulate a hypothetical randomized experiment, i.e., the target trial, that mimics the design features of a true experiment, including a clear definition of time zero with synchronization of treatment assignment and determination of eligibility. We review a recent observational analysis that explicitly emulated a target trial of screening colonoscopy using insurance claims from U.S. Medicare. We then compare this explicit emulation with alternative, simpler observational analyses that do not synchronize treatment assignment and eligibility determination at time zero and/or do not allow for repeated eligibility. This empirical comparison suggests that lack of an explicit emulation of the target trial leads to biased estimates, and shows that allowing for repeated eligibility increases the statistical efficiency of the estimates. 相似文献
Pharmaceutical Research - The aim of this work was to formulate and characterize surfactant-free glibenclamide nanoparticles using Eudragit RLPO and polyethylene glycol as sole stabilizer.... 相似文献
Objectives: The XXI Century Academy was a 6-year state-initiated intervention program that served as an alternative to basketball clubs for players in the u-14 and u-18 age groups in Spain, under guidelines established by the Spanish Basketball Federation. It was an important and unique project on talent development in basketball. To the best of the authors’ knowledge, no evidence has been reported on long-term athlete development programs in basketball worldwide. The main aim of this report is to describe the design and evaluation methods used for the XXI Century Academy as a long-term intervention program in the elite Spanish Basketball Academy, aiming to prepare basketball players to compete at the elite level.
Methods: The monitoring time lasted from 1996 to 2001. A total of 55 players were assigned to the intervention groups based on age, position, maturation level, and country of origin. During this process, participants competed in up to two categories in addition to playing competitive official matches worldwide in international tournaments in their categories and with the national team in the European and World Championships (u-14 - u-18). Participants included 1 NBA player, 3 national A Team players, 10 ACB (First Spanish League) players, 5 LEB (second League) players and 39 LEB-2 EBA (third League) players. Assessments took place in a High-Performance Sports Center (CPT FADURA-GETXO- Basque Government, Getxo, Vizcaya, Spain) and consisted of health questionnaires, anthropometric measures, blood parameters, maturation level, birth age, fitness tests, training volume and intensity, physical activity, technical and tactical training, dietary intake, supplementation and injuries. Each player was assessed 4 times per year (September, December, April, June) for 4 years (16 data points).
Results: This is a purely methodological paper describing the design and evaluation methods used in the XXI Century Project, which will be used as a basis for future reporting of results. Therefore, the results of the project will be reported in subsequent publications.
Conclusion: The viability of the Century XXI Project protocols has been described. This national project of training in basketball closely replicates the physical and technical match-play conditions for professionals and may constitute a useful training tool. 相似文献
To determine differences in maximal strength and muscle power output of the arm and leg extensor muscles, peak and mean power
during a modified standing crank-arm Wingate test, running speed, muscle extensibility, and anthropometric markers between
elite and amateurs wrestlers according to the weight classes system; 92 male wrestlers were assigned into 6 groups according
to their body mass (light, middle and heavy weight) and their competitive level (elite and amateur): Light Weight (body mass
ranged between 55 and 68 kg) in elite (LWE, n = 18) and amateur (LWA, n = 15) level; Middle Weight (body mass ranged between 68 and 84 kg) in elite (MWE, n = 18) and amateur (MWA, n = 19) level; and Heavy Weight (body mass ranged between 84 and 100 kg) in elite (HWE, n = 10) and amateur (HWA, n = 12) level. Elite wrestlers were older (8–12%), had more training experience (25–37%), fat-free mass (3–5%), maximal strength
in absolute and relative terms (8–25%), muscle power (14–30%), mean and peak power during crank-arm Wingate testing in absolute
and relative terms (13–22%), jumping height (8–17%) as well as grip (6–19%) and back strength (7–20%) compared to amateur
wrestlers. However, no differences were observed between elite and amateur groups in height, body mass index, percentage of
body fat, hamstring extensibility and running speed. The present results suggest that the higher absolute and relative values
of maximal strength, muscle power, and anaerobic metabolism, explained in part by the differences in lean mass and neural
activation patterns, will give elite wrestlers a clear advantage during the most frequently used techniques in Olympic wrestling. 相似文献
To measure a combination of novel molecular biomarkers in urine/blood samples of consecutive patients referring lower urinary tract symptoms (LUTS) not previously diagnosed, to improve prostate cancer diagnosis.
Methods
Serum and urine samples from 113 men who went consecutively to the Department of Urology of our Institution. Biomarkers analyzed were AMACR and MMP-2 levels, and GSTP1/RASSF1A methylation status, in addition to PSA levels. Sensitivity, specificity, area under the ROC (AUROC) curves, and discriminant function analysis were assessed to determine the diagnostic potential of each variable alone or in combination.
Results
Of the patients, 30.08% had PCa and the remaining ones were tumor free. Areas under the ROC (AUROC) curves were as follows: 0.476 for PSA, 0.532 for AMACR, and 0.706 for MMP-2. Sensitivity and specificity for methylation status were 53.3 and 45.9%, respectively. The combination of these biomarkers resulted in an AUROC curve of 0.788, which significantly outperformed AUROC curves for PSA (P = 0.0033) and AMACR (P = 0.0375). Sensitivity, specificity, positive and negative predictive values for the combination of biomarkers were 57.1, 96.6, 88.9, and 82.4%, respectively.
Conclusion
We conclude that analysis of this biomarker combination in body fluids improves very significantly the diagnosis of PCa compared to the PSA test. 相似文献
The 2004 discovery of EGFR mutations, followed by ALK rearrangements, ushered in a targeted therapy era for advanced non-small cell lung cancer (NSCLC). Tyrosine kinase inhibitors targeting gene alterations have substantially improved survival and quality of life for patients with NSCLC. In the last decade, rearrangements of the ROS1 oncogene have been incorporated into healthcare practice that are applicable to another small subgroup of patients who benefit from similar targeted strategies. Recent genome studies of lung adenocarcinoma have identified other possible therapeutic targets, including RET, NTRK fusions, c-MET alterations, and activating mutations in KRAS, BRAF, and HER2, all with frequencies greater than 1%. Lung cancers harbouring these genome changes can potentially be treated with agents approved for other indications or under clinical development. This review updates the therapeutic arsenal that especially targets those genes. 相似文献
Malignant pleural mesothelioma (MPM) is the most common type of malignant mesothelioma. It is a rare tumor linked to asbestos exposure and is associated with a poor prognosis. Until very recently, patients with advanced or unresectable disease had limited treatment options, primarily based on doublet chemotherapy with cisplatin and pemetrexed. In 2020 and 2021, after more than a decade with no major advances or new drugs, two phase III clinical trials published results positioning immunotherapy as a promising option for the first- and second-line treatment of MPM. Immunotherapy has revolutionized the treatment of many cancers and is also showing encouraging results in malignant mesothelioma. Both immune checkpoint inhibition and dual cytotoxic T-lymphocyte–associated antigen 4 and programmed death-ligand 1 pathway blockade resulted in significantly improved overall survival in randomized phase III trials. In the CheckMate 743 trial, first-line therapy with nivolumab plus ipilimumab outperformed standard chemotherapy, while in the CONFIRM trial, nivolumab outperformed placebo in patients previously treated with chemotherapy. These two trials represent a major milestone in the treatment of MPM and are set to position immunotherapy as a viable alternative for treatment-naïve patients and patients with progressive disease after chemotherapy. 相似文献