In this article,we introduce a flexible model-free approach to sufficient dimension reduction analysis using the expectation of conditional difference *** any strict conditions,such as linearity condition or constant ...
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In this article,we introduce a flexible model-free approach to sufficient dimension reduction analysis using the expectation of conditional difference *** any strict conditions,such as linearity condition or constant covariance condition,the method estimates the central subspace exhaustively and efficiently under linear or nonlinear relationships between response and *** method is especially meaningful when the response is *** also studiedthe√n-consistency and asymptotic normality of the *** efficacy of our method is demonstrated through both simulations and a real data analysis.
We study the problem of finding the optimal dosage in early stage clinical trials through the multiarmed bandit lens. We advocate the use of the Thompson Sampling principle, a flexible algorithm that can accommodate d...
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We study the problem of finding the optimal dosage in early stage clinical trials through the multiarmed bandit lens. We advocate the use of the Thompson Sampling principle, a flexible algorithm that can accommodate different types of monotonicity assumptions on the toxicity and efficacy of the doses. For the simplest version of Thompson Sampling, based on a uniform prior distribution for each dose, we provide finite-time upper bounds on the number of sub-optimal dose selections, which is unprecedented for dose-finding algorithms. Through a large simulation study, we then show that variants of Thompson Sampling based on more sophisticated prior distributions outperform state-of-the-art dose identification algorithms in different types of dose-finding studies that occur in phase I or phase I/II trials.
Objective Previous studies have shown that ex utero intrapartum therapy(EXIT)is safe and feasible for newborns with congenital diaphragmatic hernia(CDH).This study reports our experience with EXIT in fetuses with CDH ...
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Objective Previous studies have shown that ex utero intrapartum therapy(EXIT)is safe and feasible for newborns with congenital diaphragmatic hernia(CDH).This study reports our experience with EXIT in fetuses with CDH in an attempt to explore the efficacy of EXIT on the survival rate of this *** A retrospective analysis of the clinical data of 116 children with CDH was *** children were assigned to EXIT and non-EXIT *** score matching(PSM)toward clinical data was performed,and the clinical characteristics and outcomes were *** survival at discharge as the main outcome,logistic regression analysis was carried out to explore the efficacy of EXIT on *** During the study period,30 of 116 children received *** PSM,the survival rates of the EXIT group and the non-EXIT group were 82.76%(24/29)and 48.28%(14/29),respectively(p=0.006).EXIT(OR=0.083,95%CI=0.013to 0.525,p=0.008),liver herniation(OR=16.955,95%CI=2.342 to 122.767,p=0.005),and gestational age at diagnosis(OR=0.662,95%CI=0.497 to 0.881,p=0.005)were independent mortality-related risk factors of all children with ***-nine of 116 children underwent *** PSM,the postoperative survival rates of the EXIT group and non-EXIT group were 84.6%(22/26)and 76.9%(20/26),respectively(p=0.754).Liver herniation(OR=10.451,95%CI=1.641 to 66.544,p=0.013)and gestational age at diagnosis(OR=0.736,95%CI=0.577 to 0.938,p=0.013)were independent mortality-related risk factors of children after *** EXIT can be performed safely for selected prenatally diagnosed CDH neonates with potentially better survival and does not cause more maternal complications compared with traditional cesarean section.
Phase I dose-finding trials in oncology seek to find the maximum tolerated dose (MTD) of a drug under a specific schedule. Evaluating drug-schedules aims at improving treatment safety while maintaining efficacy. Howev...
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Background Interstitial lung disease (ILD) is a recognized complication of RA. Prior studies have suggested stabilization or improvement of ILD in patients with RA (RA-ILD) treated with abatacept. [1,2] Few studies ha...
Background Interstitial lung disease (ILD) is a recognized complication of RA. Prior studies have suggested stabilization or improvement of ILD in patients with RA (RA-ILD) treated with abatacept. [1,2] Few studies have evaluated the background incidence rate of RA-ILD. Objectives To determine the incidence rate of clinically significant ILD in a cohort of patients with RA receiving abatacept + MTX versus placebo + MTX from multiple clinical trials. Methods This retrospective analysis examined pooled safety data from ten phase 3 clinical trials of patients with RA treated with background MTX in combination with abatacept or placebo. The term ‘interstitial lung’ was used to identify incidences of ILD reported as AEs in the safety data. The exposure period for each patient was censored at first incidence of clinically significant ILD, 56 days after last study drug administration, or 1 day prior to commencement of another study drug, whichever occurred first. Poisson regression models were used to estimate crude incidence rates per 100 person-years for baseline risk factors within treatment groups, and to estimate incidence rate ratios for the placebo + MTX versus abatacept + MTX treatment groups. Disease activity parameters, DAS28 (CRP) and HAQ-DI, were estimated from baseline to the time of ILD diagnosis (as reported by AEs). Results In total, 3,708 patients (10,521 person-years) treated with abatacept + MTX and 999 patients (938 person-years) treated with placebo + MTX were included. Patients treated with placebo + MTX had a higher incidence rate of ILD per 100 person-years (95% CI) versus those treated with abatacept + MTX (0.43 [0.16–1.14] vs 0.10 [0.05–0.18], respectively; Figure 1). The incidence rate ratio of placebo + MTX versus abatacept + MTX treatment groups for the total population was 4.49 (95% CI, 1.23–13.42). For all subpopulations stratified by baseline risk factors (where ≥ 1 patient in each treatment group had an ILD event), incidence rate ratios wer
BackgroundClostridioides difficileinfection (CDI) may be life-threatening, and individuals aged ≥ 65 years are at increased risk. CDI burden among Medicare fee-for-service enrollees and nursing home residents in the ...
Background
Clostridioides difficile
infection (CDI) may be life-threatening, and individuals aged ≥ 65 years are at increased risk. CDI burden among Medicare fee-for-service enrollees and nursing home residents in the United States have been characterized previously. The present study aimed to describe the incidence of CDI among Medicare Advantage Enrollees (MAEs), who account for 34% of all Medicare beneficiaries with enrollment increasing annually since 2004.
Methods
De-identified claims data for this retrospective cohort study were collected from the Optum® Clinformatics® Data Mart and included MAEs aged ≥ 65 years with continuous enrollment for ≥ 1 year before January 1, 2016, followed through death or disenrollment. CDI incidence was defined using the International Classification of Diseases 9th Revision diagnosis code of 008.45 or 10th Revision code of A04.7 (other than admitting diagnosis) or by treatment with nontopical metronidazole, oral vancomycin, or fidaxomicin within 14 days of CDI test. Incident CDI cases were identified from January 1 to December 31, 2016, and required that no CDI occurred within the previous 60 days in 2016. Incidence in 2016 was calculated as CDI cases and CDI patients per 100,000 person-years (PY) of observation time.
Results
Of 2,542,341 MAEs analyzed, 15,201 patients (0.6%) experienced a total of 18,842 incident CDI episodes. Overall, incidence rates were 762.8 CDI cases and 616.5 CDI patients per 100,000 PY. Incidence increased with age (539.6, 847.3, and 1259.6 cases per 100,000 PY in patients aged 65‒74 years, 75‒84 years, and ≥ 85 years, respectively). Most episodes (50.9%) were community acquired; the remaining 37.7% and 11.4% of episodes were hospital acquired and indeterminate, respectively. CDI patients were more likely than non-CDI patients to be older (mean age, 78.3 vs. 76.1 years,
P <
0.0001), be women (64.5% vs. 58.1%,
P <
0.0001), or have comorbidities (mean Charlson comorbidity index score, 4.5 vs. 1.8,
P
< 0.0001
In a seminal article on population pharmacokinetic modeling, researchers demonstrated how means and variances of pharmacokinetic parameters for a patient population could be inferred from sparse data collected under c...
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