Cainbynum3778

Marginal structural models (MSMs) with inverse probability weighted estimators (IPWEs) are widely used to estimate causal effects of treatment sequences on longitudinal outcomes in the presence of time-varying confounding and dependent censoring. However, IPWEs for MSMs can be inefficient and unstable if weights are estimated by maximum likelihood. To improve the performance of IPWEs, covariate balancing weight (CBW) methods have been proposed and recently extended to MSMs. However, existing CBW methods for MSMs are inflexible for practical use because they often do not handle dependent censoring, nonbinary treatments, and longitudinal outcomes (instead of eventual outcomes at a study end). In this paper, we propose a joint calibration approach to CBW estimation for MSMs that can accommodate (1) both time-varying confounding and dependent censoring, (2) binary and nonbinary treatments, (3) eventual outcomes and longitudinal outcomes. We develop novel calibration restrictions by jointly eliminating covariate associations with both treatment assignment and censoring processes after weighting the observed data sample (i.e., to optimize covariate balance in finite samples). Two different methods are proposed to implement the calibration. Simulations show that IPWEs with calibrated weights perform better than IPWEs with weights from maximum likelihood and the "Covariate Balancing Propensity Score" method. Amlexanox We apply our method to a natural history study of HIV for estimating the effects of highly active antiretroviral therapy on CD4 cell counts over time.

Early mobilization (EM) is beneficial in critical care units and in older hospitalized patients, but little is known about EM in older adults with acute cardiovascular disease.

Consecutive admissions of adults ≥80years old to a Cardiac Intensive Care Unit (CICU) prior to and following implementation of a nurse-driven EM program were reviewed. Mobility was measured using the Level of Function (LOF) Mobility Scale, which ranges from 0 (bed immobile) to 5 (able to walk >20 meters). The primary outcome was discharge home.

There were 412 patients included (N = 234, intervention; N = 178, preintervention). There was no difference in age between groups (overall 86.3 ± 4.8years old) or sex (overall female N = 215, 52.2%). In the intervention group, functional impairment was present in 89 patients (38.0%) prehospitalization and in 209 patients (89.3%) on admission. Nearly half of patients (N = 107; 45.7%) improved their LOF by ≥1 during admission. Mobilization occurred during nearly all opportunities (838/850; 98.6%), and most mobility activities were completed (2,207/2,553; 86.4%). Adverse events were rare (5/2,207 activities [0.2% adverse event rate]) and transient. Patients in the intervention group were more likely than patients in the preintervention group to be discharged home (74.4 vs. 65.7%, P = 0.047, respectively) and had a lower rate of in-hospital death (6.4 vs. 14.6%, P = 0.006, respectively). There was no difference in mean length of hospital stay, 30-day emergency department visit or hospital re-admission.

EM is safe in older adults in the CICU and is associated with reduced discharge to healthcare facility and in-hospital mortality.

EM is safe in older adults in the CICU and is associated with reduced discharge to healthcare facility and in-hospital mortality.

Enhanced levels of catecholestradiols, 2-hydroxyestradiol (2-OHE2) or 4-hydroxyestradiol (4-OHE2), are reported in endometriosis. During gestation, catecholestradiol activation of adrenergic receptors (AR) elevates estrogen receptor (ER)-independent proliferation of uterine arterial endothelial cells.

To investigate β-AR-mediated catecholestradiol effects on human endometrial stromal cell (HESC) and epithelial cell survival in endometriosis.

β-AR immunostaining of eutopic and ectopic endometria (n = 9). Assays for cell viability, 5-bromo-2'-deoxyuridine proliferation, apoptosis, quantitative PCR, and estrogenicity (alkaline phosphatase activity), as well as siRNA β-AR silencing and immunoblot analyses of cultured HESCs or Ishikawa cells treated with control or 2-OHE2 or 4-OHE2 ±β-AR antagonist or ±p38 MAPK inhibitor.

University research institution.

Women with or without endometriosis.

None.

β-AR expression in eutopic vs ectopic endometria and regulation of HESC survival by 2-OHE2 and 4-OHE2.

at endometriosis.

Catecholestradiols increase endometrial cell survival by an ER-independent β-AR-mediated p38 MAPK activation, suggesting that agents blocking β-AR (e.g., propranolol) or inhibiting 2-OHE2- or 4-OHE2-generating enzymes (i.e., CYP1A1/B1) could treat endometriosis.

Prostate cancer (PCa) is one of the leading causes of cancer-related death among the male population worldwide. Unfortunately, current medical treatments fail to prevent PCa progression in a high percentage of cases; therefore, new therapeutic tools to tackle PCa are urgently needed. Biguanides and statins have emerged as antitumor agents for several endocrine-related cancers.

To evaluate (1) the putative in vivo association between metformin and/or statins treatment and key tumor and clinical parameters and (2) the direct effects of different biguanides (metformin/buformin/phenformin), statins (atorvastatin/simvastatin/lovastatin), and their combination, on key functional endpoints and associated signalling mechanisms.

An exploratory/observational retrospective cohort of patients with PCa (n = 75) was analyzed. Moreover, normal and tumor prostate cells (normal [RWPE-cells/primary prostate cell cultures]; tumor [LNCaP/22RV1/PC3/DU145 cell lines]) were used to measure proliferation/migration/tumorsphere-nd statins significantly reduced tumor aggressiveness in PCa, with this effect being more potent (in vitro and in vivo) when both compounds are combined. Therefore, given the demonstrated clinical safety of biguanides and statins, our results suggest a potential therapeutic role of these compounds, especially their combination, for the treatment of PCa.

Telehealth is an increasingly common approach to improve healthcare delivery, especially within the Veterans Health Administration and Department of Defense (DoD). Telehealth has diminished many challenges to direct access for clinical follow-up; however, the use of mobile telehealth for specialty rehabilitative care is emerging and is referred to as telerehabilitation. As early adopters of telehealth, the Veterans Affairs and DoD have supported collaborated efforts for programs designed to increase the access and quality of rehabilitative care while improving the functional ability of our service members (SMs) and veterans with lower limb amputation (LLA). The DoD and Veterans Health Administration collaborated on a Mobile Device Outcomes-based Rehabilitation Program (MDORP) to help injured SMs and veterans with LLA. The MDORP project utilized a mobile health system called the Rehabilitative Lower Limb Orthopedic Accommodating Device (ReLOAD) to assess walking quality. The ReLOAD system includes real-time auditory biofeedback to notify the user of their most prominent gait deviation and then recommends exercises that address specific balance and strength impairments.