Estimation of Conditional Power for Cluster-Randomized Trials with Interval-Censored Endpoints

Cluster-randomized trials (CRTs) of infectious disease preventions often yield correlated, interval-censored data: dependencies may exist between observations from the same cluster, and event occurrence may be assessed only at intermittent clinic visits. This data structure must be accounted for when conducting interim monitoring and futility assessment for CRTs. In this article, we propose a flexible framework for conditional power estimation when outcomes are correlated and interval-censored. Under the assumption that the survival times follow a shared frailty model, we first characterize the correspondence between the marginal and cluster-conditional survival functions, and then use this relationship to semiparametrically estimate the cluster-specific survival distributions from the available interim data. We incorporate assumptions about changes to the event process over the remainder of the trial---as well as estimates of the dependency among observations in the same cluster---to extend these survival curves through the end of the study. Based on these projected survival functions we generate correlated interval-censored observations, and then calculate the conditional power as the proportion of times (across multiple full-data generation steps) that the null hypothesis of no treatment effect is rejected. We evaluate the performance of the proposed method through extensive simulation studies, and illustrate its use on a large cluster-randomized HIV prevention trial

A Reduction in Serum Cytokine Levels Parallels Healing of Venous Ulcers in Patients Undergoing Compression Therapy

AbstractIntroduction vascular endothelial growth factor (VEGF) and tumour necrosis factor alpha (TNFα) have been specifically implicated in the tissue damage associated with chronic venous disease (CVD). Furthermore, production of both factors is known to be upregulated in vessel wall cells subject to hypertension. The aim of this study was to determine the local venous levels of VEGF and TNFα in limbs with venous ulcers before and after treatment with graduated compression. Patients and methods eight patients with venous ulcers and 8 patients with varicose veins only were included in the study. For ulcer patients, serum samples were taken from the superficial veins in lower limbs and repeated after 4 weeks of treatment with 4-layered graduated compression. Serum from the arms of the same patients served as controls. Determination of the concentrations of VEGF and TNFα proteins were performed with sandwich enzyme-linked immunosorbent assays. Results both groups of patients had elevated levels of VEGF and TNFα. In patients with venous ulcers there was a reduction in the levels of both cytokines to below control values with treatment. These changes correlated with healing of the ulcers as determined by reduction in ulcer size. Conclusion these data, for the first time, suggest a central role for both TNFα and VEGF in the pathogenesis of venous ulceration which may constitute a causative link between venous hypertension and tissue pathology

Integrating access to care and tumor patterns by race and age in the Carolina Breast Cancer Study, 2008–2013

Purpose: Understanding breast cancer mortality disparities by race and age is complex due to disease heterogeneity, comorbid disease, and the range of factors influencing access to care. It is important to understand how these factors group together within patients. Methods: We compared socioeconomic status (SES) and comorbidity factors in the Carolina Breast Cancer Study Phase 3 (CBCS3, 2008–2013) to those for North Carolina using the 2010 Behavioral Risk Factor Surveillance Study. In addition, we used latent class analysis of CBCS3 data to identify covariate patterns by SES/comorbidities, barriers to care, and tumor characteristics and examined their associations with race and age using multinomial logistic regression. Results: Major SES and comorbidity patterns in CBCS3 participants were generally similar to patterns in the state. Latent classes were identified for SES/comorbidities, barriers to care, and tumor characteristics that varied by race and age. Compared to white women, black women had lower SES (odds ratio (OR) 6.3, 95% confidence interval (CI) 5.2, 7.8), more barriers to care (OR 5.6, 95% CI 3.9, 8.1) and several aggregated tumor aggressiveness features. Compared to older women, younger women had higher SES (OR 0.5, 95% CI 0.4, 0.6), more barriers to care (OR 2.1, 95% CI 1.6, 2.9) and aggregated tumor aggressiveness features. Conclusions: CBCS3 is representative of North Carolina on comparable factors. Patterns of access to care and tumor characteristics are intertwined with race and age, suggesting that interventions to address disparities will need to target both access and biology

Kinematic and dynamic analysis of a spatial one-DOF foldable tensegrity mechanism

This paper presents a mechanical analysis of a spatial 1-DOF tensegrity mechanism created by connecting three planar tensegrity mechanisms to form a triangular prism. The subsequent investigation produced kinematic and dynamic models that allow the workspace-boundary singularities and minimum energy configuration to be determined. Singularities were found to occur when the mechanism is folded in the vertical X, Y plane or in the horizontal X, Z plane. The minimum energy configuration, formed by the angle between the horizontal plane and the actuated strut, was found to be θ= π/4. However, when the system was linearized to determine the analytic solution for the dynamics, the minimum energy configuration become θ = 1 due to the inherent error produced by the system linearization. The dynamic response of the mechanism to an initial small displacement was determined for each case of critically damped, overdamped, and underdamped systems

Adherence to Endocrine Therapy and Racial Outcome Disparities in Breast Cancer

The disparity in outcomes of breast cancer for Black compared with White women in the U.S. is well known and persistent over time, with the largest disparities appearing among women with hormone receptor-positive (HR+) cancers. The racial gap in breast cancer survival first emerged in the 1980s, a time of significantmen treatment advances in early-stage breast cancer, including the introduction of adjuvant endocrine therapy. Since that time, the gap has continued to widen despite steady advances in treatment and survival of breast cancer overall. Although advanced stage at presentation and unfavorable biology undoubtedly contribute to racial differences in survival of HR+ breast, treatment disparities are increasingly acknowledged to play a key role as well. The recent recognition of racial differences in endocrine therapy use may be a key explanatory factor in the persistent racial gap in mortality of HR+ disease, and may be a key focus of intervention to improve breast cancer outcomes for Black women. Implications for Practice: Black women with hormone receptor–positive breast cancer experience the greatest racial disparity in survival among all breast cancer subtypes. This survival gap appears consistently across studies and is not entirely explained by differences in presenting stage, tumor biology as assessed by genomic risk scores, or receipt of chemotherapy. Recent research highlights lower adherence to endocrine therapy (ET) for Black women. Health systems and individual providers should focus on improving communication about the importance of ET use, sharing decisions around ET, providing appropriate support for side effects and other ET-related concerns, and equitably delivering survivorship care, including ET adherence assessment

Burden of lymphedema in long-term breast cancer survivors by race and age

Background: Risk assessment for breast cancer–related lymphedema has emphasized upper-limb symptoms and treatment-related risk factors. This article examined breast cancer–related lymphedema after surgery, overall and in association with broader demographic and clinical features. Methods: The Carolina Breast Cancer Study phase 3 followed participants for breast cancer–related lymphedema from baseline (on average, 5 months after breast cancer diagnosis) to 7 years after diagnosis. Among 2645 participants, 552 self-reported lymphedema cases were identified. Time-to-lymphedema curves and inverse probability weighted conditional Cox proportional hazards model were used to evaluate whether demographics and clinical features were associated with breast cancer–related lymphedema. Results: Point prevalence of breast cancer–related lymphedema was 6.8% at baseline, and 19.9% and 23.8% at 2 and 7 years after diagnosis, respectively. Most cases had lymphedema in the arm (88%-93%), whereas 14% to 27% presented in the trunk and/or breast. Beginning approximately 10 months after diagnosis, younger Black women had the highest risk of breast cancer–related lymphedema and older non-Black women had the lowest risk. Positive lymph node status, larger tumor size (>5 cm), and estrogen receptor–negative breast cancer, as well as established risk factors such as higher body mass index, removal of more than five lymph nodes, mastectomy, chemotherapy, and radiation therapy, were significantly associated with increased hazard (1.5- to 3.5-fold) of lymphedema. Conclusions: Findings highlight that hazard of breast cancer–related lymphedema differs by demographic characteristics and clinical features. These factors could be used to identify those at greatest need of lymphedema prevention and early intervention. Lay summary: In this study, the aim was to investigate breast cancer–related lymphedema (BCRL) burden. This study found that risk of BCRL differs by race, age, and other characteristics

Extracting antipsychotic polypharmacy data from electronic health records: developing and evaluating a novel process

Background Antipsychotic prescription information is commonly derived from structured fields in clinical health records. However, utilising diverse and comprehensive sources of information is especially important when investigating less frequent patterns of medication prescribing such as antipsychotic polypharmacy (APP). This study describes and evaluates a novel method of extracting APP data from both structured and free-text fields in electronic health records (EHRs), and its use for research purposes. Methods Using anonymised EHRs, we identified a cohort of patients with serious mental illness (SMI) who were treated in South London and Maudsley NHS Foundation Trust mental health care services between 1 January and 30 June 2012. Information about antipsychotic co-prescribing was extracted using a combination of natural language processing and a bespoke algorithm. The validity of the data derived through this process was assessed against a manually coded gold standard to establish precision and recall. Lastly, we estimated the prevalence and patterns of antipsychotic polypharmacy. Results Individual instances of antipsychotic prescribing were detected with high precision (0.94 to 0.97) and moderate recall (0.57-0.77). We detected baseline APP (two or more antipsychotics prescribed in any 6-week window) with 0.92 precision and 0.74 recall and long-term APP (antipsychotic co-prescribing for 6 months) with 0.94 precision and 0.60 recall. Of the 7,201 SMI patients receiving active care during the observation period, 338 (4.7 %; 95 % CI 4.2-5.2) were identified as receiving long-term APP. Two second generation antipsychotics (64.8 %); and first -second generation antipsychotics were most commonly co-prescribed (32.5 %). Conclusions These results suggest that this is a potentially practical tool for identifying polypharmacy from mental health EHRs on a large scale. Furthermore, extracted data can be used to allow researchers to characterize patterns of polypharmacy over time including different drug combinations, trends in polypharmacy prescribing, predictors of polypharmacy prescribing and the impact of polypharmacy on patient outcomes

A scalable quantum computer with an ultranarrow optical transition of ultracold neutral atoms in an optical lattice

We propose a new quantum-computing scheme using ultracold neutral ytterbium atoms in an optical lattice. The nuclear Zeeman sublevels define a qubit. This choice avoids the natural phase evolution due to the magnetic dipole interaction between qubits. The Zeeman sublevels with large magnetic moments in the long-lived metastable state are also exploited to address individual atoms and to construct a controlled-multiqubit gate. Estimated parameters required for this scheme show that this proposal is scalable and experimentally feasible.Comment: 6 pages, 6 figure

Breast cancer treatment patterns by age and time since last pregnancy in the Carolina Breast Cancer Study Phase III

Purpose: To describe breast cancer treatment patterns among premenopausal women by age and time since last pregnancy. Methods: Data were analyzed from 1179 women diagnosed with premenopausal breast cancer in the Carolina Breast Cancer Study. Of these, 160 had a recent pregnancy (within 5 years of cancer diagnosis). Relative frequency differences (RFDs) and 95% confidence intervals (CIs) were used to compare cancer stage, treatment modality received, treatment initiation delay (> 30 days), and prolonged treatment duration (> 2 to > 8 months depending on the treatment received) by age and recency of pregnancy. Results: Recently postpartum women were significantly more likely to have stage III disease [RFD (95% CI) 12.2% (3.6%, 20.8%)] and to receive more aggressive treatment compared to nulliparous women. After adjustment for age, race and standard clinical tumor characteristics, recently postpartum women were significantly less likely to have delayed treatment initiation [RFD (95% CI) − 11.2% (− 21.4%, − 1.0%)] and prolonged treatment duration [RFD (95% CI) − 17.5% (− 28.0%, − 7.1%)] and were more likely to have mastectomy [RFD (95% CI) 14.9% (4.8%, 25.0%)] compared to nulliparous. Similarly, younger women (< 40 years of age) were significantly less likely to experience prolonged treatment duration [RFD (95% CI) − 5.6% (− 11.1%, − 0.0%)] and more likely to undergo mastectomy [RFD (95% CI) 10.6% (5.2%, 16.0%)] compared to the study population as a whole. Conclusion: These results suggest that recently postpartum and younger women often received prompt and aggressive breast cancer treatment. Higher mortality and recurrence among recently pregnant women are unlikely to be related to undertreatment