Exact confidence intervals in the presence of interference

For two-stage randomized experiments assuming partial interference, exact confidence intervals are proposed for treatment effects on a binary outcome. Empirical studies demonstrate the new intervals have narrower width than previously proposed exact intervals based on the Hoeffding inequality

Randomization inference for treatment effects on a binary outcome: J. RIGDON AND M. G. HUDGENS

Two methods are developed for constructing randomization based confidence sets for the average effect of a treatment on a binary outcome. The methods are nonparametric and require no assumptions about random sampling from a larger population. Both of the resulting 1 − α confidence sets are exact in the sense that the probability of containing the true treatment effect is at least 1 − α. Both types of confidence sets are also guaranteed to have width no greater than one. In contrast, a previously proposed asymptotic confidence interval is not exact and may have width greater than one. The first approach combines Bonferroni adjusted prediction sets for the attributable effects in the treated and untreated. The second method entails inverting a permutation test. Simulations are presented comparing the two randomization based confidence sets with the asymptotic interval as well as the standard Wald confidence interval and a commonly used exact interval for the difference in binomial proportions. Results show for small to moderate sample sizes that the permutation confidence set attains the narrowest width on average among the methods that maintain nominal coverage. Extensions that allow for stratifying on categorical baseline covariates are also discussed

12-Month Outcomes of the US Patient Cohort in the SONATA Pivotal IDE Trial of Transcervical Ablation of Uterine Fibroids.

Objective: The prospective SONATA pivotal Investigational Device Exemption (IDE) trial was performed in the United States (US) and Mexico to examine the safety and effectiveness of transcervical fibroid ablation (TFA) in the treatment of symptomatic uterine fibroids. This is an analysis of 12-month clinical outcomes in the US cohort. Methods: TFA with the Sonata System was performed on women with symptomatic uterine fibroids. The 12-month co-primary endpoints were reduction in menstrual blood loss and freedom from surgical reintervention. Symptom severity, quality of life, patient satisfaction, safety, and reductions in uterine and fibroid volumes were also evaluated. Results: One hundred twenty-five patients were enrolled and treated in the US. Both co-primary endpoints were achieved in this US-based cohort, as 65.3% of patients reported ≥50% reduction in menstrual bleeding and 99.2% of patients were free from surgical reintervention. Symptom improvement was noted by 97.4% of patients and 98.3% were satisfied. Ninety-five percent of patients reported reduced menstrual bleeding at 12 months, and 86.8% noted \u3e20% reduction. Significant mean improvements at 12 months were realized in both symptom severity and health-related quality of life (33.8 points and 45.8 points, respectively; all P\u3c0.0001). Mean maximal fibroid volume reduction per patient was 63.8%. There was a 0% incidence of device related adverse events. Mean length of stay was 2.5 hrs and 50% of patients returned to normal activity within 1 day. Conclusion: This analysis of US patients in the SONATA pivotal IDE trial demonstrates results consistent with those in the full cohort. TFA with Sonata significantly reduced fibroid symptoms with a low surgical reintervention rate through 12 months. These results support the efficacy and safety of the Sonata system as a first-line treatment for women affected by symptomatic uterine fibroids

Generalizing Evidence from Randomized Trials using Inverse Probability of Sampling Weights

Results obtained in randomized trials may not easily generalize to target populations. Whereas in randomized trials the treatment assignment mechanism is known, the sampling mechanism by which individuals are selected to participate in the trial is typically not known and assuming random sampling from the target population is often dubious. We consider an inverse probability of sampling weighted (IPSW) estimator for generalizing trial results to a target population. The IPSW estimator is shown to be consistent and asymptotically normal. A consistent sandwich-type variance estimator is derived and simulation results are presented comparing the IPSW estimator to a previously proposed stratified estimator. The methods are then utilized to generalize results from two randomized trials of HIV treatment to all people living with HIV in the US

Change-point models to estimate the limit of detection

In many biological and environmental studies, measured data is subject to a limit of detection. The limit of detection is generally defined as the lowest concentration of analyte that can be differentiated from a blank sample with some certainty. Data falling below the limit of detection is left-censored, falling below a level that is easily quantified by a measuring device. A great deal of interest lies in estimating the limit of detection for a particular measurement device. In this paper we propose a change-point model to estimate the limit of detection using data from an experiment with known analyte concentrations. Estimation of the limit of detection proceeds by a two-stage maximum likelihood method. Extensions are considered that allow for censored measurements and data from multiple experiments. A simulation study is conducted demonstrating that in some settings the change-point model provides less biased estimates of the limit of detection than conventional methods. The proposed method is then applied to data from an HIV pilot study

Expression of p16INK4a as a biomarker of T-cell aging in HIV-infected patients prior to and during antiretroviral therapy

The p16INK4a tumor suppressor gene is a mediator of cellular senescence and has been suggested to be a biomarker of ‘molecular’ age in several tissues including T-cells. To determine the association of both active and suppressed HIV infection with T-cell aging, T-cell p16INK4a expression was compared between 60 HIV+ suppressed subjects, 23 HIV+ untreated subjects, and 18 contemporaneously collected HIV-negative controls, as well as 148 HIV-negative historical samples. Expression did not correlate with chronologic age in untreated HIV+ patients, consistent with an effect of active HIV replication on p16INK4a expression. In patients on cART with suppressed viral loads, however, p16INK4a levels were similar to uninfected controls and correlated with chronologic age, with a trend toward an inverse correlation with CD4 count. These data show that p16INK4a is a reliable biomarker of T cell aging in HIV+ patients with suppressed viral loads and suggest that poor CD4 cell recovery on cART may be associated with increased T-cell expression of p16INK4a, a marker of cellular senescence

Disclosure of sexual orientation to health professionals in China: results from an online cross-sectional study: Tang W et al.

Background: Many men who have sex with men (MSM) in China are “in the closet.” The low rate of disclosure may impact sexual behaviours, testing for HIV and other sexually transmitted infections (STIs), and diseases transmission. This study examines factors associated with overall sexual orientation disclosure and disclosure to healthcare professionals

Measuring the contribution of γδ T cells to the persistent HIV reservoir

Objective:To study the contribution of γδ T cells to the persistent HIV reservoir.Design:Fifteen HIV-seropositive individuals on suppressive ART were included. We performed parallel quantitative viral outgrowth assays (QVOA) of resting CD4+ T (rCD4) cells in the presence or absence of γδ T cells.Methods:Resting αβ+CD4+ T cells were magnetically isolated from PBMCs using two different custom cocktails, only one kit contained antibodies to deplete γδ T cells, resulting in two populations: rCD4 cells and rCD4 cells depleted of γδ cells. Frequency of infection was analyzed by QVOA and DNA measurements.Results:Recovery of replication-competent HIV from cultures of rCD4 cells was similar in 11 individuals despite the presence of γδ T cells. In four donors, HIV recovery was lower when γδ T cells were present. Expression of the cytotoxic marker CD16+ on Vδ2 cells was the only variable associated with the lower HIV recovery. Our results highlight the potency of those responses since a mean of 10000 γδ T cells were present within 2.5 million rCD4 cells. However, despite the low frequency of γδ T cells, the presence of cytotoxic Vδ2 cells correlated with lower HIV recovery from cultures of rCD4 cells.Conclusion:Results of this study show that quantification of the contribution of γδ T cells to the reservoir is challenging because of their low numbers compared with conventional rCD4 cells and highlights the potent antiviral function of γδ T cells and the impact of their presence on the frequency of latent HIV infection

A germ-free humanized mouse model shows the contribution of resident microbiota to human-specific pathogen infection

Germ-free (GF) mice, which are depleted of their resident microbiota, are the gold standard for exploring the role of the microbiome in health and disease; however, they are of limited value in the study of human-specific pathogens because they do not support their replication. Here, we develop GF mice systemically reconstituted with human immune cells and use them to evaluate the role of the resident microbiome in the acquisition, replication and pathogenesis of two human-specific pathogens, Epstein–Barr virus (EBV) and human immunodeficiency virus (HIV). Comparison with conventional (CV) humanized mice showed that resident microbiota enhance the establishment of EBV infection and EBV-induced tumorigenesis and increase mucosal HIV acquisition and replication. HIV RNA levels were higher in plasma and tissues of CV humanized mice compared with GF humanized mice. The frequency of CCR5+ CD4+ T cells throughout the intestine was also higher in CV humanized mice, indicating that resident microbiota govern levels of HIV target cells. Thus, resident microbiota promote the acquisition and pathogenesis of two clinically relevant human-specific pathogens

Comparing the effectiveness of a crowdsourced video and a social marketing video in promoting condom use among Chinese men who have sex with men: a study protocol

Crowdsourcing has been used to spur innovation and increase community engagement in public health programmes. Crowdsourcing is the process of giving individual tasks to a large group, often involving open contests and enabled through multisectoral partnerships. Here we describe one crowdsourced video intervention in which a video promoting condom use is produced through an open contest. The aim of this study is to determine whether a crowdsourced intervention is as effective as a social marketing intervention in promoting condom use among high-risk men who have sex with men (MSM) and transgender male-to-female (TG) in China