Prevention of Coronary Artery Disease in Women.

PURPOSE OF REVIEW: Cardiovascular disease remains the leading cause of morbidity and mortality in women. Women were historically underrepresented in landmark trials for which cardiovascular guidelines are based on and are prone to gender-specific risk factors that predispose to coronary heart disease. RECENT FINDINGS: More attention has been made on gender and pregnancy-associated risk factors such as autoimmune disorders and preeclampsia. The most recent guidelines have reflected the need to consider risk-enhancing factors that are unaccounted for in traditional risk assessment tools. As the population ages and the burden of cardiovascular disease in women increases, it is crucial to continue focusing on preventative of cardiovascular disease in women.

Anticoagulation During Pregnancy with a Mechanical Pulmonary Valve: Patient and Medical Perspective.

This article discusses the challenges of supporting a successful pregnancy in a woman with multiple prosthetic heart valves and a complicated cardiac history, from both the patient and provider perspective. The patient is a 29-year-old female with truncus arteriosus type I with initial neonatal VSD closure and right ventricular to pulmonary artery conduit. At the age of 13, she subsequently required truncal and pulmonary valve replacements with mechanical prostheses. Standardizing an approach to anticoagulation in pregnancy in women with prosthetic heart valves is not always possible. Her story demonstrates the importance of an innovative approach to unique cases; by extrapolating what is known about pregnancy and prosthetic heart valves, cardiologists can provide the best outcomes. Simultaneously, non-directive counseling is essential throughout this period to engage the patient in shared decision-making when balancing risks and benefits of each approach to anticoagulation.

Incorporating Within-Host Diversity in Phylogenetic Analyses for Detecting Clusters of New HIV Diagnoses.

BACKGROUND: Phylogenetic analyses of HIV sequences are used to detect clusters and inform public health interventions. Conventional approaches summarize within-host HIV diversity with a single consensus sequence per host of the pol gene, obtained from Sanger or next-generation sequencing (NGS). There is growing recognition that this approach discards potentially important information about within-host sequence variation, which can impact phylogenetic inference. However, whether alternative summary methods that incorporate intra-host variation impact phylogenetic inference of transmission network features is unknown. METHODS: We introduce profile sampling, a method to incorporate within-host NGS sequence diversity into phylogenetic HIV cluster inference. We compare this approach to Sanger- and NGS-derived pol and near-whole-genome consensus sequences and evaluate its potential benefits in identifying molecular clusters among all newly-HIV-diagnosed individuals over six months at the largest HIV center in Rhode Island. RESULTS: Profile sampling cluster inference demonstrated that within-host viral diversity impacts phylogenetic inference across individuals, and that consensus sequence approaches can obscure both magnitude and effect of these impacts. Clustering differed between Sanger- and NGS-derived consensus and profile sampling sequences, and across gene regions. DISCUSSION: Profile sampling can incorporate within-host HIV diversity captured by NGS into phylogenetic analyses. This additional information can improve robustness of cluster detection.

Burden of prematurity-associated recurrent wheezing: caregiver missed work in the D-Wheeze trial.

OBJECTIVE: This study describes the burden of prematurity-associated wheezing in black infants with respect to caregiver missed work. STUDY DESIGN: We analyzed data from the D-Wheeze trial (ClinicalTrials.gov identifier NCT01601847). Black infants between 28-0/7 to 36-6/7 weeks' gestational age at birth receiving <28 days of supplemental oxygen were enrolled. The primary outcome was missed work to care for the infant in the first year. RESULTS: 147/277 (53.1%) infants had caregivers who reported time off. In an adjusted model, vitamin D supplementation (OR 0.52 [95% CI 0.30-0.89]; P = 0.018), recurrent wheeze (OR 2.26 [95% CI, 1.15-4.44]; P = 0.018), and other children in the household <5 years old (OR 0.45 [95% CI 0.26-0.78]; P = 0.004) were significantly associated with caregiver missed work. CONCLUSIONS: Black premature infants had a significant burden of caregiver missed work, emphasizing the impact of prematurity-associated wheezing.

Gp41 and Gag amino acids linked to HIV-1 protease inhibitor-based second-line failure in HIV-1 subtype A from Western Kenya.

INTRODUCTION: Failure of protease-inhibitor (PI)-based second-line antiretroviral therapy (ART) with medication adherence but no protease drug resistance mutations (DRMs) is not well understood. This study investigated the involvement of gp41 and gag as alternative mechanisms, not captured by conventional resistance testing and particularly relevant in resource-limited settings where third-line ART is limited. METHODS: We evaluated gp41 and gag for unique amino acids in seven subtype A infected Kenyans failing second-line therapy with no PI resistance yet detectable lopinavir (query dataset), compared to seven similar-setting patients with PI resistance or undetectable lopinavir and 69 publically available subtype A Kenyan whole-genomes sequences. RESULTS: Three gp41 (607T, 641L, 721I) and four gag (124S, 143V, 339P, 357S) amino acids were significantly more frequent in the query dataset compared to the other datasets, with significantly high co-occurrence. CONCLUSION: The genotypic analysis of a unique group of HIV-1 subtype A infected patients, identified seven amino acids that could potentially contribute to a multi-gene mechanism of PI-based ART failure in the absence of PI DR mutations.

Improved HIV-1 Viral Load Monitoring Capacity Using Pooled Testing With Marker-Assisted Deconvolution.

OBJECTIVE: Improve pooled viral load (VL) testing to increase HIV treatment monitoring capacity, particularly relevant for resource-limited settings. DESIGN: We developed marker-assisted mini-pooling with algorithm (mMPA), a new VL pooling deconvolution strategy that uses information from low-cost, routinely collected clinical markers to determine an efficient order of sequential individual VL testing and dictates when the sequential testing can be stopped. METHODS: We simulated the use of pooled testing to ascertain virological failure status on 918 participants from 3 studies conducted at the Academic Model Providing Access to Healthcare in Eldoret, Kenya, and estimated the number of assays needed when using mMPA and other pooling methods. We also evaluated the impact of practical factors, such as specific markers used, prevalence of virological failure, pool size, VL measurement error, and assay detection cutoffs on mMPA, other pooling methods, and single testing. RESULTS: Using CD4 count as a marker to assist deconvolution, mMPA significantly reduces the number of VL assays by 52% [confidence interval (CI): 48% to 57%], 40% (CI: 38% to 42%), and 19% (CI: 15% to 22%) compared with individual testing, simple mini-pooling, and mini-pooling with algorithm, respectively. mMPA has higher sensitivity and negative/positive predictive values than mini-pooling with algorithm, and comparable high specificity. Further improvement is achieved with additional clinical markers, such as age and time on therapy, with or without CD4 values. mMPA performance depends on prevalence of virological failure and pool size but is insensitive to VL measurement error and VL assay detection cutoffs. CONCLUSIONS: mMPA can substantially increase the capacity of VL monitoring.