Hematopoietic cell transplantation and HIV cure: where we are and what next?

The report of the so-called Berlin patient cured of HIV with hematopoietic stem cell transplantation and a few other studies raised tremendous hope, excitement, and curiosity in the field. The National Heart, Lung and Blood Institute of the National Institutes of Health convened a Working Group to address emerging heart, lung, and blood research priorities related to HIV infection. Hematopoietic cells could contribute to HIV cure through allogeneic or autologous transplantation of naturally occurring or engineered cells with anti-HIV moieties. Protection of central memory T cells from HIV infection could be a critical determinant of achieving a functional cure. HIV cure can only be achieved if the virus is eradicated from reservoirs in resting T cells and possibly other hematopoietic cells. The Working Group recommended multidisciplinary efforts leveraging HIV and cell therapy expertise to answer the critical need to support research toward an HIV cure.

Improved quality of care for cardiovascular disease for Latinos seen in high proportion Latino vs low proportion Latino clinics.

BACKGROUND: Primary care practices that concentrate linguistically and culturally appropriate services for Latinos may result in higher cardiology consultation rates and improved process measure performance for patients with coronary artery disease (CAD) and congestive heart failure (CHF). METHODS: Multivariable Cox proportional-hazards regression was used to assess differences in referral at high proportion (HP) vs low proportion (LP) practices. Multivariable Poisson regression was used to assess the frequency of follow-up consultation. RESULTS: Among the 9,761 patients, 9,168 had CAD, 4,444 had CHF, and 3,851 had both conditions. Latinos comprised 11% of the CAD cohort and 11% of the CHF cohort. Multivariable analyses showed higher consultation rates for Latinos at HP practices for CAD and CHF. Blacks and Whites at HP practices had no significant differences in rates of consultation compared to those in LP practices. Latinos at HP practices had 25% more consultations for CAD and 23% more consultations for CHF than Latinos at LP practices. Latinos at HP clinics had higher overall mean quality performance on clinical measures for both CAD and CHF. Latinos at an LP clinic had the largest improvement in quality performance with consultation. CONCLUSIONS: Among Latinos with CAD or CHF receiving care within a single large academic care network, Latino patients at HP practices have higher rates of cardiologist consultation and performance on CVD process measures compared to Latino patients at LP practices. Elucidating the essential components of individual practice environments that provide higher quality of care for Latinos will allow for well designed systems to reduce health care disparities.

The Testosterone Trials: Seven coordinated trials of testosterone treatment in elderly men.

Background The prevalence of low testosterone levels in men increases with age, as does the prevalence of decreased mobility, sexual function, self-perceived vitality, cognitive abilities, bone mineral density, and glucose tolerance, and of increased anemia and coronary artery disease. Similar changes occur in men who have low serum testosterone concentrations due to known pituitary or testicular disease, and testosterone treatment improves the abnormalities. Prior studies of the effect of testosterone treatment in elderly men, however, have produced equivocal results. Purpose To describe a coordinated set of clinical trials designed to avoid the pitfalls of prior studies and to determine definitively whether testosterone treatment of elderly men with low testosterone is efficacious in improving symptoms and objective measures of age-associated conditions. Methods We present the scientific and clinical rationale for the decisions made in the design of this set of trials. Results We designed The Testosterone Trials as a coordinated set of seven trials to determine if testosterone treatment of elderly men with low serum testosterone concentrations and symptoms and objective evidence of impaired mobility and/or diminished libido and/or reduced vitality would be efficacious in improving mobility (Physical Function Trial), sexual function (Sexual Function Trial), fatigue (Vitality Trial), cognitive function (Cognitive Function Trial), hemoglobin (Anemia Trial), bone density (Bone Trial), and coronary artery plaque volume (Cardiovascular Trial). The scientific advantages of this coordination were common eligibility criteria, common approaches to treatment and monitoring, and the ability to pool safety data. The logistical advantages were a single steering committee, data coordinating center and data and safety monitoring board, the same clinical trial sites, and the possibility of men participating in multiple trials. The major consideration in participant selection was setting the eligibility criterion for serum testosterone low enough to ensure that the men were unequivocally testosterone deficient, but not so low as to preclude sufficient enrollment or eventual generalizability of the results. The major considerations in choosing primary outcomes for each trial were identifying those of the highest clinical importance and identifying the minimum clinically important differences between treatment arms for sample size estimation. Potential limitations Setting the serum testosterone concentration sufficiently low to ensure that most men would be unequivocally testosterone deficient, as well as many other entry criteria, resulted in screening approximately 30 men in person to randomize one participant. Conclusion Designing The Testosterone Trials as a coordinated set of seven trials afforded many important scientific and logistical advantages but required an intensive recruitment and screening effort.

Prevalence, prospective risk markers, and prognosis associated with the presence of left ventricular diastolic dysfunction in young adults: the coronary artery risk development in young adults study.

The authors sought to determine the prevalence, prospective risk markers, and prognosis associated with diastolic dysfunction in the Coronary Artery Risk Development in Young Adults (CARDIA) Study. The CARDIA Study cohort includes approximately equal proportions of white and black men and women. The authors collected data on risk markers at year 0 (1985-1986), and echocardiography was done at year 5 when the participants were 23-35 years of age. Participants were followed for 20 years (through 2010) for a composite endpoint of all-cause mortality, myocardial infarction, heart failure, and stroke. Diastolic function was defined according to a validated hierarchical classification algorithm. In the 2,952 participants included in the primary analysis, severe diastolic dysfunction was present in 1.1% and abnormal relaxation was present in 9.3%. Systolic blood pressure at year 0 was associated with both severe diastolic dysfunction and abnormal relaxation 5 years later, whereas exercise capacity and pulmonary function abnormalities were associated only with abnormal relaxation 5 years later. After multivariate adjustment, the hazard ratios for the composite endpoint in participants with severe diastolic dysfunction and abnormal relaxation were 4.3 (95% confidence interval: 2.0, 9.3) and 1.6 (95% confidence interval: 1.1, 2.5), respectively. Diastolic dysfunction in young adults is associated with increased morbidity and mortality, and the identification of prospective risk markers associated with diastolic dysfunction could allow for targeted primary prevention efforts.

Differences in specialist consultations for cardiovascular disease by race, ethnicity, gender, insurance status, and site of primary care.

BACKGROUND: Consultation with cardiologists may improve the quality of ambulatory care and reduce disparities for patients with heart disease. We assessed the use of cardiology consultations and the associated quality by race/ethnicity, gender, insurance status, and site of care. METHODS AND RESULTS: In a retrospective cohort, we examined electronic records of 9761 adults with coronary artery disease or congestive heart failure (CHF) receiving primary care at practices affiliated with 2 academic medical centers during 2000 to 2005. During this period, 79.6% of patients with coronary artery disease and 90.3% of patients with CHF had a cardiology consultation. In multivariate analyses, women were less likely to receive a consultation than men for both conditions (coronary artery disease: hazard ratio, 0.89; 95% CI, 0.85 to 0.93; CHF: hazard ratio, 0.93; 95% CI, 0.87 to 0.99). Women also had 15% fewer follow-up consultations than men (P<0.001). Similarly, patients at community health centers were less likely to receive a consultation (coronary artery disease: hazard ratio, 0.79; 95% CI, 0.74 to 0.84; CHF: hazard ratio, 0.77; 95% CI: 0.71 to 0.84) and had 20% fewer follow-up consultations (P<0.001) relative to those at hospital-based practices. Black and Hispanic patients with CHF had 13% fewer follow-up consultations than white patients (P=0.01 and P=0.04, respectively). In adjusted analyses, consultation was associated with better processes of care compared with no consultation (P<0.001), particularly for women (P<0.001 for interaction between consultation and gender). CONCLUSIONS: Among ambulatory patients with coronary artery disease or CHF, women and those at community health centers have less access to cardiologists. Consultation is associated with better quality of care and narrows the gender gap in quality.

Addressing disparities in sudden cardiac arrest care and the underutilization of effective therapies.

Sudden cardiac arrest (SCA) is the most common cause of death in the Unites States. Despite its major impact on public health, significant challenges exist at the patient, provider, public, and policy levels with respect to raising more widespread awareness and understanding of SCA risks, identifying patients at risk for SCA, addressing barriers to SCA care, and eliminating disparities in SCA care and outcomes. To address many of these challenges, the Duke Center for the Prevention of Sudden Cardiac Death at the Duke Clinical Research Institute (Durham, NC) held a think tank meeting on December 7, 2009, convening experts on this issue from clinical cardiology, cardiac electrophysiology, health policy and economics, the US Food and Drug Administration, the Centers for Medicare and Medicaid Services, the Agency for Health Care Research and Quality, and device and pharmaceutical manufacturers. The specific goals of the meeting were to examine existing educational tools on SCA for patients, health care providers, and the public and explore ways to enhance and disseminate these tools; to propose a framework for improved identification of patients at risk of SCA; and to review the latest data on disparities in SCA care and explore ways to reduce these disparities. This article summarizes the discussions that occurred at the meeting.

Eliminating the Sex and Gender Gap and Transforming the Cardiovascular Health of All Women.

Critical to eliminating the sex and gender gap in cardiovascular health is addressing known differences in disease burden, disparities in treatment and clinical outcomes, and the scientific importance of sex as a biological variable that influences resilience, pathophysiology, and ultimately the health of women. Furthermore, key disparities exist at the intersection of sex/gender and race/ethnicity where women of color are disproportionately affected by higher burden of disease and poorer outcomes in several cardiovascular conditions. Through efforts to galvanize strategic partnerships, The NHLBI Strategic Vision sets forth research priorities across all of its objectives relevant to the cardiovascular health of women; it encourages strategic partnerships in both establishing and implementing research priorities. The Vision promotes a promise of precision medicine that embraces sex as its highest order, leverages an integrated approach to data science, explores sex influences on molecular underpinnings of disease, and advances sex-specific and race-sex interaction analyses toward the elimination of gaps in the cardiovascular care and health of all women.

A Report of the 24th Annual Congress on Women's Health-Workshop on Transforming Women's Health: From Research to Practice.

Sex and gender are critical contributors to overall health and disease, and considering both in research informs the development of prevention strategies and treatment interventions for both men and women. The National Institutes of Health (NIH) Office of Research on Women's Health sponsored a preconference workshop on this topic at the 24th Annual Women's Health Congress, which was held in Crystal City, VA, in April 2016. The workshop featured presentations by NIH intramural and extramural scientists who presented data on a variety of topics including polycystic kidney disease, vaccine protection, depression, drug addiction, and cardiovascular disease. In this publication, we discuss the major points of each presentation and demonstrate the importance of considering sex and gender in biomedical research.

A Report of the Women's Health Congress Workshop on The Health of Women of Color: A Critical Intersection at the Corner of Sex/Gender and Race/Ethnicity.

Women of color face unique health challenges that differ significantly from those of other women and men of color. To bring these issues to light, the National Institutes of Health (NIH) Office of Research on Women's Health sponsored a preconference workshop at the 23rd Annual Women's Health Congress, which was held in Washington, DC, in April 2015. The workshop featured presentations by NIH intramural and extramural scientists who provided insight on the disparities of a wide range of conditions, including cancer, cardiovascular disease, the risk of HIV infection, and disability in an aging population. In this study, we highlight the major points of each presentation and the ensuing discussion.