Non-Medical Characteristics Affect Referral for Advanced Heart Failure Services: a Retrospective Review.

BACKGROUND: Patients with advanced heart failure (AHF) are extensively evaluated before heart transplantation or left ventricular assist device (LVAD) eligibility. Patients are assessed for medical need and psychosocial or economic factors that may affect success post-treatment. For patients to be evaluated, however, they first must be referred. This study investigated social and economic factors affecting AHF referral, specialist visits, or treatment. METHODS: Patients with heart failure (n = 24,258) were reviewed at one large hospital system over 4 years. Independent variables age, sex, marital status, race/ethnicity, preferred language, smoking, and insurance status were assessed for the outcomes of referral, clinic visit, and treatment by Chi-square and ANOVA. In-house and 1-year mortality were evaluated by logistic regression, and time-to-event was assessed by the Cox proportional hazards model. RESULTS: Younger (HR 0.934, 95% CI 0.925-0.943), male (HR 2.216, 95% CI 1.544-3.181), and publicly insured (HR 1.298 [95% CI 1.038, 1.623]) patients were more likely to be referred, while unmarried (HR 0.665, 95% CI 0.488-0.905) and smoking (HR 0.549, 95% CI 0.389-0.776) patients had fewer referrals. Younger, married, and nonsmoking patients were more likely to have a clinic visit. Younger age, White race, and Hispanic/Latino ethnicity were associated with receiving a heart transplant, and LVAD recipients were more likely Hispanic/Latino ethnicity. Advanced age, Hispanic/Latino ethnicity, and smoking were associated with 1-year mortality after heart failure diagnosis. CONCLUSIONS: Disparities in access exist before evaluation for AHF therapies. Improving access at the levels of referral and evaluation is a necessary step toward achieving equity in organ allocation.

We want to help: ethical challenges of medical migration and brain waste during a pandemic.

Health worker shortages in many countries are reaching crisis levels, exacerbated by factors associated with the COVID-19 pandemic. In New Zealand, the medical specialists union has called for a health workforce emergency to be declared, yet at the same time, many foreign-trained healthcare workers are unable to stay in the country or unable to work. While their health systems differ, countries such as New Zealand, the USA and the UK at least partially rely on international medical graduates (IMGs) to ensure access to health services, particularly in underserved communities. This paper focuses on the challenges faced by many IMGs, particularly those that constrain their capacity to live and work in the countries that rely on their skills. These challenges give rise to two ethical problems. First, they represent a failure of reciprocity towards IMGs; second, they represent a source of harm, both to IMGs themselves and to communities whose healthcare service depends on contributions made by IMGs. We argue that brain waste and disvaluing the contributions of IMGs and other foreign-trained health professionals have significant costs for maintaining a functional healthcare system, costs which must be adequately recognised and counted.

Conditions of Global Health Crisis Decision-Making-An Ethical Analysis.

The circumstances of a public health emergency (PHE) shape reasoning and decision-making in ways that deviate from routine circumstances, where adherence to established values, principles, and methodologies is expected. Understanding what drives these deviations is critical to assessing their ethical consequences. In this paper we describe four conditions that influence decision-making during PHEs, in particular regarding the deployment and conduct of research on experimental or novel biomedical interventions. These four conditions are politicization, urgency, uncertainty, and fear. We argue that taken together these four conditions create pressure to address the most visible targets of immediate crisis events, driving emphasis on research and development of biomedical interventions. However, this emphasis raises ethical concerns regarding the extent to which attention to and investment in the underlying causes of PHEs, particularly impoverished global public health infrastructure, is diminished as a result.

Synergistic Disparities and Public Health Mitigation of COVID-19 in the Rural United States.

Public health emergencies expose social injustice and health disparities, resulting in calls to address their structural causes once the acute crisis has passed. The COVID-19 pandemic is highlighting and exacerbating global, national, and regional disparities in relation to the benefits and burdens of undertaking critical basic public health mitigation measures such as physical distancing. In the United States, attempts to address the COVID-19 pandemic are complicated by striking racial, economic, and geographic inequities. These synergistic inequities exist in both urban and rural areas but take on a particular character and impact in areas of rural poverty. Rural areas face a diverse set of structural challenges, including inadequate public health, clinical, and other infrastructure and economic precarity, hampering the ability of communities and individuals to implement mitigation measures. Public health ethics demands that personnel address both the tactical, real-time adjustment of typical mitigation tools to improve their effectiveness among the rural poor as well as the strategic, longer-term structural causes of health and social injustice that continue to disadvantage this population.

Comparing pharmacologic measures of tenofovir exposure in a U.S. pre-exposure prophylaxis randomized trial.

CLINICAL TRIAL REGISTRATION: Clinical Trials.gov NCT00131677.

Advancing Ethical Neuroscience Research.

As neuroscience research advances, researchers, clinicians, and other stakeholders will face a host of ethical challenges. The Presidential Commission for the Study of Bioethical Issues (Bioethics Commission) has published two reports that provide recommendations on how to advance research endeavors ethically. The commission addressed, among other issues, how to prioritize different types of neuroscience research and how to include research participants who have impaired consent capacity. The Bioethics Commission's recommendations provide a foundation for ethical guidelines as neuroscience research advances and progresses.

Randomized trial of clinical safety of daily oral tenofovir disoproxil fumarate among HIV-uninfected men who have sex with men in the United States.

OBJECTIVES: To evaluate the clinical safety of daily tenofovir disoproxil fumarate (TDF) among HIV-negative men who have sex with men. DESIGN: Randomized, double-blind, placebo-controlled trial. Participants were randomized 1:1:1:1 to immediate or delayed study drug (TDF, 300 mg orally per day, or placebo). METHODS: Four hundred healthy HIV-uninfected men who have sex with men reporting anal sex with another man within the previous 12 months enrolled in Atlanta, Boston, and San Francisco. HIV serostatus, clinical and laboratory adverse events (AEs), adherence (pill count, Medication Event Monitoring System, and self-report), and sexual and other sociobehavioral data were assessed at 3-month intervals for 24 months. Primary outcomes were clinical safety, assessed by incidence of AEs and laboratory abnormalities. RESULTS: Study drug was initiated by 373 (93%) participants (186 TDF and 187 placebo), of whom 325 (87%) completed the final study visit. Of 2428 AEs reported among 334 (90%) participants, 2366 (97%) were mild or moderate in severity. Frequencies of commonly reported AEs did not differ significantly between TDF and placebo arms. In multivariable analyses, back pain was more likely among TDF recipients (P = 0.04); these reports were not associated with documented fractures or other objective findings. There were no grade ≥3 creatinine elevations; grades 1 and 2 creatinine increases were not associated with TDF receipt. Estimated percentage of study drug doses taken was 92% by pill count and 77% by Medication Event Monitoring System. Seven seroconversions occurred: 4 on placebo and 3 among delayed arm participants not yet on study drug. CONCLUSIONS: Daily oral TDF was well tolerated, with reasonable adherence. No significant renal concerns were identified.

Sexual risk behavior among HIV-uninfected men who have sex with men participating in a tenofovir preexposure prophylaxis randomized trial in the United States.

OBJECTIVE: To evaluate for changes in sexual behaviors associated with daily pill use among men who have sex with men (MSM) participating in a preexposure prophylaxis trial. DESIGN: Randomized, double-blind, placebo-controlled trial. Participants were randomized 1:1:1:1 to receive tenofovir disoproxil fumarate or placebo at enrollment or after a 9-month delay and followed for 24 months. METHODS: Four hundred HIV-negative MSM reporting anal sex with a man in the past 12 months and meeting other eligibility criteria enrolled in San Francisco, Atlanta, and Boston. Sexual risk was assessed at baseline and quarterly visits using Audio Computer-Assisted Self-Interview. The association of pill taking with sexual behavior was evaluated using logistic and negative-binomial regressions for repeated measures. RESULTS: Overall indices of behavioral risk declined or remained stable during follow-up. Mean number of partners and proportion reporting unprotected anal sex declined during follow-up (P < 0.05), and mean unprotected anal sex episodes remained stable. During the initial 9 months, changes in risk practices were similar in the group that began pills immediately vs. those in the delayed arm. These indices of risk did not differ significantly after initiation of pill use in the delayed arm or continuation of study medication in the immediate arm. Use of poppers, amphetamines, and sexual performance-enhancing drugs were independently associated with one or more indices of sexual risk. CONCLUSIONS: There was no evidence of risk compensation among HIV-uninfected MSM in this clinical trial. Monitoring for risk compensation should continue now that preexposure prophylaxis has been shown to be efficacious in MSM and other populations and will be provided in open-label trials and other contexts.

Antiretroviral preexposure prophylaxis for heterosexual HIV transmission in Botswana.

BACKGROUND: Preexposure prophylaxis with antiretroviral agents has been shown to reduce the transmission of human immunodeficiency virus (HIV) among men who have sex with men; however, the efficacy among heterosexuals is uncertain. METHODS: We randomly assigned HIV-seronegative men and women to receive either tenofovir disoproxil fumarate and emtricitabine (TDF-FTC) or matching placebo once daily. Monthly study visits were scheduled, and participants received a comprehensive package of prevention services, including HIV testing, counseling on adherence to medication, management of sexually transmitted infections, monitoring for adverse events, and individualized counseling on risk reduction; bone mineral density testing was performed semiannually in a subgroup of participants. RESULTS: A total of 1219 men and women underwent randomization (45.7% women) and were followed for 1563 person-years (median, 1.1 years; maximum, 3.7 years). Because of low retention and logistic limitations, we concluded the study early and followed enrolled participants through an orderly study closure rather than expanding enrollment. The TDF-FTC group had higher rates of nausea (18.5% vs. 7.1%, P<0.001), vomiting (11.3% vs. 7.1%, P=0.008), and dizziness (15.1% vs. 11.0%, P=0.03) than the placebo group, but the rates of serious adverse events were similar (P=0.90). Participants who received TDF-FTC, as compared with those who received placebo, had a significant decline in bone mineral density. K65R, M184V, and A62V resistance mutations developed in 1 participant in the TDF-FTC group who had had an unrecognized acute HIV infection at enrollment. In a modified intention-to-treat analysis that included the 33 participants who became infected during the study (9 in the TDF-FTC group and 24 in the placebo group; 1.2 and 3.1 infections per 100 person-years, respectively), the efficacy of TDF-FTC was 62.2% (95% confidence interval, 21.5 to 83.4; P=0.03). CONCLUSIONS: Daily TDF-FTC prophylaxis prevented HIV infection in sexually active heterosexual adults. The long-term safety of daily TDF-FTC prophylaxis, including the effect on bone mineral density, remains unknown. (Funded by the Centers for Disease Control and Prevention and the National Institutes of Health; TDF2 ClinicalTrials.gov number, NCT00448669.).

"Research participants want to feel they are better off than they were before research was introduced to them": engaging cameroonian rural plantation populations in HIV research.

BACKGROUND: During a period of evolving international consensus on how to engage communities in research, facilitators and barriers to participation in HIV prevention research were explored in a rural plantation community in the coastal region of Cameroon. METHODS: A formative rapid assessment using structured observations, focus group discussions (FGD), and key informant interviews (KIIs) was conducted with a purposive non-probabilistic sample of plantation workers and their household members. Eligibility criteria included living or working >1 year within the plantation community and age >18 years. Both rapid and in-depth techniques were used to complete thematic analysis. RESULTS: Sixty-five persons participated in the study (6 FGDs and 12 KIIs). Participants viewed malaria and gastrointestinal conditions as more common health concerns than HIV. They identified three factors as contributing to HIV risk: concurrent sexual relationships, sex work, and infrequent condom use. Interviewees perceived that the community would participate in HIV research if it is designed to: (1) improve community welfare, (2) provide comprehensive health services and treatment for illnesses, (3) protect the personal information of participants, especially those who test positive for HIV, (4) provide participant incentives, (5) incorporate community input, and (6) minimize disruptions to "everyday life". Barriers to participation included: (1) fear of HIV testing, (2) mistrust of researchers given possible disrespect or intolerance of plantation community life and lack of concern for communication, (3) time commitment demands, (3) medical care and treatment that would be difficult or costly to access, and (4) life disruptions along with potential requirements for changes in behaviour (i.e., engage in or abstain from alcohol use and sex activities). CONCLUSIONS: Consistent with UNAIDS guidelines for good participatory practice in HIV prevention research, study participants placed a high premium on researchers' politeness, trust, respect, communication, tolerance and empathy towards their community. Plantation community members viewed provision of comprehensive health services as an important community benefit likely to enhance HIV research participation.

Bone mineral density in HIV-negative men participating in a tenofovir pre-exposure prophylaxis randomized clinical trial in San Francisco.

BACKGROUND: Pre-exposure prophylaxis (PrEP) trials are evaluating regimens containing tenofovir-disoproxil fumarate (TDF) for HIV prevention. We determined the baseline prevalence of low bone mineral density (BMD) and the effect of TDF on BMD in men who have sex with men (MSM) in a PrEP trial in San Francisco. METHODS/FINDINGS: We evaluated 1) the prevalence of low BMD using Dual Energy X-ray Absorptiometry (DEXA) in a baseline cohort of 210 HIV-uninfected MSM who screened for a randomized clinical trial of daily TDF vs. placebo, and 2) the effects of TDF on BMD in a longitudinal cohort of 184 enrolled men. Half began study drug after a 9-month delay to evaluate changes in risk behavior associated with pill-use. At baseline, 20 participants (10%) had low BMD (Z score≤-2.0 at the L2-L4 spine, total hip, or femoral neck). Low BMD was associated with amphetamine (OR = 5.86, 95% CI 1.70-20.20) and inhalant (OR = 4.57, 95% CI 1.32-15.81) use; men taking multivitamins, calcium, or vitamin D were less likely to have low BMD at baseline (OR = 0.26, 95% CI 0.10-0.71). In the longitudinal analysis, there was a 1.1% net decrease in mean BMD in the TDF vs. the pre-treatment/placebo group at the femoral neck (95% CI 0.4-1.9%), 0.8% net decline at the total hip (95% CI 0.3-1.3%), and 0.7% at the L2-L4 spine (95% CI -0.1-1.5%). At 24 months, 13% vs. 6% of participants experienced >5% BMD loss at the femoral neck in the TDF vs. placebo groups (p = 0.13). CONCLUSIONS: Ten percent of HIV-negative MSM had low BMD at baseline. TDF use resulted in a small but statistically significant decline in BMD at the total hip and femoral neck. Larger studies with longer follow-up are needed to determine the trajectory of BMD changes and any association with clinical fractures. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00131677.

Talking about sex in Botswana: social desirability bias and possible implications for HIV-prevention research.

Evaluations of the safety, effectiveness, and feasibility of HIV prevention interventions rely on self-reported sexual behaviour data. The accuracy of such data has sometimes been questioned. The absence of a so-called objective measure of sexual behaviour complicates this. Social desirability bias (SDB) is a key factor affecting the accuracy of self-reports. Individual, semi-structured interviews focusing on possible causes of and solutions to SDB were conducted with 30 Batswana women such as those who might enrol in planned vaginal microbicide trials. Respondents pointed to shame and the fear of public talk about them as key factors contributing to inaccurate self-reports, and they stressed the importance of privacy and confidentiality. Interviewer characteristics such as age, gender and personality were often viewed as likely to affect their candour. Alternative interviewing techniques such as audio computer-assisted self-interviewing (ACASI) were appealing to some for the potential to reduce embarrassment; others were sceptical. The possible implications for HIV-prevention research are presented.

Factors affecting the delivery of HIV/AIDS prevention programs by community-based organizations.

Community based organizations (CBOs) play a frontline role in HIV/AIDS prevention activities. CBOs face formidable challenges to effective delivery of HIV prevention services including client characteristics such as homelessness and CBO characteristics such as limited resources and staff turnover. Despite these obstacles, CBOs are generally well positioned to deliver services to specific high-risk populations because they understand their local communities and are connected to the groups they serve. [C1]This qualitative study illustrates that structural, sociocultural, organizational, and individual client factors both facilitate and act as barriers to delivery of HIV prevention services. These challenges and successes help identify critical technical assistance needs.