Lisa C. Welch

End-of-life care in black and white: race matters for medical care of dying patients and their families.

Objectives: To compare the end‐of‐life medical care experienced by African‐American and white decedents and their families.

Physicians "missing in action": family perspectives on physician and staffing problems in end-of-life care in the nursing home.

Objectives: To understand the roles of physicians and staff in nursing homes in relation to end‐of‐life care through narrative interviews with family members close to a decedent.

Stage of Life Course and Social Support as a Mediator of Mood State among Persons with Disability

Objective:This research seeks to determine which aspects of social support are most effective in mediating mood state amongworking-age and elderly adults with disability (N= 442). Methods:Participants were identified through random-digit dialing of telephone exchanges and administration of a disability screen. Multiple regression was used to model multiple aspects of social support while holding sociodemographic and disability indicators constant. Results:Analyses revealed that network size and confidence in the reliability of helping networks are significantly and negatively related to depressed mood. Confidant supportwas related to lower levels of depressed mood for younger respondents only. Neither marital status, advisor support, nor social integration were related to mood. Discussion:Both instrumental and emotional support are key in mediating depressed mood among this population. We conclude that all types of social support are not equally effective in mediating mood among people with disability.

A Single Phosphorodiamidate Morpholino Oligomer Targeting VP24 Protects Rhesus Monkeys against Lethal Ebola Virus Infection

ABSTRACT Ebola viruses (EBOV) cause severe disease in humans and nonhuman primates with high mortality rates and continue to emerge in new geographic locations, including several countries in West Africa, the site of a large ongoing outbreak. Phosphorodiamidate morpholino oligomers (PMOs) are synthetic antisense molecules that are able to target mRNAs in a sequence-specific fashion and suppress translation through steric hindrance. We previously showed that the use of PMOs targeting a combination of VP35 and VP24 protected rhesus monkeys from lethal EBOV infection. Surprisingly, the present study revealed that a PMOplus compound targeting VP24 alone was sufficient to confer protection from lethal EBOV infection but that a PMOplus targeting VP35 alone resulted in no protection. This study further substantiates recent data demonstrating that VP24 may be a key virulence factor encoded by EBOV and suggests that VP24 is a promising target for the development of effective anti-EBOV countermeasures. IMPORTANCE Several West African countries are currently being ravaged by an outbreak of Ebola virus (EBOV) that has become a major epidemic affecting not only these African countries but also Europe and the United States. A better understanding of the mechanism of virulence of EBOV is important for the development of effective treatments, as no licensed treatments or vaccines for EBOV disease are currently available. This study of phosphorodiamidate morpholino oligomers (PMOs) targeting the mRNAs of two different EBOV proteins, alone and in combination, demonstrated that targeting a single protein was effective at conferring a significant survival benefit in an EBOV lethal primate model. Future development of PMOs with efficacy against EBOV will be simplified if only one PMO is required instead of a combination, particularly in terms of regulatory approval. Several West African countries are currently being ravaged by an outbreak of Ebola virus (EBOV) that has become a major epidemic affecting not only these African countries but also Europe and the United States. A better understanding of the mechanism of virulence of EBOV is important for the development of effective treatments, as no licensed treatments or vaccines for EBOV disease are currently available. This study of phosphorodiamidate morpholino oligomers (PMOs) targeting the mRNAs of two different EBOV proteins, alone and in combination, demonstrated that targeting a single protein was effective at conferring a significant survival benefit in an EBOV lethal primate model. Future development of PMOs with efficacy against EBOV will be simplified if only one PMO is required instead of a combination, particularly in terms of regulatory approval.

Vigilant at the End of Life: Family Advocacy in the Nursing Home

BACKGROUND Increasing numbers of Americans die in nursing homes. Little is known about the roles and experiences of family members of persons who die in nursing homes. METHODS The authors conducted 54 qualitative telephone interviews of close family or friends of individuals who had spent at least 48 hours in the last month of life in a nursing home. Respondents had earlier participated in a national survey that found 587 of 1578 decedents (37.2%) received end-of-life nursing home care. In qualitative interviews respondents described the last year of life, focusing on the nursing home experience. Interviews were analyzed by a multidisciplinary team to identify key themes of areas of concern. RESULTS An important interview theme revealed families often felt the need to advocate for their dying relative because of low expectations or experiences with poor quality nursing home care. They noted staff members who did not fully inform them about what to expect in the dying process. Respondents reported burden and gratification in care they themselves provided, which sometimes entailed collaboration with staff. Interviews also identified ways hospice care impacted families, including helping to relieve family burden. CONCLUSIONS End-of-life advocacy takes on increased urgency when those close to the dying resident have concerns about basic care and do not understand the dying course. Enhancing communication, preparing families at the end of life, and better understanding of hospice are likely to increase family trust in nursing home care, improve the care of dying residents, and help reduce family burden.

Patients' experiences of seeking health care for lower urinary tract symptoms†

A gap between experiencing symptoms and receiving effective treatment persists for people with lower urinary tract symptoms (LUTS), even for those who seek health care. In order to better understand how patients experience treatment seeking for LUTS, we interviewed a racially diverse sample of 90 men and women with a range of LUTS about their experiences seeking care. Thematic analysis revealed that patients often disclosed urinary symptoms first to primary care providers during a general examination or a visit for another health problem. Patients seek provider assistance typically when symptoms have intensified or are causing worry, and a desire for treatment trumps potential embarrassment; among women patients, feeling comfortable with a provider also is important for disclosing LUTS.

Race and ethnic differences in health beliefs about lower urinary tract symptoms.

Background:Health beliefs are an important mediator between the experience of symptoms and health behaviors, and these beliefs can vary by race or ethnicity. Objectives:The aim of this study was to better understand the gap between experiencing symptoms and not seeking medical care by examining health beliefs about lower urinary tract symptoms across race and ethnic groups. Method:Qualitative, semistructured interviews were conducted with 35 Black, Hispanic, and White people who reported at least one urinary symptom but had not spoken with a healthcare provider about the symptom(s). Drawing on Shaws framework of health behavior and outcomes, a range of beliefs was examined: cause, consequence, continuation, and treatability. Interviews were transcribed, coded, and analyzed for themes according to race or ethnic background. Results:The belief that lower urinary tract symptoms are a typical part of aging and not amenable to medical treatment was most common among White respondents. Black respondents more commonly attributed their symptoms to personal behaviors over which they had control and therefore did not require medical care. Hispanic respondents appeared more often to live with uncertainty about the cause of their symptoms and an accompanying concern about a future health consequence. Discussion:The combination of a range of health beliefs to form a cognitive representation made sense of the behavior of not seeking medical care. The finding that sociocultural differences shaped these cognitive representations underscores the need for cultural competency in patient assessment and education. Results have implications for theories of health behavior and indicate further research with larger samples, additional psychosocial influences, and other symptoms.

Gendered Uncertainty and Variation in Physicians’ Decisions for Coronary Heart Disease The Double-Edged Sword of “Atypical Symptoms”

Nonmedical factors and diagnostic certainty contribute to variation in clinical decision making, but the process by which this occurs remains unclear. We examine how physicians’ interpretations of patient sex-gender affect diagnostic certainty and, in turn, decision making for coronary heart disease. Data are from a factorial experiment of 256 physicians who viewed 1 of 16 video vignettes with different patient-actors presenting the same symptoms of coronary heart disease. Physician participants completed a structured interview and provided a narrative about their decision-making processes. Quantitative analysis showed that diagnostic uncertainty reduces the likelihood that physicians will order tests and medications appropriate for an urgent cardiac condition in particular. Qualitative analysis revealed that a subset of physicians applied knowledge that women have “atypical symptoms” as a generalization, which engendered uncertainty for some. Findings are discussed in relation to social-psychological processes that underlie clinical decision making and the social framing of medical knowledge.

Delayed Time-to-Treatment of an Antisense Morpholino Oligomer Is Effective against Lethal Marburg Virus Infection in Cynomolgus Macaques

Marburg virus (MARV) is an Ebola-like virus in the family Filovirdae that causes sporadic outbreaks of severe hemorrhagic fever with a case fatality rate as high as 90%. AVI-7288, a positively charged antisense phosphorodiamidate morpholino oligomer (PMOplus) targeting the viral nucleoprotein gene, was evaluated as a potential therapeutic intervention for MARV infection following delayed treatment of 1, 24, 48, and 96 h post-infection (PI) in a nonhuman primate lethal challenge model. A total of 30 cynomolgus macaques were divided into 5 groups of 6 and infected with 1,830 plaque forming units of MARV subcutaneously. AVI-7288 was administered by bolus infusion daily for 14 days at 15 mg/kg body weight. Survival was the primary endpoint of the study. While none (0 of 6) of the saline group survived, 83–100% of infected monkeys survived when treatment was initiated 1, 24, 48, or 96 h post-infection (PI). The antisense treatment also reduced serum viremia and inflammatory cytokines in all treatment groups compared to vehicle controls. The antibody immune response to virus was preserved and tissue viral antigen was cleared in AVI-7288 treated animals. These data show that AVI-7288 protects NHPs against an otherwise lethal MARV infection when treatment is initiated up to 96 h PI.

Efficacy of favipiravir (T-705) in nonhuman primates infected with Ebola virus or Marburg virus

ABSTRACT Favipiravir is a broad‐spectrum antiviral agent that has demonstrated efficacy against Ebola virus (EBOV) in rodents. However, there are no published reports of favipiravir efficacy for filovirus infection of nonhuman primates (NHPs). Here we evaluated the pharmacokinetic profile of favipiravir in NHPs, as well as in vivo efficacy against two filoviruses, EBOV and Marburg virus (MARV). While no survival benefit was observed in two studies employing once‐ or twice‐daily oral dosing of favipiravir during EBOV infection of NHPs, an antiviral effect was observed in terms of extended time‐to‐death and reduced levels of viral RNA. However, oral dosing in biosafety level‐4 (BSL‐4) presents logistical and technical challenges, and repeated anesthesia events may potentially worsen survival outcome in animals. For the third study of treatment of MARV infection, we therefore made use of catheters, jackets, and tethers for intravenous (IV) dosing and blood collection, which minimized the requirement for repeated anesthesia events. When MARV infection was treated with IV favipiravir, five of six animals (83%) survived infection, while all untreated NHPs succumbed. An accompanying report presents the results of favipiravir treatment of EBOV infection in mice. HighlightsDuring the course of the West African Ebola epidemic, we evaluated the activity of favipiravir in nonhuman primates.Once‐daily or twice‐daily oral dosing with favipiravir did not lead to improved survival following EBOV infection.An antiviral effect against EBOV was observed in terms of increased time‐to‐death and reduction in viral RNA levels.In both EBOV studies, plasma favipiravir levels exceeded the EBOV EC50.Twice‐daily intravenous dosing resulted in 83% survival following MARV infection, while all untreated animals died.