Non-Traditional Surrogate Decision Makers for Hospitalized Older Adults

Background Without advanced preparation of legal documents, state law determines who may serve as a surrogate decision maker for patients in hospitals. Objectives To examine the relationship characteristics associated with traditional versus non-traditional healthcare surrogates who are making medical decisions for patients in hospitals. Research Design Secondary analysis of a baseline cross-sectional survey of a larger prospective observational study. Subjects 364 patient/ surrogate dyads consisting of patients age 65 years and older admitted to the medical or medical ICU services who lacked decision making capacity based on a physician assessment and also had a surrogate available. Results This study of surrogate decision makers for hospitalized older adults found that the relationships of non-traditional surrogates such as, nieces, nephews, and friends serving in the surrogate role is nearly identical to those of traditional, first degree relatives serving as a surrogate. Over two-thirds (71.2%) of non-traditional surrogates saw the patient in person at least weekly compared to 80.8% of legal surrogates (p-value .9023). Almost all traditional and non-traditional surrogates discussed the patient’s medical preferences with the patient (96.9% of legal surrogates and 89.2% of non-traditional surrogates; p=0.0510). Conclusion This study shows that both traditional and non-traditional surrogates, who are a patient’s primary care giver have similar relationships with patients. The findings of this study suggest that requiring family members such as grandchildren to take the extra step of formal appointment through a legal channel may not be necessary to protect patients. Therefore, broader state laws expanding the list of surrogates authorized by state statute to include more non-traditional surrogates may be necessary

Assessment of Discordance Between Surrogate Care Goals and Medical Treatment Provided to Older Adults With Serious Illness

Importance: An important aspect of high-quality care is ensuring that treatments are in alignment with patient or surrogate decision-maker goals. Treatment discordant with patient goals has been shown to increase medical costs and prolong end-of-life difficulties. Objectives: To evaluate discordance between surrogate decision-maker goals of care and medical orders and treatments provided to hospitalized, incapacitated older patients. Design, setting, and participants: This prospective cohort study included 363 patient-surrogate dyads. Patients were 65 years or older and faced at least 1 major medical decision in the medical and medical intensive care unit services in 3 tertiary care hospitals in an urban Midwestern area. Data were collected from April 27, 2012, through July 10, 2015, and analyzed from October 5, 2018, to December 5, 2019. Main outcomes and measures: Each surrogate's preferred goal of care was determined via interview during initial hospitalization and 6 to 8 weeks after discharge. Surrogates were asked to select the goal of care for the patient from 3 options: comfort-focused care, life-sustaining treatment, or an intermediate option. To assess discordance, the preferred goal of care as determined by the surrogate was compared with data from medical record review outlining the medical treatment received during the target hospitalization. Results: A total of 363 dyads consisting of patients (223 women [61.4%]; mean [SD] age, 81.8 [8.3] years) and their surrogates (257 women [70.8%]; mean [SD] age, 58.3 [11.2] years) were included in the analysis. One hundred sixty-nine patients (46.6%) received at least 1 medical treatment discordant from their surrogate's identified goals of care. The most common type of discordance involved full-code orders for patients with a goal of comfort (n = 41) or an intermediate option (n = 93). More frequent in-person contact between surrogate and patient (adjusted odds ratio [AOR], 0.43; 95% CI, 0.23-0.82), patient residence in an institution (AOR, 0.44; 95% CI, 0.23-0.82), and surrogate-rated quality of communication (AOR, 0.98; 95% CI, 0.96-0.99) were associated with lower discordance. Surrogate marital status (AOR for single vs married, 1.92; 95% CI, 1.01-3.66), number of family members involved in decisions (AOR for ≥2 vs 0-1, 1.84; 95% CI, 1.05-3.21), and religious affiliation (AOR for none vs any, 4.87; 95% CI, 1.12-21.09) were associated with higher discordance. Conclusions and relevance: This study found that discordance between surrogate goals of care and medical treatments for hospitalized, incapacitated patients was common. Communication quality is a modifiable factor associated with discordance that may be an avenue for future interventions

“I Felt Like a Superhero”: The Experience of Responding to Drug Overdose Among Individuals Trained in Overdose Prevention

BACKGROUND: Overdose prevention programs (OPPs) train people who inject drugs and other community members to prevent, recognise and respond to opioid overdose. However, little is known about the experience of taking up the role of an overdose responder for the participants. METHODS: We present findings from qualitative interviews with 30 participants from two OPPs in Los Angeles, CA, USA from 2010 to 2011 who had responded to at least one overdose since being trained in overdose prevention and response. RESULTS: Being trained by an OPP and responding to overdoses had both positive and negative effects for trained responders . Positive effects include an increased sense of control and confidence, feelings of heroism and pride, and a recognition and appreciation of one\u27s expertise. Negative effects include a sense of burden, regret, fear, and anger, which sometimes led to cutting social ties, but might also be mitigated by the increased empowerment associated with the positive effects. CONCLUSION: Findings suggest that becoming an overdose responder can involve taking up a new social role that has positive effects, but also confers some stress that may require additional support. OPPs should provide flexible opportunities for social support to individuals making the transition to this new and critical social role. Equipping individuals with the skills, technology, and support they need to respond to drug overdose has the potential to confer both individual and community-wide benefits

Validation of the Family Inpatient Communication Survey

CONTEXT: Although many family members who make surrogate decisions report problems with communication, there is no validated instrument to accurately measure surrogate/clinician communication for older adults in the acute hospital setting. OBJECTIVES: The objective of this study was to validate a survey of surrogate-rated communication quality in the hospital that would be useful to clinicians, researchers, and health systems. METHODS: After expert review and cognitive interviewing (n = 10 surrogates), we enrolled 350 surrogates (250 development sample and 100 validation sample) of hospitalized adults aged 65 years and older from three hospitals in one metropolitan area. The communication survey and a measure of decision quality were administered within hospital days 3 and 10. Mental health and satisfaction measures were administered six to eight weeks later. RESULTS: Factor analysis showed support for both one-factor (Total Communication) and two-factor models (Information and Emotional Support). Item reduction led to a final 30-item scale. For the validation sample, internal reliability (Cronbach's alpha) was 0.96 (total), 0.94 (Information), and 0.90 (Emotional Support). Confirmatory factor analysis fit statistics were adequate (one-factor model, comparative fit index = 0.981, root mean square error of approximation = 0.62, weighted root mean square residual = 1.011; two-factor model comparative fit index = 0.984, root mean square error of approximation = 0.055, weighted root mean square residual = 0.930). Total score and subscales showed significant associations with the Decision Conflict Scale (Pearson correlation -0.43, P < 0.001 for total score). Emotional Support was associated with improved mental health outcomes at six to eight weeks, such as anxiety (-0.19 P < 0.001), and Information was associated with satisfaction with the hospital stay (0.49, P < 0.001). CONCLUSION: The survey shows high reliability and validity in measuring communication experiences for hospital surrogates. The scale has promise for measurement of communication quality and is predictive of important outcomes, such as surrogate satisfaction and well-being

The Family Navigator: A pilot intervention to support intensive care unit family surrogates

Background Although communication problems between family surrogates and intensive care unit (ICU) clinicians have been documented, there are few effective interventions. Nurses have the potential to play an expanded role in ICU communication and decision making. Objectives To conduct a pilot randomized controlled trial of the Family Navigator (FN), a distinct nursing role to address family members’ unmet communication needs early in an ICU stay. Methods An inter-disciplinary team developed the FN protocol. A randomized controlled pilot intervention trial of the FN was performed in a tertiary referral hospital ICU to test the feasibility and acceptability of the intervention. The intervention addressed informational and emotional communication needs through daily contact using structured clinical updates, emotional and informational support modules, family meeting support and follow-up phone calls. Results Twenty-six surrogate/patient pairs (13 per study arm) were enrolled. Surrogates randomized to the intervention had contact with the FN 90% or more of eligible patient days. All surrogates agreed or strongly agreed that they would recommend the FN to other families. Open-ended comments from both surrogates and clinicians were uniformly positive. For both groups, 100% of baseline data collection interviews and 81% of 6–8 week follow-up interviews were completed. Conclusions A fully integrated nurse empowered to facilitate decision making is a feasible intervention in the ICU setting. It is well-received by ICU families and staff. A larger randomized controlled trial is needed to demonstrate an impact on important outcomes, such as surrogate well-being and decision quality

Ammonia fiber expansion (AFEX) pretreatment of lignocellulosic biomass

Lignocellulosic materials are plant-derived feedstocks, such as crop residues (e.g., corn stover, rice straw, and sugar cane bagasse) and purpose-grown energy crops (e.g., miscanthus, and switchgrass) that are available in large quantities to produce biofuels, biochemicals, and animal feed. Plant polysaccharides (i.e., cellulose, hemicellulose, and pectin) embedded within cell walls are highly recalcitrant towards conversion into useful products. Ammonia fiber expansion (AFEX) is a thermochemical pretreatment that increases accessibility of polysaccharides to enzymes for hydrolysis into fermentable sugars. These released sugars can be converted into fuels and chemicals in a biorefinery. Here, we describe a laboratory-scale batch AFEX process to produce pretreated biomass on the gram-scale without any ammonia recycling. The laboratory-scale process can be used to identify optimal pretreatment conditions (e.g., ammonia loading, water loading, biomass loading, temperature, pressure, residence time, etc.) and generates sufficient quantities of pretreated samples for detailed physicochemical characterization and enzymatic/microbial analysis. The yield of fermentable sugars from enzymatic hydrolysis of corn stover pretreated using the laboratory-scale AFEX process is comparable to pilot-scale AFEX process under similar pretreatment conditions. This paper is intended to provide a detailed standard operating procedure for the safe and consistent operation of laboratory-scale reactors for performing AFEX pretreatment of lignocellulosic biomass

The Association of Surrogate Decision Makers’ Religious and Spiritual Beliefs with End of Life Decisions

Context: Although religion and spirituality are important to surrogate decision makers, little is known about the role of religion in decision making regarding life-sustaining treatments. Objectives: To determine the relationships between dimensions of religion and spirituality and medical treatment decisions made by surrogates. Methods: This prospective observational study enrolled patient/surrogate dyads from three hospitals in one metropolitan area. Eligible patients were 65 years or older and admitted to the medicine or medical intensive care services. Baseline surveys between hospital days 2 and 10 assessed seven dimensions of religion and spirituality. Chart reviews of the electronic medical record and regional health information exchange six months after enrollment identified the use of life-sustaining treatments and hospice for patients who died. Results: There were 291 patient/surrogate dyads. When adjusting for other religious dimensions, demographic, and illness factors, only surrogates' belief in miracles was significantly associated with a lower surrogate preference for do-not-resuscitate status (adjusted odds ratio [aOR] 0.39; 95% CI 0.19, 0.78). Among patients who died, higher surrogate intrinsic religiosity was associated with lower patient receipt of life-sustaining treatments within the last 30 days (aOR 0.66; 95% CI 0.45, 0.97). Belief in miracles (aOR 0.30; 95% CI 0.10, 0.96) and higher intrinsic religiosity (aOR 0.70; 95% CI 0.53, 0.93) were associated with lower hospice utilization. Conclusion: Few religious variables are associated with end-of-life preferences or treatment. Belief in miracles and intrinsic religiosity may affect treatment and should be identified and explored with surrogates by trained chaplains or other clinicians with appropriate training

Engineering HIV-1-resistant T-cells from short-hairpin RNA-expressing hematopoietic stem/progenitor cells in humanized BLT mice

Down-regulation of the HIV-1 coreceptor CCR5 holds significant potential for long-term protection against HIV-1 in patients. Using the humanized bone marrow/liver/thymus (hu-BLT) mouse model which allows investigation of human hematopoietic stem/progenitor cell (HSPC) transplant and immune system reconstitution as well as HIV-1 infection, we previously demonstrated stable inhibition of CCR5 expression in systemic lymphoid tissues via transplantation of HSPCs genetically modified by lentiviral vector transduction to express short hairpin RNA (shRNA). However, CCR5 down-regulation will not be effective against existing CXCR4-tropic HIV-1 and emergence of resistant viral strains. As such, combination approaches targeting additional steps in the virus lifecycle are required. We screened a panel of previously published shRNAs targeting highly conserved regions and identified a potent shRNA targeting the R-region of the HIV-1 long terminal repeat (LTR). Here, we report that human CD4+ T-cells derived from transplanted HSPC engineered to co-express shRNAs targeting CCR5 and HIV-1 LTR are resistant to CCR5- and CXCR4- tropic HIV-1-mediated depletion in vivo. Transduction with the combination vector suppressed CXCR4- and CCR5- tropic viral replication in cell lines and peripheral blood mononuclear cells in vitro. No obvious cytotoxicity or interferon response was observed. Transplantation of combination vector-transduced HSPC into hu-BLT mice resulted in efficient engraftment and subsequent stable gene marking and CCR5 down-regulation in human CD4+ T-cells within peripheral blood and systemic lymphoid tissues, including gut-associated lymphoid tissue, a major site of robust viral replication, for over twelve weeks. CXCR4- and CCR5- tropic HIV-1 infection was effectively inhibited in hu-BLT mouse spleen-derived human CD4+ T-cells ex vivo. Furthermore, levels of gene-marked CD4+ T-cells in peripheral blood increased despite systemic infection with either CXCR4- or CCR5- tropic HIV-1 in vivo. These results demonstrate that transplantation of HSPCs engineered with our combination shRNA vector may be a potential therapy against HIV disease.This work was supported by grants from the California Institute for Regenerative Medicine (CIRM grant DR1-01431 to ISYC), the National Institutes of Health (1RO1HL086409 and 3RO1HL086409-03S1 to DSA and 5T32AI060567), and the University of California Los Angeles AIDS Institute/Center for AIDS Research (5P30AI028697). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Role of the mesoamygdaloid dopamine projection in emotional learning

Amygdala dopamine is crucially involved in the acquisition of Pavlovian associations, as measured via conditioned approach to the location of the unconditioned stimulus (US). However, learning begins before skeletomotor output, so this study assessed whether amygdala dopamine is also involved in earlier 'emotional' learning. A variant of the conditioned reinforcement (CR) procedure was validated where training was restricted to curtail the development of selective conditioned approach to the US location, and effects of amygdala dopamine manipulations before training or later CR testing assessed. Experiment 1a presented a light paired (CS+ group) or unpaired (CS- group) with a US. There were 1, 2 or 10 sessions, 4 trials per session. Then, the US was removed, and two novel levers presented. One lever (CR+) presented the light, and lever pressing was recorded. Experiment 1b also included a tone stimulus. Experiment 2 applied intra-amygdala R(+) 7-OH-DPAT (10 nmol/1.0 A mu l/side) before two training sessions (Experiment 2a) or a CR session (Experiment 2b). For Experiments 1a and 1b, the CS+ group preferred the CR+ lever across all sessions. Conditioned alcove approach during 1 or 2 training sessions or associated CR tests was low and nonspecific. In Experiment 2a, R(+) 7-OH-DPAT before training greatly diminished lever pressing during a subsequent CR test, preferentially on the CR+ lever. For Experiment 2b, R(+) 7-OH-DPAT infusions before the CR test also reduced lever pressing. Manipulations of amygdala dopamine impact the earliest stage of learning in which emotional reactions may be most prevalent