Educational and occupational aspirations of adolescent and young adult cancer survivors: a qualitative analysis.

PURPOSE: Adolescent and young adult cancer survivors (AYACS) are patients diagnosed with cancer between 15 and 39 years of age. AYACS are often derailed from planned educational and occupational endeavors due to disruption from cancer treatment and its consequences. The study objective was to examine how a personal cancer diagnosis impacted AYACS' experiences related to these endeavors. METHODS: Semi-structured interviews were conducted as part of a larger study assessing psychosocial challenges among a younger AYACS subset aged 15-25 years old at the time of cancer diagnosis. Interviews were coded based on responses and were used to develop themes related to educational and occupational endeavors. RESULTS: Data were collected from 35 participants. Five themes emerged: (1) Pauses in educational attainment had a detrimental effect on educational goals for some participants, but further solidified and sculpted educational plans for others; (2) Although participants experienced challenges accomplishing educational goals, supportive school environments helped surmount these challenges; (3) Participants reflected on rethinking career aspirations, though some desired to pursue the same occupation planned before cancer diagnosis; (4) Participants experienced challenges, including physical and cognitive limitations, upon returning to work; and (5) Participants valued autonomy and normalcy through work and appreciated supportive and flexible work environments. CONCLUSIONS: AYACS prioritize professional achievement, yet encounter challenges in achieving professional goals. Our findings create a foundation for developing and testing prospective interventions to promote continuance of school and work during cancer treatment when feasible, and proactive reintegration strategies for those who paused professional goals due to cancer treatment.

The Impact of Health Communication Research on Medical and Health Professional Education and Training.

In this essay, we review how health communication scholarship has been translated into various communication skills trainings (CSTs), we present four case studies of how health communication research informed the development and implementation of specific CSTs, and we reflect on how we can productively define "impact" in looking back as well as looking forward within this line of research.

Adoption and Discontinuance of Innovation Packages: A Longitudinal Study of Transitions in COVID-19 Mitigation.

The past decades have seen growing interest and application of interventions targeting the change of multiple behaviors at once. We advance this work by using the diffusion of innovations theory (DOI) to consider constellations of behaviors as innovation packages: multiple innovations that are logically related, interdependent in their use or effects, and often promoted as a set (Rogers, 2003). In addition, we embraced DOI's focus on behavioral decisions as a continual process that can include adoption and discontinuance over time, especially as new innovations (e.g., COVID-19 vaccine) appear. To that end, we conducted a latent transition analysis of COVID-19 mitigation behaviors (N = 697; 97% received a COVID-19 vaccine) across three time points in the pandemic: initial outbreak; a secondary, record-breaking rise in cases; and after the CDC recommended that fully vaccinated adults could discontinue wearing masks. This analysis allowed us to identify latent classes based on shared behavioral patterns and transitions between classes over time. The results showed evidence of three possible packages: (a) a package of traditional, symptom-management behaviors (covering coughs and sneezes, staying home if ill, and seeking medical care), (b) a package of just-novel COVID-19 behaviors (wearing masks, keeping six feet apart, and avoiding mass gatherings), and (c) a package of all COVID-19 mitigation behaviors. Movement between classes exemplified adoption and discontinuance of different packages, as well as widespread discontinuance with the replacement innovation: COVID-19 vaccines. Additional analyses showed that increases in hope were associated with sustained and delayed adoption; decreases in social approval were associated with discontinuance. Future directions in theorizing around innovation packages are discussed.

A randomised controlled trial of a nutrition and a decision support intervention to enable partnerships with families of critically ill patients.

AIMS AND OBJECTIVES: The aim of the study was to investigate the effect of supporting family members to partner with health professionals on nutrition intakes and decision-making and to evaluate intervention and study feasibility. BACKGROUND: Family partnerships can improve outcomes for critically ill patients and family members. Interventions that support families to engage with health professionals require evaluation. DESIGN: A multi-centre, randomised, parallel group superiority Phase II randomised controlled trial. METHODS: In nine intensive care units (ICUs) across three countries, critically ill patients ≥60 years, or those 55-59 years with advanced chronic diseases and expected ICU length of stay >72 h and their family member were enrolled between 9 May 2017 and 31 March 2020. Participants were randomised (1:1:1) to either a decision support or nutrition optimisation family-centred intervention, or usual care. Primary outcomes included protein and energy intake during ICU and hospital stay (nutrition intervention) and family satisfaction (decision support). Study feasibility was assessed as a composite of consent rate, intervention adherence, contamination and physician awareness of intervention assignment. RESULTS: We randomised 135 patients/family members (consent rate 51.7%). The average rate of randomisation was 0.5 (0.13-1.53) per month. Unavailability (staff/family) was the major contributor to families not being approached for consent. Declined consent was attributed to families feeling overwhelmed (58/126, 46%). Pandemic visitor restrictions contributed to early study cessation. Intervention adherence for the decision support intervention was 76.9%-100.0% and for the nutrition intervention was 44.8%-100.0%. Nutritional adequacy, decisional conflict, satisfaction with decision-making and overall family satisfaction with ICU were similar for all groups. CONCLUSIONS: Active partnerships between family members and health professionals are important but can be challenging to achieve in critical care contexts. We were unable to demonstrate the efficacy of either intervention. Feasibility outcomes suggest further refinement of interventions and study protocol may be warranted. RELEVANCE TO CLINICAL PRACTICE: Interventions to promote family partnerships in critical illness are needed but require a greater understanding of the extent to which families want and are able to engage and the activities in which they have most impact. REPORTING METHOD: This study has been reported following the Consolidated Standards of Reporting Trials (CONSORT) and the Template for Intervention Description and Replication (TIDieR) guidelines. PATIENT OR PUBLIC CONTRIBUTION: Patients and caregivers were engaged in and contributed to the development and subsequent iterations of the two family-centred interventions use in this study. CLINICAL TRIAL REGISTRATION NUMBER: Trial registration. CLINICALTRIALS: gov, ID: NCT02920086. Registered on 30 September 2016. First patient enrolled on 9 May 2017 https://clinicaltrials.gov/ct2/results?cond=&term=NCT02920086&cntry=&state=&city=&dist=.

Extending the Theory of Normative Social Behavior: Collective Norms, Opinion Leadership, and Masking During the COVID-19 Pandemic.

Novel, public behaviors, such as masking, should be susceptible to normative influence. This paper advances the theory of normative social behavior by considering a new set of moderators of normative influence - superdiffuser traits - and by clarifying the antecedents and consequences of exposure to collective norms. We use data from a two-wave survey of a cohort living in one U.S. county during the pandemic (N = 913) to assess normative effects on masking. We also used a bipartite network (based on people shopping for food in the same stores) to examine exposure to collective norms. The results show different superdiffuser traits have distinct effects on the relationship between perceived injunctive norms and masking intentions. Exposure to collective norms influences masking, but this influence depends on how people interact with their social environments. Network analysis shows that behavioral homophily is a significant predictor of selective exposure to collective norms earlier (but not later) in the pandemic. Implications for understanding normative influence in a context where opinion leadership matters are discussed.

Flight Teams' Learning Needs Assessment on Ultrasound: A Mixed Methods Approach.

OBJECTIVE: The goal of this study was to understand flight clinicians' learning needs and attitudes with regard to a prehospital ultrasound curriculum. METHODS: In this convergent mixed methods study, 21 prehospital clinicians completed a questionnaire, and 20 attended a 1-hour focus group to explore attitudes regarding learning ultrasound. These participants were from a single emergency medical service agency. RESULTS: Five themes emerged from the focus group transcripts and were supported by the quantitative data: 1) theme 1, hands-on training in ultrasound is a highly preferred modality; 2) theme 2, emergency medical service providers desire learning integrated into shifts and real-life practice; 3) theme 3, prehospital providers express concerns about training and maintenance of competency; 4) theme 4, participants recognize the need for quality control during the training phase and after; and 5) theme 5, participants were enthusiastic about how ultrasound could help guide clinical decision making and potentially improve patient outcomes. CONCLUSION: Those who participated in an evidence-based assessment of prehospital ultrasound needs and barriers were experienced flight clinicians who would use prehospital ultrasound if made available. These adult learners indicated their preferred learning method would be using standardized patients, simulators, and hands-on in the field with physicians. They preferred follow-up courses and simulators to maintain competency.

Exploring Behavioral Typologies to Inform COVID-19 Health Campaigns: A Person-Centered Approach.

As the United States continues to be ravaged by COVID-19, it becomes increasingly important to implement effective public health campaigns to improve personal behaviors that help control the spread of the virus. To design effective campaigns, research is needed to understand the current mitigation intentions of the general public, diversity in those intentions, and theoretical predictors of them. COVID-19 campaigns will be particularly challenging because mitigation involves myriad, diverse behaviors. This study takes a person-centered approach to investigate data from a survey (N = 976) of Pennsylvania adults. Latent class analysis revealed five classes of mitigation: one marked by complete adherence with health recommendations (34% of the sample), one by complete refusal (9% of the sample), and three by a mixture of adherence and refusal. Statistically significant covariates of class membership included relatively positive injunctive norms, risk due to essential workers in the household, personal knowledge of someone who became infected with COVID-19, and belief that COVID-19 was a leaked biological weapon. Additionally, trait reactance was associated with non-adherence while health mavenism was associated with adherence. These findings may be used to good effect by local healthcare providers and institutions, and also inform broader policy-making decisions regarding public health campaigns to mitigate COVID-19.

Multiple Goals Theory and Communication Quality Analysis for Fellows Communication Training.

Background: End-of-life communication skills are vital to high-quality critical care. Patients and families often report deficiencies in end-of-life communication by providers. However, formalized training is difficult to implement and study on a large scale. Furthermore, curricula are often designed with early-stage clinical trainees in mind and are not tailored to advanced clinician learners. Objective: The goal of this pilot study was to explore educational and practical implications of using Multiple Goals Theory (MGT), Communication Quality Analysis (CQA), and communication logs as a three-pronged, reflective communication curriculum for advanced trainees. Methods: We describe design and qualitative evaluation of a novel, pilot, longitudinal curricular intervention for pulmonary and critical care fellows and program directors at a tertiary academic medical center. The 2-year longitudinal communication curriculum incorporates 1) a theoretical framework from communication science (MGT), with 2) a novel training modality of analyzing audio-recorded intensive care unit family meetings (CQA), and 3) written communication logs after an intensive care unit family meeting. Results: The sample included 13 pulmonary and critical care medicine fellows and two program directors. Qualitative thematic analysis was conducted on seven fellow interviews and on 23 communication logs completed. Four themes emerged from interviews: 1) fellows incorporated the skills into real-life practice and found the curriculum useful and valuable; 2) a key takeaway from MGT was the deemphasis of task goals; 3) CQA was an engaging opportunity for self-reflection and learning; and 4) written communication logs were perceived as helpful in theory but too burdensome in practice. Findings from analyses of the communication logs included that most fellows' writing was brief and without substantial reflection. Conclusion: Many scholars have argued that communication theory can impact practice, but few have recognized the potential of theory and methods, such as MGT and CQA, as educational tools. Our findings demonstrate that MGT is a feasible and useful theoretical framework for improving communication skills among advanced trainees, and CQA fosters meaningful self-reflection about practice. Communication logs were not feasible or useful training tools in this context, but CQA workshops helped fulfill the goals of narrative reflection. Next steps are to implement this curriculum in more programs and measure changes in behavior acquisition and clinical care.

What Counts as a Surrogate Decision?

When patients lose decision-making capacity, others must make surrogate decisions on their behalf. What counts as a surrogate decision might seem self-evident. But as clinician-researchers in the field of advance care planning, we have found that it is not always so clear-cut. In this paper, we describe how and why this is a matter of concern, a novel approach for assessing whether a surrogate decision occurred, and findings from this assessment.

Feasibility and Acceptability of a Novel Intensive Care Unit Communication Intervention ("Let's Talk") and Initial Assessment Using the Multiple Goals Theory of Communication.

Background: Family members of intensive care unit (ICU) patients often report poor communication, feeling unprepared for ICU family meetings, and poor psychological outcomes after decision-making. The objective of this study was to create a tool to prepare families for ICU family meetings and assess feasibility of using Communication Quality Analysis (CQA) to measure communication quality of family meetings. Methods: This observational study was conducted at an academic tertiary care center in Hershey, PA from March 2019 to 2020. Phase 1a involved conceptual design. Phase 1b entailed acceptability testing of 2 versions of the tool (text-only, comic) with 9 family members of non-capacitated ICU patients; thematic analysis of semi-strucutred interviews was conducted. Phase 1c assessed feasibility of applying CQA to audio-recorded ICU family meetings (n = 17); 3 analysts used CQA to assess 6 domains of communication quality. Wilcoxon Signed Rank tests were used to interpret CQA scores. Results: Four themes emerged from Phase 1b interviews: participants 1) found the tool useful for meeting preparation and organizing thoughts, 2) appreciated emotional content, 3) preferred the comic form (67%), and 4) had indifferent or negative perceptions about specific elements. In Phase 1c, clinicians scored higher on the CQA content and engagement domains; family members scored higher on the emotion domain. CQA scores in the relationship and face domains had the lowest quality ratings. Conclusions: Let's Talk may help families become better prepared for ICU family meetings. CQA provides a feasible approach to assessing communication quality that identifies specific areas of strengths and weaknesses in communication.

Navigation-Based Telehealth Informed Decision-Making for Prostate Cancer Screening in Black Men.

The rapid increase in telehealth has the potential to bring informed decision-making for prostate cancer screening (PCS) at the population level to high-risk individuals. We utilized a global technology platform of electronic health records data repositories (TriNetX) to determine its utility for Navigator-guided decision-making aid for PCS in Black men ages 45-79 years with no history of prostate cancer and PSA testing. Patients from Pennsylvania were invited to participate in a telehealth-delivered informed decision-making session for PCS. Focus groups, social learning theory, visual diagrams, and quantitative data on PCS risks and benefits were used to develop the content of the sessions, which included numerical discussions of risks vs. benefits in Black men. Participants completed several surveys, including baseline demographic and numeracy questionnaires, a one-on-one telehealth session with a trained Navigator, post-Navigation surveys, and an optional follow-up session with a urologist. Eighty-seven participants were consented and recruited. Although the mean numeracy score was only 1.9 out of 6, more than 90% rated as good or excellent that the sessions aided their PCS decision-making skills. This study indicates that Navigation by telehealth offers the ability to assist in informed decision-making for PCS at the population level.

Leadership Perspectives on Nursing Home Operations From Crisis to Control: A Mixed Methods Study.

OBJECTIVES: Nursing home (NH) leaders remain challenged to deliver quality care, despite the COVID-19 transition to an endemic phase. This study describes NH leadership perspectives on preparing and maintaining quality care during times of diminishing resources as experienced through the COVID-19 pandemic to gain insight on how best to support NHs moving forward. DESIGN: This was a cross-sectional, parallel convergent mixed methods study. SETTING AND PARTICIPANTS: This study reports quantitative data from N = 5001 NHs across 12 states along with qualitative data from a subsample of NH leaders (N = 15). METHODS: Publicly reported survey data were analyzed using descriptive statistics. Individual in-depth interviews with NH leaders conducted at 12-month follow-up were analyzed using inductive thematic coding organized by a guiding framework. Data were integrated using convergent analysis and a joint display. RESULTS: NH leaders (licensed administrators, clinical directors, and managers) reported resident and staff infection rates, and access to resources (such as personal protective equipment and testing supplies) that aligned with national trends. Leaders described their NHs (n = 14; 43% rural; 71% not for profit) to be in varied states of operational readiness (standard, contingency, crisis) to support quality infection prevention and control (IPC) at the transition to the endemic COVID-19 phase. Leadership reported continued challenges in addressing resident and staff vaccinations, securing testing supplies, obtaining financial resources to maintain acceptable levels of personal protective equipment, continued staffing shortages, and issues in implementing isolation practices in current facilities. CONCLUSION AND IMPLICATIONS: NH leaders continue to struggle delivering quality IPC care post-pandemic and require focused support in several areas. Clinical practice guidelines should include IPC practices to prevent the infection and spread of any COVID-19 variant in this endemic phase. Policies should support continued reporting of IPC-related metrics and adequate funding to account for the long-term financial burden NHs face.

Cost-Savings of Do Not Resuscitate Orders Among Elderly Patients With Heart Failure in the United States.

Do-not-resuscitate (DNR) orders should preclude the use of cardiopulmonary resuscitation and may be associated with patient outcomes for patients hospitalized with heart failure (HF). This study examined the association between DNR and costs, mortality, and length of stay. The study cohort was a national sample of 700 922 hospital admissions of patients aged >65 with a primary diagnosis of HF. Elderly HF patients who died with a DNR had cost-savings of $5640 ( P < 0.001). Patients with a DNR order were 8.9% points more likely to die before discharge than patients without ( P < 0.001), and patients who died with a DNR had a significantly shorter hospital stay by 1.51 days ( P < 0.001). DNR orders among elderly patients with HF are associated with cost-savings, as well as a higher mortality and shorter length of stay. In addition to primary benefits, advance care planning may aid in containing costs of care at end of life for HF.

The Value of Advance Care Planning for Spokespersons of Patients With Advanced Illness.

CONTEXT: Advance Care Planning (ACP) has fallen under scrutiny primarily because research has not consistently demonstrated patient-focused benefits. OBJECTIVES: To better understand how spokespersons regard, engage with, and find value in ACP during decision-making for their loved ones. METHODS: This qualitative analysis was part of a randomized controlled trial involving spokespersons of patients with advanced illness who had completed ACP. After making a medical decision on behalf of their loved one (or that loved one's death), semi-structured interviews explored spokespersons' experience of decision-making and if (and how) ACP played a role. Thematic analysis was conducted on interview transcripts. RESULTS: From 120 interviews, five themes emerged: 1) Written advance directives (ADs) helped increase spokespersons' confidence that decisions were aligned with patient wishes (serving as a physical reminder of previous discussions and increasing clarity during decision-making and family conflict); 2) Iterative discussions involving ACP facilitated "In the moment" decision-making; 3) ADs and ACP conversations helped spokespersons feel more prepared for future decisions; 4) Spokespersons sometimes felt there was "no choice" regarding their loved one's medical care; and 5) Regrets and second-guessing were the most common negative emotions experienced by spokespersons. CONCLUSION: Considering the recent debate about the utility of ACP and ADs, this analysis highlights the value of ACP for spokespersons involved in surrogate decision-making. Reframing the goals of ACP in terms of their benefit for spokespersons (and identifying appropriate outcome measures) may provide additional perspective on the utility of ACP.

Provider Perspectives of Transitions of Care at a Tertiary Care Children's Hospital With a Hospitalist-Run Discharge Clinic.

Children's hospitals are discharging patients to home with increasingly complex outpatient needs, making safe transitions of care (ToCs) of vital importance. Our study involved a survey of both outpatient providers and pediatric hospitalists associated with our medical center to better describe providers' views on the ToC process. The survey included questions assessing views on patient care responsibilities, resource availability, our hospitalist-run postdischarge clinic (PDC), and comfort with telemedicine. Our hospitalists generally believed that primary care providers (PCPs) did not have adequate access to important ToC elements, whereas PCPs felt their access was adequate. Both provider types felt it was the inpatient team's responsibility to manage patient events between discharge and PCP follow-up and that a hospitalist-run PDC may reduce interim emergency room visits. This study challenges perceptions about the ToC process in children and describes a generalizable approach to assessing provider perceptions surrounding the ToC within individual health systems.

Intrinsic Traits Such as Personality and Decision-Making Style are Predictive of Stress in Surrogate Decision-Makers.

Introduction: Despite its prominence in psychology, little is known about how personality traits play a role in the stress experiences of surrogate decision-makers. We tested the hypothesis that intrinsic traits (personality and decision-making styles) would be related to surrogates' stress in order to learn whether screening or tailoring interventions based on personality traits could help support surrogate decision-makers. Methods: This pre-specified secondary analysis evaluated data from an interventional study with dyads of patients with advanced chronic illness and their spokespersons. Measures included stress after decision-making or patient death (Impact of Events-Revised), personality (Big Five Index; BFI) and decision-making style (maximization and regret scales). Multivariate linear regressions explored the impact of personality on the stress experience; linear regressions independently modeled the impact of maximization and regret on the stress experience. Results: Of 38 spokespersons, 89.5% were women, 97.4% non-Hispanic, and 29.0% had a college degree or higher. In univariate analyses, total stress was correlated with neuroticism (r = .56, P < .01), higher scores on the regret (r = .55, P < .01) and maximization (r = .48, P < .05). In adjusted models, BFI was significantly associated with total stress (R2 = 27.08, P = .02). However, only neuroticism was independently associated with total stress. Conclusions: Personality traits, particularly neuroticism, and decision-making styles predicted heightened stress in spokespersons of patients with advanced chronic illness. If ACP interventions are intended to reduce spokesperson stress, personality and decision-making style scales may help identify spokespersons most likely to benefit from ACP interventions.

Current Perception of Diversity in Academic Radiology: A Mixed Methods Study of Radiology Program Directors.

OBJECTIVES: To assess the perceived state of diversity in Radiology Residency Programs in the United States and to evaluate the level of acceptance for diversity, equity, and inclusion (DEI) initiatives. METHODS: An electronic survey was conducted of the Radiology Residency Programs in the United States in December 2021 and January 2022. Respondents were recruited by email sent to the members of the Association of University Radiologists who were Radiology Residency Program Directors. Quantitative and Qualitative analyses were performed. RESULTS: Of the 198 emails sent out to the Radiology Program Directors, 53 completed surveys were returned (response rate of 27%). Although some progress has been made in increasing the number of women and Asians in Academic Radiology, there is persisting imbalance of the numbers of African American and Latinx radiologists which comprise far less than 25% of the physician workforce. Nearly half of the respondents reported having a Vice Chair of DEI. Three themes emerged from the qualitative analysis. Most respondents agreed that diversity should be considered when recruiting faculty and residents. Many noted a strong commitment to DEI but they felt there was room for improvement in formalizing efforts to aid in recruitment of underrepresented minorities. Diversity education was more likely mandatory for residents and optional for faculty. CONCLUSION: Academic Radiology programs are recognizing the value of internal DEI leadership roles. Radiologists are implementing DEI initiatives and making intentional changes in the recruitment of diverse radiologists. More concerted efforts are needed to increase the low numbers of African American and Latinx radiologists. Effective evaluation metrics for various DEI programs are needed to assess how successful these endeavors are in creating lasting changes.

A mixed methods study exploring requests for unproven COVID therapies such as ivermectin and healthcare distrust in the rural South.

The COVID-19 pandemic has led to contentious discourse regarding unproven COVID-19 therapies (UCTs),(e.g. ivermectin). Despite recommendations against it, ivermectin remains, in some areas, highly demanded. The goal of this study is to understand patient and provider perspectives about UCTs (e.g., ivermectin) and how responses to requests for UCTs impact healthcare distrust. This mixed methods observational study was conducted in a rural healthcare system in the Southern United States. Adults (n = 26) with a history of COVID-19 or clinicians (n = 8) from the same system were interviewed using questionnaires assessing healthcare distrust and qualitatively interviewed exploring perceptions about UCTs. Patient themes were: 1) Importance of anecdotal stories for decision-making; 2) Use of haphazard approaches to 'research'; 3) Strong distrust of government and healthcare organizations; 4) Inherent trust in local healthcare; 5) Decision-making as weighing pros/cons; and 6) Feeling a right to try medications. High survey medians indicated high distrust with differences of 8.5 points for those who requested/used ivermectin versus those who did not (p = 0.027). Clinician themes were: 1) Frustration when patients trust social media over clinicians; 2) Acceptance of community beliefs about UCTs; 3) Distrust originating outside of the healthcare system; 4) Feeling torn about prescribing UCTs to build trust; and 5) Variable educational strategies. When clinicians are perceived as aligned with government, this may void patients' trust of clinicians. Clinicians should leverage trust in local healthcare and distance themselves from distrusted information sources. Ethical questions arise regarding appropriateness of acquiescing to patient requests for ivermectin for building trust.

AYA-UNITE: Lessons Learned on Intervention Development Promoting Social and Physical Health of Adolescent/Young Adult Cancer Survivors.

Adolescent/young adult cancer survivors (AYACS) struggle with poor psychosocial health related to social disruptions due to cancer diagnosis, impacting long-term goal achievement and overall health. In particular, social health promotion is overlooked in AYACS' care. AYA-UNITE, a sociobehavioral exercise intervention pilot for AYACS 15-21 years of age at cancer diagnosis, was designed to foster AYACS' social and physical health. AYA-UNITE was a 12-week group-based virtual exercise program incorporating strength training and aerobic activity. In this brief report, we account AYA-UNITE's conceptual design, lessons learned through AYA-UNITE intervention development, and opportunities for improvement in implementing effective AYACS psychosocial interventions (NCT03778658).

Dopamine D1 Agonists: First Potential Treatment for Late-Stage Parkinson's Disease.

Current pharmacotherapy has limited efficacy and/or intolerable side effects in late-stage Parkinson's disease (LsPD) patients whose daily life depends primarily on caregivers and palliative care. Clinical metrics inadequately gauge efficacy in LsPD patients. We explored if a D1/5 dopamine agonist would have efficacy in LsPD using a double-blind placebo-controlled crossover phase Ia/b study comparing the D1/5 agonist PF-06412562 to levodopa/carbidopa in six LsPD patients. Caregiver assessment was the primary efficacy measure because caregivers were with patients throughout the study, and standard clinical metrics inadequately gauge efficacy in LsPD. Assessments included standard quantitative scales of motor function (MDS-UPDRS-III), alertness (Glasgow Coma and Stanford Sleepiness Scales), and cognition (Severe Impairment and Frontal Assessment Batteries) at baseline (Day 1) and thrice daily during drug testing (Days 2-3). Clinicians and caregivers completed the clinical impression of change questionnaires, and caregivers participated in a qualitative exit interview. Blinded triangulation of quantitative and qualitative data was used to integrate findings. Neither traditional scales nor clinician impression of change detected consistent differences between treatments in the five participants who completed the study. Conversely, the overall caregiver data strongly favored PF-06412562 over levodopa in four of five patients. The most meaningful improvements converged on motor, alertness, and functional engagement. These data suggest for the first time that there can be useful pharmacological intervention in LsPD patients using D1/5 agonists and also that caregiver perspectives with mixed method analyses may overcome limitations using methods common in early-stage patients. The results encourage future clinical studies and understanding of the most efficacious signaling properties of a D1 agonist for this population.