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Importance Despite the benefits of goals-of-care (GOC) communication, many hospitalized individuals never communicate their goals or preferences to clinicians. Objective To assess whether a GOC video intervention delivered by palliative care educators (PCEs) increased the rate of GOC documentation. Design, Setting, and Participants This pragmatic, stepped-wedge cluster randomized clinical trial included patients aged 65 years or older admitted to 1 of 14 units at 2 urban hospitals in New York and Boston from July 1, 2021, to October 31, 2022. Intervention The intervention involved PCEs (social workers and nurses trained in GOC communication) facilitating GOC conversations with patients and/or their decision-makers using a library of brief, certified video decision aids available in 29 languages. Patients in the control period received usual care. Main Outcome and Measures The primary outcome was GOC documentation, which included any documentation of a goals conversation, limitation of life-sustaining treatment, palliative care, hospice, or time-limited trials and was obtained by natural language processing. Results A total of 10 802 patients (mean [SD] age, 78 [8] years; 51.6% male) were admitted to 1 of 14 hospital units. Goals-of-care documentation during the intervention phase occurred among 3744 of 6023 patients (62.2%) compared with 2396 of 4779 patients (50.1%) in the usual care phase (P < .001). Proportions of documented GOC discussions for Black or African American individuals (865 of 1376 [62.9%] vs 596 of 1125 [53.0%]), Hispanic or Latino individuals (311 of 548 [56.8%] vs 218 of 451 [48.3%]), non-English speakers (586 of 1059 [55.3%] vs 405 of 863 [46.9%]), and people living with Alzheimer disease and related dementias (520 of 681 [76.4%] vs 355 of 570 [62.3%]) were greater during the intervention phase compared with the usual care phase. Conclusions and Relevance In this stepped-wedge cluster randomized clinical trial of older adults, a GOC video intervention delivered by PCEs resulted in higher rates of GOC documentation compared with usual care, including among Black or African American individuals, Hispanic or Latino individuals, non-English speakers, and people living with Alzheimer disease and related dementias. The findings suggest that this form of patient-centered care delivery may be a beneficial decision support tool. Trial Registration ClinicalTrials.gov Identifier:NCT04857060

IntroductionDespite the known benefit to patients and families, discussions about goals, values and preferences for medical care in advancing serious illness often do not occur. Many system and clinician factors, such as patient and clinician reticence and shortage of specialty palliative care teams, contribute to this lack of communication. To address this gap, we designed an intervention to promote goals-of-care conversations and palliative care referrals in the hospital setting by using trained palliative care educators and video decision aids. This paper presents the rationale, design and methods for a trial aimed at addressing barriers to goals-of-care conversations for hospitalised adults aged 65 and older and those with Alzheimer’s disease and related Dementias, regardless of age.Methods and analysisThe Video Image about Decisions to Improve Ethical Outcomes with Palliative Care Educators is a pragmatic stepped wedge, cluster randomised controlled trial, which aims to improve and extend goals-of-care conversations in the hospital setting with palliative care educators trained in serious illness communication and video decision aids. The primary outcome is the proportion of patients with goals-of-care documentation in the electronic health record. We estimate that over 9000 patients will be included.Ethics and disseminationThe Institutional Review Board (IRB) at Boston Medical Center will serve as the single IRB of record for all regulatory and ethical aspects of this trial. BMC Protocol Number: H-41482. Findings will be presented at national meetings and in publications. This trial is registered at ClinicalTrials.gov.Trial registration numberNCT04857060; ClinicalTrials.gov

Many older adults with advanced cancer never communicate goals of care or treatment preferences to their clinicians, raising the risk that care received will not match their values. Scalable models of care may help surmount this barrier. To test whether a combined patient and clinician intervention increased the rate of advance care planning (ACP) documentation in large health care systems. This stepped-wedge cluster randomized clinical trial using an open cohort design included patients aged 65 years or older with advanced cancer seen at oncology clinics in 3 health care systems located in the US South, Midwest, and Mid-Atlantic regions from April 1, 2020, to November 30, 2022. Data collection ended in 2024. The intervention involved delivering brief evidence-based patient-facing video decision aids available in 25 languages as well as goals-of-care communication training to oncology clinicians. Patients in the control period received usual care. The primary outcome was ACP documentation, which included any electronic health record documentation of a goals-of-care conversation, palliative care, hospice, or limitation of life-sustaining treatments, identified via a validated natural language processing program. Analysis was performed on an intention-to-treat basis. Twenty-nine practices, comprising 13 800 unique eligible patients with a total of 29 357 repeated measurements, were included (mean [SD] age, 74.5 [6.6] years; 52.3% men [15 344 of 29 357 measurements]). The proportion of patients with ACP documentation was greater in the intervention phase compared with the usual care phase (adjusted rate difference, 6.8% [95% CI, 2.8%-10.8%]; P < .001). ACP documentation in the intervention phase occurred among 3980 of 15 754 patients (25.3%) (goals-of-care conversation, 21.4% [3377 of 15 754]; palliative care, 9.6% [1517 of 15 754]; hospice, 5.4% [847 of 15 754]; and limitation of life-sustaining treatments, 7.2% [1128 of 15 754]). In comparison, ACP documentation in the usual care phase occurred among 2834 of 13 603 patients (20.8%) (goals-of-care conversation, 16.8% [2281 of 13 603]; palliative care, 9.5% [1287 of 13 603]; hospice, 5.3% [724 of 13 603]; and limitation of life-sustaining treatments, 8.4% [1149 of 13 603]). In this stepped-wedge cluster randomized clinical trial for older adults with advanced cancer, a bundled evidence-based decision aid and communication training intervention increased the proportion of older patients with ACP documentation. This approach offers an innovative paradigm with a clinically meaningful increase in ACP documentation, a widely used quality metric that reflects high-quality patient-centered care delivery. ClinicalTrials.gov Identifier: NCT03609177.

We have recently reported that the RD114-pseudotyped MFGS-gp91phox vector achieves unprecedented levels of correction of the NADPH-oxidase gp91phox (approved gene symbol CYBB) defect in CD34(+) cells from patients with X-linked chronic granulomatous disease in the NOD/SCID mouse model. Considering clinical use of this vector, we transplanted autologous mobilized peripheral blood CD34(+) progenitor cells, transduced with the RD114-MFGS-gp91phox vector, into two healthy rhesus macaques following nonmyeloablative conditioning. The moderately high levels of in vivo marking seen in the first months following transduction decreased and stabilized at about 8 months posttransplant. Marking for both healthy animals after 15 months was 0.3 to 1.3 vector copies per 100 cells in lymphocytes, neutrophils, and monocytes. Vector insertion analyses performed by linear amplification-mediated PCR and sequencing identified 32 and 45 separate insertion sites in the animals. Identical insertion sites were found in myeloid cells and lymphocytes, demonstrating the successful transduction of lymphomyeloid progenitors. Some inserts landed in the vicinity of genes controlling cell cycle and proliferation. Statistical analyses of insertion sites 1 year posttransplant suggest a high diversity of insertion sites despite low marking.

Wild-type murine onco-retroviruses cause cancer in part by insertional mutagenesis, but until recently, cancers had not been observed in humans or animals subjected to marking or treatment with the highly modified murine retrovirus vectors in current use. Recently, mutagenesis activation of the LMO-2 gene was observed to be associated with the development of lymphoid leukemia several years after two infants with X-SCID had their immune systems restored by gene therapy with a therapeutic onco-retrovirus vector. Insertional mutagenesis activation of other oncogenes associated with development of cancers has been reported in vector-marked mice. These observations highlight the importance of encouraging many investigators to conduct large animal marking studies which follow the insertional pattern of vectors planned for human treatments. We have recently reported that a very high titer RD114 pseudotyped MFGS-gp91phox vector achieves unprecedented levels of correction of the oxidase defect in CD34+ cells from patients with X-linked chronic granulomatous disease in the NOD/SCID mouse model. In anticipation of considering clinical use of this vector, we transduced mobilized peripheral blood CD34+ cells (PBSC CD34+) of two healthy rhesus macaques with the RD114-MFGS-gp91phox. Transduced PBSC CD34+ with an average two vector copies per cell were transplanted on culture day 4 into two non-myeloablative (2× 300 Rads) irradiated animals. The moderately high levels of in vivo marking (>6%) seen in the first months following gene marking decreased and stabilized at about 8 months post transplant. Marking for animal J976 and D406 at 15 and 19 months, respectively is 1.3% and 0.3% in B lymphocytes, 0.3% and 0.3% in neutrophils and 0.7% and 0.4% in T lymphocytes at which time the animals remained healthy. Vector insertion analysis was performed by LAM-PCR, using gel electrophoresis and GeneScan analysis to demonstrate that despite the relative low marking at 10 months and later animal D406 had more than 25 and animal J976 had more than 40 separate insertional events. 34% of integration sites are located in coding regions. No predominant clone was seen to emerge over time and no patterns of insertion site preferences were detected up to this point.