Efficacy and safety of voretigene neparvovec (AAV2-hRPE65v2) in patients with RPE65-mediated inherited retinal dystrophy: a randomised, controlled, open-label, phase 3 trial.

BACKGROUND: Phase 1 studies have shown potential benefit of gene replacement in RPE65-mediated inherited retinal dystrophy. This phase 3 study assessed the efficacy and safety of voretigene neparvovec in participants whose inherited retinal dystrophy would otherwise progress to complete blindness. METHODS: In this open-label, randomised, controlled phase 3 trial done at two sites in the USA, individuals aged 3 years or older with, in each eye, best corrected visual acuity of 20/60 or worse, or visual field less than 20 degrees in any meridian, or both, with confirmed genetic diagnosis of biallelic RPE65 mutations, sufficient viable retina, and ability to perform standardised multi-luminance mobility testing (MLMT) within the luminance range evaluated, were eligible. Participants were randomly assigned (2:1) to intervention or control using a permuted block design, stratified by age (<10 years and ≥10 years) and baseline mobility testing passing level (pass at ≥125 lux vs <125 lux). Graders assessing primary outcome were masked to treatment group. Intervention was bilateral, subretinal injection of 1·5 × 1011 vector genomes of voretigene neparvovec in 0·3 mL total volume. The primary efficacy endpoint was 1-year change in MLMT performance, measuring functional vision at specified light levels. The intention-to-treat (ITT) and modified ITT populations were included in primary and safety analyses. This trial is registered with ClinicalTrials.gov, number NCT00999609, and enrolment is complete. FINDINGS: Between Nov 15, 2012, and Nov 21, 2013, 31 individuals were enrolled and randomly assigned to intervention (n=21) or control (n=10). One participant from each group withdrew after consent, before intervention, leaving an mITT population of 20 intervention and nine control participants. At 1 year, mean bilateral MLMT change score was 1·8 (SD 1·1) light levels in the intervention group versus 0·2 (1·0) in the control group (difference of 1·6, 95% CI 0·72-2·41, p=0·0013). 13 (65%) of 20 intervention participants, but no control participants, passed MLMT at the lowest luminance level tested (1 lux), demonstrating maximum possible improvement. No product-related serious adverse events or deleterious immune responses occurred. Two intervention participants, one with a pre-existing complex seizure disorder and another who experienced oral surgery complications, had serious adverse events unrelated to study participation. Most ocular events were mild in severity. INTERPRETATION: Voretigene neparvovec gene replacement improved functional vision in RPE65-mediated inherited retinal dystrophy previously medically untreatable. FUNDING: Spark Therapeutics.

Lifelong Learning Indicators in Medical Students After a Novel Communication Skills Session.

CONTEXT: A growth mindset and mastery approach have gained attention as useful learning orientations in medical education, however few studies of interventions to foster these orientations exist. OBJECTIVES: We sought to discover whether a communication skills session on delivering serious news could foster a communication growth mindset and/or a mastery approach in medical students. METHODS: This was an interventional survey study of third-year medical students before and after a session on delivering serious news. Students were administered a communication mindset survey before and after the session; achievement goal and learning environment surveys were administered after the session. Chi-square tests were used to assess the difference in pre and post mindsets. Logistic regression was used to determine the odds of achieving a mastery approach with pre- and post-communication growth mindset as the independent variables. RESULTS: Students' communication growth mindset increased from 79% (n = 186) before the intervention to 92% (n = 142) after the intervention. Achievement goal analysis demonstrated that 64% (n = 91) of students had a mastery approach, 14% (n = 20) had a performance approach and 22% (n = 32) had an avoidant approach. Ninety-nine percent (n = 151) felt the session provided a safe learning environment. The odds of having a mastery approach correlated with both pre and post-intervention growth mindset, with post-session growth mindset having the strongest correlation. CONCLUSIONS: A novel communication skills session on delivering serious news fostered a communication growth mindset in third year medical students. Most students exhibited a mastery approach to learning; this approach was more likely when they had a growth mindset.

Evaluation of a Palliative Care Longitudinal Curriculum for Medical Students Using the Context-Input-Process-Product Model.

Palliative care (PC) longitudinal curricula are increasingly being recognized as important in Undergraduate Medical Education (UME). They are however, not yet commonplace, and where they do exist may be implemented without a systematic, prospective approach to curriculum evaluation. This paper describes an implementation of a new longitudinal curriculum at the Perelman School of Medicine (PSOM) at the University of Pennsylvania. We used the Context Input Process Product (CIPP) model, a holistic evaluation model, to assess the local environment, design the curriculum, guide the improvement process, and evaluate outcomes. Comprehensive models such as CIPP provide a more robust approach to curriculum evaluation than outcomes-only models and may be of use to other programs who are implementing new curricula or improving upon existing programs.

Lessons Learned About System-Level Improvement in Serious Illness Communication: A Qualitative Study of Serious Illness Care Program Implementation in Five Health Systems.

BACKGROUND: Serious illness communication is a key element of high-quality care, but it is difficult to implement in practice. The Serious Illness Care Program (SICP) is a multifaceted intervention that contributes to more, earlier, and better serious illness conversations and improved patient outcomes. This qualitative study examined the organizational and implementation factors that influenced improvement in real-world contexts. METHODS: The authors performed semistructured interviews of 30 health professionals at five health systems that adopted SICP as quality improvement initiatives to investigate the organizational and implementation factors that appeared to influence improvement. RESULTS: After SICP implementation across the organizations studied, approximately 4,661 clinicians have been trained in serious illness communication and 56,712 patients had had an electronic health record (EHR)-documented serious illness conversation. Facilitators included (1) visible support from leaders, who financially invested in an implementation team and champions, expressed the importance of serious illness communication as an institutional priority, and created incentives for training and documenting serious illness conversations; (2) EHR and data infrastructure to foster performance improvement and accountability, including an accessible documentation template, a reporting system, and customized data feedback for clinicians; and (3) communication skills training and sustained support for clinicians to problem-solve communication challenges, reflect on communication experiences, and adapt the intervention. Inhibitors included leadership inaction, competing priorities and incentives, variable clinician acceptance of EHR and data tools, and inadequate support for clinicians after training. CONCLUSION: Successful implementation appeared to rely on multilevel organizational strategies to prioritize, reward, and reinforce serious illness communication. The insights derived from this research may function as an organizational road map to guide implementation of SICP or related quality initiatives.

Concerning Confidence: Serious Illness Conversations During the Medicine Acting Internship.

Background: Despite increased recognition that physician-patient communication represents a key competency for medical trainees, relatively little is known about student exposures to conversations about serious illness. Objective: To characterize student experiences with multiple types of serious illness conversations during their medicine acting internship (AI). Design: This is a cross-sectional survey. Setting/Subjects: Final-year medical students who had completed a medicine AI within one year at one U.S. medical school. Measurements: Exposures to and perceptions of multiple conversation domains (discussions with upset patients/families, breaking bad news, assessing code status, and conversations about limiting or withdrawing life-sustaining treatments). Results: We collected 82 survey responses (78% response rate). Students reported multiple exposures across most domains, some of which included leading conversations without supervision or formal instruction. In most domains, at least 50% of students reported confidence in their ability to lead unsupervised conversations moving forward. Conclusions: After a four-week AI, students reported multiple exposures to a variety of serious illness conversations. Some reported having these conversations without supervision. Student confidence in their ability to lead these conversations independently was higher than has been previously reported in other small studies. Further exploration is required to better understand these trends, and targeted curricular development may be indicated.

Mid-Career Training to Advance Palliative Care.

The demand for specialist palliative medicine physicians, advanced practice providers, and other team members outstrips supply. Traditional paths to specialty practice will not meet projected need. Therefore, innovation and research are required. One innovation is the training of midcareer professionals; those who have been in practice and want to change to palliative care. Barriers to leaving practice and returning to traditional training are high; not the least of which is the opportunity cost. In this roundtable, experts discuss what they have learned from current research, and point the way to additional needed research.

Looking Back, and Ahead: A Call to Action for Increasing the Hospice and Palliative Medicine Specialty Pipeline.

Thanks to the efforts of many individuals and organizations, the field of Hospice and Palliative Medicine (HPM) has undergone unprecedented growth over the last two decades. To meet the needs of seriously ill patients and families in inpatient, outpatient community setting in the future, the field of HPM must develop innovative strategies to expand the specialist workforce pipeline. With 148 programs participating in the National Residency Matching Program and 285 matched applicants in 2019, the specialty of HPM can barely replace those who are retiring or leaving the field. We call for a renewed and coordinated effort to increase the applicant pool for HPM fellowship positions, as well as greater access to specialist HPM training through expanded traditional fellowship programs and innovative specialist training pathways. Without such an expansion, our specialty will struggle to serve those patients and families who need us most.

Integrating Advance Care Planning Into Practice.

Advanced respiratory diseases progress over time and often lead to death. As the condition worsens, patients may lose medical decision-making ability. Advance care planning (ACP) is a process in which patients receive information about their diagnosis and prognosis; discuss values, goals, and fears; articulate preferences about life-sustaining treatments and end-of-life care; and appoint a surrogate medical decision maker. This process may result in written documentation of patient preferences or the appointment of a health-care power of attorney (HCPOA). ACP discussions have multiple benefits for patients and their surrogate decision makers, including ensuring that the care provided is aligned with the patient's goals and preferences and decreasing stress, anxiety, and burden in surrogates. Time and provider comfort are often cited barriers to ACP, so it may be necessary for clinicians to gain experience in conversations and identify the patients most likely to benefit from ACP discussions. Two new Current Procedural Terminology (CPT) codes, 99497 and 99498, have been recognized by the Centers for Medicare and Medicaid Services (CMS) as of January 1, 2016 and are intended to incentivize clinicians to engage in ACP discussions with their patients earlier and with more frequency. This manuscript reviews the benefits and barriers to ACP in patients with advanced respiratory disease and provides guidance on the use of the new CPT codes for reimbursement of these conversations.

Electronic Goals of Care Alerts: An Innovative Strategy to Promote Primary Palliative Care.

CONTEXT: Given the shortage of palliative care specialists, strategies are needed to promote primary palliative care by nonpalliative care providers. Electronic reminders are frequently used in medicine to standardize practice, but their effectiveness in encouraging goals of care discussions is not well understood. OBJECTIVES: To determine whether brief education and electronic alerts increase the frequency of goals of care discussions. METHODS: All general medicine services at a large academic medical center were included. Each medicine team received brief education on rounds about goals of care communication tool. When a newly admitted patient met predefined criteria, an electronic alert that included the tool was sent to the patient's resident and attending physicians within 48 hours. RESULTS: Of 352 admissions screened over a four-week period, 18% met one or more criteria. The combination of alerts and education increased documentation of goals of care in the medical record from 20.5% (15/73) to 44.6% (25/56) of patients (risk ratio 2.17, 95% CI 1.23-3.72). There were no significant changes in code status, noncode status limitations in care, or palliative care consultation. CONCLUSION: The combination of brief education and electronic goals of care alerts significantly increased documented goals of care discussions. This intervention is simple and feasible in many settings, but larger studies are needed to determine impact on patient outcomes.

Comparison of pediatric and adult hospice patients using electronic medical record data from nine hospices in the United States, 2008-2012.

BACKGROUND: Most pediatric hospice patients receive services from agencies typically oriented to adults. Information regarding how pediatric hospice patients differ from adult hospice patients is lacking. OBJECTIVE: We aim to assess differences between pediatric and adult hospice patients regarding patient characteristics and outcomes. METHODS: We compiled a retrospective inception cohort of patients enrolled at nine hospices in the CHOICE network (Coalition of Hospices Organized to Investigate Comparative Effectiveness) between August 1, 2008 and June 30, 2012. Measurements included patient characteristics and outcomes, including discharge from hospice and site of death. RESULTS: Among 126,620 hospice patients, 986 (0.8%) were 18 years of age or younger. Pediatric patients were less likely to have an admitting diagnosis of cancer (odds ratio [OR] 0.62; 95% confidence interval [CI]: 0.54-0.72). Although children were less likely to use oxygen at enrollment (OR 0.31; 95% CI: 0.26-0.37), they were more likely to have an enteral feeding tube (OR 4.04; 95% CI: 3.49-4.67). Pediatric patients were half as likely as adults to have a do-not-resuscitate order (DNR) order upon hospice enrollment (OR 0.52; 95% CI: 0.46-0.59). The average hospice length of stay for pediatric patients was longer than that of adults (103 days versus 66 days, p<0.001). Children were more likely to leave hospice care (OR 2.59; 95% CI: 2.00-3.34), but among patients who died while enrolled in hospice, pediatric patients were more likely to die at home (OR 3.25; 95% CI: 2.27-3.88). CONCLUSIONS: Pediatric hospice patients differ from adult patients in their broader range of underlying diagnoses and their use of hospice services.