Summary 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.

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Pediatric hospice patients differ from adult patients in their broader range of underlying diagnoses and their use of hospice services.

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.

In 2011, the internal medicine (IM) training program at the Hospital of the University of Pennsylvania (HUP) implemented night float rotations on most of its inpatient teaching services. There were no formal educational offerings for night float rotations because all teaching conferences were held during daytime hours. Residents identified this lack of formal education on night float as an area for improvement. A group of IM residents developed a resident-led night float curriculum. The curriculum had 2 objectives: (1) to provide regular overnight conferences for interns, and (2) to provide junior and senior residents with formal opportunities to teach interns. InterventionHUP is a 776-bed, university-affiliated, urban tertiary care center. At implementation, night float residents covered general medicine, oncology, and subspecialty services in teams of 1 intern and 1 resident, or 2 interns and 1 resident, with some services covered by a single resident. Residents rotating in intensive care units did not participate in the curriculum.The new curriculum consisted of a morning intake report and an overnight conference. The morning intake report was designed to provide residents with formative, real-time feedback on clinical management. It was attended by all night float residents who were not staying on the floor to present patients on rounds, a volunteer faculty member, and, 1 day a week, a resident on a short-call admitting day rotation. Morning report occurred 3 mornings a week, after the night teams had signed out to their daytime counterparts. The report consisted of a brief presentation of a challenging admission or decompensating patient from the previous night's shift. Residents rotated responsibility for presenting cases. The goal of the conference was to discuss patient management with the volunteer faculty member.The overnight conference was a 21-topic lecture series focusing on common clinical scenarios (B O X); topics were selected to improve postgraduate year (PGY)-1 residents' ability to recognize and manage clinical emergencies at night. The participants were PGY-1s (learners) and PGY2s/PGY-3s (teachers). Teachers led a 30-minute lesson held between 11 PM and 2 AM. Flexibility was built into the design to accommodate variations in clinical responsibilities. The conference was scheduled 4 nights per week (rotation switch days and weekends were excluded). To maximize resident buy-in and minimize teacher preparation, prepared teaching scripts were created for each topic by a group of volunteer PGY-2s/PGY-3s. We asked that scripts include 3 to 4 clear learning objectives and 1 or 2 literature references. Most scripts were case based, with questions designed to actively involve learners in discussion. To encourage PGY-1 attendance and minimize distractions, nonteaching PGY-2s/PGY-3s were asked to hold their interns' cell phones during conference. Outcomes to Date