Cost Utility of Voretigene Neparvovec for Biallelic RPE65-Mediated Inherited Retinal Disease

Objective

The gene therapy voretigene neparvovec (VN) is the first Food and Drug Administration–approved treatment for vision loss owing to the ultra-rare RPE65-mediated inherited retinal disorders. We modeled the cost-utility of VN compared with standard of care (SoC).

A Last Gift

Here at the Center, we had the privilege of seeing how Dan Callahan lived out his last days and weeks. True to his nature, Dan never stopped thinking or writing. Indeed, his wife Sidney told me that he finished his last essay one day before his death, on July 16th, insisting that she help him get to the computer so he could discuss it with a colleague. “It's my last one,” he told her with his characteristic self‐awareness. Dan also chose the last topic he would focus on: climate change. At a December 2018 board meeting, Dan presented his desire to develop a workshop to explore the ways in which bioethics in general, and The Hastings Center in particular, might be able to make a valuable contribution to addressing the problem of global warming.     

Tanzania IR Initiative: Training the First Generation of Interventional Radiologists

Despite a population of nearly 60 million, there is currently not a single interventional radiologist in Tanzania. Based on an Interventional Radiology (IR) Readiness Assessment, the key obstacles to establishing IR in Tanzania are the lack of training opportunities and limited availability of disposable equipment. An IR training program was designed and initiated, which relies on US-based volunteer teams of IR physicians, nurses, and technologists to locally train radiology residents, nurses, and technologists. Preliminary results support this strategy for addressing the lack of training opportunities and provide a model for introducing IR to other resource-limited settings.     

A Systematic Review and Meta-Analysis of the Prevalence of Post-Traumatic Stress Disorder among Homeless People

Post-traumatic stress disorder (PTSD) is common among homeless people and is associated with an increased risk of mortality from suicide, medical causes, and drug-related problems. However, there are no previous systematic review and meta-analysis studies that reported the consolidated magnitude of PTSD among homeless people. A literature search was conducted on PubMed, Embase, and Scopus to discover pertinent studies that determined the prevalence of PTSD among the homeless. Articles were evaluated by titles, abstracts, and full-text. Comprehensive meta-analysis software was used to conduct the meta-analysis. Subgroup and sensitivity analysis were performed and Cochran’s Q- and the I² test were used to assess heterogeneity. The evidence of publication bias was evaluated by using Egger’s test and visual inspection of the symmetry in funnel plots. From the total, 19 studies with 20,364 participants across seven countries were included in the final analysis. Our meta-analysis revealed that the pooled prevalence of PTSD among homeless people was 27.38% (95% CI; 21.95–33.57). In our subgroup analysis, we found that the prevalence of PTSD was considerably high as measured by the screening instrument (35.93%) than the diagnostic instrument (23.57% %). The prevalence of PTSD among homeless showed a significant variation by the location of the studies, the instruments used to measure PTSD as well as the quality of the included studies. This review showed that the pooled prevalence estimate of PTSD among homeless peoples was remarkably high (27.38%). Early screening and treatment of PTSD among homeless peoples are warranted to alleviate suffering.

     

The Pedagogical Challenges of Teaching High School Bioethics: Insights from the Exploring Bioethics Curriculum

A belief that high school students have the cognitive ability to analyze and assess moral choices and should be encouraged to do so but have rarely been helped to do so was the motivation for developing Exploring Bioethics, a six‐module curriculum and teacher guide for grades nine through twelve on ethical issues in the life sciences. A multidisciplinary team of bioethicists, science educators, curriculum designers, scientists, and high school biology teachers worked together on the curriculum under a contract between the National Institutes of Health and Education Development Center, a nonprofit research and development organization with a long history of innovation in science education. At the NIH, the Department of Bioethics within the Clinical Center and the Office of Science Education within the Office of the Director guided the project.Our overarching goal for Exploring Bioethics was to introduce students to bioethics as a field of inquiry and to enable them to develop ethical reasoning skills so they could move beyond “gut reactions” to more nuanced positions.     

Lower functioning patients demonstrate atypical hip joint loading before and following total hip arthroplasty for osteoarthritis

Previous studies have established that up to 1 year post total hip arthroplasty (THA), patients do not recover normal function and the magnitude of hip joint loading remains reduced compared to healthy individuals. However, the temporal nature of the loading profile has not been considered to identify individuals who are at a greater risk of poor functional outcomes following THA. This study aimed to determine changes to the profile and magnitude of the resultant hip joint reaction force before and up to 6 months post-primary THA, and factors associated with atypical loading profiles. Hip joint loading was computed using a personalized lower-limb musculoskeletal model in 43 participants awaiting primary THA for osteoarthritis (mean age: SD = 65, 14 years; body mass index: SD = 30, 5 kg/m²) before and up to 6 months after THA. Atypical, single-peak loading profiles were observed for 11 patients before surgery, where four showed a single peak at 6 months. Patients displaying a single-peak profile walked slower (mean difference: −0.4 m/s) compared to individuals displaying double-peak profile (P = <.001) and had significantly reduced sagittal plane hip range of motion during gait (mean difference −9.6°, P = <.001). Self-reported pain, function, and stiffness did not differentiate between patients with a single or double-peak loading profile. Individuals with a single-peak force profile did not meet the minimal clinically important hip range of motion during gait and would be classified as low-functioning THA patients. Clinical Relevance: The temporal nature of the force profile may help to identify individuals who are at the greatest risk of poor functional outcomes after THA.     

Transarterial Embolization of Liver Cancer in a Transgenic Pig Model

PurposeTo develop and characterize a porcine model of liver cancer that could be used to test new locoregional therapies.Materials and MethodsLiver tumors were induced in 18 Oncopigs (transgenic pigs with Cre-inducible TP53^R167H and KRAS^G12D mutations) by using an adenoviral vector encoding the Cre-recombinase gene. The resulting 60 tumors were characterized on multiphase contrast-enhanced CT, angiography, perfusion, micro-CT, and necropsy. Transarterial embolization was performed using 40–120 μm (4 pigs) or 100–300 μm (4 pigs) Embosphere microspheres. Response to embolization was evaluated on imaging. Complications were determined based on daily clinical evaluation, laboratory results, imaging, and necropsy.ResultsLiver tumors developed at 60/70 (86%) inoculated sites. Mean tumor size was 2.1 cm (range, 0.3–4 cm) at 1 week. Microscopically, all animals developed poorly differentiated to undifferentiated carcinomas accompanied by a major inflammatory component, which resembled undifferentiated carcinomas of the human pancreatobiliary tract. Cytokeratin and vimentin expression confirmed epithelioid and mesenchymal differentiation, respectively. Lymph node, lung, and peritoneal metastases were seen in some cases. On multiphase CT, all tumors had a hypovascular center, and 17/60 (28%) had a hypervascular rim. After transarterial embolization, noncontrast CT showed retained contrast medium in the tumors. Follow-up contrast-enhanced scan showed reduced size of tumors after embolization using either 40–120 μm or 100–300 μm Embosphere microspheres, while untreated tumors showed continued growth.ConclusionsLiver tumors can be induced in a transgenic pig and can be successfully treated using bland embolization.