Ethical considerations for HIV cure-related research at the end of life

Abstract Background The U.S. National Institute of Allergies and Infectious Diseases (NIAID) and the National Institute of Mental Health (NIMH) have a new research priority: inclusion of terminally ill persons living with HIV (PLWHIV) in HIV cure-related research. For example, the Last Gift is a clinical research study at the University of California San Diego (UCSD) for PLWHIV who have a terminal illness, with a prognosis of less than 6 months. Discussion As end-of-life (EOL) HIV cure research is relatively new, the scientific community has a timely opportunity to examine the related ethical challenges. Following an extensive review of the EOL and HIV cure research ethics literature, combined with deliberation from various stakeholders (biomedical researchers, PLWHIV, bioethicists, and socio-behavioral scientists) and our experience with the Last Gift study to date, we outline considerations to ensure that such research with terminally ill PLWHIV remains ethical, focusing on five topics: 1) protecting autonomy through informed consent, 2) avoiding exploitation and fostering altruism, 3) maintaining a favorable benefits/risks balance, 4) safeguarding against vulnerability through patient-participant centeredness, and 5) ensuring the acceptance of next-of-kin/loved ones and community stakeholders. Conclusion EOL HIV cure-related research can be performed ethically and effectively by anticipating key issues that may arise. While not unique to the fields of EOL or HIV cure-related research, the considerations highlighted can help us support a new research approach. We must honor the lives of PLWHIV whose involvement in research can provide the knowledge needed to achieve the dream of making HIV infection curable

Phototherapy trends in dermatology 2015–2018

Background Trends in phototherapy utilization including its main clinical indications were last characterized by Luersen et al. for the time period of 1997–2010. In this study, we update data on the use of phototherapy in the United States from 2015 to 2018. Methods We queried the National Ambulatory Medical Care Survey (NAMCS) data on the number of phototherapy visits as well as demographics and associated dermatoses. Results There were approximately 1.31 million outpatient phototherapy visits during the study period with a decreasing trend over time. Leading indications for phototherapy were dermatitis not otherwise specified (NOS), (25.7%) followed by atopic dermatitis (AD) (11.7%), and pruritus (9.7%). Conclusion There is a downtrend in the use of phototherapy from 2015 to 2018. Psoriasis is no longer the main indication for phototherapy, which may be due to the advent of highly effective novel biologics

Anti-drug antibodies of IL-17 inhibitors for psoriasis: a systematic review

Biologics may elicit the production of anti-drug antibodies (ADAs), the clinical significance of which is not fully understood. ADA development in psoriasis patients on IL-17 inhibitors was evaluated by incidence, impact on efficacy, and relationship with adverse events. We systematically searched PubMed, Cochrane, and Embase databases, identifying 456 references. Seventeen studies met inclusion criteria. ADA incidence was: 0% to 5.5% (secukinumab), 11% to 19.4% (ixekizumab), 0% to 3.3% (brodalumab), and 19% to 39% (bimekizumab). Neutralizing antibody incidence was: 0% to 1.5% (secukinumab), 0% to 3.5% (ixekizumab), and 0% (brodalumab). ADA presence alone with secukinumab, ixekizumab, and bimekizumab did not impact drug efficacy. Brodalumab was the only one of the IL-17 inhibitors, which showed a reduction in efficacy in ADA + patients. In one analysis, high ADA titers to ixekizumab were associated with diminished treatment response. ADAs to secukinumab and bimekizumab were not associated with adverse events. There were limited data on ADAs and safety with ixekizumab or brodalumab. Overall, when monitoring patients on secukinumab, ADAs, titers, and the presence of neutralizing antibodies were not prognostic of outcomes. However, monitoring for ADAs with brodalumab and measuring titers with ixekizumab may be of value clinically

"[It] is now my responsibility to fulfill that wish:" Clinical and rapid autopsy staff members' experiences and perceptions of HIV reservoir research at the end of life.

IntroductionLittle is known about the effects of HIV reservoir research at the end of life on staff members involved. Staff members' perceptions and experiences were assessed related to their involvement in the Last Gift, a rapid autopsy study at the University of California San Diego enrolling people living with HIV who are terminally ill and have a desire to contribute to HIV cure-related research.MethodsTwo focus group discussions consisting of clinical (n = 7) and rapid research autopsy (n = 8) staff members were conducted to understand the perspectives of staff members and the impact the Last Gift rapid autopsy study had on them. The total sample consisted of 66.7% females and 33.3% males and was ethnically diverse (66.7% Caucasian, 6.7% African American, 20.0% Asian descent, 6.7% Hispanic descent and American Indian) with a range of experience in the HIV field from 1 year to 30 years.ResultsQualitative focus group data revealed five major themes underlying study staff members' multilayered mental and practical involvement: 1) positive perceptions of the Last Gift study, with sub-themes including Last Gift study participants' altruism, fulfillment, and control at the end of life, 2) perceptions of staff members' close involvement in the Last Gift study, with sub-themes related to staff members' cognitive processing, self-actualization and fulfillment, stress management and resilience, coping mechanisms, and gratitude toward Last Gift participants and toward the study itself, 3) considerations for successful and sustainable study implementation, such as ethical awareness and sustained community and patient engagement, 4) collaborative learning and organizational processes and the value of interdependence between staff members, and 5) considerations for potential study scale-up at other clinical research sites.DiscussionUnderstanding staff members' nuanced emotional and procedural experiences is crucial to the Last Gift study's sustainability and will inform similar cure research studies conducted with people living with HIV at the end of life. The study's potential reproducibility depends on a robust research infrastructure with established, interdependent clinical and rapid autopsy teams, continuous community engagement, and an ethical and well-informed engagement process with people living with HIV

"[It] is now my responsibility to fulfill that wish:" Clinical and rapid autopsy staff members' experiences and perceptions of HIV reservoir research at the end of life.

IntroductionLittle is known about the effects of HIV reservoir research at the end of life on staff members involved. Staff members' perceptions and experiences were assessed related to their involvement in the Last Gift, a rapid autopsy study at the University of California San Diego enrolling people living with HIV who are terminally ill and have a desire to contribute to HIV cure-related research.MethodsTwo focus group discussions consisting of clinical (n = 7) and rapid research autopsy (n = 8) staff members were conducted to understand the perspectives of staff members and the impact the Last Gift rapid autopsy study had on them. The total sample consisted of 66.7% females and 33.3% males and was ethnically diverse (66.7% Caucasian, 6.7% African American, 20.0% Asian descent, 6.7% Hispanic descent and American Indian) with a range of experience in the HIV field from 1 year to 30 years.ResultsQualitative focus group data revealed five major themes underlying study staff members' multilayered mental and practical involvement: 1) positive perceptions of the Last Gift study, with sub-themes including Last Gift study participants' altruism, fulfillment, and control at the end of life, 2) perceptions of staff members' close involvement in the Last Gift study, with sub-themes related to staff members' cognitive processing, self-actualization and fulfillment, stress management and resilience, coping mechanisms, and gratitude toward Last Gift participants and toward the study itself, 3) considerations for successful and sustainable study implementation, such as ethical awareness and sustained community and patient engagement, 4) collaborative learning and organizational processes and the value of interdependence between staff members, and 5) considerations for potential study scale-up at other clinical research sites.DiscussionUnderstanding staff members' nuanced emotional and procedural experiences is crucial to the Last Gift study's sustainability and will inform similar cure research studies conducted with people living with HIV at the end of life. The study's potential reproducibility depends on a robust research infrastructure with established, interdependent clinical and rapid autopsy teams, continuous community engagement, and an ethical and well-informed engagement process with people living with HIV

Attitudes and perceptions of next-of-kin/loved ones toward end-of-life HIV cure-related research: A qualitative focus group study in Southern California.

As end-of-life (EOL) HIV cure-related research expands, understanding perspectives of participants' next-of-kin (NOK) is critical to maintaining ethical study conduct. We conducted two small focus groups and two one-on-one interviews using focus group guides with the NOK of Last Gift study participants at the University of California, San Diego (UCSD). Participating NOK included six individuals (n = 5 male and n = 1 female), including a grandmother, grandfather, partner, spouse, and two close friends. Researchers double-coded the transcripts manually for overarching themes and sub-themes using an inductive approach. We identified six key themes: 1) NOK had an accurate, positive understanding of the Last Gift clinical study; 2) NOK felt the study was conducted ethically; 3) Perceived benefits for NOK included support navigating the dying/grieving process and personal growth; 4) Perceived drawbacks included increased sadness, emotional stress, conflicted wishes between NOK and study participants, and concerns around potential invasiveness of study procedures at the EOL; 5) NOK expressed pride in loved ones' altruism; and 6) NOK provided suggestions to improve the Last Gift study, including better communication between staff and themselves. These findings provide a framework for ethical implementation of future EOL HIV cure-related research involving NOK

Differential sensitivity of structural, diffusion, and resting‐state functional MRI for detecting brain alterations and verbal memory impairment in temporal lobe epilepsy

ObjectivesTemporal lobe epilepsy (TLE) is known to affect large-scale gray and white matter networks, and these network changes likely contribute to the verbal memory impairments observed in many patients. In this study, we investigate multimodal imaging patterns of brain alterations in TLE and evaluate the sensitivity of different imaging measures to verbal memory impairment.MethodsDiffusion tensor imaging (DTI), volumetric magnetic resonance imaging (vMRI), and resting-state functional MRI (rs-fMRI) were evaluated in 46 patients with TLE and 33 healthy controls to measure patterns of microstructural, structural, and functional alterations, respectively. These measurements were obtained within the white matter directly beneath neocortex (ie, superficial white matter [SWM]) for DTI and across neocortex for vMRI and rs-fMRI. The degree to which imaging alterations within left medial temporal lobe/posterior cingulate (LMT/PC) and left lateral temporal regions were associated with verbal memory performance was evaluated.ResultsPatients with left TLE and right TLE both demonstrated pronounced microstructural alterations (ie, decreased fractional anisotropy [FA] and increased mean diffusivity [MD]) spanning the entire frontal and temporolimbic SWM, which were highly lateralized to the ipsilateral hemisphere. Conversely, reductions in cortical thickness in vMRI and alterations in the magnitude of the rs-fMRI response were less pronounced and less lateralized than the microstructural changes. Both stepwise regression and mediation analyses further revealed that FA and MD within SWM in LMT/PC regions were the most robust predictors of verbal memory, and that these associations were independent of left hippocampal volume.SignificanceThese findings suggest that microstructural loss within the SWM is pronounced in patients with TLE, and injury to the SWM within the LMT/PC region plays a critical role in verbal memory impairment