Guilt By Genetic Association: The Fourth Amendment and the Search of Private Genetic Databases by Law Enforcement

Over the course of 2018, a number of suspects in unsolved crimes have been identified through the use of GEDMatch, a public online genetic database. Law enforcement’s use of GEDMatch to identify suspects in cold cases likely does not constitute a search under the Fourth Amendment because the genetic information hosted on the website is publicly available. Transparency reports from direct-to-consumer (DTC) genetic testing providers like 23andMe and Ancestry suggest that federal and state officials may now be requesting access to private genetic databases as well. Whether law enforcement’s use of private DTC genetic databases to search for familial relatives of a suspect’s genetic profile constitutes a search within the meaning of the Fourth Amendment is far less clear. A strict application of the third-party doctrine suggests that individuals have no expectation of privacy in genetic information that they voluntarily disclose to third parties, including DTC providers. This Note, however, contends that the U.S. Supreme Court’s recent decision in Carpenter v. United States overwhelmingly supports the proposition that genetic information disclosed to third-party DTC providers is subject to Fourth Amendment protection. Approximately fifteen million individuals in the United States have already submitted their genetic information to DTC providers. The genetic information held by these providers can reveal a host of highly intimate details about consumers’ medical conditions, behavioral traits, genetic health risks, ethnic background, and familial relationships. Allowing law enforcement warrantless access to investigate third-party DTC genetic databases circumvents their consumers’ reasonable expectations of privacy by exposing this sensitive genetic information to law enforcement without any meaningful oversight. Furthermore, individuals likely reasonably expect that they retain ownership over their uniquely personal genetic information despite their disclosure of that information to a thirdparty provider. This Note therefore asserts that the third-party doctrine does not permit law enforcement to conduct warrantless searches for suspects on private DTC genetics databases under the Fourth Amendment

Expressing the human proteome for affinity proteomics: optimising expression of soluble protein domains and in vivo biotinylation

The generation of affinity reagents to large numbers of human proteins depends on the ability to express the target proteins as high-quality antigens. The Structural Genomics Consortium (SGC) focuses on the production and structure determination of human proteins. In a 7-year period, the SGC has deposited crystal structures of >800 human protein domains, and has additionally expressed and purified a similar number of protein domains that have not yet been crystallised. The targets include a diversity of protein domains, with an attempt to provide high coverage of protein families. The family approach provides an excellent basis for characterising the selectivity of affinity reagents. We present a summary of the approaches used to generate purified human proteins or protein domains, a test case demonstrating the ability to rapidly generate new proteins, and an optimisation study on the modification of >70 proteins by biotinylation in vivo. These results provide a unique synergy between large-scale structural projects and the recent efforts to produce a wide coverage of affinity reagents to the human proteome

Family carer experiences of hospice care at home: qualitative findings from a mixed methods realist evaluation

This document is the Accepted Manuscript version of a published work that appeared in final form in [Palliative Medicine]. To access the final edited and published work see https://doi.org/10.1177/02692163231206027Background: Hospice-at-home aims to enable patients approaching end-of-life to die at home and support their carers. A wide range of different service models exists but synthesised evidence on how best to support family carers to provide sustainable end-of -life care at home is limited. Aim: To explore what works best to promote family carers’ experiences of hospice-at-home. Design: Realist evaluation with mixed methods. This paper focuses on qualitative interviews with carers (to gain their perspective and as proxy for patients) and service providers from twelve case study sites in England. Interviews were coded and programme theories were refined by the research team including two public members. Setting/participants: Interviews with carers (involved daily) of patients admitted to hospice-at-home services (n=58) and hospice-at-home staff (n=78). Results: Post bereavement, 76.4% of carers thought that they had received as much help and support as they needed and most carers (75.8%) rated the help and support as excellent or outstanding. Of six final programme theories capturing key factors relevant to providing optimum services, those directly relevant to carer experiences were: integration and co-ordination of services; knowledge, skills and ethos of hospice staff; volunteer roles; support directed at the patient–carer dyad. Conclusions: Carers in hospice-at-home services identified care to be of a higher quality than generic community services. Hospice staff were perceived as having ‘time to care’, communicated well and were comfortable with dying and death. Hands-on care was particularly valued in the period close to death

Optimum Hospice at Home Services for End-of-Life care: realist evaluation and co-production

Overview: Hospice at home (H@H) services aim to enable people to have a “good death” at home. While this accords with UK policy, statutory services are ill-equipped to meet this demand and there is limited evidence from the perspective of service users, as participants or co-producers, of what aspects are most helpful. Our evaluation asked what features of H@H models work, for whom, how and under what circumstances? We combined a realist evaluation with co-production embedded throughout: phase 1 - a national survey to map service provision and models of H@H care; phase 2 - qualitative and economic data collection with commissioners, service providers and patient-carer dyads; phase 3 - national consensus workshops with stakeholders. The funding application was developed in partnership with ten public members. Two of these became co-applicants, both former carers with experience of hospice services. Utilising a co-production approach, the lay co-applicants contributed to all stages of the research process and were an integral part of the project team. This paper focuses on their role in qualitative data analysis (phase 2); developing and refining programme theories and testing context-mechanism-outcome (CMO) configurations. Key points: The co-applicants initially participated in clearly delineated tasks such as commenting on patient/carer resources. At the end of phase 1, they requested greater involvement, which translated into participating in data analysis. Additional training in realist philosophy and data analysis was provided. The co-applicants attended team coding meetings. Preparation included listening to and reading carer interviews, and coded according to provisional CMOs. Co-applicants fed back at coding meetings as part of the iterative process of refining CMOs. They provided a fresh perspective on the data, reflecting on the underlying narrative that proved invaluable in helping researchers to step back from the minutiae of coding and consider the carer’s perspective. Implications: Public members as an integral part of a realist research team add a different lens to interrogating CMO configurations, enhancing rigour in developing programme theories. While the process evolved overtime, we would recommend early discussions around what activities co-applicants would like to participate in, training requirements, time commitment and emotional demands

Optimum models of hospice at home services for end-of-life care in England: a realist-informed mixed-methods evaluation.

Abstract Background Many people prefer to die at home when the time comes. Hospice at home services aim to support patients to achieve this. A range of hospice at home services exist; some services have been evaluated, but there has been limited evidence synthesis. Objectives The main objective was to find out what models of hospice at home services work best, for whom and in what circumstances. Other objectives supported this aim, including an analysis of the health economic costs of hospice at home models. Design The study was an overarching, non-interventional, realist evaluation comprising three phases. Phase 1 was a survey of hospice at home services. Phase 2 involved 12 case studies, grouped into four models on the basis of size and 24 hours per day, 7 days per week (24/7), operations, from which quantitative and health economics data were gathered. Qualitative interview data from bereaved carers, commissioners and providers were analysed to generate context–mechanism–outcome configurations. Phase 3 comprised stakeholder consensus meetings. Setting Hospice at home services across England. Participants A total of 70 hospice at home managers responded to the survey. A total of 339 patient and family/informal carer dyads were recruited; 85 hospice at home providers and commissioners were interviewed. A total of 88 stakeholders participated in consensus meetings. Main outcome measures The quality of dying and death of patients was assessed by bereaved carers (using the Quality of Dying and Death questionnaire). A patient’s use of services was collected using the Ambulatory and Home Care Record. Results Hospice at home services varied; two-thirds were mainly charitably funded, and not all operated 24/7. Most patients (77%) had cancer. Hospice at home services overall provided care that was likely to deliver ‘a good death’, and 73% of patients died in their preferred place. Six context–mechanism–outcome configurations captured factors relevant to providing optimum hospice at home services: (1) sustainability (of the hospice at home service); (2) volunteers (use of, in the hospice at home service); (3) integration and co-ordination (with the wider health and social care system); (4) marketing and referral (of the hospice at home service); (5) knowledge, skills and ethos (of hospice at home staff); and (6) support directed at the carer at home. Key markers of a good service included staff who had time to care, providing hands-on care; staff whose knowledge and behaviour promoted supportive relationships and confidence through the process of dying; and services attending to the needs of the informal carer. Areas of potential improvement for most hospice at home services were the use of volunteers in hospice at home, and bereavement care. Limitations The study had the following limitations – heterogeneity of hospice at home services, variations in numbers and patient clinical statuses at recruitment, a low Quality of Dying and Death questionnaire response rate, and missing data. Only patients with an informal carer involved on a daily basis were eligible for the study. Conclusions Hospice at home services delivered high-quality care and a ‘good death’, with the majority of patients dying in their stated preferred place. Hospice at home providers can improve their impact by focusing on the features identified that deliver the best patient outcomes. Commissioners can facilitate patient preference and reduce the number of hospital deaths by working with hospice at home services to secure their financial sustainability and increase the numbers and range of patients admitted to hospice at home services. Future research Future research should explore the use of volunteers in the hospice at home setting and evaluate approaches to bereavement support. Funding This project was funded by the National Institute for Health and Care Research (NIHR) Health and Social Care Delivery Research programme and will be published in full in Health and Social Care Delivery Research; Vol. 10, No. 24. See the NIHR Journals Library website for further project informatio

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Guilt By Genetic Association: The Fourth Amendment and the Search of Private Genetic Databases by Law Enforcement

Over the course of 2018, a number of suspects in unsolved crimes have been identified through the use of GEDMatch, a public online genetic database. Law enforcement’s use of GEDMatch to identify suspects in cold cases likely does not constitute a search under the Fourth Amendment because the genetic information hosted on the website is publicly available. Transparency reports from direct-to-consumer (DTC) genetic testing providers like 23andMe and Ancestry suggest that federal and state officials may now be requesting access to private genetic databases as well. Whether law enforcement’s use of private DTC genetic databases to search for familial relatives of a suspect’s genetic profile constitutes a search within the meaning of the Fourth Amendment is far less clear. A strict application of the third-party doctrine suggests that individuals have no expectation of privacy in genetic information that they voluntarily disclose to third parties, including DTC providers. This Note, however, contends that the U.S. Supreme Court’s recent decision in Carpenter v. United States overwhelmingly supports the proposition that genetic information disclosed to third-party DTC providers is subject to Fourth Amendment protection. Approximately fifteen million individuals in the United States have already submitted their genetic information to DTC providers. The genetic information held by these providers can reveal a host of highly intimate details about consumers’ medical conditions, behavioral traits, genetic health risks, ethnic background, and familial relationships. Allowing law enforcement warrantless access to investigate third-party DTC genetic databases circumvents their consumers’ reasonable expectations of privacy by exposing this sensitive genetic information to law enforcement without any meaningful oversight. Furthermore, individuals likely reasonably expect that they retain ownership over their uniquely personal genetic information despite their disclosure of that information to a thirdparty provider. This Note therefore asserts that the third-party doctrine does not permit law enforcement to conduct warrantless searches for suspects on private DTC genetics databases under the Fourth Amendment