Changes in Nursing Home Populations Challenge Practice and Policy.

U.S. nursing homes (NH) have a growing prevalence of individuals with severe mental illness (SMI) and substance use disorders (SUD), and an associated increasing proportion of people under 65. We explored how Directors of Nursing (DONs) perceive challenges and strategies in caring for these populations. We conducted semi-structured telephone interviews with 32 DONs from diverse facilities around the U.S. Participants reported that people with SUD and SMI often present behavioral challenges requiring resource intensive responses, while regulations constrain optimal medication treatment. Younger individuals are considered more demanding of staff and impatient with traditional NH activities designed for older people. Some NHs report they screen out people with behavioral health disorders; they tend to be concentrated in NHs in economically disadvantaged communities. Individuals may remain in NHs because suitable settings for discharge are unavailable. These developments constitute a back door "re-institutionalization" of people with behavioral health disorders, and a growing crisis.

Readmission Reduction Strategies for Patients Discharged to Skilled Nursing Facilities: A Case Study From 2 Hospital Systems in 1 City.

BACKGROUND: Some hospitals seek integration with skilled nursing facilities (SNFs) to reduce readmissions while others focus more on patients discharged home. PURPOSE: Our objective was to understand different approaches for readmission reduction for patients discharged to SNFs based on contrasting strategies from 2 competing hospital systems. METHODS: Employing a case study methodology, we compared 1 hospital system that integrated with SNFs to a competing system that did not. We compared interview data from clinical and administrative staff and publicly reported rehospitalization rate changes from the 2 systems. RESULTS: Analysis of integrating hospital system interviews noted providing patients detailed discharge information and educating SNF staff regarding care protocols. Integrated hospital system all-cause readmission rates declined by nearly 1 percentage point more than the nonintegrated hospital system (coefficient, -0.008; 95% confidence interval, -0.003 to -0.012) between 2014 and 2017. CONCLUSION: As hospitals explore care transition improvements to SNFs, developing more embedded relationships highlights one approach to improve value.

Strategy and risk sharing in hospital-postacute care integration.

ISSUE/TREND: Postacute care has been identified as a primary area for cost containment. The continued shift of payment structures from volume to value has often put hospitals at the forefront of addressing postacute care cost containment. However, hospitals continue to struggle with models to manage patients in postacute care institutions, such as skilled nursing facilities or in home health agencies. Recent research has identified postacute care network development as one mechanism to improve outcomes for patients sent to postacute care providers. Many hospitals, though, have not utilized this strategy for fear of not adhering to Centers for Medicare & Medicaid Services requirements that patients are given choice when discharged to postacute care. MANAGERIAL APPROACH: A hospital's approach to postacute care integration will be dictated by environmental uncertainty and the level of embeddedness hospitals have with potential postacute care partners. Hospitals, though, must also consider how and when to extend shared savings to postacute care partners, which will be based on the complexity of the risk-sharing calculation, the ability to maintain network flexibility, and the potential benefits of preserving competition and innovation among the network members. For hospital leaders, postacute care network development should include a robust and transparent data management process, start with an embedded network that maintains network design flexibility, and include a care management approach that includes patient-level coordination. CONCLUSION: The design of care management models could benefit from elevating the role of postacute care providers in the current array of risk-based payment models, and these providers should consider developing deeper relationships with select postacute care providers to achieve cost containment.

Barriers to a Timely Discharge From Short-Term Care in VA Community Living Centers.

This study aimed to identify the barriers to a timely discharge from short-term care in Veterans Health Administration (VHA) Community Living Centers (CLCs). Ninety-nine interviews were conducted with CLC staff in leadership and direct-care positions in eight varied CLCs. Major themes identified through qualitative analysis as barriers to a timely discharge were a lack of patients' financial resources, low social support, and reluctance of some veterans and staff to view a timely veteran discharge as their goal. Staff also perceived that barriers were much more difficult to overcome in regions where community-based long-term services and supports were limited or nonexistent. Because VHA has lagged behind Medicaid more generally in terms of investment in these types of services, additional strategies are warranted to achieve the important policy goal of deinstitutionalizing VHA care and returning veterans to their homes in the community.

The Prevalence of Culture Change Practice in US Nursing Homes: Findings From a 2016/2017 Nationwide Survey.

BACKGROUND AND OBJECTIVES: Given the dynamic nursing home (NH) industry and evolving regulatory environment, depiction of contemporary NH culture-change (person/resident-centered) care practice is of interest. Thus, we aimed to portray the 2016/2017 prevalence of NH culture change-related processes and structures and to identify factors associated with greater practice prevalence. RESEARCH DESIGN AND METHODS: We administered a nationwide survey to 2142 NH Administrators at NHs previously responding to a 2009/2010 survey. Seventy-four percent of administrators (1583) responded (with no detectable nonresponse bias) enabling us to generalize (weighted) findings to US NHs. From responses, we created index scores for practice domains of resident-centered care, staff empowerment, physical environment, leadership, and family and community engagement. Facility-level covariate data came from the survey and the Certification and Survey Provider Enhanced Reporting system. Ordered logistic regression identified the factors associated with higher index scores. RESULTS: Eighty-eight percent of administrators reported some facility-level involvement in NH culture change, with higher reported involvement consistently associated with higher domain index scores. NHs performed the best (82.6/100 weighted points) on the standardized resident-centered care practices index, and had the lowest scores (54.8) on the family and community engagement index. Multivariable results indicate higher index scores in NHs with higher leadership scores and in states having Medicaid pay-for-performance with culture change-related quality measures. CONCLUSIONS: The relatively higher resident-centered care scores (compared with other domain scores) suggest an emphasis on person-centered care in many US NHs. Findings also support pay-for-performance as a potential mechanism to incentivize preferred NH practice.

Qualitative perspectives of primary care providers who treat Medicaid managed care patients.

BACKGROUND: Declining job satisfaction and concurrent reductions in Medicaid participation among primary care providers have been documented, but there is limited qualitative work detailing their first-hand experiences treating Medicaid patients. The objective of this study is to describe the experiences of some primary care providers who treat Medicaid patients using in-depth qualitative analysis. METHODS: We conducted qualitative interviews with 15 primary care providers treating Medicaid patients in a Northeastern state. Participant recruitment efforts focused on including different types of primary care providers practicing in diverse settings. Qualitative interviews were conducted using a semi-structured interview protocol. We developed a coding scheme to analyze interview transcripts and identify themes. RESULTS: Providers expressed challenges effectively meeting their patients' needs under current policy. They described low Medicaid reimbursement and underinvestment in care coordination programs to adequately address the social determinants of health. Providers shared other concerns including poor access to behavioral health services, discontinuous Medicaid coverage due to enrollment and renewal policies, and limited reimbursement for alternative pain treatment. Providers offered their own suggestions for the allocation of financial investments, Medicaid policy, and primary care practice. CONCLUSIONS: Underinvestment in primary care in Medicaid may detract from providers' professional satisfaction and hinder care coordination for Medicaid patients with complex healthcare needs. Policy solutions that improve the experience of primary care providers serving Medicaid patients are urgently needed to ensure sustainability of the workforce and improve care delivery.

Professional development and exposure to geriatrics: medical student perspectives from narrative journals.

Teaching professionalism is an important goal in American medical education. With the aging of the U.S. population, it is critical to understand how medical students develop professional behaviors when caring for older adults. Exposure to geriatrics and older patients can enhance students' professional development with patients of all ages and across different specialties. Medical students learn explicit and implicit messages during their education. In addition to helping to evaluate curricula, reflective journaling encourages individual development and helps in revealing how medical students become professionals. In this study, medical student volunteers described their responses to new geriatrics content in their curriculum, encounters with older patients in clinical settings, and their evolving physician identities. Multidisciplinary team analysis elicited 10 themes regarding: evaluation of geriatrics within the curriculum, recognition of geriatrics principles, and attitudes regarding aging and professional development over time. This article focuses on the impact of geriatrics exposure on students' professional development, revealing ways that students think about professionalism and older patients. Medical educators should consider journaling to help foster and gauge students' professional development.

Medicare and Medicaid Reimbursement Rates for Nursing Homes Motivate Select Culture Change Practices But Not Comprehensive Culture Change.

Components of nursing home (NH) culture change include resident-centeredness, empowerment, and home likeness, but practices reflective of these components may be found in both traditional and "culture change" NHs. We use mixed methods to examine the presence of culture change practices in the context of an NH's payer sources. Qualitative data show how higher pay from Medicare versus Medicaid influences implementation of select culture change practices, and quantitative data show NHs with higher proportions of Medicare residents have significantly higher (measured) environmental culture change implementation. Findings indicate that heightened coordination of Medicare and Medicaid could influence NH implementation of reform practices.

Overcoming resistance to culture change: nursing home administrators' use of education, training, and communication.

Nursing home culture change is becoming more prevalent, and research has demonstrated its benefits for nursing home residents and staff-but little is known about the role of nursing home administrators in culture change implementation. The purpose of this study was to determine what barriers nursing home administrators face in implementing culture change practices, and to identify the strategies used to overcome them. The authors conducted in-depth individual interviews with 64 administrators identified through a nationally representative survey. Results showed that a key barrier to culture change implementation reported by administrators was staff, resident, and family member resistance to change. Most nursing home administrators stressed the importance of using communication, education and training to overcome this resistance. Themes emerging around the concepts of communication and education indicate that these efforts should be ongoing, communication should be reciprocal, and that all stakeholders should be included.

"Would You Do That in Your Home?" Making Nursing Homes Home-like in Culture Change Implementation.

Qualitative interviews with nursing home administrators reveal innovative and cost-conscious ways to physically modify facilities that help institute culture change practices. Telephone interviews were conducted following a national survey of nursing home nursing directors and administrators. In this cross-sectional snapshot of administrator experiences, motivations for making facilities more home-like and less institutional and creative responses to challenges are described. State and corporate support and regulator encouragement are noted that help their reform efforts. Administrators note that small steps to create a more home-like environment can result in a positive impact that minimizes disruption to existing care processes. They describe how they respond to challenges, such as the physical plant and high costs, and note how comparative shopping, cost-conscious physical improvements, and continuous involvement of staff and residents contribute to successful efforts. Their examples illustrate novel ways to humanize long-term care facilities that other nursing homes can emulate.

Administrator Perspectives on the Impact of COVID-19 on the Administration of the Patient Driven Payment Model in U.S. Skilled Nursing Facilities.

The Patient Driven Payment Model (PDPM) was implemented in U.S. skilled nursing facilities (SNFs) in October 2019, shortly before COVID-19. This new payment model aimed to reimburse SNFs for patients' nursing needs rather than the previous model which reimbursed based on the volume of therapy received. Through 156 semi-structured interviews with 40 SNF administrators from July 2020 to December 2021, this qualitative study clarifies the impact of COVID-19 on the administration of PDPM at SNFs. Interview data were analyzed using modified grounded theory and thematic analysis. Our findings show that SNF administrators shifted focus from management of the PDPM to COVID-19-related delivery of care adaptations, staff shortfalls, and decreased admissions. As the pandemic abated, administrators re-focused their attention to PDPM. Policy makers should consider the continued impacts of the pandemic at SNFs, particularly on delivery of care, admissions, and staffing, on the ability of SNF administrators to administer a new payment model.

Rethinking Infection Control: Nursing Home Administrator Experiences during the COVID-19 Pandemic.

OBJECTIVE: To examine nursing home administrator perspectives of infection control practices in nursing homes at the height of the COVID-19 pandemic and characterize lessons learned. DESIGN: Descriptive qualitative study. SETTING AND PARTICIPANTS: Administrators from 40 nursing homes across 8 diverse health care markets in the United States. METHODS: Semistructured interviews were conducted via telephone or Zoom with nursing home administrators. Interviews were repeated at 3-month intervals, for a total of 4 interviews per participant between July 2020 and December 2021 (n = 156). Qualitative analysis of interview transcripts used modified grounded theory and thematic analysis to identify overarching themes. RESULTS: Three major themes emerged reflecting administrator experiences managing infection control practices and nursing home operations at the height of the COVID-19 pandemic. First, administrators reported that the more stringent infection control protocols implemented to manage and mitigate COVID-19 at their facilities increased awareness and understanding of the importance of infection control; second, administrators reported incorporating higher standards of infection control practices into facility-level policies, emergency preparedness plans, and staff training; and third, administrators said they and their executive leadership were reevaluating and upgrading their facilities' physical structures and operational processes for better infection control infrastructure in preparation for future pandemics or other public health crises. CONCLUSIONS AND IMPLICATIONS: Insights from this study's findings suggest important next steps for restructuring and improving nursing home infection control protocols and practices in preparation for future pandemics and public health emergencies. Nursing homes need comprehensive, standardized infection control training and upgrading of physical structures to improve ventilation and facilitate isolation practices when needed. Furthermore, nursing home emergency preparedness plans need better integration with local, state, and federal agencies to ensure effective communication, proper resource tracking and allocation, and coordinated, rapid response during future public health crises.

Preparing to care for an aging population: medical student reflections on their clinical mentors within a new geriatrics curriculum.

Reflective writing techniques such as journaling help provide insights into the process by which medical students are mentored and develop into practicing physicians. The authors sought to analyze medical students' journals regarding their mentored experiences within a new geriatrics curriculum at a U.S. medical school. Thirty preclinical and clinical medical student journalers participated in this project. The authors employed qualitative analytic techniques using an interdisciplinary team process. Three major themes emerged: (a) exposure to clinical mentors challenged medical students' preconceptions regarding older adults and geriatric medicine; (b) students learned new medical knowledge and techniques from observing their mentors; and (c) students provided positive and negative assessments of their mentors. Reflective journaling provides important insights into the process by which medical students draw upon mentored clinical experiences during their training. Such mentorship may be particularly relevant to promoting their interest in geriatrics.

"It's Not a Sprint, It's a Marathon": Stages of Managing a Nursing Home Throughout the Pandemic.

OBJECTIVES: To qualitatively examine the impact of COVID-19 on nursing homes over the course of the pandemic from the perspective of nursing home administrators. DESIGN: In-depth, semi-structured interviews with nursing home administrators, repeated 3 months apart for a total of 4 each from July 2020 through December 2021. SETTINGS AND PARTICIPANTS: Administrators from a total of 40 nursing homes from 8 health care markets across the United States. METHODS: Interviews were conducted virtually or via phone. The research team identified overarching themes using applied thematic analysis, and iteratively coded transcribed interviews. RESULTS: Nursing home administrators across the United States reported challenges of managing nursing homes during a pandemic. We found their experiences could generally be categorized into 4 stages, not necessarily coinciding with surge levels of the virus. The initial stage was characterized by fear and confusion. The second stage, by a "new normal," a term administrators used to report feeling better prepared for an outbreak and how residents, staff, and families began to adjust to life with COVID. Administrators started using the phrase "a light at the end of the tunnel" to describe the third stage, characterized by the hope associated with the availability of vaccinations. The fourth stage was marked by "caregiver fatigue" as nursing homes experienced numerous breakthrough cases. Some challenges, like staffing issues and uncertainty about the future, were reported throughout the pandemic, as was a continued mission to keep residents safe. CONCLUSIONS AND IMPLICATIONS: As the ability of nursing homes to provide safe, effective care faces unprecedented and continued challenges, the insights reported here from longitudinal perspectives of nursing home administrators may help policy makers develop solutions to encourage high-quality care. Knowing how the needs for resources and support vary across the progression of these stages has the potential to be helpful in addressing these challenges.

COVID-19 Vaccination Among Skilled Nursing Facility Staff: Challenges and Strategies Identified by Administrators.

COVID-19 vaccinations are critical for mitigating outbreaks and reducing mortality for skilled nursing facility (SNF) residents and staff, yet uptake among SNF staff varies widely and remains suboptimal. Understanding which strategies are successful for promoting staff vaccination, and examining the relationship between vaccination policies and staff retention/turnover is key for identifying best practices. We conducted repeated interviews with SNF administrators at 3-month intervals between July 2020 and December 2021 (n = 156 interviews). We found that COVID-19 vaccines were initially met with both enthusiasm and skepticism by SNF staff. Administrators reported strategies to increase staff vaccine acceptance, including incentives, one-on-one education, and less stringent personal protective equipment requirements. Federal and state vaccination mandates further promoted vaccine uptake. This combination of mandates with prioritization of the vaccine by SNFs and their leadership was successful at increasing staff vaccination acceptance, which may be critical to increase staff booster uptake from its current suboptimal levels.

Provider beliefs about the ideal design of an opioid deprescribing and substitution intervention for older adults.

PURPOSE: Opportunities exist to meaningfully reduce suboptimal prescription opioid use among older adults. Deprescribing is one possible approach to reducing suboptimal use. Appropriate interventions should outline how to carefully taper opioids, closely monitor adverse events, substitute viable alternative and affordable nonopioid pain treatments, and initiate medications for opioid use disorder to properly manage use disorders, as needed. We sought to document and understand provider perceptions to begin developing effective and safe opioid deprescribing interventions. METHODS: We conducted 3 semistructured focus groups that covered topics such as participant perspectives on opioid deprescribing in older adults, how to design an ideal intervention, and how to identify potential barriers or facilitators in implementing an intervention. Focus group transcripts were double coded and qualitatively analyzed to identify overarching themes. RESULTS: Healthcare providers (n = 17), including physicians, pharmacists, nurses, social workers, and administrative staff, participated in 3 focus groups. We identified 4 key themes: (1) involve pharmacists in deprescribing and empower them as leaders of an opioid deprescribing service; (2) ensure tight integration and close collaboration throughout the deprescribing process from the inpatient to outpatient settings; (3) more expansive inclusion criteria than age alone; and (4) provision of access to alternative pharmacological and nonpharmacological pain management modalities to patients. CONCLUSION: Our findings, which highlight various healthcare provider beliefs about opioid deprescribing interventions, are expected to serve as a framework for other organizations to develop and implement interventions. Future studies should incorporate patients' and family caregivers' perspectives.

Examination of Staffing Shortages at US Nursing Homes During the COVID-19 Pandemic.

Importance: Staffing shortages have been widely reported in US nursing homes during the COVID-19 pandemic, but traditional quantitative research analyses have found mixed evidence of staffing shortfalls. Objective: To examine whether nursing home administrator perspectives can provide context for conflicting aggregate staffing reports in US nursing homes during the COVID-19 pandemic. Design, Setting, and Participants: In a qualitative study, convergent mixed-methods analysis integrating qualitative and quantitative data sets was used. Semistructured qualitative interviews were conducted between July 14, 2020, and December 16, 2021. Publicly available national Payroll Based Journal data were retrieved from January 1, 2020, to September 30, 2022, on 40 US nursing homes in 8 health care markets that varied by region and nursing home use patterns. Staffing and resident measures were derived from Payroll Based Journal data and compared with national trends for 15 436 US nursing homes. Nursing home administrators were recruited for interviews. Of the 40 administrators who consented to participate, 4 were lost to follow-up. Exposure: Four repeated, semistructured qualitative interviews with participants were conducted. Interview questions focused on the changes noted during the COVID-19 pandemic in nursing homes. Main Outcomes and Measures: Thematic description of nursing home administrator compensatory strategies to provide context for quantitative analyses on nursing home staffing levels during the COVID-19 pandemic. Results: A total of 156 interviews were completed with 40 nursing home administrators. Administrators reported experiencing staff shortages during the COVID-19 pandemic and using compensatory strategies, such as overtime, cross-training, staff-to-resident ratio adjustments, use of agency staff, and curtailing admissions, to maintain operations and comply with minimum staffing regulations. Payroll Based Journal data measures graphed from January 1, 2020, to September 30, 2022, supported administrator reports showing that study facilities had reductions in staff hours, increased use of agency staff, and decreased resident census. Findings were similar to national trends. Conclusions and Relevance: In this qualitative, convergent mixed-methods study, nursing home administrators reported the major staffing strain they experienced at their facilities and the strategies they used to offset staffing shortages. Their experiences provide context to quantitative analyses on aggregate nursing home census data. The short-term compensatory measures administrators used to comply with regulations and maintain operations may be detrimental to the long-term stability of this workforce.

Computers in the examination room and the electronic health record: physicians' perceived impact on clinical encounters before and after full installation and implementation.

PURPOSE: We compared physicians' self-reported attitudes and behaviours regarding electronic health record (EHR) use before and after installation of computers in patient examination rooms and transition to full implementation of an EHR in a family medicine training practice to identify anticipated and observed effects these changes would have on physicians' practices and clinical encounters. METHODS: We conducted two individual qualitative interviews with family physicians. The first interview was before and second interview was 8 months later after full implementation of an EHR and computer installation in the examination rooms. Data were analysed through project team discussions and subsequent coding with qualitative analysis software. RESULTS: At the first interviews, physicians frequently expressed concerns about the potential negative effect of the EHR on quality of care and physician-patient interaction, adequacy of their skills in EHR use and privacy and confidentiality concerns. Nevertheless, most physicians also anticipated multiple benefits, including improved accessibility of patient data and online health information. In the second interviews, physicians reported that their concerns did not persist. Many anticipated benefits were realized, appearing to facilitate collaborative physician-patient relationships. Physicians reported a greater teaching role with patients and sharing online medical information and treatment plan decisions. CONCLUSIONS: Before computer installation and full EHR implementation, physicians expressed concerns about the impact of computer use on patient care. After installation and implementation, however, many concerns were mitigated. Using computers in the examination rooms to document and access patients' records along with online medical information and decision-making tools appears to contribute to improved physician-patient communication and collaboration.

"Now at least we have something to call it": Patient and care partner experiences receiving an amyloid PET scan.

BACKGROUND: The primary objective of this paper was to examine perspectives and experiences of individuals with cognitive impairment who received an amyloid PET scan and their care partners, with regard to the process, logistics, and decision-making associated with receiving an amyloid PET scan and its results. METHODS: Structured telephone interviews were conducted with 200 randomly sampled scan recipient/care partner dyads from the CARE IDEAS study. The audio-recorded, transcribed responses were analyzed using an inductive qualitative content analytic approach. RESULTS: Participating individuals and care partners described their experiences in seeking a diagnosis for memory issues, including decision-making and logistics involved with receiving an amyloid PET scan. Participants discussed the factors contributing to their decision to seek a diagnosis for their memory issues and their hopes and expectations in completing the scan. Participants also described the trajectory of this process, and although some described relatively straightforward trajectories, others described problems associated with identifying appropriate providers and coordinating care across numerous providers to obtain a diagnosis for their memory issues. Participants described an additional challenge of physicians attributing cognitive decline to normal aging, rather than signs of a neurodegenerative disorder. CONCLUSIONS: Findings shed light on the barriers and delays that individuals and care partners experience in connecting with physicians and obtaining a comprehensive evaluation for cognitive problems. Results from this study have implications for physicians who provide care to older adults, and specifically highlight the need for greater care coordination and clearer communication with and systems of referral for patients.

Measuring implementation fidelity in a cluster-randomized pragmatic trial: development and use of a quantitative multi-component approach.

BACKGROUND: In pragmatic trials, on-site partners, rather than researchers, lead intervention delivery, which may result in implementation variation. There is a need to quantitatively measure this variation. Applying the Framework for Implementation Fidelity (FIF), we develop an approach for measuring variability in site-level implementation fidelity. This approach is then applied to measure site-level fidelity in a cluster-randomized pragmatic trial of Music & MemorySM (M&M), a personalized music intervention targeting agitated behaviors in residents living with dementia, in US nursing homes (NHs). METHODS: Intervention NHs (N = 27) implemented M&M using a standardized manual, utilizing provided staff trainings and iPods for participating residents. Quantitative implementation data, including iPod metadata (i.e., song title, duration, number of plays), were collected during baseline, 4-month, and 8-month site visits. Three researchers developed four FIF adherence dimension scores. For Details of Content, we independently reviewed the implementation manual and reached consensus on six core M&M components. Coverage was the total number of residents exposed to the music at each NH. Frequency was the percent of participating residents in each NH exposed to M&M at least weekly. Duration was the median minutes of music received per resident day exposed. Data elements were scaled and summed to generate dimension-level NH scores, which were then summed to create a Composite adherence score. NHs were grouped by tercile (low-, medium-, high-fidelity). RESULTS: The 27 NHs differed in size, resident composition, and publicly reported quality rating. The Composite score demonstrated significant variation across NHs, ranging from 4.0 to 12.0 [8.0, standard deviation (SD) 2.1]. Scaled dimension scores were significantly correlated with the Composite score. However, dimension scores were not highly correlated with each other; for example, the correlation of the Details of Content score with Coverage was τb = 0.11 (p = 0.59) and with Duration was τb = - 0.05 (p = 0.78). The Composite score correlated with CMS quality star rating and presence of an Alzheimer's unit, suggesting face validity. CONCLUSIONS: Guided by the FIF, we developed and used an approach to quantitatively measure overall site-level fidelity in a multi-site pragmatic trial. Future pragmatic trials, particularly in the long-term care environment, may benefit from this approach. TRIAL REGISTRATION: Clinicaltrials.gov NCT03821844. Registered on 30 January 2019, https://clinicaltrials.gov/ct2/show/NCT03821844 .