Study protocol for a hospital-to-home transitional care intervention for older adults with multiple chronic conditions and depressive symptoms: a pragmatic effectiveness-implementation trial.

BACKGROUND: Older adults (> 65 years) with multiple chronic conditions (MCC) and depressive symptoms experience frequent transitions between hospital and home. Care transitions for this population are often poorly coordinated and fragmented, resulting in increased readmission rates, adverse medical events, decreased patient satisfaction and safety, and increased caregiver burden. There is a dearth of evidence on best practices in the provision of transitional care for older adults with MCC and depressive symptoms transitioning from hospital-to-home. This paper presents a protocol for a two-armed, multi-site pragmatic effectiveness-implementation trial of Community Assets Supporting Transitions (CAST), an evidence-informed nurse-led six-month intervention that supports older adults with MCC and depressive symptoms transitioning from hospital-to-home. The Collaborative Intervention Planning Framework is being used to engage patients and other key stakeholders in the implementation and evaluation of the intervention and planning for intervention scale-up to other communities. METHODS: Participants will be considered eligible if they are > 65 years, planned for discharged from hospital to the community in three Ontario locations, self-report at least two chronic conditions, and screen positive for depressive symptoms. A total of 216 eligible and consenting participants will be randomly assigned to the control (usual care) or intervention (CAST) arm. The intervention consists of tailored care delivery comprising in-home visits, telephone follow-up and system navigation support. The primary measure of effectiveness is mental health functioning of the older adult participant. Secondary outcomes include changes in physical functioning, depressive symptoms, anxiety, perceived social support, patient experience, and health and social service use and cost, from baseline to 6- and 12-months. Caregivers will be assessed for caregiver strain, depressive symptoms, anxiety, health-related quality of life, and health and social service use and costs. Descriptive and qualitative data from older adult and caregiver participants, and the nurse interventionists will be used to examine implementation of the intervention, how the intervention is adapted within each study region, and its potential for sustainability and scalability to other jurisdictions. DISCUSSION: A nurse-led transitional care strategy may provide a feasible and effective means for improving health outcomes and patient/caregiver experience and reduce service use and costs in this vulnerable population. TRIAL REGISTRATION: # NCT03157999 . Registration Date: April 4, 2017.

Engagement of older adults with multimorbidity as patient research partners: Lessons from a patient-oriented research program.

BACKGROUND: Patient "engagement" in health research broadly refers to including people with lived experience in the research process. Although previous reviews have systematically summarized approaches to engaging older adults and their caregivers in health research, there is currently little guidance on how to meaningfully engage older adults with multimorbidity as research partners. OBJECTIVES: This paper describes the lessons learned from a patient-oriented research program, the Aging, Community and Health Research Unit (ACHRU), on how to engage older adults with multimorbidity as research partners. Over the past 7-years, over 40 older adults from across Canada have been involved in 17 ACHRU projects as patient research partners. METHODS: We developed this list of lessons learned through iterative consensus building with ACHRU researchers and patient partners. We then met to collectively identify and summarize the reported successes, challenges and lessons learned from the experience of engaging older adults with multimorbidity as research partners. RESULTS: ACHRU researchers reported engaging older adult partners across many phases of the research process. Five challenges and lessons learned were identified: 1) actively finding patient partners who reflect the diversity of older adults with multimorbidity, 2) developing strong working relationships with patient partners, 3) providing education and support for both patient partners and researchers, 4) using flexible approaches for engaging patients, and 5) securing adequate resources to enable meaningful engagement. CONCLUSION: The lessons learned through this work may provide guidance to researchers on how to facilitate meaningful engagement of this vulnerable and understudied subgroup in the patient engagement literature.

Effectiveness of a nurse-led hospital-to-home transitional care intervention for older adults with multimorbidity and depressive symptoms: A pragmatic randomized controlled trial.

OBJECTIVE: To evaluate the effectiveness of a nurse-led hospital-to-home transitional care intervention versus usual care on mental functioning (primary outcome), physical functioning, depressive symptoms, anxiety, perceived social support, patient experience, and health service use costs in older adults with multimorbidity (≥ 2 comorbidities) and depressive symptoms. DESIGN AND SETTING: Pragmatic multi-site randomized controlled trial conducted in three communities in Ontario, Canada. Participants were allocated into two groups of intervention and usual care (control). PARTICIPANTS: 127 older adults (≥ 65 years) discharged from hospital to the community with multimorbidity and depressive symptoms. INTERVENTION: This evidence-based, patient-centred intervention consisted of individually tailored care delivery by a Registered Nurse comprising in-home visits, telephone follow-up and system navigation support over 6-months. OUTCOME MEASURES: The primary outcome was the change in mental functioning, from baseline to 6-months. Secondary outcomes were the change in physical functioning, depressive symptoms, anxiety, perceived social support, patient experience, and health service use cost, from baseline to 6-months. Intention-to-treat analysis was performed using ANCOVA modeling. RESULTS: Of 127 enrolled participants (63-intervention, 64-control), 85% had six or more chronic conditions. 28 participants were lost to follow-up, leaving 99 (47 -intervention, 52-control) participants for the complete case analysis. No significant group differences were seen for the baseline to six-month change in mental functioning or other secondary outcomes. Older adults in the intervention group reported receiving more information about health and social services (p = 0.03) compared with the usual care group. CONCLUSIONS: Although no significant group differences were seen for the primary or secondary outcomes, the intervention resulted in improvements in one aspect of patient experience (information about health and social services). The study sample fell below the target sample (enrolled 127, targeted 216), which can account for the non-significant findings. Further research on the impact of the intervention and factors that contribute to the results is recommended. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT03157999.

Molecular umbrellas: a novel class of candidate topical microbicides to prevent human immunodeficiency virus and herpes simplex virus infections.

Molecular umbrella compounds may function as novel topical microbicides to prevent human immunodeficiency virus (HIV) and herpes simplex virus (HSV) infections. In a preliminary structure-activity investigation, one umbrella compound, designated Spm8CHAS, was identified which inhibited both HIV and HSV infections with no cellular toxicity. The objectives of the current studies were to define its spectrum of antiviral activity, characterize its mechanism of action, and explore the possibility of combining Spm8CHAS with HIV-specific reverse transcriptase inhibitors. Spm8CHAS inhibited infections by laboratory and clinical R5 and X4 clade B and clade C HIV strains in cell culture. Ectocervical tissue explants exposed to HIV-1(BaL) in the presence of Spm8CHAS were completely protected (50% inhibitory concentration [IC(50)], 13.6 microg/ml), and transfer of virus to target T cells via migratory cells was abolished (IC(50), 3.8 microg/ml). Spm8CHAS inhibited HSV-2 infection of epithelial cells 10,000-fold if present throughout the infection. Notably, adding Spm8CHAS to cultures following HSV entry significantly reduced viral infection, indicating that the drug also acts postentry. Subsequent studies indicated that Spm8CHAS blocks cell-to-cell spread of HSV. Confocal microscopy using a fluorescently labeled analog of Spm8CHAS demonstrated that this conjugate crosses the plasma cell membrane and is transported to the nucleus. Combinations of Spm8CHAS with UC-781 or 9-[R-2-(phosphonylmethoxy)propyl] adenine monohydrate in vitro exhibited additive anti-HIV activity with preserved anti-HSV activity. The abilities of Spm8CHAS to inhibit primary isolates of HIV, block HSV infection postentry, and cross cell membranes support the development of a combination microbicide containing Spm8CHAS with an HIV-specific reverse transcriptase inhibitor to prevent both HIV and HSV infections by multiple mechanisms.

Persulfated molecular umbrellas as anti-HIV and anti-HSV agents.

A series of persulfated molecular umbrellas have been synthesized from putrescine, spermidine, spermine, lysine, and cholic acid (1a, 2a, 3a, 4a, and 5a) and their anti-HIV and anti-HSV activities determined. Despite it size, the most active of these conjugates (5a) was able to cross phospholipid bilayers made from 1-palmitoyl-2-oleyol-sn-glycero-3-phosphocholine (POPC) and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylglycerol (POPG). The unique combination of anti-viral activity, an ability to cross hydrophobic barriers, a lack of cytotoxicity, and a simple three-step synthesis from biogenic starting material suggests that 5a and related conjugates may be exploitable as a novel class of anti-viral agents for systemic and topical applications.