Centenarians and extremely old people living with frailty can elicit durable SARS-CoV-2 spike specific IgG antibodies with virus neutralization functions following virus infection as determined by serological study.

BACKGROUND: The SARS-CoV-2 (Severe Acute Respiratory Syndrome coronavirus 2) has led to more than 165 million COVID-19 cases and >3.4 million deaths worldwide. Epidemiological analysis has revealed that the risk of developing severe COVID-19 increases with age. Despite a disproportionate number of older individuals and long-term care facilities being affected by SARS-CoV-2 and COVID-19, very little is understood about the immune responses and development of humoral immunity in the extremely old person after SARS-CoV-2 infection. Here we conducted a serological study to investigate the development of humoral immunity in centenarians following a SARS-CoV-2 outbreak in a long-term care facility. METHODS: Extreme aged individuals and centenarians who were residents in a long-term care facility and infected with or exposed to SARS-CoV-2 were investigated between April and June 2020 for the development of antibodies to SARS-CoV-2. Blood samples were collected from positive and bystander individuals 30 and 60 days after original diagnosis of SARS-CoV-2 infection. Plasma was used to quantify IgG, IgA, and IgM isotypes and subsequent subclasses of antibodies specific for SARS-CoV-2 spike protein. The function of anti-spike was then assessed by virus neutralization assays against the native SARS-CoV-2 virus. FINDINGS: Fifteen long-term care residents were investigated for SARS-CoV-2 infection. All individuals had a Clinical Frailty scale score ≥5 and were of extreme older age or were centenarians. Six women with a median age of 98.8 years tested positive for SARS-CoV-2. Anti-spike IgG antibody titers were the highest titers observed in our cohort with all IgG positive individuals having virus neutralization ability. Additionally, 5 out of the 6 positive participants had a robust IgA anti-SARS-CoV-2 response. In all 5, antibodies were detected after 60 days from initial diagnosis.

Considering Frailty in SARS-CoV-2 Vaccine Development: How Geriatricians Can Assist.

The COVID-19 pandemic has disproportionately impacted frail older adults, especially residents of long-term care (LTC) facilities. This has appropriately led to prioritization of frail older adults and LTC residents, and those who care for them, in the vaccination effort against COVID-19. Older adults have distinct immunological, clinical, and practical complexity, which can be understood through a lens of frailty. Even so, frailty has not been considered in studies of COVID-19 vaccines to date, leading to concerns that the vaccines have not been optimally tailored for and evaluated in this population even as vaccination programs are being implemented. This is an example of how vaccines are often not tested in Phase 1/2/3 clinical trials in the people most in need of protection. We argue that geriatricians, as frailty specialists, have much to contribute to the development, testing and implementation of COVID-19 vaccines in older adults. We discuss roles for geriatricians in ten stages of the vaccine development process, covering vaccine design, trial design, trial recruitment, establishment and interpretation of illness definitions, safety monitoring, consideration of relevant health measures such as frailty and function, analysis methods to account for frailty and differential vulnerability, contributions in regulatory and advisory roles, post-marketing surveillance, and program implementation and public health messaging. In presenting key recommendations pertinent to each stage, we hope to contribute to a dialogue on how to push the field of vaccinology to embrace the complexity of frailty. Making vaccines that can benefit frail older adults will benefit everyone in the fight against COVID-19.

COVID-19, frailty and long-term care: Implications for policy and practice.

Older adults have been disproportionately affected by the COVID-19 pandemic, with many outbreaks occurring in Long Term Care Facilities (LTCFs). We discuss this vulnerability among LTCF residents using an ecological framework, on levels spanning from the individual to families and caregivers, institutions, health services and systems, communities, and contextual government policies. Challenges abound for fully understanding the burden of COVID-19 in LTCF, including differences in nomenclature, data collection systems, cultural differences, varied social welfare models, and (often) under-resourcing of the LTC sector. Registration of cases and deaths may be limited by testing capacity and policy, record-keeping and reporting procedures. Hospitalization and death rates may be inaccurate depending on atypical presentations and whether or not residents' goals of care include escalation of care and transfer to hospital. Given the important contribution of frailty, use of the Clinical Frailty Scale (CFS) is discussed as a readily implementable measure, as are lessons learned from the study of frailty in relation to influenza. Biomarkers hold emerging promise in helping to predict disease severity and address the puzzle of why some frail LTCF residents are resilient to COVID-19, either remaining test-negative despite exposure or having asymptomatic infection, while others experience the full range of illness severity including critical illness and death. Strong and coordinated surveillance and research focused on LTCFs and their frail residents is required. These efforts should include widespread assessment of frailty using feasible and readily implementable tools such as the CFS, and rigorous reporting of morbidity and mortality in LTCFs.

The Canadian Frailty Priority Setting Partnership: Research Priorities for Older Adults Living with Frailty.

BACKGROUND: Patient engagement in research priority-setting is intended to democratize research and increase impact. The objectives of the Canadian Frailty Priority Setting Partnership (PSP) were to engage people with lived or clinical experience of frailty, and produce a list of research priorities related to care, support, and treatment of older adults living with frailty. METHODS: The Canadian Frailty PSP was supported by the Canadian Frailty Network, coordinated by researchers in Toronto, Ontario and followed the methods of the James Lind Alliance, which included establishing a Steering Group, inviting partner organizations, gathering questions related to care, support and treatment of older adults living with frailty, processing the data and prioritizing the questions. RESULTS: In the initial survey, 799 submissions were provided by 389 individuals and groups. The 647 questions that were within scope were categorized, merged, and summarized, then checked against research evidence, creating a list of 41 unanswered questions. Prioritization took place in two stages: first, 146 individuals and groups participated in survey and their responses short-listed 22 questions; and second, an in-person workshop was held on September 26, 2017 in Toronto, Ontario where these 22 questions were discussed and ranked. CONCLUSION: Researchers and research funders can use these results to inform their agendas for research on frailty. Strategies are needed for involving those with lived experience of frailty in research.

Adherence to "No Transfer to Hospital" Advance Directives Among Nursing Home Residents.

OBJECTIVES: Many older adults in long-term care (LTC) experience acute health crises but are at high risk of transfer distress and in-hospital morbidity and mortality. Residents often complete advance directives (ADs) regarding future care wishes, including directives for hospital transfers. This study aims to estimate the prevalence of, and adherence to, "no transfer to hospital" ADs in LTC, and to explore the circumstances leading to transfers against previously expressed directives. DESIGN: We conducted a mixed methods study in 10 nursing homes in Nova Scotia, Canada. A total of 748 resident charts and Emergency Health Services (EHS) database notes were reviewed from 3 time periods spanning implementation of a new primary care model, Care by Design (CBD). MEASURES: ADs were divided into those requesting transfer to hospital vs on-site management only, which were then analyzed in relation to actual hospital transfers. Reasons for EHS calls, management, and qualitative data were derived from the EHS database. Resident variables were obtained from LTC charts. Measures were compared between time periods. RESULTS: ADs were complete in 92.4% of charts. Paramedics were called for 80.5% of residents, and 73.6% were transferred to hospital, 51.3% of whom had explicit ADs to the contrary. The majority of those were transferred for fall-related injuries, followed by medical illness. Unclear care plans, symptom control, and perceived need for investigations and procedures all influenced transfer decisions. CONCLUSIONS/IMPLICATIONS: The use of "no transfer to hospital" directives did not appear to impact the number of residents being transferred to acute care. Half of those transferred to hospital had explicit ADs to the contrary, largely driven by fall-related injury. The high incidence of injury-related transfers highlights an important gap in advance care planning. Clarifying transfer preferences for injury management in advance directives may lead to better end-of-life experiences for residents and improve effective resource utilization.

Complete chloroplast genome of Prunus rufa (Rosaceae), a wild flowering cherry endemic to the Himalayan region.

Prunus rufa is a species of Prunus native to the Himalayan region. We determined the first complete chloroplast genome of P. rufa using a genome skimming approach. The cp genome was 157,723 bp long, with a large single-copy region (LSC) of 85,860 bp and a small single-copy region (SSC) of 19,081 bp separated by a pair of inverted repeats (IRs) of 26,391 bp each. It encodes 129 genes, including 84 protein-coding genes, 37 tRNA genes, and 8 ribosomal RNA genes. We also reconstructed the phylogeny of Prunus sensu lato using maximum-likelihood (ML) method, including our data and previously reported cp genomes of related taxa. The phylogenetic analysis indicated that P. rufa is closely related to Prunus cerasoides.

Polypharmacy and use of potentially inappropriate medications in long-term care facilities: does coordinated primary care make a difference?

OBJECTIVES: Polypharmacy is both common and harmful for frail residents of long-term care facilities (LTCF). We aimed to study rates of polypharmacy and potentially inappropriate medications (PIMs) before and after the implementation of a new model of coordinated primary care in LTCF, 'Care by Design (CBD)'. METHODS: This was an observational before/after study in 10 LTCFs in Halifax, NS, Canada. Chart reviews were conducted for 529 LTCF residents for whom medication use was available. Both regularly scheduled and PRN medications were included but topical, inhaled and other non-systemic agents were excluded. Polypharmacy was defined as the concomitant use of more than 10 medications. PIMs were identified using Beers Criteria. KEY FINDINGS: Mean age of LTCF residents was older pre- versus post-CBD (85.7 versus 82.1 years; P = 0.0015). The burden of polypharmacy was high, but decreased significantly from 86.8% pre-CBD to 79.5% post-CBD (P = 0.046). The mean number of medications per resident decreased from 16.7 (SD 5.6) pre- to 15.5 (SD 6.2) post-CBD (P = 0.037). Residents with dementia were taking fewer medications both overall and following the implementation of CBD (mean 15.9, SD 0.6 pre-CBD versus 14.4, SD 0.4 post-CBD; P = 0.04). PIM rates were high and showed no change with CBD (86.2% versus 81.1%, P = 0.16). CONCLUSIONS: Polypharmacy was the norm of this sample of LTCF residents. Implementation of coordinated care through the CBD model was associated with a small decrease in polypharmacy but not overall use of PIMs. Further targeted efforts are required to substantially reduce both polypharmacy and PIMs in clinical practice.

Reversing Frailty Levels in Primary Care Using the CARES Model.

BACKGROUND: The purpose of this manuscript was to evaluate the effectiveness of the Community Actions and Resources Empowering Seniors (CARES) model in measuring and mitigating frailty among community-dwelling older adults. METHODS: The CARES model is based on a goal-oriented multidisciplinary primary care plan which combines a comprehensive geriatric assessment (CGA) with health coaching. A total of 51 older adults (82 ± 7 years; 33 females) participated in the pilot phase of this initiative. Frailty was measured using the Clinical Frailty Scale (CFS) and the Frailty Index (FI-CGA) at baseline and at six-month follow-up. RESULTS: The FI-CGA at follow-up (0.21 ± 0.08) was significantly lower than the FI-CGA at baseline (0.24 ± 0.08), suggesting an average reduction of 1.8 deficits. Sixty-one per cent of participants improved their FI-CGA and 38% improved CFS categories. Participants classified as vulnerable/frail at baseline were more responsive to the intervention compared to non-frail participants. CONCLUSION: Pilot data showed that it is feasible to assess frailty in primary care and that the CARES intervention might have a positive effect on frailty, a promising finding that requires further investigations. General practitioners who participate in the CARES model can now access their patients' FI-CGA scores at point of service through their electronic medical records.

Improving Continuity of Care Reduces Emergency Department Visits by Long-Term Care Residents.

INTRODUCTION: Care by Design™ (CBD) (Canada), a model of coordinated team-based primary care, was implemented in long-term care facilities (LTCFs) in Halifax, Nova Scotia, Canada, to improve access to and continuity of primary care and to reduce high rates of transfers to emergency departments (EDs). METHODS: This was an observational time series before and after the implementation of CBD (Canada). Participants are LTCF residents with 911 Emergency Health Services calls from 10 LTCFs, representing 1424 beds. Data were abstracted from LTCF charts and Emergency Health Services databases. The primary outcome was ambulance transports from LTCFs to EDs. Secondary outcomes included access (primary care physician notes in charts) and continuity (physician numbers and contacts). RESULTS: After implementation of CBD (Canada), transports from LTCFs to EDs were reduced by 36%, from 68 to 44 per month (P = .01). Relational and informational continuity of care improved with resident charts with ≥10 physician notes, increasing 38% before CBD to 55% after CBD (P = .003), and the median number of chart notes increased from 7 to 10 (P = .0026). Physicians contacted before 911 calls and onsite assessment increased from 38% to 54% (P = .01) and 3.7% to 9.2% (P = .03), respectively, before CBD to after CBD. CONCLUSION: A 34% reduction in overall transports from LTCFs to EDs is likely attributable to improved onsite primary care, with consistent physician and team engagement and improvements in continuity of care.

Care by design: New model of coordinated on-site primary and acute care in long-term care facilities.

PROBLEM ADDRESSED: A recently implemented model of care in long-term care facilities (LTCFs) called Care by Design addresses concerns about a previously uncoordinated care system, a reduction in family physician services, and high rates of ambulance transports to emergency departments. OBJECTIVE OF PROGRAM: Care by Design is designed to increase access to care and continuity and quality of care by family physicians, reduce unwanted and unnecessary transfers to the emergency department, and lessen the burden on care teams including physicians and nurses in LTCFs. PROGRAM DESCRIPTION: The core of Care by Design is a dedicated family physician for each LTCF floor, with regular on-site visits; physician on-call coverage, 24 hours a day, 7 days a week; and standing orders and protocols. Care by Design also includes a comprehensive geriatric assessment tool, an interdisciplinary team approach, access to a dedicated extended care paramedic program to respond to urgent care needs, and ongoing performance measurement. CONCLUSION: Care by Design aims to improve on-site care for LTCF residents and family physicians' experiences with providing care in several ways, including increased clinical efficiency, communication, and continuity, and appropriate support within the interdisciplinary team model.

A Long-Term Care-Comprehensive Geriatric Assessment (LTC-CGA) Tool: Improving Care for Frail Older Adults?

BACKGROUND: Most older adults living in long-term care facilities (LTCF) are frail and have complex care needs. Holistic understanding of residents' health status is key to providing good care. Comprehensive Geriatric Assessment (CGA) is a valid assessment method which aims to embrace complexity. Here we aimed to study a CGA that has been modified for use in long-term care (the LTC-CGA) and to investigate its acceptability and usefulness to stakeholders and users. METHODS: This mixed methods study, conducted in 10 LTCFs in Halifax, Nova Scotia, reviewed 598 resident charts from pre- and post-implementation of the LTC-CGA. Qualitative methods explored stakeholder perspectives (physicians, nurses, paramedics, administrators, residents and families) though focus groups. RESULTS: The LTC-CGA was present in 78% of LTCF charts in the post -implementation, period though it did not appear in acute care charts of transferred residents, despite the intention that it accompany residents between care sites. Some items had suboptimal completion rates (e.g., Advance Directives at 56.4%), though these were located in other sections of the LTCF chart (98.2%). Nevertheless, qualitative findings suggest the LTC-CGA describes a clinical baseline health status which enabled timely and informed clinical decision-making. CONCLUSIONS: The LTC-CGA is a useful resource whose full capacity may not yet have been realized.

A new long-term care facilities model in nova scotia, Canada: protocol for a mixed methods study of care by design.

BACKGROUND: Prior to the implementation of a new model of care in long-term care facilities in the Capital District Health Authority, Halifax, Nova Scotia, residents entering long-term care were responsible for finding their own family physician. As a result, care was provided by many family physicians responsible for a few residents leading to care coordination and continuity challenges. In 2009, Capital District Health Authority (CDHA) implemented a new model of long-term care called "Care by Design" which includes: a dedicated family physician per floor, 24/7 on-call physician coverage, implementation of a standardized geriatric assessment tool, and an interdisciplinary team approach to care. In addition, a new Emergency Health Services program was implemented shortly after, in which specially trained paramedics dedicated to long-term care responses are able to address urgent care needs. These changes were implemented to improve primary and emergency care for vulnerable residents. Here we describe a comprehensive mixed methods research study designed to assess the impact of these programs on care delivery and resident outcomes. The results of this research will be important to guide primary care policy for long-term care. OBJECTIVE: We aim to evaluate the impact of introducing a new model of a dedicated primary care physician and team approach to long-term care facilities in the CDHA using a mixed methods approach. As a mixed methods study, the quantitative and qualitative data findings will inform each other. Quantitatively we will measure a number of indicators of care in CDHA long-term care facilities pre and post-implementation of the new model. In the qualitative phase of the study we will explore the experience under the new model from the perspectives of stakeholders including family doctors, nurses, administration and staff as well as residents and family members. The proposed mixed method study seeks to evaluate and make policy recommendations related to primary care in long-term care facilities with a focus on end-of-life care and dementia. METHODS: This is a mixed methods study with concurrent quantitative and qualitative phases. In the quantitative phase, a retrospective time series study is being conducted. Planned analyses will measure indicators of clinical, system, and health outcomes across three time periods and assess the effect of Care by Design as a whole and its component parts. The qualitative methods explore the experiences of stakeholders (ie, physicians, nurses, paramedics, care assistants, administrators, residents, and family members) through focus groups and in depth individual interviews. RESULTS: Data collection will be completed in fall 2013. CONCLUSIONS: This study will generate a considerable amount of outcome data with applications for care providers, health care systems, and applications for program evaluation and quality improvement. Using the mixed methods design, this study will provide important results for stakeholders, as well as other health systems considering similar programs. In addition, this study will advance methods used to research new multifaceted interdisciplinary health delivery models using multiple and varied data sources and contribute to the discussion on evidence based health policy and program development.

Is chytridiomycosis driving Darwin's frogs to extinction?

Darwin's frogs (Rhinoderma darwinii and R. rufum) are two species of mouth brooding frogs from Chile and Argentina that have experienced marked population declines. Rhinoderma rufum has not been found in the wild since 1980. We investigated historical and current evidence of Batrachochytrium dendrobatidis (Bd) infection in Rhinoderma spp. to determine whether chytridiomycosis is implicated in the population declines of these species. Archived and live specimens of Rhinoderma spp., sympatric amphibians and amphibians at sites where Rhinoderma sp. had recently gone extinct were examined for Bd infection using quantitative real-time PCR. Six (0.9%) of 662 archived anurans tested positive for Bd (4/289 R. darwinii; 1/266 R. rufum and 1/107 other anurans), all of which had been collected between 1970 and 1978. An overall Bd-infection prevalence of 12.5% was obtained from 797 swabs taken from 369 extant individuals of R. darwinii and 428 individuals representing 18 other species of anurans found at sites with current and recent presence of the two Rhinoderma species. In extant R. darwinii, Bd-infection prevalence (1.9%) was significantly lower than that found in other anurans (7.3%). The prevalence of infection (30%) in other amphibian species was significantly higher in sites where either Rhinoderma spp. had become extinct or was experiencing severe population declines than in sites where there had been no apparent decline (3.0%; x(2) = 106.407, P<0.001). This is the first report of widespread Bd presence in Chile and our results are consistent with Rhinoderma spp. declines being due to Bd infection, although additional field and laboratory investigations are required to investigate this further.

Diagnosis and treatment of dementia: 5. Nonpharmacologic and pharmacologic therapy for mild to moderate dementia.

BACKGROUND: Practising physicians frequently seek advice on the most effective interventions for dementia. In this article, we provide practical guidance on nonpharmacologic and pharmacologic interventions for the management of mild to moderate dementia based on recommendations from the Third Canadian Consensus Conference on the Diagnosis and Treatment of Dementia. METHODS: We developed evidence-based guidelines using systematic literature searches, with specific criteria for the selection and quality assessment of articles, and a clear and transparent decision-making process. We selected articles published from January 1996 to December 2005 that dealt with the management of mild to moderate stages of Alzheimer disease and other forms of dementia. Recommendations based on the literature review were drafted and voted on. Consensus required 80% or more agreement by participants. Subsequent to the conference, we searched for additional articles published from January 2006 to April 2008 using the same major keywords and secondary search terms. We graded the strength of the evidence using the criteria of the Canadian Task Force on Preventive Health Care. RESULTS: We identified 1615 articles, of which 954 were selected for further study. From a synthesis of the evidence in these studies, we made 48 recommendations for the management of mild to moderate dementia (28) and dementia with a cerebrovascular component (8) as well as recommendations for addressing ethical issues (e.g., disclosure of the diagnosis) (12). The updated literature review did not change these recommendations. An exercise program is recommended for patients with mild to moderate dementia. Physicians should decide whether to prescribe a cholinesterase inhibitor on an individual basis, balancing anticipated benefits with the potential for harm. For mild mood and behavioural concerns, nonpharmacologic approaches should be considered first. INTERPRETATION: Although the available therapies for dementia can help with the management of symptoms, there is a need to develop more effective interventions.

Diagnosis and treatment of dementia: 4. Approach to management of mild to moderate dementia.

BACKGROUND: The management of mild to moderate dementia presents complex and evolving challenges. Practising physicians are often uncertain about the appropriate approaches to issues such as the disclosure of the diagnosis, driving and caregiver support. In this article, we provide practical guidance on management based on recommendations from the Third Canadian Consensus Conference on the Diagnosis and Treatment of Dementia. METHODS: We developed evidence-based guidelines using systematic literature searches, with specific criteria for the selection and quality assessment of articles, and a clear and transparent decision-making process. We selected articles published from January 1996 to December 2005 that dealt with the management of mild to moderate stages of Alzheimer disease and other forms of dementia. Recommendations based on the literature review were drafted and voted on. Consensus required 80% or more agreement by participants. Subsequent to the conference, we searched for additional articles published from January 2006 to April 2008 using the same major keywords and secondary search terms. We graded the strength of evidence using the criteria of the Canadian Task Force on Preventive Health Care. RESULTS: We identified 1615 articles, of which 954 were selected for further study. From a synthesis of the evidence in these studies, we made 48 recommendations for the management of mild to moderate dementia (28) and dementia with a cerebrovascular component (8) as well as recommendations for addressing ethical issues (e.g., disclosure of the diagnosis) (12). The updated literature review did not change these recommendations. In brief, patients and their families should be informed of the diagnosis. Although the specifics of managing comorbid conditions might require modification, standards of care and treatment targets would not change because of a mild dementia. The use of medications with anticholinergic effects should be minimized. There should be proactive planning for driving cessation, since this will be required at some point in the course of progressive dementia. The patient's ability to drive should be determined primarily on the basis of his or her functional abilities. An important aspect of care is supporting the patient's primary caregiver. INTERPRETATION: Much has been learned about the care of patients with mild to moderate dementia and the support of their primary caregivers. There is a pressing need for the development, and dissemination, of collaborative systems of care.

Management of mild to moderate Alzheimer's disease and dementia.

The authors were charged with making a series of evidence-based recommendations that would provide concrete advice on all aspects of the management of mild to moderate stages of dementia and Alzheimer's disease (AD). The recommendations were primarily targeted to primary care physicians practicing in Canada. The assigned topic area did not include either the assessment of a patient with suspected dementia or the prevention of AD and other dementias. An extensive examination of the available literature was conducted. Explicit criteria for grading the strength of recommendations and the level of evidence supporting them were used. The 28 evidence-based recommendations agreed on are presented in this article.