Systematic review of research barriers, facilitators, and stakeholders in long-term care and geriatric settings, and a conceptual mapping framework to build research capacity.

BACKGROUND: Older adults are underrepresented in research. Heterogeneity of research processes in this population, specifically in long-term care (LTC) and geriatric acute care (GAC), is not well described and may impede the design, planning, and conduct of research. In this study, we identified, quantified, and mapped stakeholders, research stages, and transversal themes of research processes, to develop a mapping framework to improve research capacity by better characterizing this heterogeneity. METHODS: Multicomponent mixed methods study. An environmental scan was used to initiate a preliminary framework. We conducted a systematic literature search on processes, barriers, and methods for clinical research in GAC and LTC to extract and update stakeholders, research stages, and themes. Importance and interactions of elements were synthesized via heatmaps by number of articles, mentions, and content intersections. RESULTS: For our initial framework and environmental scan, we surveyed 24 stakeholders. Of 9277 records, 68 articles were included in our systematic review and allowed us to identify 12 stakeholders, 13 research stages, 17 transversal themes (either barriers, facilitators, general themes, or recommendations), and 1868 intersections. Differences in relative importance between LTC and GAC emerged for stakeholders (staff, managers vs. caregivers, ethics committees), and for research stages (funding, facility recruitment vs. ethics, individual recruitment). Crucial themes according to specific stakeholders were collaboration for the research team; communication, trust, and human resources for managers; heterogeneity for patients and residents. A heatmap framework synthesizing vital stakeholders and themes per research stage was generated. CONCLUSIONS: We identified and quantified the interactions between stakeholders, stages, and themes to characterize heterogeneity in LTC and GAC research. Our framework may serve as a blueprint to co-construct and improve each stage of the research process.

The Association Between Somatic Symptom Disorders and Neurocognitive Disorders: A Systematic Review.

OBJECTIVE: Onset of neuropsychiatric symptoms in older adults may represent prodromal manifestations of neurodegenerative disorders. The association between the onset of somatic symptom and related disorders (SSRD) and the subsequent development of neurodegenerative disorders remains unclear. A critical review of studies describing the association between SSRD and neurodegenerative disorders, such as Alzheimer's disease, Parkinson's disease, Frontotemporal dementia, and Lewy body dementia was performed. OBJECTIVE: To critically review studies describing the association between SSRD and neurodegenerative disorders, such as Alzheimer's disease, Parkinson's disease, Frontotemporal dementia, and Lewy body dementia. METHODS: A systematic review of Web of Science Core databases was carried out from inception of databases up to May 2021 to identify observational studies pertaining to both SSRD and neurodegenerative disorders. Data was extracted and compiled regarding subjects enrolled, age at onset of the SSRD and at onset of the neurodegenerative disorders, and specific SSRD manifestations and underlying neuropathologies reported. RESULTS: Thirteen articles were included. Of the 123 identified subjects with SSRD at baseline, 34.1% developed a neurodegenerative disorder, with 80.9% of these being a Lewy body spectrum disorder. The interval between onset of SSRD manifestations and subsequent development of a neurodegenerative disorder was less than 3 years for half of the cases. Of the 1,494 subjects with a neurodegenerative disorder at baseline retrieved, SSRD manifestations were reported in 33.4% of Lewy body spectrum disorders cases. Onset of SSRD manifestations antedated or was concomitant to the diagnosis of the Lewy body spectrum disorder in 65.6% of cases. CONCLUSION: While limited, current evidence suggests a possible association between late-onset SSRD and the subsequent development of neurodegenerative disorders, notably Lewy body spectrum disorders.

Institutional, therapeutic, and individual factors associated with 30-day mortality after COVID-19 diagnosis in Canadian long-term care facilities.

BACKGROUND: Canadian long-term care facility (LTCF) residents experienced higher death rates compared to other countries during the first wave of the COVID-19 pandemic. This cohort study analyzes the individual, therapeutic, and institutional factors associated with death in LTCFs. METHODS: Institutional data for 17 LTCFs in Montreal, Canada were obtained from local administrative registries. Individual data for 1197 residents infected by SARS-CoV-2 between February 23 and July 11, 2020 were obtained through chart reviews. A multivariable modified Poisson regression model, which accounted for LTCF clustering, was used to identify resident and facility covariates associated with 30-day mortality after COVID-19 diagnosis. RESULTS: Severe shortage of licensed practical nurses (RR 2.60 95% CI 1.20-5.61) and medium-sized facilities compared to smaller-sized facilities (RR 2.73 95% CI 1.23-6.07) were associated with 30-day mortality. Later COVID-19 diagnosis (RR 0.98 95% CI 0.97-0.99 per additional day) was associated with survival. Individual risk factors for death included age (RR 1.33 95% CI 1.23-1.45 per additional 10 years), male sex (RR 1.46 95% CI 1.24-1.71), functional impairment (RR 1.08 95% CI 1.04-1.12 per unit increase of SMAF), as well as a diagnosis of congestive heart failure (RR 1.31 95% CI 1.04-1.66) and neurocognitive disorder (RR 1.31 95% CI 1.01-1.70). Among severe cases, anticoagulation was associated with survival (RR 0.70 95% CI 0.51-0.96). CONCLUSIONS: This study identified practical nurse shortages and facility size as institutional risk factors for COVID-19 death. Anticoagulation was associated with survival among severe cases.

Sleep apnea and the risk of dementia: A systematic review and meta-analysis.

Sleep apnea (SA) is potentially a modifiable risk factor for dementia. However, its associations to specific aetiologies of dementia remain uncertain. A systematic review and meta-analysis of cohort studies investigating the association between sleep apnea and specific aetiologies of dementia, including Alzheimer's disease (AD), Parkinson's disease (PD), Lewy body dementia (LBD), vascular dementia (VaD), and frontotemporal dementia (FTD) was performed. The use of biomarkers to support clinical diagnoses in eligible studies was collected. Eleven studies were included, comprising 1,333,424 patients. Patients with sleep apnea had an increased risk of developing any type of neurocognitive disorder (HR: 1.43 [95% CI 1.26-1.62]), Alzheimer's disease (HR: 1.28 [95% CI 1.16-1.41]), and Parkinson's disease (HR: 1.54 [95% CI 1.30-1.84]). No statistically significant association was found for vascular dementia. One study reported a two-fold increased risk for Lewy body dementia (HR: 2.06 [95% CI 1.45-2.91]). No studies investigated the risk for frontotemporal dementia and none of the studies reported results pertaining to biomarkers. Sleep apnea is associated with a significantly increased risk of dementia, particularly for Alzheimer's disease and Parkinson's disease, but not for vascular dementia. Future studies should look at the impact of sleep apnea on specific dementia biomarkers.

Appraising clinical applicability of studies: mapping and synthesis of current frameworks, and proposal of the FrACAS framework and VICORT checklist.

BACKGROUND: Not all research findings are translated to clinical practice. Reasons for lack of applicability are varied, and multiple frameworks and criteria exist to appraise the general applicability of epidemiological and clinical research. In this two-part study, we identify, map, and synthesize frameworks and criteria; we develop a framework to assist clinicians to appraise applicability specifically from a clinical perspective. METHODS: We conducted a literature search in PubMed and Embase to identify frameworks appraising applicability of study results. Conceptual thematic analysis was used to synthesize frameworks and criteria. We carried out a framework development process integrating contemporary debates in epidemiology, findings from the literature search and synthesis, iterative pilot-testing, and brainstorming and consensus discussions to propose a concise framework to appraise clinical applicability. RESULTS: Of the 4622 references retrieved, we identified 26 unique frameworks featuring 21 criteria. Frameworks and criteria varied by scope and level of aggregation of the evidence appraised, target user, and specific area of applicability (internal validity, clinical applicability, external validity, and system applicability). Our proposed Framework Appraising the Clinical Applicability of Studies (FrACAS) classifies studies in three domains (research, practice informing, and practice changing) by examining six criteria sequentially: Validity, Indication-informativeness, Clinical relevance, Originality, Risk-benefit comprehensiveness, and Transposability (VICORT checklist). CONCLUSIONS: Existing frameworks to applicability vary by scope, target user, and area of applicability. We introduce FrACAS to specifically assess applicability from a clinical perspective. Our framework can be used as a tool for the design, appraisal, and interpretation of epidemiological and clinical studies.

The state of frailty in research: A mapping review of its clinical applicability to practice.

Research on frailty has expanded in the last decade, but direct evidence supporting its implementation in clinical practice may be limited. This mapping review synthesizes the contexts-of-use and overall clinical applicability of recent pre-COVID frailty research. We sampled 476 articles from articles published on frailty in PubMed and EMBASE in 2017-2018, of which 150 articles were fully appraised for the contexts-of-use, definitions, and interventions. A clinical applicability framework was used to classify articles as practice-changing, practice-informing, or not practice-informing. Of the 476 sampled articles, 31% (n = 150) used frailty in functions that could inform a clinical indication: predictor or mediator (26%, n = 125), selection criterion (3%, n = 15), and effect modifier (2%, n = 10). Articles spanned all health disciplines, and cohort studies comprised 91% (n = 137) of studies and trials 9% (n = 13). Thirty-eight frailty definitions using varied cut-offs and a wide range of interventions were identified. Among all articles, 13% (n = 63) of articles were practice-informing, 2% (n = 11) potentially practice-changing, and 0.2% (n = 1) clearly practice-changing. Lack of well-defined intervention and identifiable effect (96%) or originality (83%) were predominant reasons reducing applicability. Only a minority of recent frailty research provides direct evidence of applicability to practice. Future research on frailty should focus on translating frailty, as a risk factor, into a clinical indication and address definition ambiguity.

Delirium and Inflammation in Older Adults Hospitalized for COVID-19: A Cohort Study.

PURPOSE: The occurrence and predictors of delirium in older adults hospitalized for coronavirus disease 2019 (COVID-19) have not been well described. Highlighting the association with inflammatory markers may be useful for identifying delirium. This study aimed to determine the prevalence and incidence of delirium and explore its association with the C-reactive protein (CRP). PATIENTS AND METHODS: This cohort study of adults aged 65 and older with a COVID-19 diagnosis took place at an academic healthcare institution between April and May 2020. COVID-19 was diagnosed by positive nasopharyngeal swab. Serum levels of CRP were collected as a marker of systemic inflammation. The primary outcome was the prevalence and incidence of delirium. Delirium was diagnosed primarily during a patient's stay in hospital based on the Diagnostic and Statistical Manual of Mental Disorders Fifth Edition (DSM-5). To ensure that no delirium diagnosis was missed during hospital stay, clinical records were reviewed by clinicians with geriatric medicine training for retrospective diagnoses. RESULTS: A total of 127 patients aged 65 and older were hospitalized with a diagnosis of COVID-19. The median age was 82 years (IQR: 74-88), with 54 (43%) females. Overall, delirium was present in 62 (49%) patients: manifestations of delirium were present on the first day of hospitalization in 53 of these cases (86%), while 9 cases (14%) developed delirium during hospitalization. After controlling for age and sex, the mean CRP value over the first 3 days since arrival was associated with a higher risk of delirium (OR 1.35; 95% CI: 1.01-1.85) for every 50 mg/L increase. CONCLUSION: In this cohort of older adults hospitalized for COVID-19, delirium was highly prevalent. An early increase in CRP levels should raise suspicion about the occurrence of delirium and could improve its diagnosis.

Clinical Correlates and Implications of the Reliability of the Frailty Index in the Canadian Longitudinal Study on Aging.

BACKGROUND: Deficit accumulation frailty indices (FIs) are widely used to characterize frailty. FIs vary in number and composition of items; the impact of this variation on reliability and clinical applicability is unknown. METHOD: We simulated 12 000 studies using a set of 70 candidate deficits in 12 080 community-dwelling participants 65 years and older. For each study, we varied the number (5, 10, 15, 25, 35, 45) and composition (random selection) of items defining the FI and calculated descriptive and predictive estimates: frailty score, prevalence, frailty cutoff, mortality odds ratio, predicted probability of mortality for FI = 0.28 (prevalence threshold), and FI cutoff predicting 10% mortality over the follow-up. We summarized the estimates' medians and spreads (0.025-0.975 quantiles) by number of items and calculated intraclass correlation coefficients (ICCs). RESULTS: Medians of frailty scores were 0.11-0.12 with decreasing spreads from 0.04-0.24 to 0.10-0.14 for 5-item and 45-item FIs. The median cutoffs identifying 15% as frail was 0.19-0.20 and stable; the spreads decreased with more items. However, medians and spreads for the prevalence of frailty (median: 11%-3%), mortality odds ratio (median: 1.24-2.19), predicted probability of mortality (median: 8%-17%), and FI cutoff predicting 10% mortality (median: 0.38-0.20) varied markedly. ICC increased from 0.19 (5-item FIs) to 0.84 (45-item FIs). CONCLUSIONS: Variability in the number and composition of items of individual FIs strongly influences their reliability. Estimates using FIs may not be sufficiently stable for generalizing results or direct application. We propose avenues to improve the development, reporting, and interpretation of FIs.

Health Heterogeneity in Older Adults: Exploration in the Canadian Longitudinal Study on Aging.

BACKGROUND: A widely held dictum in aging research is that heterogeneity in health increases with age, but the basis for this claim has not been fully investigated. We examined heterogeneity at different ages across health characteristics to describe variation and trends; we investigated the comparative importance of between-age versus within-age heterogeneity. DESIGN: This was a cohort study. SETTING: Community-dwelling older adults. PARTICIPANTS: A total of 30,097 adults aged 45 to 86 years, from the Canadian Longitudinal Study on Aging, were included. MEASUREMENTS: Thirty-four health characteristics in eight domains (physical measures, vital signs, physiological measures, physical performance, function/disability, chronic conditions, frailty, laboratory values) were assessed cross-sectionally. We used regression models to examine heterogeneity in health characteristics (using absolute deviation) and domains (using effective variance) in relation to age. Comparison between between-age and within-age heterogeneity was quantified by estimating the age threshold at which the former exceeds the latter. RESULTS: Of the 34 health characteristics, 17 showed increased heterogeneity, 8 decreased, and 9 no association with age. The associations between heterogeneity and age increased generally but were nonlinear for most domains and nonmonotonic for some. We observed peak heterogeneity at approximately 70 years. Between-age heterogeneity, compared with within-age heterogeneity, was most important for forced expiratory volume in 1 second and grip strength but varied across characteristics. CONCLUSION: Overall health heterogeneity increases with age but does not uniformly increase across all variables and domains. Heterogeneity in aging reinforces the need for geriatric assessment and personalized care, depending on which health characteristics are assessed, their measurement properties, and their referent group. Our findings suggest further research to develop improved single-dimension and multidimensional instruments, as well as specific vital and laboratory reference ranges for older adults.

Predicting Risk of Atherosclerotic Cardiovascular Disease Using Pooled Cohort Equations in Older Adults With Frailty, Multimorbidity, and Competing Risks.

Background Assessment of atherosclerotic cardiovascular disease (ASCVD) risk is crucial for prevention and management, but the performance of the pooled cohort equations in older adults with frailty and multimorbidity is unknown. We evaluated the pooled cohort equations in these subgroups and the impact of competing risks. Methods and Results In 4249 community-dwelling adults, aged ≥65 years, from the CHS (Cardiovascular Health Study), we calculated 10-year risk of hard ASCVD. Frailty was determined using the Fried phenotype. Latent class analysis was used to identify individuals with multimorbidity patterns using chronic conditions. We assessed discrimination using the C-statistic and calibration by comparing predicted ASCVD risks with estimated risk using cause-specific and cumulative incidence models, by multimorbidity patterns and frailty status. A total of 917 (21.6%) participants had an ASCVD event, and 706 (16.6%) had a competing event of death. C-statistic was 0.68 in men and 0.69 in women; calibration was good when compared with cause-specific and cumulative incidence estimated risks (males, -0.1% and 3.3%; females, 0.6% and 1.4%). Latent class analysis identified 4 patterns: minimal disease, cardiometabolic, low cognition, musculoskeletal-lung depression. In the cardiometabolic pattern, ASCVD risk was overpredicted compared with cumulative incidence risk in men (7.4%) and women (6.8%). Risk was underpredicted in men (-10.7%) and women (-8.2%) with frailty compared with cause-specific risk. Miscalibration occurred mostly at high predicted risk ranges. Conclusions ASCVD prediction was good in this cohort of adults aged ≥65 years. Although calibration varied by multimorbidity patterns, frailty, and competing risks, miscalibration was mostly present at high predicted risk ranges and thus less likely to alter decision making for primary prevention therapy.

Investigation of Methods to Extract Fetal Electrocardiogram from the Mother's Abdominal Signal in Practical Scenarios.

Monitoring of fetal electrocardiogram (fECG) would provide useful information about fetal wellbeing as well as any abnormal development during pregnancy. Recent advances in flexible electronics and wearable technologies have enabled compact devices to acquire personal physiological signals in the home setting, including those of expectant mothers. However, the high noise level in the daily life renders long-entrenched challenges to extract fECG from the combined fetal/maternal ECG signal recorded in the abdominal area of the mother. Thus, an efficient fECG extraction scheme is a dire need. In this work, we intensively explored various extraction algorithms, including template subtraction (TS), independent component analysis (ICA), and extended Kalman filter (EKF) using the data from the PhysioNet 2013 Challenge. Furthermore, the modified data with Gaussian and motion noise added, mimicking a practical scenario, were utilized to examine the performance of algorithms. Finally, we combined different algorithms together, yielding promising results, with the best performance in the F1 score of 92.61% achieved by an algorithm combining ICA and TS. With the data modified by adding different types of noise, the combination of ICA-TS-ICA showed the highest F1 score of 85.4%. It should be noted that these combined approaches required higher computational complexity, including execution time and allocated memory compared with other methods. Owing to comprehensive examination through various evaluation metrics in different extraction algorithms, this study provides insights into the implementation and operation of state-of-the-art fetal and maternal monitoring systems in the era of mobile health.

The Interplay Between Post-traumatic Stress Disorder and Dementia: A Systematic Review.

BACKGROUND: Post-traumatic stress disorder (PTSD) has been reported to increase the risk for dementia in veterans and civilians. Conversely, case reports have described the delayed onset of PTSD in individuals developing dementia, suggesting a complex relationship between these two conditions. OBJECTIVES: To critically review studies investigating the association between PTSD and dementia and to assess the evidence for a bidirectional relationship between the two conditions. METHODS: A systematic review of Web of Science Core databases was carried out from inception of databases up to November 2018 to identify observational studies pertaining to both PTSD and dementia. Populations enrolled, stressors and neuropathologies, and main outcomes of studies were extracted, in addition to age at trauma and at onset of PTSD and dementia. The different temporal relationships between trauma and onset of the conditions were characterized. RESULTS: Twenty-five articles were included in the review; 14 articles assessed the association of PTSD with subsequent dementia and 11 articles reported the delayed onset of PTSD with the onset of dementia. Most reported traumas occurred in early-life (<40 years) and were related to war combat experiences. PTSD in mid-life (between 40 and 60 years of age) was associated with an increased risk of late-onset dementia. Numerous case series reported the delayed onset of PTSD in Alzheimer's disease and vascular dementia. CONCLUSION: Current evidence suggests that PTSD and dementia have a bidirectional relationship: PTSD increases the risk for late-onset dementia and dementia increases the risk for delayed-onset PTSD in those who experienced a significant trauma earlier in life.

Anaemia and depletion of iron stores as risk factors for postpartum depression: a literature review.

PURPOSE: Iron-deficiency and anaemia are common in pregnant and postpartum women because of increasing iron demand and blood loss. Many women also enter pregnancy with pre-depleted iron stores. We reviewed the evidence linking anaemia and/or iron-deficiency to postpartum depression (PPD). METHODS: We identified seventeen studies in four databases including randomized-controlled trials (RCTs) and observational studies assessing the impact of anaemia, iron-deficiency and iron supplementation on the risk of PPD. We extracted data on sample size, geographical region, obstetrical complications, measures of depression, haemoglobin, iron levels and intake of iron supplementation and critically appraised the results from the studies. RESULTS: Eight out of ten studies found higher risk for PPD (r - 0.19 to -0.43 and ORs 1.70-4.64) in anaemic women. Low ferritin in the postpartum period but not during pregnancy was associated with increased risk of PPD. Iron supplementation in the postpartum period decreased risk of PPD in four out of five studies, whereas it did not protect from PPD if given during pregnancy. Limitations include study heterogeneity, discrepancy of prevalence of PPD and usage of a screening tool for evaluation of PPD. CONCLUSION: Anaemia and/or iron-deficiency may contribute to PPD in at-risk women. Further studies should elucidate the association between these entities.

Multimorbidity Patterns, Frailty, and Survival in Community-Dwelling Older Adults.

BACKGROUND: Frailty and multimorbidity are independent prognostic factors for mortality, but their interaction has not been fully explored. We investigated the importance of multimorbidity patterns in older adults with the same level of frailty phenotype. METHODS: In a cohort of 7,197 community-dwelling adults aged 65 years and older, physical frailty status (robust, pre-frail, frail) was defined using shrinking, exhaustion, inactivity, slowness, and weakness. Latent class analysis was used to identify individuals with multimorbidity patterns based on 10 self-reported chronic conditions. We estimated hazard ratios (HR) and incidence rate differences (IRDs) for mortality comparing multimorbidity patterns within each frailty state. RESULTS: Five multimorbidity classes were identified: minimal disease (24.7%), cardiovascular disease (29.0%), osteoarticular disease (27.3%), neuropsychiatric disease (8.9%), and high multisystem morbidity (10.0%). Within each frailty state, the mortality rate per 1,000 person-years over 4 years was greatest in the neuropsychiatric class and lowest in the minimal disease class: robust (56.3 vs 15.7; HR, 2.11 [95% CI: 1.05, 4.21]; IRD, 24.1 [95% CI: -11.2, 59.3]), pre-frail (85.3 vs 40.4; HR, 1.74 [95% CI: 1.28, 2.37]; IRD, 27.1 [95% CI: 7.6, 46.7]), and frail (218.1 vs 96.4; HR, 2.05 [95% CI: 1.36, 3.10]; IRD, 108.4 [95% CI: 65.0, 151.9]). Although HRs did not vary widely by frailty, the excess number of deaths, as reflected by IRDs, increased with greater frailty level. CONCLUSIONS: Considering both multimorbidity patterns and frailty is important for identifying older adults at greater risk of mortality. Of the five patterns identified, the neuropsychiatric class was associated with lower survival across all frailty levels.

Home-based mobile fetal/maternal electrocardiogram acquisition and extraction with cloud assistance.

Electrocardiogram (ECG) monitoring of the fetus during pregnancy, before and during labor, can provide crucial information for the assessment of fetal well-being and development, as well as labor progress. An out-of-clinics fetal ECG monitoring system may pave the way for instant diagnosis, suggesting immediate intervention, which could help reduce the fetal mortality rate. In this paper, we present an unobtrusive fetal maternal ECG monitoring system which can operate in the home setting. The acquisition of the mother's abdominal ECG is done using the non-contact electrode approach. The extraction of the fetal ECG from the combined fetal/maternal ECG signal is investigated using both Fast Independent Component Analysis (FastICA) and RobustICA algorithms. An accelerometer is integrated for motion artifact detection which would help reduce interferences due to movement. The device also is connected to a cloud server, allowing doctors to access the data in real time.

Therapeutic trial design for frontotemporal dementia and related disorders.

The frontotemporal dementia (FTD) spectrum is a heterogeneous group of neurodegenerative syndromes with overlapping clinical, molecular and pathological features, all of which challenge the design of clinical trials in these conditions. To date, no pharmacological interventions have been proven effective in significantly modifying the course of these disorders. This study critically reviews the construct and methodology of previously published randomised controlled trials (RCTs) in FTD spectrum disorders in order to identify limitations and potential reasons for negative results. Moreover, recommendations based on the identified gaps are elaborated in order to guide future clinical trial design. A systematic literature review was carried out and presented in conformity with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses criteria. A total of 23 RCTs in cohorts with diagnoses of behavioural and language variants of FTD, corticobasal syndrome and progressive supranuclear palsy syndrome were identified out of the 943 citations retrieved and were included in the qualitative review. Most studies identified were early-phase clinical trials that were small in size, short in duration and frequently underpowered. Diagnoses of populations enrolled in clinical trials were based on clinical presentation and rarely included precision-medicine tools, such as genetic and molecular testing. Uniformity and standardisation of research outcomes in the FTD spectrum are essential. Several elements should be carefully considered and planned in future clinical trials. We anticipate that precision-medicine approaches will be crucial to adequately address heterogeneity in the FTD spectrum research.