Trends in Hyperpolypharmacy Before and After Nursing Home Admission Among Older Adults in Ontario, Canada.

OBJECTIVES: To examine trends in the prevalence of hyperpolypharmacy prior to and following nursing home admission in Ontario, Canada. METHODS: We conducted a cohort study of adults aged 75+ years admitted to nursing homes between 2017 and 2020 using health administrative data (n = 61,470). The prevalence of hyperpolypharmacy (≥10 dispensed drugs) was assessed quarterly from ten years prior to 1.5 years following admission. RESULTS: Over ten years, the prevalence of hyperpolypharmacy increased from 4.4% to 12.0% (+0.2% per quarter, [p <0.001]) and further increased after admission (13.8%). Antidepressants (three-fold), antipsychotics (seven-fold) and cholinesterase inhibitors (14-fold) increased significantly over ten years prior to admission, while cardiovascular medications peaked 4 to 5 years prior to admission. CONCLUSIONS: While hyperpolypharmacy increased nearly three-fold in the ten years prior to nursing home admission, patterns varied by drug class. Increasing hyperpolypharmacy throughout the life course suggests opportunities exist for medication reconciliation in community and nursing home settings.

An optimised method to isotopically label pure synthetic peptides 'in-house' for absolute quantification in bottom-up proteomics.

RATIONALE: Heavy-labelled internal standards increasingly represent the gold standard for absolute quantitation in mass spectrometry (MS)-based bottom-up proteomics. The biggest drawbacks of using these standards are that they have high costs and lengthy lead times. METHODS: We describe an efficient, low-cost optimised method to enable 'in-house' heavy labelling of synthetic tryptic peptides for absolute quantification using tandem LC-MS/MS mass spectrometry. Our methodology uses 18O water in a trypsin-catalysed oxygen exchange reaction at the carboxyl terminus with the overall aim of reducing the costs and lead time associated with sourcing heavy standards from commercial vendors. RESULTS: Step-by-step instructions are provided on how to execute this protocol with high-throughput adaptations utilising a 96-well plate and a liquid-handling robot. Detailed notes on experimental setup, tips for troubleshooting and suggested improvements to maximise labelling efficiencies are highlighted to achieve the best results. Under optimum conditions, labelling efficiencies of peptides can reach from 95% to 100%. CONCLUSIONS: The application of the 'in-house' labelled standards in generating calibration curves to quantify endogenous peptide concentrations is just as effective as using the synthetically sourced standards while also having great cost reduction implications as well as saving time spent waiting for peptides to arrive. The protocol is highly adaptable and can be customized to fit the specific setup of any laboratory, maximizing achievable labelling efficiencies.

Functional Social Support Subtypes Are Associated With Executive Function in Middle-Aged and Older Adults: Findings From the Baseline Comprehensive Cohort of the Canadian Longitudinal Study on Aging.

OBJECTIVES: We investigated whether functional social support-the degree to which one perceives support is available when needed-is associated with executive function, a key cognitive domain for everyday functioning and adaptation to change. METHODS: Analyses (n = 23,491) utilized cross-sectional data from the Comprehensive cohort of the Canadian Longitudinal Study on Aging (CLSA), a population-based study of community-dwelling adults aged 45-85 years. Executive function was assessed by neurocognitive battery. Perceived social support was measured using the 19-item Medical Outcomes Study-Social Support Survey. Logistic regression models were adjusted for sociodemographic, health, and social covariates. RESULTS: Positive social interactions as well as affectionate and emotional/informational functional social support were positively associated with executive function. DISCUSSION: Social support plays an important role in cognitive health. Diversifying social programming beyond tangible social support to target other subtypes of support may help preserve executive function in middle-aged and older adults.

Investigation of health care use and a possible prodrome before the first attack in NMOSD and MOGAD.

BACKGROUND: Prodromal phases are well recognized in many inflammatory and neurodegenerative diseases, including multiple sclerosis. We evaluated the possibility of a prodrome in aquaporin-4 antibody positive (AQP4+) neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein antibody disease (MOGAD) using health administrative data. METHODS: We investigated individuals with AQP4 + NMOSD and MOGAD, confirmed by medical chart review, in Ontario, Canada. Each NMOSD and MOGAD participant was matched 1:5 to general population controls by sex, birth year, immigrant status, and region. Total outpatient visits and hospitalizations were compared in the 5 years preceding the incident attack in multivariable negative binomial models. RESULTS: We identified 96 people with AQP4 + NMOSD, matched to 479 controls, and 61 people with MOGAD, matched to 303 controls. In the 5 years preceding the incident attack, health care use was elevated for outpatient visits and hospitalizations for the NMOSD cohort (adjusted rate ratio (aRR): 1.47; 95% confidence interval (CI): 1.25-1.73; aRR: 1.67; 95% CI: 1.19-2.36, respectively) but not for MOGAD. Rate ratios steadily increased in NMOSD for outpatient visits in the 2 years preceding the incident attack. CONCLUSION: Our findings support a prodromal phase preceding clinical onset of AQP4 + NMOSD. Earlier recognition and management of NMOSD patients may be possible.

Prescribing Trends for Oral Vancomycin and Fidaxomicin after Guideline and Formulary Changes in Ontario, Canada: An Interrupted Time-Series Analysis.

Background: Clostridioides difficile is a pathogen causing diarrheal illness, which can be treated with vancomycin or fidaxomicin. Objective: To evaluate changes in monthly prescription volumes for oral vancomycin and fidaxomicin in Ontario community pharmacies following implementation of the 2017 and 2021 updates to guidelines from the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA) and after a 2019 provincial formulary change for vancomycin. Methods: An interrupted time-series analysis was conducted from November 2015 to October 2021 using monthly projected prescription volumes obtained from IQVIA's Compuscript database. Level and slope (trend) changes in prescribing were assessed using segmented linear regression. Results: The volume of vancomycin prescriptions increased by 74 prescriptions per month (95% confidence interval [CI] 16 to 132) following implementation of the 2017 guideline update and by 73 prescriptions per month (95% CI 13 to 133) after the 2019 formulary change; however, no statistically significant changes were observed after implementation of the 2021 guideline update. No significant trend changes were observed for fidaxomicin. Conclusion: Guidelines and formulary changes were correlated with increased volume of vancomycin prescriptions.

Contexte: Le Clostridioides difficile est un agent pathogène provoquant une maladie diarrhéique pouvant être traitée avec de la vancomycine ou de la fidaxomicine. Objectif: Évaluer les changements de volume mensuel des prescriptions de vancomycine et de fidaxomicine par voie orale dans les pharmacies communautaires de l'Ontario après la mise en œuvre des lignes directrices actualisées en 2017 et 2021 de l'Infectious Diseases Society of America (IDSA) et de la Society for Healthcare Epidemiology of America (SHEA) et à la suite d'une modification au régime d'assurance-médicaments pour la vancomycine à l'échelle provinciale en 2019. Méthodologie: Une analyse de séries chronologiques interrompues a été réalisée de novembre 2015 à octobre 2021 à l'aide des volumes mensuels de prescriptions projetés qui ont été obtenus grâce à la base de données Compuscript d'IQVIA. Les changements du volume des prescriptions et de son évolution dans le temps (le niveau et la pente, respectivement) ont été évalués à l'aide d'une régression linéaire segmentée. Résultats: Le volume des prescriptions de vancomycine a augmenté de 74 prescriptions par mois (intervalle de confiance [IC] à 95 % 16­132) après la mise en œuvre des lignes directrices actualisées en 2017; il a augmenté de 73 prescriptions par mois (IC à 95 % 13­133) après la modification du régime d'assurance-médicaments de 2019; cependant, aucun changement statistiquement significatif n'a été observé après la mise en œuvre des lignes directrices actualisées en 2021. Aucun changement significatif de tendance n'a été observé pour la fidaxomicine. Conclusion: Les lignes directrices et les modifications du régime d'assurance-médicaments étaient corrélées à une augmentation du volume des prescriptions de vancomycine.

Associations between specialized dementia care, COVID-19 and central nervous system medication use in assisted living: a population-based repeated cross-sectional study.

BACKGROUND: Assisted living (AL) is an increasingly common residential setting for persons with dementia; yet concerns exist about sub-optimal care of this population in AL given its lower levels of staffing and services. Our objectives were to (i) examine associations between AL setting (dementia care vs. other), COVID-19 pandemic waves, and prevalent antipsychotic, antidepressant, anti-dementia, benzodiazepine, and anticonvulsant drug use among residents with dementia/cognitive impairment, and (ii) explore associations between resident and home characteristics and prevalent medication use. METHODS: We conducted a population-based, repeated cross-sectional study using linked clinical and health administrative databases for all publicly funded AL homes in Alberta, Canada, examined between January 2018 - December 2021. The quarterly proportion of residents dispensed a study medication was examined for each setting and period (pandemic vs. comparable historical [2018/2019 combined]) focusing on four pandemic waves (March-May 2020, September 2020-February 2021, March-May 2021, September-December 2021). Log-binomial GEE models estimated prevalence ratios (PR) for period (pandemic vs. historical periods), setting (dementia care vs. other) and period-setting interactions, adjusting for resident (age, sex) and home (COVID-19 cases, health region, ownership) characteristics. RESULTS: On March 1, 2020, there were 2,779 dementia care and 3,013 other AL residents (mean age 83, 69% female) with dementia/cognitive impairment. Antipsychotic use increased during waves 2-4 in both settings, but this was more pronounced in dementia care than other AL during waves 3 and 4 (e.g., adjusted [adj]PR 1.20, 95% CI 1.14-1.27 vs. adjPR 1.09, 95% CI 1.02-1.17, interaction p = 0.023, wave 3). Both settings showed a statistically significant but modest increase in antidepressant use and decrease in benzodiazepine use. For dementia care AL residents only, there was a statistically significant increase in gabapentinoid use during several waves (e.g., adjPR 1.32, 95% CI 1.10-1.59, wave 3). Other than a modest decrease in prevalent anti-dementia drug use for both settings in wave 2, no other significant pandemic effects were observed. CONCLUSIONS: The persistence of the pandemic-associated increase in antipsychotic and antidepressant use in AL residents coupled with a greater increase in antipsychotic and gabapentinoid use for dementia care settings raises concerns about the attendant risks for residents with cognitive impairment.

Association of Disease Trajectory and Place of Care with End-of-Life Burdensome Transitions: A Retrospective Cohort Study.

OBJECTIVES: End-of-life (EOL) transitions to hospital can be burdensome for older adults and may contribute to poor outcomes. We investigated the association of disease trajectory and place of care with EOL burdensome transitions. DESIGN: Retrospective cohort study using administrative data. SETTING/PARTICIPANTS: Ontarians aged ≥65 years who died between 2015 and 2018 and received long-term care (LTC) or home care 6 months before death. METHODS: Disease trajectories were defined based on EOL functional decline: terminal illness, organ failure, frailty, sudden death, and other. Places of care included LTC, EOL home care, and non-EOL home care. Burdensome transitions were defined as early (≥3 hospitalizations for any reason or ≥2 hospitalizations due to pneumonia, urinary tract infection, sepsis, or dehydration in the last 90 days of life) or late (≥1 hospitalizations for any reason in the last 3 days of life). Multinomial logistic regression tested for effect modification between disease trajectory and places of care on burdensome transitions. RESULTS: Of 110,776 decedents, 40.7% had organ failure, 37.5% had frailty, and 12.8% had a terminal illness, with the remainder in sudden death or other categories. Most were in LTC (62.5%), and 37.5% received home care, with 6.8% receiving designated EOL home care and 30.7% non-EOL home care. There was a significant interaction (P < .001) between disease trajectory and care settings. Compared with terminal illness, organ failure was associated with increased odds of early transitions across all care settings [odds ratios (ORs) ranging 1.14-1.21]. Frailty was associated with increased odds of early transitions solely for non-EOL home care recipients (OR 1.17, 95% CI 1.06-1.28). Organ failure and frailty were associated with increased odds of late transitions across all settings, with organ failure having greater odds in LTC (organ failure OR 2.29, 95% CI 2.02-2.60, vs frailty OR 1.79, 95% CI 1.58-2.04). CONCLUSIONS AND IMPLICATIONS: Disparities exist in burdensome transitions, notably for noncancer decedents with organ failure in LTC. Enhancing palliative care may help reduce burdensome transitions and improve patient outcomes.

EXploring Patterns of Use and Effects of Adult Day Programs to Improve Trajectories of Continuing Care (EXPEDITE): Protocol for a Retrospective Cohort Study.

BACKGROUND: Adult day programs provide critical supports to older adults and their family or friend caregivers. High-quality care in the community for as long as possible and minimizing facility-based continuing care are key priorities of older adults, their caregivers, and health care systems. While most older adults in need of care live in the community, about 10% of newly admitted care home residents have relatively low care needs that could be met in the community with the right supports. However, research on the effects of day programs is inconsistent. The methodological quality of studies is poor, and we especially lack robust, longitudinal research. OBJECTIVE: Our research objectives are to (1) compare patterns of day program use (including nonuse) by province (Alberta, British Columbia, and Manitoba) and time; (2) compare characteristics of older adults by day program use pattern (including nonuse), province, and time; and (3) assess effects of day programs on attendees, compared with a propensity score-matched cohort of older nonattendees in the community. METHODS: In this population-based retrospective cohort study, we will use clinical and health administrative data of older adults (65+ years of age) who received publicly funded continuing care in the community in the Canadian provinces of Alberta, British Columbia, and Manitoba between January 1, 2012, and December 31, 2024. We will compare patterns of day program use between provinces and assess changes over time. We will then compare characteristics of older adults (eg, age, sex, physical or cognitive disability, area-based deprivation indices, and caregiver availability or distress) by pattern of day program use or nonuse, province, and time. Finally, we will create a propensity score-matched comparison group of older adults in the community, who have not attended a day program. Using time-to-event models and general estimating equations, we will assess whether day program attendees compared with nonattendees enter care homes later; use emergency, acute, or primary care less frequently; experience less cognitive and physical decline; and have better mental health. RESULTS: This will be a 3-year study (July 1, 2024, to June 30, 2027). We received ethics approvals from the relevant ethics boards. Starting on July 1, 2024, we will work with the 3 provincial health systems on data access and linkage, and we expect data analyses to start in early 2025. CONCLUSIONS: This study will generate robust Canadian evidence on the question whether day programs have positive, negative, or no effects on various older adult and caregiver outcomes. This will be a prerequisite to improving the quality of care provided to older adults in day programs, ultimately improving the quality of life of older adults and their caregivers. TRIAL REGISTRATION: ClinicalTrials.gov NCT06440447; https://clinicaltrials.gov/study/NCT06440447. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/60896.

Comparison of hospitalization events among residents of assisted living and nursing homes during COVID-19: Do settings respond differently during public health crises?

BACKGROUND: COVID-19 and resulting health system and policy decisions led to significant changes in healthcare use by nursing homes (NH) residents. It is unclear whether healthcare outcomes were similarly affected among older adults in assisted living (AL). This study compared hospitalization events in AL and NHs during COVID-19 pandemic waves 1 through 4, relative to historical periods. METHODS: This was a population-based, repeated cross-sectional study using linked clinical and health administrative databases (January 2018 to December 2021) for residents of all publicly subsidized AL and NH settings in Alberta, Canada. Setting-specific monthly cohorts were derived for pandemic (starting March 1, 2020) and comparable historical (2018/2019 combined) periods. Monthly rates (per 100 person-days) of all-cause hospitalization, hospitalization with delayed discharge, and hospitalization with death were plotted and rate ratios (RR) estimated for period (pandemic wave vs historical comparison), setting (AL vs NH) and period-setting interactions, using Poisson regression with generalized estimating equations, adjusting for resident and home characteristics. RESULTS: On March 1, 2020, there were 9,485 AL and 14,319 NH residents, comparable in age (mean 81 years), sex (>60% female) and dementia prevalence (58-62%). All-cause hospitalization rates declined in both settings during waves 1 (AL: adjusted RR 0.60, 95%CI 0.51-0.71; NH: 0.74, 0.64-0.85) and 4 (AL: 0.76, 0.66-0.88; NH: 0.65, 0.56-0.75) but unlike NHs, AL rates were not significantly lower during wave 2 (and increased 27% vs NH, January 2021). Hospitalization with delayed discharge increased in NHs only (during and immediately after wave 1). Both settings showed a significant increase in hospitalization with death in wave 2, this increase was larger and persisted longer for AL. CONCLUSIONS: Pandemic-related changes in hospitalization events differed for AL and NH residents and by wave, suggesting unique system and setting factors driving healthcare use and outcomes in these settings in response to this external stress.

Antipsychotic Discontinuation and New Trazodone Use in Ontario Nursing Homes: Evidence of Medication Substitution.

OBJECTIVES: An unintended consequence of efforts to reduce antipsychotic medications in nursing homes is the increase in use of other psychotropic medications; however, evidence of substitution remains limited. Our objective was to measure individual-level prescribing patterns consistent with substitution of trazodone for antipsychotics. DESIGN: Retrospective cohort study. SETTING AND PARTICIPANTS: Residents of Ontario nursing homes aged 66-105 years with an admission assessment between April 1, 2010, and March 31, 2019, who were receiving an antipsychotic and had no antidepressant medication use at admission to the nursing home. METHODS: We used linked health administrative data to examine changes in medication use over three quarterly assessments following admission. Antipsychotic and trazodone use were measured at each assessment. The rate of trazodone initiation was compared between residents no longer dispensed an antipsychotic (discontinued) and those with an ongoing antipsychotic (continued) using discrete time survival analysis, controlling for baseline resident characteristics. RESULTS: We identified 13,306 residents dispensed an antipsychotic with no antidepressant use at admission (mean age 84 years, 61.5% women, 82.8% with dementia). As of the first quarterly assessment, nearly 20% of residents no longer received an antipsychotic and 9% received a new trazodone medication. Over time, residents who discontinued antipsychotics had a rate of trazodone initiation that was 82% higher compared to residents who continued (adjusted hazard ratio 1.82, 95% CI 1.66-2.00). CONCLUSIONS AND IMPLICATIONS: Residents admitted to a nursing home with antipsychotic use had a higher rate of trazodone initiation if they discontinued (vs continued) an antipsychotic. These findings suggest antipsychotic substitution with trazodone after entering a nursing home.

The Effect of COVID-19 Vaccination on Outpatient Antibiotic Prescribing in Older Adults: A Self-Controlled Risk-Interval Study.

BACKGROUND: Coronavirus disease 2019 (COVID-19) vaccination has been associated with reduced outpatient antibiotic prescribing among older adults with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We assessed the impact of COVID-19 vaccination on outpatient antibiotic prescribing in the broader population of older adults, regardless of SARS-CoV-2 infection status. METHODS: We included adults aged ≥65 years who received their first, second, and/or third COVID-19 vaccine dose from December 2020 to December 2022. We used a self-controlled risk-interval design and included cases who received an antibiotic prescription 2-6 weeks before vaccination (pre-vaccination or control interval) or after vaccination (post-vaccination or risk interval). We used conditional logistic regression to estimate the odds of being prescribed (1) any antibiotic, (2) a typical "respiratory" infection antibiotic, or (3) a typical "urinary tract" infection antibiotic (negative control) in the post-vaccination interval versus the pre-vaccination interval. We accounted for temporal changes in antibiotic prescribing using background monthly antibiotic prescribing counts. RESULTS: 469 923 vaccine doses met inclusion criteria. The odds of receiving any antibiotic or a respiratory antibiotic prescription were lower in the post-vaccination versus pre-vaccination interval (aOR, .973; 95% CI, .968-.978; aOR, .961; 95% CI, .953-.968, respectively). There was no association between vaccination and urinary antibiotic prescriptions (aOR, .996; 95% CI, .987-1.006). Periods with high (>10%) versus low (<5%) SARS-CoV-2 test positivity demonstrated greater reductions in antibiotic prescribing (aOR, .875; 95% CI, .845-.905; aOR, .996; 95% CI, .989-1.003, respectively). CONCLUSIONS: COVID-19 vaccination was associated with reduced outpatient antibiotic prescribing in older adults, especially during periods of high SARS-CoV-2 circulation.

Excess Deaths in Assisted Living and Nursing Homes during the COVID-19 Pandemic in Alberta, Canada.

OBJECTIVES: Assisted living (AL) is a significant and growing congregate care option for vulnerable older adults designed to reduce the use of nursing homes (NHs). However, work on excess mortality in congregate care during the COVID-19 pandemic has primarily focused on NHs with only a few US studies examining AL. The objective of this study was to assess excess mortality among AL and NH residents with and without dementia or significant cognitive impairment in Alberta, Canada, during the first 2 years of the COVID-19 pandemic, relative to the 3 years before. DESIGN: Population-based, retrospective cohort study. SETTING AND PARTICIPANTS: Residents who lived in an AL or NH facility operated or contracted by the Provincial health care system to provide publicly funded care in Alberta between January 1, 2017, and December 31, 2021. METHODS: We used administrative health care data, including Resident Assessment Instrument - Home Care (RAI-HC, AL) and Minimum Data Set 2.0 (RAI-MDS 2.0, NHs) records, linked with data on residents' vital statistics, COVID-19 testing, emergency room registrations, and hospital stays. The outcome was excess deaths during COVID-19 (ie, the number of deaths beyond that expected based on pre-pandemic data), estimated, using overdispersed Poisson generalized linear models. RESULTS: Overall, the risk of excess mortality [adjusted incidence rate ratio (95% confidence interval)] was higher in ALs than in NHs [1.20 (1.14-1.26) vs 1.10 (1.07-1.13)]. Weekly peaks in excess deaths coincided with COVID-19 pandemic waves and were higher among those with diagnosed dementia or significant cognitive impairment in both, AL and NHs. CONCLUSIONS AND IMPLICATIONS: Finding excess mortality within both AL and NH facilities should lead to greater focus on infection prevention and control measures across all forms of congregate housing for vulnerable older adults. The specific needs of residents with dementia in particular will have to be addressed.

The association between memory, COVID-19 testing, and COVID-19 incidence in middle-aged and older adults: a prospective analysis of the CLSA.

We investigated the association between pre-COVID-19 memory function and (a) receipt of a COVID-19 test and (b) incidence of COVID-19 using the COVID-19 Questionnaire Study (CQS) of the Canadian Longitudinal Study on Aging (CLSA). The CQS included 28,565 middle-aged and older adults. We regressed receipt of a COVID-19 test on participants' immediate and delayed recall memory scores and re-ran the regression models with COVID-19 incidence as the outcome. All regression models were adjusted for sociodemographic, lifestyle, and health covariates. In the analytical sample (n = 21,930), higher delayed recall memory (better memory) was significantly associated with lower COVID-19 incidence. However, this association was not significant for immediate recall memory. Immediate and delayed recall memory were not associated with receipt of a COVID-19 test. Health policymakers and practitioners may viewmemory status as a potential risk for COVID-19. Memory status may not be a barrier to COVID-19 testing.

Use of Nonhuman Sera as a Highly Cost-Effective Internal Standard for Quantitation of Multiple Human Proteins Using Species-Specific Tryptic Peptides: Applicability in Clinical LC-MS Analyses.

Quantitation of proteins using liquid chromatography-tandem mass spectrometry (LC-MS/MS) is complex, with a multiplicity of options ranging from label-free techniques to chemically and metabolically labeling proteins. Increasingly, for clinically relevant analyses, stable isotope-labeled (SIL) internal standards (ISs) represent the "gold standard" for quantitation due to their similar physiochemical properties to the analyte, wide availability, and ability to multiplex to several peptides. However, the purchase of SIL-ISs is a resource-intensive step in terms of cost and time, particularly for screening putative biomarker panels of hundreds of proteins. We demonstrate an alternative strategy utilizing nonhuman sera as the IS for quantitation of multiple human proteins. We demonstrate the effectiveness of this strategy using two high abundance clinically relevant analytes, vitamin D binding protein [Gc globulin] (DBP) and albumin (ALB). We extend this to three putative risk markers for cardiovascular disease: plasma protease C1 inhibitor (SERPING1), annexin A1 (ANXA1), and protein kinase, DNA-activated catalytic subunit (PRKDC). The results show highly specific, reproducible, and linear measurement of the proteins of interest with comparable precision and accuracy to the gold standard SIL-IS technique. This approach may not be applicable to every protein, but for many proteins it can offer a cost-effective solution to LC-MS/MS protein quantitation.

Circulating sphingolipids and relationship to cardiac remodelling before and following a low-energy diet in asymptomatic Type 2 Diabetes.

BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) is a heterogenous multi-system syndrome with limited efficacious treatment options. The prevalence of Type 2 diabetes (T2D) continues to rise and predisposes patients to HFpEF, and HFpEF remains one of the biggest challenges in cardiovascular medicine today. Novel therapeutic targets are required to meet this important clinical need. Deep phenotyping studies including -OMIC analyses can provide important pathogenic information to aid the identification of such targets. The aims of this study were to determine; 1) the impact of a low-energy diet on plasma sphingolipid/ceramide profiles in people with T2D compared to healthy controls and, 2) if the change in sphingolipid/ceramide profile is associated with reverse cardiovascular remodelling. METHODS: Post-hoc analysis of a randomised controlled trial (NCT02590822) including adults with T2D with no cardiovascular disease who completed a 12-week low-energy (∼810 kcal/day) meal-replacement plan (MRP) and matched healthy controls (HC). Echocardiography, cardiac MRI and a fasting blood for lipidomics were undertaken pre/post-intervention. Candidate biomarkers were identified from case-control comparison (fold change > 1.5 and statistical significance p < 0.05) and their response to the MRP reported. Association between change in biomarkers and change indices of cardiac remodelling were explored. RESULTS: Twenty-four people with T2D (15 males, age 51.1 ± 5.7 years), and 25 HC (15 male, 48.3 ± 6.6 years) were included. Subjects with T2D had increased left ventricular (LV) mass:volume ratio (0.84 ± 0.13 vs. 0.70 ± 0.08, p < 0.001), increased systolic function but impaired diastolic function compared to HC. Twelve long-chain polyunsaturated sphingolipids, including four ceramides, were downregulated in subjects with T2D at baseline. Three sphingomyelin species and all ceramides were inversely associated with LV mass:volume. There was a significant increase in all species and shift towards HC following the MRP, however, none of these changes were associated with reverse cardiac remodelling. CONCLUSION: The lack of association between change in sphingolipids/ceramides and reverse cardiac remodelling following the MRP casts doubt on a causative role of sphingolipids/ceramides in the progression of heart failure in T2D. TRIAL REGISTRATION: NCT02590822.

Incidence and prevalence of paediatric-onset multiple sclerosis in two Canadian provinces: a population-based study representing over half of Canada's population.

BACKGROUND: Population-based studies estimating the epidemiology of paediatric-onset multiple sclerosis (PoMS) are scarce. METHODS: We accessed population-based health administrative data from two provinces in Canada, Ontario and British Columbia (BC). Individuals with PoMS were identified via a validated case definition. The index date ('MS onset') was the first demyelinating or MS specific claim recorded ≤18 years of age. We estimated the age-standardised annual incidence and prevalence of PoMS, and 95% CIs between 2003 and 2019. We used negative binomial regression models to assess the temporal changes in the annual crude incidence and prevalence of PoMS, and the ratios comparing sex groups. RESULTS: From 2003 to 2019, a total of 148 incident PoMS cases were identified in BC, and 672 in Ontario. The age-standardised annual incidence of PoMS was stable in both provinces, averaging 0.95 (95% CI 0.79 to 1.13) in BC and 0.98 (95%CI 0.84 to 1.12) in Ontario per 100 000 person-years. The incidence ratio by sex (female vs male) was also stable over the study period, averaging 1.5:1 (95% CI 1.06 to 2.08, BC) and 2.0:1 (95% CI 1.61 to 2.59, Ontario). The age-standardised prevalence per 100 000 people rose from 4.75 (2003) to 5.52 (2019) in BC and from 2.93 (2003) to 4.07 (2019) in Ontario, and the increase was statistically significant in Ontario (p=0.002). There were more female prevalent PoMS cases than males in both provinces. CONCLUSIONS: Canada has one of the highest rates of PoMS globally, and the prevalence, but not incidence, has increased over time. Allocation of resources to support the growing youth population with MS should be a priority.

Psychotropic, Anticonvulsant, and Opioid Use in Assisted Living Residents Before and During the COVID-19 Pandemic.

OBJECTIVES: To examine the associations between COVID-19 pandemic waves (1-4) and prevalent antipsychotic, antidepressant, benzodiazepine, anticonvulsant, and opioid use among assisted living (AL) residents, by setting (dementia care vs other). DESIGN: Population-based, repeated cross-sectional study. SETTING AND PARTICIPANTS: Linked clinical and health administrative databases for residents of all publicly subsidized AL homes (N = 256) in Alberta, Canada, examined from January 2018 to December 2021. Setting-specific quarterly cohorts of residents were derived for pandemic (starting March 1, 2020) and comparable historical (2018/2019 combined) periods. METHODS: The quarterly proportion of residents dispensed an antipsychotic, antidepressant, benzodiazepine, anticonvulsant, or opioid was examined for each setting and period. Log-binomial generalized estimating equations models estimated prevalence ratios (PR) for period (pandemic vs historical quarterly periods), setting (dementia care vs other AL), and period-setting interactions. RESULTS: On March 1, 2020, there were 2874 dementia care and 6611 other AL residents (mean age 82.4 vs 79.9 years, 68.2% vs 66.1% female, 93.5% vs 42.6% with dementia, respectively). Antipsychotic use increased during waves 2 to 4 for residents of both settings, but this increase was significantly greater for dementia care than other AL residents during waves 3 and 4 (eg, wave 3, PR 1.21, 95% CI 1.14-1.27 vs PR 1.12, 95% CI 1.07-1.17, interaction term P = .029). In both settings, there was a significant but modest increase in antidepressant use and a significant decrease in benzodiazepine use during several pandemic waves. For other AL residents only, there was a small statistically significant increase in anticonvulsant use during waves 2 to 4. No significant pandemic effect was observed for prevalent opioid use in either setting. CONCLUSIONS AND IMPLICATIONS: The persistence of the pandemic-associated increase in antipsychotic, antidepressant, and anticonvulsant use in AL residents, and greater increase in antipsychotic use for dementia care settings, raises concerns about the attendant risks for residents, especially those with dementia.

Nurse practitioner led implementation of huddles for staff in long term care homes during the COVID-19 pandemic.

BACKGROUND: Staff working in long-term care (LTC) homes during COVID-19 frequently reported a lack of communication, collaboration, and teamwork, all of which are associated with staff dissatisfaction, health concerns, lack of support and moral distress. Our study introduced regular huddles to support LTC staff during COVID-19, led by a Nurse Practitioner (NP). The objectives were to evaluate the process of huddle implementation and to examine differences in outcomes between categories of staff (direct care staff, allied care and support staff, and management) who attended huddles and those who did not. METHODS: All staff and management at one LTC home (< 150 beds) in Ontario, Canada were included in this pre-experimental design study. The process evaluation used a huddle observation tool and focused on the dose (duration, frequency) and fidelity (NP's adherence to the huddle guide) of implementation. The staff attending and non-attending huddles were compared on outcomes measured at post-test: job satisfaction, physical and mental health, perception of support received, and levels of moral distress. The outcomes were assessed with validated measures and compared between categories of staff using Bayesian models. RESULTS: A total of 42 staff enrolled in the study (20 attending and 22 non-attending huddles). Forty-eight huddles were implemented by the NP over 15 weeks and lasted 15 min on average. Huddles were most commonly attended by direct care staff, followed by allied care/support, and management staff. All huddles adhered to the huddle guide as designed by the research team. Topics most often addressed during the huddles were related to resident care (46%) and staff well-being (34%). Differences were found between staff attending and non-attending huddles: direct care staff attending huddles reported lower levels of overall moral distress, and allied care and support staff attending huddles perceived higher levels of support from the NP. CONCLUSIONS: NP-led huddles in LTC homes may positively influence staff outcomes. The process evaluation provided some understanding of why the huddles may have been beneficial: the NP addressed resident care issues which were important to staff, encouraged a collaborative approach to solving issues on the unit, and discussed their well-being. TRIAL REGISTRATION NUMBER: NCT05387213, registered on 24/05/2022.

The impact of the COVID-19 pandemic on blood culture practices and bloodstream infections.

IMPORTANCE: Bacterial infections are a significant cause of morbidity and mortality worldwide. In the wake of the COVID-19 pandemic, previous studies have demonstrated pandemic-related shifts in the epidemiology of bacterial bloodstream infections (BSIs) in the general population and in specific hospital systems. Our study uses a large, comprehensive data set stratified by setting [community, long-term care (LTC), and hospital] to uniquely demonstrate how the effect of the COVID-19 pandemic on BSIs and testing practices varies by healthcare setting. We showed that, while the number of false-positive blood culture results generally increased during the pandemic, this effect did not apply to hospitalized patients. We also found that many infections were likely under-recognized in patients in the community and in LTC, demonstrating the importance of maintaining healthcare for these groups during crises. Last, we found a decrease in infections caused by certain pathogens in the community, suggesting some secondary benefits of pandemic-related public health measures.