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.

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.

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.

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.

Coronavirus Disease 2019 Vaccination Is Associated With Reduced Outpatient Antibiotic Prescribing in Older Adults With Confirmed Severe Acute Respiratory Syndrome Coronavirus 2: A Population-Wide Cohort Study.

BACKGROUND: Antibiotics are frequently prescribed unnecessarily in outpatients with coronavirus disease 2019 (COVID-19). We sought to evaluate factors associated with antibiotic prescribing in outpatients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. METHODS: We performed a population-wide cohort study of outpatients aged ≥66 years with polymerase chain reaction-confirmed SARS-CoV-2 from 1 January 2020 to 31 December 2021 in Ontario, Canada. We determined rates of antibiotic prescribing within 1 week before (prediagnosis) and 1 week after (postdiagnosis) reporting of the positive SARS-CoV-2 result, compared to a self-controlled period (baseline). We evaluated predictors of prescribing, including a primary-series COVID-19 vaccination, in univariate and multivariable analyses. RESULTS: We identified 13 529 eligible nursing home residents and 50 885 eligible community-dwelling adults with SARS-CoV-2 infection. Of the nursing home and community residents, 3020 (22%) and 6372 (13%), respectively, received at least 1 antibiotic prescription within 1 week of a SARS-CoV-2 positive result. Antibiotic prescribing in nursing home and community residents occurred, respectively, at 15.0 and 10.5 prescriptions per 1000 person-days prediagnosis and 20.9 and 9.8 per 1000 person-days postdiagnosis, higher than the baseline rates of 4.3 and 2.5 prescriptions per 1000 person-days. COVID-19 vaccination was associated with reduced prescribing in nursing home and community residents, with adjusted postdiagnosis incidence rate ratios (95% confidence interval) of 0.7 (0.4-1) and 0.3 (0.3-0.4), respectively. CONCLUSIONS: Antibiotic prescribing was high and with little or no decline following SARS-CoV-2 diagnosis but was reduced in COVID-19-vaccinated individuals, highlighting the importance of vaccination and antibiotic stewardship in older adults with COVID-19.

Variation and Correlation of Potential Unintended Consequences of Antipsychotic Reduction in Ontario Nursing Homes Over Time.

BACKGROUND: Potentially inappropriate antipsychotic use has declined in nursing homes over the past decade; however, increases in the documentation of relevant clinical indications (eg, delusions) and the use of other psychotropic medications have raised concerns about diagnosis upcoding and medication substitution. Few studies have examined how these trends over time vary across and within nursing homes, information that may help to support antipsychotic reduction efforts. OBJECTIVE: To jointly model facility-level time trends in potentially inappropriate antipsychotic use, antidepressant use, and the indications used to define appropriate antipsychotic use. RESEARCH DESIGN: We conducted a repeated cross-sectional study of all nursing homes in Ontario, Canada between April 1, 2010 and December 31, 2019 using linked health administrative data (N=649). Each nursing home's quarterly prevalence of potentially inappropriate antipsychotic use, antidepressant use, and relevant indications were measured as outcome variables. With time as the independent variable, multivariate random effects models jointly estimated time trends for each outcome across nursing homes and the correlations between time trends within nursing homes. RESULTS: We observed notable variations in the time trends for each outcome across nursing homes, especially for the relevant indications. Within facilities, we found no correlation between time trends for potentially inappropriate antipsychotic and antidepressant use ( r =-0.0160), but a strong negative correlation between time trends for potentially inappropriate antipsychotic use and relevant indications ( r =-0.5036). CONCLUSIONS: Nursing homes with greater reductions in potentially inappropriate antipsychotics tended to show greater increases in the indications used to define appropriate antipsychotic use-possibly leading to unmonitored use of antipsychotics.

Changes in the Initiation of Antipsychotics and Trazodone Over Time: A Cohort Study of New Admissions to Nursing Homes in Ontario, Canada.

OBJECTIVES: To investigate whether trazodone is being initiated in lieu of antipsychotics following antipsychotic reduction efforts, this study described changes in medication initiation over time. METHODS: We conducted a retrospective cohort study of new admissions to nursing homes in Ontario, Canada between April 2010 and December 2019 using health administrative data (N = 61,068). The initiation of antipsychotic and trazodone use was compared by year of admission using discrete time survival analysis and stratified by history of dementia. RESULTS: Relative to residents admitted in 2014, antipsychotic initiation significantly decreased in later years (e.g., 2017 admission year hazard odds ratio [HOR2017]=0.72 [95% confidence interval (95%CI)=0.62-0.82]) while trazodone initiation modestly increased (e.g., HOR2017=1.09 [95%CI=0.98-1.21]). The relative increase in trazodone initiation was larger among residents with dementia (e.g., HOR2017Dem =1.22 [95%CI=1.07-1.39]). CONCLUSIONS: Differences in which medications were started following nursing home admission were observed and suggest trazodone may be initiated in lieu of antipsychotics.

Development and validation of a hospital frailty risk measure using Canadian clinical administrative data.

BACKGROUND: Accessible measures specific to the Canadian context are needed to support health system planning for older adults living with frailty. We sought to develop and validate the Canadian Institute for Health Information (CIHI) Hospital Frailty Risk Measure (HFRM). METHODS: Using CIHI administrative data, we conducted a retrospective cohort study involving patients aged 65 years and older who were discharged from Canadian hospitals from Apr. 1, 2018, to Mar. 31, 2019. We used a 2-phase approach to develop and validate the CIHI HFRM. The first phase, construction of the measure, was based on the deficit accumulation approach (identification of age-related conditions using a 2-year look-back). The second phase involved refinement into 3 formats (continuous risk score, 8 risk groups and binary risk measure), with assessment of their predictive validity for several frailty-related adverse outcomes using data to 2019/20. We assessed convergent validity with the United Kingdom Hospital Frailty Risk Score. RESULTS: The cohort consisted of 788 701 patients. The CIHI HFRM included 36 deficit categories and 595 diagnosis codes that cover morbidity, function, sensory loss, cognition and mood. The median continuous risk score was 0.111 (interquartile range 0.056-0.194, equivalent to 2-7 deficits); 35.1% (n = 277 000) of the cohort were found at risk of frailty (≥ 6 deficits). The CIHI HFRM showed satisfactory predictive validity and reasonable goodness-of-fit. For the continuous risk score format (unit = 0.1), the hazard ratio (HR) for 1-year risk of death was 1.39 (95% confidence interval [CI] 1.38-1.41), with a C-statistic of 0.717 (95% CI 0.715-0.720); the odds ratio for high users of hospital beds was 1.85 (95% CI 1.82-1.88), with a C-statistic of 0.709 (95% CI 0.704-0.714), and the HR of 90-day admission to long-term care was 1.91 (95% CI 1.88-1.93), with a C-statistic of 0.810 (95% CI 0.808-0.813). Compared with the continuous risk score, using a format of 8 risk groups had similar discriminatory ability and the binary risk measure had slightly weaker performance. INTERPRETATION: The CIHI HFRM is a valid tool showing good discriminatory power for several adverse outcomes. The tool can be used by decision-makers and researchers by providing information on hospital-level prevalence of frailty to support system-level capacity planning for Canada's aging population.

CBT for Youth Anxiety: How Does It Fit Within Community Mental Health?

PURPOSE OF REVIEW: We review (1) the empirical literature for cognitive behavioral therapy (CBT) for youth anxiety delivered in community settings, (2) the use of online delivery methods in this process, and (3) identified barriers and facilitators to implementation of CBT for youth anxiety in community mental health clinics (CMHCs). We provide suggestions for future work. RECENT FINDINGS: Meta-analytic reviews of effectiveness studies suggest that outcomes comparable to those of efficacy studies can be achieved in community settings, particularly when in-session exposures occur. Several online programs support delivery of these services, with an evidence base that is promising. The notable barrier to the implementation of services is the cost of implementation and sustainability. Organizational factors such as leadership, culture, and climate are consistently identified as barriers and facilitators depending on their valence and appear to be related to implementation outcomes (e.g., on provider attitudes). The current findings need to be integrated into future studies, with a focus on further identifying facilitators (e.g., champions and online programs) of implementation. There is also the need for efforts to address organizational and individual barriers and to compare ways to reduce costs.

Caregiver Involvement and Concerns with Care of Residents of Assisted Living before and during the COVID-19 Pandemic.

INTRODUCTION: Family/friend caregivers play an essential role in promoting the physical and mental health of older adults in need of care - especially during the COVID-19 pandemic and especially in assisted living (AL) homes, where resident care needs are similarly complex as in long-term care homes but fewer staffing resources and services are available. However, little research is available on caregiver involvement and concerns with care of AL residents prior to and during waves 1 and 2 of the COVID-19 pandemic. This study addressed this important knowledge gap. METHODS: This prospective cohort study used baseline and follow-up online surveys with primary caregivers to AL residents in Western Canada who were 65 years or older and had lived in the AL home for at least 3 months before Mar 1, 2020. Surveys assessed the following outcomes in the 3 months prior to and during waves 1 and 2 of the pandemic: sociodemographics, 5 ways of visiting or communicating with residents, involvement in 16 care tasks, concerns with 9 resident physical/mental health conditions, perceived lack of resident access to 7 care services, and whether caregivers felt well informed and involved with resident care. RESULTS: Based on 386 caregiver responses, in-person visits dropped significantly in wave 1 of the pandemic and so did caregiver involvement in nearly all care tasks. While these rates increased in wave 2, most did not return to pre-pandemic levels. Correspondingly, caregiver concerns (already high before the pandemic) substantially increased in wave 1 and stayed high in wave 2. These were particularly elevated among caregivers who did not feel well informed/involved with resident care. CONCLUSIONS: Restricted in-person visiting disrupted resident care and was associated with worse perceptions of resident health and well-being. Continued caregiver involvement in resident care and communication with caregivers even during lockdowns is key to mitigating these issues.

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.

Caregivers' Concerns About Assisted Living Residents' Mental Health During the COVID-19 Pandemic: A Cross-Sectional Survey Study.

Family or friend caregivers' concerns about assisted living (AL) residents' mental health are reflective of poor resident and caregiver mental health. COVID-19-related visiting restrictions increased caregiver concerns, but research on these issues in AL is limited. Using web-based surveys with 673 caregivers of AL residents in Western Canada, we assessed the prevalence and correlates of moderate to severe caregiver concerns about residents' depressed mood, loneliness, and anxiety in the 3 months before and after the start of the COVID-19 pandemic. Caregiver concerns doubled after the start of the pandemic (resident depressed mood: 23%-50%, loneliness: 29%-62%, anxiety: 24%-47%). Generalized linear mixed models identified various modifiable risk factors for caregiver concerns (e.g., caregivers' perception that residents lacked access to counseling services or not feeling well informed about and involved in resident care). These modifiable factors can be targeted in efforts to prevent or mitigate caregiver concerns and resident mental health issues.

Pharmacists' knowledge, perceptions and practices regarding frailty: A cross-sectional survey across practice settings in Canada.

Background: Data on Canadian pharmacists' knowledge and perceptions about frailty in older adults and its assessment in pharmacy practice are scarce. Methods: A cross-sectional survey of 349 Canadian pharmacists was conducted to evaluate pharmacists' knowledge, perceptions and practices regarding frailty. Descriptive analyses summarized responses by practice setting, and a multivariable logistic regression model examined associations between respondent characteristics and the likelihood of assessing frailty. Results: Most respondents were female (70%), aged ≤34 years (47%), Canadian graduates (83%), from Ontario/Quebec (51%) and from urban centres (58%). Although a significant proportion agreed it is important for pharmacists to know (80%) and assess (56%) patient frailty status, only 36% reported assessing frailty in practice. Respondents exclusively practising in a community pharmacy were significantly less likely to agree that it is important for a pharmacist to know or assess frailty status and to report assessing it. Factors associated with a greater likelihood of assessment included positive beliefs about the importance of knowing a patient's frailty status and having a greater proportion of older patients with cognitive or functional impairment in practice. Discussion: Findings suggest that pharmacists generally agree with the importance of understanding frailty as it relates to the appropriate use of medications, but most do not assess it. Further research is needed to identify the barriers to assessing frailty, while guidance is needed on which of the available screening tools can best be integrated into a clinical pharmacy practice. Conclusion: There is an opportunity to improve pharmaceutical care for older adults by providing pharmacists the means and resources to assess frailty in practice.

Determination of N7-glycidamide guanine adducts in human blood DNA following exposure to dietary acrylamide using liquid chromatography/tandem mass spectrometry.

RATIONALE: Acrylamide is classified as a probable human carcinogen that is metabolised to glycidamide, which can covalently bind to DNA. The aim of this study was to investigate the formation of N7-glycidamide guanine (N7-GA-Gua) adducts in human blood DNA following exposure to acrylamide present in carbohydrate-rich foods as part of the normal human diet. METHODS: Lymphocyte DNA was extracted from blood samples obtained from healthy human volunteers. Following thermal depurination of the DNA samples, N7-GA-Gua adducts were quantified using a validated liquid chromatography/tandem mass spectrometry (LC/MS/MS) method incorporating a stable isotope labelled internal standard. Estimated dietary acrylamide intake was recorded by completion of food frequency questionnaires for the 24 hours prior to volunteer blood donation. RESULTS: An LC/MS/MS method was validated with a limit of detection of 0.25 fmol and a lower limit of quantitation of 0.50 fmol on column. N7-GA-Gua adducts were detected in human blood DNA with the levels ranging between 0.3 to 6.3 adducts per 108 nucleotides. The acrylamide intake was calculated from the food frequency questionnaires ranging between 20.0 and 78.6 µg. CONCLUSIONS: Identification and quantification of N7-GA-Gua adducts in the blood DNA of healthy volunteers suggests that dietary acrylamide exposure may lead to the formation of DNA adducts. This important finding warrants further investigation to ascertain a correlation between environmental/dietary acrylamide exposure and levels of DNA adducts.

Staff perceptions of the consequences of COVID-19 on quality of dementia care for residents in Ontario long-term care homes.

OBJECTIVES: The first wave of the COVID-19 pandemic necessitated extensive infection control measures in long-term care (LTC) and had a significant impact on staffing and services. Anecdotal reports indicate that this negatively affected LTC residents' quality of care and wellbeing, but there is scarce evidence on the effects of COVID-19 on quality of dementia care in LTC. METHODS: From December 2020 to March 2021, we conducted a cross-sectional online survey among staff who worked in LTC homes in Ontario, Canada. Survey questions examined staffs' perceptions of the impact of COVID-19 on dementia quality of care during the initial wave of the COVID-19 pandemic (beginning 1 March 2020). RESULTS: There were a total of 227 survey respondents; more than half reported both worsened overall quality of care (51.3%) and worsening of a majority of specific quality of care measures (55.5%). Measures of cognitive functioning, mobility and behavioural symptoms were most frequently described as worsened. Medical and allied/support staff had the highest odds of reporting overall worsened quality of care, while specialized behavioural care staff and those with more experience in LTC were less likely to. LTC home factors including rural location and smaller size, staffing challenges, higher number of outbreaks and less COVID-19 preparedness were associated with increased odds of perceived worsening of quality of dementia care outcomes. CONCLUSIONS: These findings suggest that COVID-19 pandemic restrictions and related effects such as inadequate staffing may have contributed to poor quality of care and outcomes for those with dementia in LTC.

Incidence of neurological and psychiatric comorbidity over time: a population-based cohort study in Ontario, Canada.

INTRODUCTION: Comprehensive, population-based investigations of the extent and temporality of associations between common neurological and psychiatric disorders are scarce. METHODS: This retrospective cohort study used linked health administrative data for Ontarians aged 40-85 years on 1 April 2002, to estimate the adjusted rate of incident dementia, Parkinson's disease (PD), stroke or mood/anxiety disorder (over 14 years) according to the presence and time since diagnosis of a prior disorder. Sex differences in the cumulative incidence of a later disorder were also examined. RESULTS: The cohort included 5,283,546 Ontarians (mean age 56.2 ± 12.1 years, 52% female). The rate of dementia was significantly higher for those with prior PD (adjusted hazard ratio [adjHR] 4.05, 95% confidence interval [CI] 3.99-4.11); stroke (adjHR 2.49, CI 2.47-2.52) and psychiatric disorder (adjHR 1.79, CI 1.78-1.80). The rate of PD was significantly higher for those with prior dementia (adjHR 2.23, CI 2.17-2.30) and psychiatric disorder (adjHR 1.77, CI 1.74-1.81). The rate of stroke was significantly higher among those with prior dementia (adjHR 1.56, CI 1.53-1.58). Prior dementia (adjHR 2.36, CI 2.33-2.39), PD (adjHR 1.80, CI 1.75-1.85) and stroke (adjHR 1.47, CI 1.45-1.49) were associated with a higher rate of an incident psychiatric disorder. Generally, associations were strongest in the 6 months following a prior diagnosis and demonstrated a J-shape relationship over time. Significant sex differences were evident in the absolute risks for several disorders. CONCLUSIONS: The observed nature of bidirectional associations between these neurological and psychiatric disorders indicates opportunities for earlier diagnosis and interventions to improve patient care.

Prevalence and correlates of anxiety and depression in caregivers to assisted living residents during COVID-19: a cross-sectional study.

BACKGROUND: Family and friend caregivers play significant roles in advocating for and ensuring quality health and social care of residents in Assisted Living (AL) homes. However, little is known about how the COVID-19 pandemic and related visitor restrictions affected their health and mental well-being. We examined the prevalence and correlates of anxiety and depressive symptoms among caregivers of AL residents during the initial wave of COVID-19 in two Canadian provinces. METHODS: A cross-sectional web-based survey was conducted among family/friend caregivers of AL residents in Alberta and British Columbia (Oct 28, 2020-Mar 31, 2021) to collect data on their sociodemographic, health and caregiving characteristics, as well as concerns about residents' health and social care before and during the first wave of the pandemic. A clinically significant anxiety disorder and depressive symptoms were assessed with the GAD-7 and CES-D10 instruments, respectively. Separate multivariable (modified) Poisson regression models identified caregiver correlates of each mental health condition. RESULTS: Among the 673 caregivers completing the survey (81% for Alberta residents), most were women (77%), white (90%) and aged ≥ 55 years (81%). Clinically significant anxiety and depression were present in 28.6% and 38.8% of caregivers respectively. Both personal stressors (comorbidity level, income reduction, low social support) and caregiving stressors exacerbated by the pandemic were independently associated with caregiver anxiety and depression. The latter included increased concern about the care recipients' depression (adjusted risk ratio [adjRR] = 1.84, 95% confidence interval [CI] 1.19-2.85 for caregiver anxiety and adjRR = 1.75, 95% CI 1.26-2.44 for caregiver depressive symptoms) and reported intention to withdraw the resident from AL because of COVID-19 (adjRR = 1.24, 95%CI 0.95-1.63 for caregiver anxiety and adjRR = 1.37, 95%CI 1.13-1.67 for caregiver depressive symptoms). CONCLUSIONS: Caregivers of residents in AL homes reported significant personal and caregiving-related stressors during the initial wave of COVID-19 that were independently associated with an increased likelihood of experiencing clinically significant anxiety and depressive symptoms. Healthcare providers and AL staff should be aware of the prevalence and varied correlates of caregivers' mental health during public health crises so that appropriate screening and support may identified and implemented.

Barriers and facilitators to person-centred infection prevention and control: results of a survey about the Dementia Isolation Toolkit.

BACKGROUND: People working in long-term care homes (LTCH) face difficult decisions balancing the risk of infection spread with the hardship imposed on residents by infection control and prevention (ICP) measures. The Dementia Isolation Toolkit (DIT) was developed to address the gap in ethical guidance on how to safely and effectively isolate people living with dementia while supporting their personhood. In this observational study, we report the results of a survey of LTCH staff on barriers and facilitators regarding isolating residents, and the impact of the DIT on staff moral distress. METHODS: We completed an online cross-sectional survey. Participants (n = 207) were staff working on-site in LTCH in Ontario, Canada since March 1, 2020, with direct or indirect experience with the isolation of residents. LTCH staff were recruited through provincial LTCH organizations, social media, and the DIT website. Survey results were summarized, and three groups compared, those: (1) unfamiliar with, (2) familiar with, and (3) users of the DIT. RESULTS: 61% of respondents identified distress of LTCH staff about the harmful effects of isolation on residents as a major barrier to effective isolation. Facilitators for isolation included delivery of 1:1 activity in the resident's room (81%) and designating essential caregivers to provide support (67%). Almost all respondents (84%) reported an increase in moral distress. DIT users were less likely to report an impact of moral distress on job satisfaction (odds ratio (OR) 0.41, 95% CI 0.19-0.87) with 48% of users reporting the DIT was helpful in reducing their level of moral distress. CONCLUSIONS: Isolation as an ICP measure in LTCH environments creates moral distress among staff which is a barrier to its effectiveness. ICP guidance to LTCH would be strengthened by the inclusion of a dementia-specific ethical framework that addresses how to minimize the harms of isolation on both residents and staff.

Prevalence of prescription and non-prescription polypharmacy by frailty and sex among middle-aged and older Canadians.

Background: Estimates of polypharmacy have primarily been derived from prescription claims, and less is known about the use of non-prescription medications (alone or in combination with prescription medications) across the frailty spectrum or by sex. Our objectives were to estimate the prevalence of polypharmacy (total, prescription, non-prescription, and concurrent prescription and non-prescription) overall, and by frailty, sex and broad age group. Data: Canadian Health Measures Survey, Cycle 5, 2016 to 2017. Methods: Among Canadians aged 40 to 79 years, all prescription and non-prescription medications used in the month prior to the survey were documented. Polypharmacy was defined as using five or more medications total (prescription and non-prescription), prescription only and non-prescription only. Concurrent prescription and non-prescription use was defined as two or more and three or more of each. Frailty was defined using a 31-item frailty index (FI) and categorized as non-frail (FI ≤ 0.1) and pre-frail or frail (FI > 0.1). Survey-weighted descriptive statistics were calculated overall and age standardized. Results: We analyzed 2,039 respondents, representing 16,638,026 Canadians (mean age of 56.9 years; 51% women). Overall, 52.4% (95% confidence interval [CI] = 47.3 to 57.4) were defined as pre-frail or frail. Age-standardized estimates of total polypharmacy, prescription polypharmacy and concurrent prescription and non-prescription medication use were significantly higher among pre-frail or frail versus non-frail adults (e.g., total polypharmacy: 64.1% versus 31.8%, respectively). Polypharmacy with non-prescription medications was common overall (20.5% [95% CI = 16.1 to 25.8]) and greater among women, but did not differ significantly by frailty. Interpretation: Polypharmacy and concurrent prescription and non-prescription medication use were common among Canadian adults, especially those who were pre-frail or frail. Our findings highlight the importance of considering non-prescribed medications when measuring the exposure to medications and the potential risk for adverse outcomes.

WHO Participates in Effectiveness Research? A Comparison of Effectiveness Trial Clinicians to National Survey Samples.

Findings from research participants in effectiveness treatment trials (i.e., randomized control trials conducted in community rather than research settings) are considered more generalizable than those from participants in efficacy trials. This is especially true for clinician participants, whose characteristics like attitudes towards evidence-based practices (EBPs) may impact treatment implementation and the generalizability of research findings from effectiveness studies. This study compared background characteristics, attitudes toward EBPs, and attitudes towards measurement-based care (MBC) among clinicians participating in a National Institute of Mental-Health (NIMH) funded effectiveness trial, the Community Study of Outcome Monitoring for Emotional Disorders in Teens (COMET), to clinician data from nationally representative U.S. survey samples. Results indicated COMET clinicians were significantly younger, less clinically experienced, and were more likely to have a training background in psychology versus other disciplines compared to national survey samples. After controlling for demographics and professional characteristics, COMET clinicians held more positive attitudes towards EBPs and MBC compared to national survey samples. Implications for implementation efforts are discussed.