Interfacing High-Throughput Electrosynthesis and Mass Spectrometric Analysis of Azines.

Combinatorial electrochemistry has great promise for accelerated reaction screening, organic synthesis, and catalysis. Recently, we described a new high-throughput electrochemistry platform, colloquially named "Legion". Legion fits the footprint of a 96-well microtiter plate with simultaneous individual control over all 96 electrochemical cells. Here, we demonstrate the versatility of Legion when coupled with high-throughput mass spectrometry (MS) for electrosynthetic product screening and quantitation. Electrosynthesis of benzophenone azine was selected as a model reaction and was arrayed and optimized using a combination of Legion and nanoelectrospray ionization MS. The combination of high-throughput synthesis with Legion and analysis via MS proves a compelling strategy for accelerating reaction discovery and optimization in electro-organic synthesis.

Hyponatremia-associated hospital visits are not reduced by early electrolyte testing in older adults starting antidepressants.

BACKGROUND: Clinical practice guidelines recommend early serum electrolyte monitoring when starting antidepressants in older adults due to the increased risk of hyponatremia. It is unclear whether this monitoring improves outcomes. METHODS: Population-based, retrospective cohort study of Ontario adults aged ≥66 years who initiated therapy with a selective serotonin reuptake inhibitor (SSRI) or selective norepinephrine reuptake inhibitor (SNRI) between April 1, 2013, and January 31, 2020. The index date was the date of the first such prescription, and the exposure of interest was serum electrolyte measurement during the subsequent 7 days. The primary outcome was any emergency department or hospital admission with hyponatremia within 8-60 days of antidepressant initiation. Poisson regression models compared individuals who had versus did not have their serum electrolytes tested in the week following SSRI/SNRI initiation, weighting by propensity score-based overlap weights. RESULTS: Among the 420,085 patients aged ≥66 years initiating treatment with an SSRI/SNRI, 26,808 (6.4%) had serum electrolytes measured in the subsequent 7 days and 6109 (1.5%) subsequently presented to hospital with hyponatremia. The time from drug initiation to hospitalization varied (median 29, interquartile range [IQR] 17-44 days), and the median sodium concentration measured in the community (136, IQR 133-138 mmol/L) was marginally higher than those at the time of hospitalization (132, IQR 130-134 mmol/L). Patients who underwent electrolyte testing in the week following SSRI/SNRI treatment were more likely to attend an emergency department (ED) or hospital with hyponatremia within 8-60 days relative to those who did not (relative risk = 2.31, 95% confidence interval: 2.16-2.46). CONCLUSIONS: Testing serum electrolytes in the week after starting an SSRI/SNRI is not associated with a reduced risk of a hospital visit with hyponatremia. These findings do not support current guidelines recommending routine electrolyte monitoring.

Association between surgery and rate of incident dementia in older adults: A population-based retrospective cohort study.

BACKGROUND: The risk of incident dementia after surgery in older adults is unclear. The study objective was to examine the rate of incident dementia among older adults after elective surgery compared with a matched nonsurgical control group. METHODS: We conducted a population-based, propensity-matched retrospective cohort study using data from linked administrative databases in Ontario, Canada. All community-dwelling individuals aged 66 years and older who underwent one of five major elective surgeries between April 1, 2007 and March 31, 2011 were included. Each surgical patient was matched 1:1 on surgical specialty of the surgeon at consultation, age, sex, fiscal year of entry, and propensity score with a patient who attended an outpatient visit with a surgeon of the same surgical specialty but did not undergo surgery. Patients were followed for up to 5 years after cohort entry for the occurrence of a new dementia diagnosis, defined from administrative data. Cause-specific hazard models were used to estimate the hazard ratio (HR) and 95% confidence interval (CI) for the association between surgery and the hazard of incident dementia. Subgroup and sensitivity analyses were performed. RESULTS: A total of 27,878 individuals (13,939 matched pairs) were included in the analysis. A total of 640 (4.6%) individuals in the surgical group and 965 (6.9%) individuals in the control group developed dementia over the 5-year follow-up period. Individuals who underwent surgery had a reduced rate of incident dementia compared with their matched nonsurgical controls (HR 0.88; 95% CI 0.80-0.97; p = 0.01). This association was persistent in most subgroups and after sensitivity analyses. CONCLUSIONS: Elective surgery did not increase the rate of incident dementia when compared with matched nonsurgical controls. This could be an important consideration for patients and surgeons when elective surgery is considered.

The Alzheimer's Disease Neuroimaging Initiative in the era of Alzheimer's disease treatment: A review of ADNI studies from 2021 to 2022.

The Alzheimer's Disease Neuroimaging Initiative (ADNI) aims to improve Alzheimer's disease (AD) clinical trials. Since 2006, ADNI has shared clinical, neuroimaging, and cognitive data, and biofluid samples. We used conventional search methods to identify 1459 publications from 2021 to 2022 using ADNI data/samples and reviewed 291 impactful studies. This review details how ADNI studies improved disease progression understanding and clinical trial efficiency. Advances in subject selection, detection of treatment effects, harmonization, and modeling improved clinical trials and plasma biomarkers like phosphorylated tau showed promise for clinical use. Biomarkers of amyloid beta, tau, neurodegeneration, inflammation, and others were prognostic with individualized prediction algorithms available online. Studies supported the amyloid cascade, emphasized the importance of neuroinflammation, and detailed widespread heterogeneity in disease, linked to genetic and vascular risk, co-pathologies, sex, and resilience. Biological subtypes were consistently observed. Generalizability of ADNI results is limited by lack of cohort diversity, an issue ADNI-4 aims to address by enrolling a diverse cohort.

Hot Excitons Cool in Metal Halide Perovskite Nanocrystals as Fast as CdSe Nanocrystals.

The idea of phonon bottlenecks has long been pursued in nanoscale materials for their application in hot exciton devices, such as photovoltaics. Decades ago, it was shown that there is no quantum phonon bottleneck in strongly confined quantum dots due to their physics of quantum confinement. More recently, it was proposed that there are hot phonon bottlenecks in metal halide perovskites due to their physics. Recent work has called into question these bottlenecks in metal halide perovskites. Here, we compare hot exciton cooling in a range of sizes of CsPbBr3 nanocrystals from weakly to strongly confined. These results are compared to strongly confined CdSe quantum dots of two sizes and degrees of quantum confinement. CdSe is a model system as a ruler for measuring hot exciton cooling being fast, by virtue of its efficient Auger-assisted processes. By virtue of 3 ps time resolution, the hot exciton photoluminescence can now be directly observed, which is the most direct measure of the presence of hot excitons and their lifetimes. The hot exciton photoluminescence decays on nearly the same 2 ps time scale on both the weakly confined perovskite and the larger CdSe quantum dots, much faster than the 10 ps cooling predicted by transient absorption experiments. The smaller CdSe quantum dot has still faster cooling, as expected from quantum size effects. The quantum dots of perovskites show extremely fast hot exciton cooling, decaying faster than detection limits of <1 ps, even faster than the CdSe system, suggesting the efficiency of Auger processes in these metal halide perovskite nanocrystals and especially in their quantum dot form. These results across a range of sizes of nanocrystals reveal extremely fast hot exciton cooling at high exciton density, independent of composition, but dependent upon size. Hence these metal halide perovskite nanocrystals seem to cool heavily following quantum dot physics.

Light Emission from CsPbBr3 Metal Halide Perovskite Nanocrystals Arises from Dual Emitting States with Distinct Lattice Couplings.

Metal halide perovskite nanocrystals are under intense investigation for their outstanding optical and electronic properties. The presence of higher fine structure states, let alone nonequilibrium processes within the fine structure, and multiexcitonic fine structure remains poorly understood due to a lack of experimental probes. Here, we use time-resolved photoluminescence (t-PL) spectroscopy with an improvement from 100 to 3 ps resolution which reveals previously unobserved spectral dynamics from excitons to multiexcitons in 15 nm CsPbBr3 nanocrystals. The simple and immediate observation from temperature dependence is a previously unobserved fine structure to the multiexcitons. Further insight is gleaned from t-PL spectral bandwidth trajectories at extrema in temperature and exciton density. The bandwidth trajectories reveal the presence of a previously unobserved fine structure in excitons as well as multiexcitons. The bandwidth trajectories reveal a complex history, from multiexciton recombination to exciton thermalization to Auger heating to lattice thermalization. Whereas the amplitude of these spectral effects is large, ∼60 meV, modeling suggests that the spectral effects are mostly phonon based illustrating the importance of the lattice on light emission from metal halide perovskite nanocrystals.

Interfacial Electromigration for Analysis of Biofluid Lipids in Small Volumes.

Lipids are important biomarkers within the field of disease diagnostics and can serve as indicators of disease progression and predictors of treatment effectiveness. Although lipids can provide important insight into how diseases initiate and progress, mass spectrometric methods for lipid characterization and profiling are limited due to lipid structural diversity, particularly the presence of various lipid isomers. Moreover, the difficulty of handling small-volume samples exacerbates the intricacies of biological analyses. In this work, we have developed a strategy that electromigrates a thin film of a small-volume biological sample directly to the air-liquid interface formed at the tip of a theta capillary. Importantly, we seamlessly integrated in situ biological lipid extraction with accelerated chemical derivatization, enabled by the air-liquid interface, and conducted isomeric structural characterization within a unified platform utilizing theta capillary nanoelectrospray ionization mass spectrometry, all tailored for small-volume sample analysis. We applied this unified platform to the analysis of lipids from small-volume human plasma and Alzheimer's disease mouse serum samples. Accelerated electro-epoxidation of unsaturated lipids at the interface allowed us to characterize lipid double-bond positional isomers. The unique application of electromigration of a thin film to the air-liquid interface in combination with accelerated interfacial reactions holds great potential in small-volume sample analysis for disease diagnosis and prevention.

Direct Observation of Higher Multiexciton Formation and Annihilation in CdSe Quantum Dots.

Most experiments on multiexcitons (MX) in quantum dots focused on the biexciton (XX), which is now well-understood. In contrast, there is little understanding of higher MX in quantum dots as a result of their difficulty to observe. Here, we apply time-resolved photoluminescence (t-PL) spectroscopy with 3 ps time resolution, sufficient to directly resolve previously unobserved spectral dynamics of a higher MX in CdSe quantum dots. These experiments resolve the controversy of the sequence of MX emissions, revealing that the higher channels sequentially populate the lower channels. There is a strong dependence of MX recombination kinetics upon a higher MX state, following a universal volume scaling law for Auger recombination for larger dots. Smaller dots show deviations for higher MX. In addition to triexcitons (3X), these experiments reveal MX up to the tetraexciton (4X). These experiments provide a direct observation of MX formation and annihilation in quantum dots. The impact of this observation is a step toward designing quantum dots to exploit higher MX processes.

In situ droplet-based on-tissue chemical derivatization for lipid isomer characterization using LESA.

In this work, we present an in situ droplet-based derivatization method for fast tissue lipid profiling at multiple isomer levels. On-tissue derivatization for isomer characterization was achieved in a droplet delivered by the TriVersa NanoMate LESA pipette. The derivatized lipids were then extracted and analyzed by the automated chip-based liquid extraction surface analysis (LESA) mass spectrometry (MS) followed by tandem MS to produce diagnostic fragment ions to reveal the lipid isomer structures. Three reactions, i.e., mCPBA epoxidation, photocycloaddition catalyzed by the photocatalyst Ir[dF(CF3)ppy]2(dtbbpy)PF6, and Mn(II) lipid adduction, were applied using the droplet-based derivatization to provide lipid characterization at carbon-carbon double-bond positional isomer and sn-positional isomer levels. Relative quantitation of both types of lipid isomers was also achieved based on diagnostic ion intensities. This method provides the flexibility of performing multiple derivatizations at different spots in the same functional region of an organ for orthogonal lipid isomer analysis using a single tissue slide. Lipid isomers were profiled in the cortex, cerebellum, thalamus, hippocampus, and midbrain of the mouse brain and 24 double-bond positional isomers and 16 sn-positional isomers showed various distributions in those regions. This droplet-based derivatization of tissue lipids allows fast profiling of multi-level isomer identification and quantitation and has great potential in tissue lipid studies requiring rapid sample-to-result turnovers.

Observing strongly confined multiexcitons in bulk-like CsPbBr3 nanocrystals.

We monitor the time-resolved photoluminescence (t-PL) from CsPbBr3 perovskite nanocrystals with a time resolution of 3 ps, which is fast enough to resolve emission from potential multiexcitonic states. Being 15 nm in length and twice the Bohr length, these nanocrystals are either weakly confined or bulk-like. In contrast to this expectation of weak confinement, emission from multiexcitons is observed with binding energies consistent with strongly confined quantum dots. In addition to emission from biexcitons, emission from triexcitons is observed. The triexciton emission includes both S and P recombination channels. Excitation with different amounts of excess energy yields the same PL spectral dynamics, indicating that there are no hot carrier effects, and the electronic structure of the absorbing states is the same. The kinetics of the multiexciton populations are presented in two ways. The kinetics are first shown in a spectrally integrated form, showing faster t-PL at higher fluences independent of excitation excess energy. Both excess energies show the same saturation response. In the second way of presenting the kinetics, the multiexciton populations are decomposed and presented as transients and saturation curves. These decomposed spectra into exciton, biexciton, and triexciton populations enable further insight into their kinetics and fluence dependence.

Amphetamine-Related Emergency Department Visits in Ontario, Canada, 2003-2020.

OBJECTIVES: Despite unregulated amphetamine use increasing, there are limited data on related emergency department (ED) visits in Canada. Our primary objective was to examine trends in amphetamine-related ED visits over time in Ontario, including by age and sex. Secondary objectives were to examine whether patient characteristics were associated with ED revisit within 6 months. METHODS: Using administrative claims and census data, we calculated annual patient- and encounter-based rates of amphetamine-related ED visits from 2003 to 2020 among individuals 18+ years of age. We also performed a retrospective cohort study of individuals with amphetamine-related ED visits between 2019 and 2020 to determine whether select factors were associated with ED revisit within 6 months. Multivariable logistic regression modelling was used to measure associations. RESULTS: The population-based rate of amphetamine-related ED visits increased nearly 15-fold between 2003 (1.9/100,000 Ontarians) and 2020 (27.9/100,000 Ontarians). Seventy-five percent of individuals returned to the ED for any reason within 6 months. Psychosis and use of other substances were both independently associated with ED revisit for any reason within 6 months (psychosis: AOR = 1.54, 95% CI = 1.30-1.83; other substances: AOR = 1.84, 95% CI = 1.57-2.15), whereas having a primary care physician was negatively associated with ED revisit (AOR = 0.77, 95% CI = 0.60-0.98). CONCLUSIONS: Increasing rates of amphetamine-related ED visits in Ontario are cause for concern. Diagnoses of psychosis and the use of other substances may serve to identify individuals who are most likely to benefit from both primary and substance-specific care.

Cognitive correlates of antisaccade behaviour across multiple neurodegenerative diseases.

Oculomotor tasks generate a potential wealth of behavioural biomarkers for neurodegenerative diseases. Overlap between oculomotor and disease-impaired circuitry reveals the location and severity of disease processes via saccade parameters measured from eye movement tasks such as prosaccade and antisaccade. Existing studies typically examine few saccade parameters in single diseases, using multiple separate neuropsychological test scores to relate oculomotor behaviour to cognition; however, this approach produces inconsistent, ungeneralizable results and fails to consider the cognitive heterogeneity of these diseases. Comprehensive cognitive assessment and direct inter-disease comparison are crucial to accurately reveal potential saccade biomarkers. We remediate these issues by characterizing 12 behavioural parameters, selected to robustly describe saccade behaviour, derived from an interleaved prosaccade and antisaccade task in a large cross-sectional data set comprising five disease cohorts (Alzheimer's disease/mild cognitive impairment, amyotrophic lateral sclerosis, frontotemporal dementia, Parkinson's disease, and cerebrovascular disease; n = 391, age 40-87) and healthy controls (n = 149, age 42-87). These participants additionally completed an extensive neuropsychological test battery. We further subdivided each cohort by diagnostic subgroup (for Alzheimer's disease/mild cognitive impairment and frontotemporal dementia) or degree of cognitive impairment based on neuropsychological testing (all other cohorts). We sought to understand links between oculomotor parameters, their relationships to robust cognitive measures, and their alterations in disease. We performed a factor analysis evaluating interrelationships among the 12 oculomotor parameters and examined correlations of the four resultant factors to five neuropsychology-based cognitive domain scores. We then compared behaviour between the abovementioned disease subgroups and controls at the individual parameter level. We theorized that each underlying factor measured the integrity of a distinct task-relevant brain process. Notably, Factor 3 (voluntary saccade generation) and Factor 1 (task disengagements) significantly correlated with attention/working memory and executive function scores. Factor 3 also correlated with memory and visuospatial function scores. Factor 2 (pre-emptive global inhibition) correlated only with attention/working memory scores, and Factor 4 (saccade metrics) correlated with no cognitive domain scores. Impairment on several mostly antisaccade-related individual parameters scaled with cognitive impairment across disease cohorts, while few subgroups differed from controls on prosaccade parameters. The interleaved prosaccade and antisaccade task detects cognitive impairment, and subsets of parameters likely index disparate underlying processes related to different cognitive domains. This suggests that the task represents a sensitive paradigm that can simultaneously evaluate a variety of clinically relevant cognitive constructs in neurodegenerative and cerebrovascular diseases and could be developed into a screening tool applicable to multiple diagnoses.

Expert elicitation of risk factors for progression to dementia in individuals with mild cognitive impairment.

INTRODUCTION: This study assesses experts' beliefs about important predictors of developing dementia in persons with mild cognitive impairment (MCI). METHODS: Structured expert elicitation, a methodology to quantify expert knowledge, was used to elicit the most important risk factors for developing dementia. We recruited 11 experts (6 neurologists, 3 geriatricians, and 2 psychiatrists). Ten experts fully participated in introductory meetings, two rounds of surveys, and discussion meetings. The data from these ten experts were utilized for this study. RESULTS: The expert elicitation identified age, CSF analysis, fluorodeoxyglucose-positron emission tomography (FDG-PET) findings, hippocampal atrophy, MoCA (or MMSE) score, parkinsonism, apathy, psychosis, informant report of cognitive symptoms, and global atrophy as the ten most important predictors of progressing to dementia in persons with MCI. DISCUSSION: Several dementia predictors are not routinely collected in existing registries, observational studies, or usual care. This might partially explain the low uptake of existing published dementia risk scores in clinical practice.

A spectroscopic overview of the differences between the absorbing states and the emitting states in semiconductor perovskite nanocrystals.

Semiconductor perovskites have been under intense investigation for their promise in optoelectronic applications and their novel and unique physical properties. There have been a variety of material implementations of perovskites from thin films to single crystals to nanocrystals. The nanocrystal form, in particular, is attractive as it enables solution processing and also spectroscopically probes both absorptive and emissive transitions. Broadly, the literature is comprised of experiments of either form, but the experiments are rarely performed in concert and are not discussed in a unified picture. For example, absorptive experiments are typically transient absorption measurements, which aim to measure carrier kinetics and dynamics. In contrast, the emissive experiments largely focus on excitonic fine structures and coupling to phonons. The time resolved emission experiments report on excited state lifetimes and their dependence on temperature. There are broad differences in the spectroscopy techniques and the questions asked in both classes of experiments. Yet there is one measure in common that suggests there are mysteries in our understanding of how the absorbing and emitting states are connected. The linewidth of emission spectra is always larger than the linewidth of absorption spectra. The question of the physics underlying linewidths is complex and is one of the central issues in perovskite nanocrystals. So why are the absorptive and emissive linewidths different? At present even this simple question has no clear answer. The more complex questions of the structure and dynamics of absorptive and emissive states are even more ambiguous. Hence there is a need to connect these experiments and the relevant states. Here, we provide an overview of the salient absorptive and emissive spectroscopy techniques in an effort to begin connecting these two disparate areas of inquiry.

Improving generalizability and study design of Alzheimer's disease cohort studies in the United States by including under-represented populations.

The poor generalizability of clinical research data due to the enrollment of highly educated, non-Latinx White participants hampers the development of therapies for Alzheimer's disease (AD). Black and Latinx older adults have a greater risk for dementia, yet it is unclear how health-care disparities and sociocultural factors influence potential AD therapies and prognosis. Low enrollment of under-represented populations may be attributable to several factors including greater exclusion due to higher rates of comorbidities, lower access to AD clinics, and the legacy of unethical treatment in medical research. This perspective outlines solutions tested in the Brain Health Registry (BHR) and the Alzheimer's Disease Neuroimaging Initiative (ADNI), including culturally-informed digital research methods, community-engaged research strategies, leadership from under-represented communities, and the reduction of exclusion criteria based on comorbidities. Our successes demonstrate that it is possible to increase the inclusion and engagement of under-represented populations into US-based clinical studies, thereby increasing the generalizability of their results.

Increasing participant diversity in AD research: Plans for digital screening, blood testing, and a community-engaged approach in the Alzheimer's Disease Neuroimaging Initiative 4.

INTRODUCTION: The Alzheimer's Disease Neuroimaging Initiative (ADNI) aims to validate biomarkers for Alzheimer's disease (AD) clinical trials. To improve generalizability, ADNI4 aims to enroll 50-60% of its new participants from underrepresented populations (URPs) using new biofluid and digital technologies. ADNI4 has received funding from the National Institute on Aging beginning September 2022. METHODS: ADNI4 will recruit URPs using community-engaged approaches. An online portal will screen 20,000 participants, 4000 of whom (50-60% URPs) will be tested for plasma biomarkers and APOE. From this, 500 new participants will undergo in-clinic assessment joining 500 ADNI3 rollover participants. Remaining participants (∼3500) will undergo longitudinal plasma and digital cognitive testing. ADNI4 will add MRI sequences and new PET tracers. Project 1 will optimize biomarkers in AD clinical trials. RESULTS AND DISCUSSION: ADNI4 will improve generalizability of results, use remote digital and blood screening, and continue providing longitudinal clinical, biomarker, and autopsy data to investigators.

Association Between Long-Term Care Facility Staffing Levels and Antipsychotic Use in US Long-Term Care Facilities.

OBJECTIVES: Inappropriate use of antipsychotics is an indicator of quality of care in long-term care (LTC) facilities. There is evidence to suggest that staffing levels in LTC may be associated with the rates of inappropriate antipsychotic use. This study sought to examine the association between staffing and antipsychotic prescribing in LTC facilities. DESIGN: Cross-sectional study investigated the association between reported staffing levels and the frequency of inappropriate antipsychotic prescribing at US LTC facilities between 2016 and 2018. SETTING AND PARTICIPANTS: Data from the Nursing Home Compare and LTCFocus datasets were linked, which contain information from the Minimum Data Set database on facility characteristics and staffing measures from the Payroll-Based Journal system. A final sample set of 10,436 facilities was used. METHODS: Descriptive statistics were calculated for all variables of interest. An unadjusted linear correlation analysis and linear regression were performed. Potential confounders were investigated by comparison across low-vs high-staffing facilities where adjusted for in regression analyses. RESULTS: The mean staff level for the facilities was identified as 3.69 (SD = 0.67) staffing hours per patient per day, and the mean antipsychotic use rate across all facilities was 15.24% (SD = 8.62%). There was a 0.75% decrease in inappropriate antipsychotic prescribing per unit increase in overall staff-to-patient ratio. When looking at staffing types, a 3.09% decrease in inappropriate antipsychotic prescribing was observed per unit increase in licensed staff hours. More specifically, we saw a 2.25% decrease per unit increase in RN staffing hours, a 1.83% decrease per unit increase in LPN staffing hours, and nursing aide staffing hours were not associated with antipsychotic use. CONCLUSIONS AND IMPLICATIONS: These findings provide support for policy-based interventions to decrease antipsychotic use in LTC facilities by improving staffing skill mix and staffing levels. The results may also inform nursing staff education and training on antipsychotic prescribing practices.

Correlates of Opioid Use Among Ontario Long-Term Care Residents and Variation by Pain Frequency and Intensity: A Cross-sectional Analysis.

BACKGROUND: Chronic non-cancer pain is common among older residents of long-term care (LTC) homes and often poorly recognized and treated. With heightened concerns regarding opioid prescribing in recent years, it is important to examine the current prevalence of opioid use and its association with resident characteristics to help identify those potentially at risk of medication harms as well as suboptimal pain management. OBJECTIVES: The aims were to estimate the prevalence and correlates of opioid use among non-palliative LTC residents and explore variation in opioid prevalence and correlates across strata defined by pain frequency and intensity. METHODS: We conducted a population-based cross-sectional study of all older (aged > 65 years) LTC residents (excluding those with cancer or receiving palliative care) in Ontario, Canada during 2018-2019. Health administrative databases were linked with standardized clinical assessment data to ascertain residents' health and pain characteristics and their opioid and other medication use. Modified Poisson regression models estimated unadjusted and adjusted associations between residents' characteristics and opioid use, overall and across strata capturing pain frequency and intensity. RESULTS: Among 75,020 eligible residents (mean age 85.1 years; 70% female), the prevalence of opioid use was 18.5% and pain was 29.4%. Opioid use ranged from 12.2% for residents with no current pain to 55.7% for those with severe pain. In adjusted models, residents newly admitted to LTC (adjusted risk ratio [aRR] = 0.60, 95% confidence interval [CI] 0.57-0.62) and with moderate to severe cognitive impairment (aRR = 0.69, 95% CI 0.66-0.72) or dementia (aRR = 0.76, 95% CI 0.74-0.79) were significantly less likely to receive an opioid, whereas residents with select conditions (e.g., arthritis, aRR = 1.37, 95% CI 1.32-1.41) and concurrently using gabapentinoids (aRR = 1.80, 95% CI 1.74-1.86), benzodiazepines (aRR = 1.33, 95% CI 1.28-1.38), or antidepressants (aRR = 1.31, 95% CI 1.27-1.35) were significantly more likely to receive an opioid. The associations observed for residents newly admitted, with dementia, and concurrently using gabapentinoids, benzodiazepines, or antidepressants were largely consistent across all pain strata. CONCLUSIONS: Our findings describe resident sub-groups at potentially higher risk of adverse health outcomes in relation to both opioid use and non-use. LTC clinical and policy changes informed by research are required to ensure the appropriate recognition and management of non-cancer pain in this setting.

Prevalence and factors associated with polypharmacy: a systematic review and Meta-analysis.

INTRODUCTION: Polypharmacy is commonly associated with adverse health outcomes. There are currently no meta-analyses of the prevalence of polypharmacy or factors associated with polypharmacy. We aimed to estimate the pooled prevalence of polypharmacy and factors associated with polypharmacy in a systematic review and meta-analysis. METHODS: MEDLINE, EMBASE, and Cochrane databases were searched for studies with no restrictions on date. We included observational studies that reported on the prevalence of polypharmacy among individuals over age 19. Two reviewers extracted study characteristics including polypharmacy definitions, study design, setting, geography, and participant demographics. The risk of bias was assessed using the Newcastle-Ottawa Scales. The main outcome was the prevalence of polypharmacy and factors associated with polypharmacy prevalence. The pooled prevalence estimates of polypharmacy with 95% confidence intervals were determined using random effects meta-analysis. Subgroup analyses were undertaken to evaluate factors associated with polypharmacy such as polypharmacy definitions, study setting, study design and geography. Meta-regression was conducted to assess the associations between polypharmacy prevalence and study year. RESULTS: 106 full-text articles were identified. The pooled estimated prevalence of polypharmacy in the 54 studies reporting on polypharmacy in all medication classes was 37% (95% CI: 31-43%). Differences in polypharmacy prevalence were reported for studies using different numerical thresholds, study setting, and publication year. Sex, study geography, study design and geographical location were not associated with differences in polypharmacy prevalence. DISCUSSION: Our review highlights that polypharmacy is common particularly among older adults and those in inpatient settings. Clinicians should be aware of populations who have an increased likelihood of experiencing polypharmacy and efforts should be made to review the appropriateness of prescribed medications and occurrence of adverse effects potentially associated with polypharmacy. CONCLUSIONS AND IMPLICATIONS: Clinicians should be aware of the common occurrence of polypharmacy and undertake efforts to minimize inappropriate polypharmacy whenever possible.