Association of Sex With Stroke and Bleeding Risk of Apixaban and Rivaroxaban in Elderly Atrial Fibrillation Patients Using Propensity Score Weights

Background: Evidence from clinical trials suggests a differential effect of sex on the effectiveness and safety of direct oral anticoagulants (DOACs) for stroke prophylaxis in atrial fibrillation (AF). Methods: This population-based cohort study examined the independent effect of sex on hemorrhage and ischemic stroke in 23,884 patients (55% females; age ≥ 66 years) with AF starting apixaban or rivaroxaban treatment in Ontario, Canada. Patients were followed for 90 days after their DOAC prescription. Using female sex as the exposure of interest, differences in baseline characteristics were balanced between sexes using inverse probability weights based on propensity scores. Applying weighted modified Poisson regression, risk ratios (RRs) were estimated for major hemorrhage, ischemic stroke/systemic embolism/transient ischemic attack (hereafter stroke), myocardial infarction, and all-cause mortality, with males as a reference. Results: Females were older, had higher predicted stroke risk (based on CHADS2 score), and had fewer comorbidities than did males. Males had a higher prevalence of coronary artery disease, diabetes, and cancer, and similar predicted bleeding risk (based on HAS-BLED score). After weighting, baseline characteristics were well balanced. The 90-day risks for hemorrhage (RR 0.96; 95% confidence interval [CI] 0.80-1.15; P = 0.69) and stroke (RR 1.01; 95% CI 0.86-1.19; P = 0.94) were similar between sexes, which remained true when assessing each DOAC separately by dosing regimen. Compared to males, females had a lower risk for myocardial infarction (RR 0.66; 95% CI 0.52-0.84; P = 0.0008), and for all-cause mortality (RR 0.76; 95% CI 0.67-0.87; P \u3c 0.0001). Conclusions: Our findings do not suggest an association of sex with the 90-day risk of hemorrhage or ischemic stroke in older AF patients prescribed apixaban or rivaroxaban

Classification of general and personal semantic details in the Autobiographical Interview

The Autobiographical Interview (AI) separates internal (episodic) and external (non-episodic) details from transcribed protocols using an exhaustive and reliable scoring system. While the details comprising the internal composite are centered on elements of episodic memory, external details are more heterogeneous as they are meant to capture a variety of non-episodic utterances: general semantics, different types of personal semantics details, metacognitive statements, repetitions, and details about off topic events. Elevated external details are consistently observed in aging and in neurodegenerative diseases. In the present study, we augmented the AI scoring system to differentiate subtypes of external details to test whether the elevation of these details in aging and in frontotemporal lobar degeneration (including mixed frontotemporal/semantic dementia [FTD/SD] and progressive non-fluent aphasia [PNFA]) would be specific to general and personal semantics or would concern all subtypes. Specifically, we separated general semantic details from personal semantic details (including autobiographical facts, self-knowledge, and repeated events). With aging, external detail elevation was observed for general and personal semantic details but not for other types of external details. In frontotemporal lobar degeneration, patients with FTD/SD (but not PNFA) generated an excess of personal semantic details but not general semantic details. The increase in personal but not general semantic details in FTD/SD is consistent with prevalent impairment of general semantic memory in SD, and with the personalization of concepts in this condition. Under standard AI instructions, external details were intended to capture off-topic utterances and were not intended as a direct measure of semantic abilities. Future investigations concerned with semantic processing in aging and in dementia could modify standard instructions of the AI to directly probe semantic content

Age-related decline in item but not spatiotemporal associative memory for a real-world event

Normal aging is typically associated with reduced ability to reconstruct the spatiotemporal context of past events, a core component of episodic memory. However, little is known about our ability to remember the order of events comprising extended real-world experiences and how this ability changes with age. We leveraged the richness and structure of a museum exhibit to address this question. Three months after visiting the exhibit, 141 adults aged 18-84 completed a test of spatiotemporal order memory and old/new recognition using pictures from the exhibit and similar lures, from which measures of associative and item memory were derived. Order discrimination accuracy was modulated by inter-item order and distance in younger and older adults, extending findings from recognition of laboratory stimuli at short delays to remote real-world experiences. In contrast to established findings from laboratory-based assessments, we observed a significant effect of aging on item memory driven by increased lure susceptibility, but no age-related reduction in spatiotemporal associative memory. These findings present novel insights into different components of memory for real-world experiences at naturalistic timescales and across the lifespan

Age-related decline in item but not spatiotemporal associative memory for a real-world event

Normal aging is typically associated with reduced ability to reconstruct the spatiotemporal context of past events, a core component of episodic memory. However, little is known about our ability to remember the order of events comprising extended real-world experiences and how this ability changes with age. We leveraged the richness and structure of a museum exhibit to address this question. Three months after visiting the exhibit, 141 adults aged 18-84 completed a test of spatiotemporal order memory and old/new recognition using pictures from the exhibit and similar lures, from which measures of associative and item memory were derived. Order discrimination accuracy was modulated by inter-item order and distance in younger and older adults, extending findings from recognition of laboratory stimuli at short delays to remote real-world experiences. In contrast to established findings from laboratory-based assessments, we observed a significant effect of aging on item memory driven by increased lure susceptibility, but no age-related reduction in spatiotemporal associative memory. These findings present novel insights into different components of memory for real-world experiences at naturalistic timescales and across the lifespan

Periconceptional Serum Creatinine and Risk of Childhood Autism Spectrum Disorder: A Research Letter

Background: Autism spectrum disorder (ASD) is a neurodevelopmental condition that manifests in early childhood, in which the maternal metabolic syndrome may be a risk factor. The kidney is a barometer of maternal metabolic syndrome duration and severity. Objective: The main objective of this study is to determine whether periconceptional kidney function is associated with ASD in early childhood. Design, Setting, and Participants: This retrospective population-based cohort study was completed in Ontario, Canada. Included were singleton children born in an Ontario hospital between April 2007 and March 2021, who were alive at age 48 months and whose mother had a recorded prepregnancy body mass index (BMI) and a measured serum creatinine (SCr) between 120 days preconception and 28 days postconception. Measurement: The main study outcome was a diagnosis of ASD between ages 24 and 48 months. Methods: Relative risks (RRs) of ASD in association with periconceptional SCr were generated using modified Poisson regression and adjusted for several confounders. Results: The cohort comprised 86 054 women, who had 89 677 liveborn children surviving to at least 48 months of age. There was no significant association between periconceptional SCr and ASD (RR: 0.86; 95 % confidence interval: [0.67, 1.10]). Limitations: Selection bias may have arisen had SCr been ordered on clinical grounds. Conclusions: Further study is warranted to determine whether prepregnancy glomerular hyperfiltration is a marker of ASD and other behavioral conditions in childhood. To do so, a more accurate measure of hyperfiltration is needed than SCr

Health Services Use and Outcomes for Hospital Admissions With a Major Cardiovascular Event Recorded in Health Care Administrative Data in Patients Receiving Maintenance Hemodialysis: A Retrospective Cohort Study

Background: Administrative data are used in studies of hemodialysis care to report cardiovascular-related hospitalizations. Showing recorded events are associated with significant health care resource use and poor outcomes would confirm that administrative data algorithms identify clinically meaningful events. Objective: The objective of this study was to describe the 30-day health service use and outcomes when a hospital admission with myocardial infarction, congestive heart failure, or ischemic stroke is recorded in administrative databases. Design: This is a retrospective review of linked administrative data. Patients and Setting: Patients receiving maintenance in-center hemodialysis in Ontario, Canada, between April 1, 2013, and March 31, 2017, were included. Measurements: Records from linked health care databases at ICES in Ontario, Canada were considered. We identified hospital admission with the most responsible diagnosis recorded as myocardial infarction, congestive heart failure, or ischemic stroke. We then assessed the frequency of common tests, procedures, consultations, post-discharge outpatient drug prescriptions, and outcomes within 30 days following the hospital admission. Methods: We used descriptive statistics to summarize results using counts and percentages for categorical variables and means with standard deviations or medians with quartile ranges for continuous variables. Results: There were 14 368 patients who received maintenance hemodialysis between April 1, 2013, and March 31, 2017. The number of events per 1000 person-years was 33.5 for hospital admissions with myocardial infarction, 34.2 for congestive heart failure, and 12.9 for ischemic stroke. The median (25th, 75th percentile) duration of hospital stay was 5 (3-10) days for myocardial infarction, 4 (2-8) days for congestive heart failure, and 9 (4-18) days for ischemic stroke. The chance of death within 30 days was 21% for myocardial infarction, 11% for congestive heart failure, and 19% for ischemic stroke. Limitations: Events, procedures, and tests recorded in administrative data can be misclassified compared with medical charts. Conclusions: In patients receiving maintenance hemodialysis, hospital admissions of major cardiovascular events routinely recorded in health administrative databases are associated with significant use of health service resources and poor health outcomes

Classification of general and personal semantic details in the Autobiographical Interview

The Autobiographical Interview (AI) separates internal (episodic) and external (non-episodic) details from transcribed protocols using an exhaustive and reliable scoring system. While the details comprising the internal composite are centered on elements of episodic memory, external details are more heterogeneous as they are meant to capture a variety of non-episodic utterances: general semantics, different types of personal semantics details, metacognitive statements, repetitions, and details about off topic events. Elevated external details are consistently observed in aging and in neurodegenerative diseases. In the present study, we augmented the AI scoring system to differentiate subtypes of external details to test whether the elevation of these details in aging and frontotemporal lobar degeneration (including mixed frontotemporal/semantic dementia [FTD/SD] and progressive non-fluent aphasia [PNFA]) would be specific to general and personal semantics or would concern all subtypes. Specifically, we separated general semantic details from personal semantic details (including autobiographical facts, self-knowledge, and repeated events). With aging, external detail elevation was observed for general and personal semantic details but not for other types of external details. In frontotemporal lobar degeneration, patients with FTD/SD (but not PNFA) generated an excess of personal semantic details ¬but not general semantic details. The increase in personal but not general semantic details in FTD/SD is consistent with prevalent impairment of general semantic memory in SD, and with the personalization of concepts in this condition. Under standard AI instructions, external details were intended to capture off-topic utterances and were not intended as a direct measure of semantic abilities. Future investigations concerned with semantic processing in aging and in dementia could modify standard instructions of the AI to directly probe semantic content

Mental health and addiction health service use by physicians compared to non-physicians before and during the COVID-19 pandemic: A population-based cohort study in Ontario, Canada.

BackgroundThe Coronavirus Disease 2019 (COVID-19) pandemic has exacerbated mental health challenges among physicians and non-physicians. However, it is unclear if the worsening mental health among physicians is due to specific occupational stressors, reflective of general societal stressors during the pandemic, or a combination. We evaluated the difference in mental health and addictions health service use between physicians and non-physicians, before and during the COVID-19 pandemic.Methods and findingsWe conducted a population-based cohort study in Ontario, Canada between March 11, 2017 and August 11, 2021 using data collected from Ontario's universal health system. Physicians were identified using registrations with the College of Physicians and Surgeons of Ontario between 1990 and 2020. Participants included 41,814 physicians and 12,054,070 non-physicians. We compared the first 18 months of the COVID-19 pandemic (March 11, 2020 to August 11, 2021) to the period before COVID-19 pandemic (March 11, 2017 to February 11, 2020). The primary outcome was mental health and addiction outpatient visits overall and subdivided into virtual versus in-person, psychiatrists versus family medicine and general practice clinicians. We used generalized estimating equations for the analyses. Pre-pandemic, after adjustment for age and sex, physicians had higher rates of psychiatry visits (aIRR 3.91 95% CI 3.55 to 4.30) and lower rates of family medicine visits (aIRR 0.62 95% CI 0.58 to 0.66) compared to non-physicians. During the first 18 months of the COVID-19 pandemic, the rate of outpatient mental health and addiction (MHA) visits increased by 23.2% in physicians (888.4 pre versus 1,094.7 during per 1,000 person-years, aIRR 1.39 95% CI 1.28 to 1.51) and 9.8% in non-physicians (615.5 pre versus 675.9 during per 1,000 person-years, aIRR 1.12 95% CI 1.09 to 1.14). Outpatient MHA and virtual care visits increased more among physicians than non-physicians during the first 18 months of the pandemic. Limitations include residual confounding between physician and non-physicians and challenges differentiating whether observed increases in MHA visits during the pandemic are due to stressors or changes in health care access.ConclusionsThe first 18 months of the COVID-19 pandemic was associated with a larger increase in outpatient MHA visits in physicians than non-physicians. These findings suggest physicians may have had larger negative mental health during COVID-19 than the general population and highlight the need for increased access to mental health services and system level changes to promote physician wellness