Mode of delivery and birth outcomes before and during COVID-19 -A population-based study in Ontario, Canada.

There is lack of clarity on whether pregnancies during COVID-19 resulted in poorer mode of delivery and birth outcomes in Ontario, Canada. We aimed to compare mode of delivery (C-section), birth (low birthweight, preterm birth, NICU admission), and health services use (HSU, hospitalizations, ED visits, physician visits) outcomes in pregnant Ontario women before and during COVID-19 (pandemic periods). We further stratified for pre-existing chronic diseases (asthma, eczema, allergic rhinitis, diabetes, hypertension). Deliveries before (Jun 2018-Feb 2020) and during (Jul 2020-Mar 2022) pandemic were from health administrative data. We used multivariable logistic regression analyses to estimate adjusted odds ratios (aOR) of delivery and birth outcomes, and negative binomial regression for adjusted rate ratios (aRR) of HSU. We compared outcomes between pre-pandemic and pandemic periods. Possible interactions between study periods and covariates were also examined. 323,359 deliveries were included (50% during pandemic). One in 5 (18.3%) women who delivered during the pandemic had not received any COVID-19 vaccine, while one in 20 women (5.2%) lab-tested positive for COVID-19. The odds of C-section delivery during the pandemic was 9% higher (aOR = 1.09, 95% CI: 1.08-1.11) than pre-pandemic. The odds of preterm birth and NICU admission were 15% (aOR = 0.85, 95% CI: 0.82-0.87) and 10% lower (aOR = 0.90, 95% CI: 0.88-0.92), respectively, during COVID-19. There was a 17% reduction in ED visits but a 16% increase in physician visits during the pandemic (aRR = 0.83, 95% CI: 0.81-0.84 and aRR = 1.16, 95% CI: 1.16-1.17, respectively). These aORs and aRRs were significantly higher in women with pre-existing chronic conditions. During the pandemic, healthcare utilization, especially ED visits (aRR = 0.83), in pregnant women was lower compared to before. Ensuring ongoing prenatal care during the pandemic may reduce risks of adverse mode of delivery and the need for acute care during pregnancy.

Obstructive sleep apnea severity, circulating biomarkers, and cancer risk.

STUDY OBJECTIVES: To determine if obstructive sleep apnea (OSA) severity and/or biomarkers of inflammation/angiogenesis are associated with incident cancer in this clinical cohort. METHODS: Consenting adult patients at the University of British Columbia Hospital between 2003-2014 completed a questionnaire about their medical history and sleep habits prior to undergoing a polysomnogram (PSG). Blood samples were collected the morning after PSG and processed for biomarkers of inflammation and angiogenesis. The clinical, PSG, and biomarker data were linked to the British Columbia Cancer Registry to ascertain incident cancer diagnoses. Cox proportional hazard regression were used to assess the association between OSA severity and biomarker concentrations with cancer risk. RESULTS: A total of 1,990 patients were included in the analysis with a mean follow-up time of 12.8 years; 181 of them (9.1%) developed cancer after PSG. OSA severity was significantly associated with cancer risk after controlling for relevant covariates (hazard ratio (HR) = 1.08 per 10 events/h apnea-hypopnea index (AHI) increase, CI = 1.02-1.15, p=0.015). In an exploratory analysis, two biomarkers were significantly associated with an increased cancer risk after controlling for relevant covariates (HR per interquartile range (IQR) pg/mL increase of endostatin = 1.45, CI = 1.12-1.87, p=0.01 and HR for IQR pg/mL increase of VCAM-1 = 1.48, CI = 1.04-2.11, p=0.03, respectively). CONCLUSIONS: OSA severity was an independent risk factor for cancer. Furthermore, two circulating markers were significantly associated with cancer risk. If these preliminary findings can be reproduced in other cohorts, biomarkers could potentially be used to prognosticate OSA patients with respect to cancer risk.

Obstructive Sleep Apnea and Mental Health Disorders in the Pediatric Population: A Retrospective Population-based Cohort Study.

RATIONALE: Information is limited about the association between obstructive sleep apnea (OSA) and mental disorders in children. OBJECTIVES: In children, (1) to evaluate the association between OSA and new mental healthcare encounters; (2) to compare mental healthcare encounters two years post- to pre-OSA treatment initiation. METHODS: We conducted a retrospective longitudinal cohort study using Ontario health administrative data (Canada). Children (0-18 years) who underwent diagnostic polysomnography (PSG) 2009-2016 and met criteria for definition of moderate-severe OSA (PSG-OSA) were propensity score weighted by baseline characteristics and compared to children who underwent a PSG in the same period but did not meet the OSA definition (PSG-No-OSA). Children were followed until March 2021. Weighted cause-specific Cox Proportional Hazards and Modified Poisson regression models were used to compare time from PSG to first mental healthcare encounter and frequency of new mental healthcare encounters per person time, respectively. Among those who underwent adenotonsillectomy (AT) or were prescribed and claimed positive airway pressure therapy (PAP), we used age-adjusted conditional logistic regression models to compare two years post- to pre-treatment odds of mental healthcare encounters. RESULTS: Of 32,791 children analyzed, 7,724 (23.6%) children met criteria for moderate-severe OSA. In PSG-OSA group, 7,080 (91.7%) were treated (AT or PAP). Compared to PSG-No-OSA, the PSG-OSA group had a shorter time from PSG to first mental healthcare encounter (HR: 1.08; 95%CI: 1.05-1.12), but less frequent mental healthcare encounters in follow-up (RR: 0.92; 95% CI: 0.87-0.97). OSA treatment (AT or PAP) was associated with lower odds of mental healthcare encounters two years post-treatment initiation compared to two years prior (OR: 0.69; 95% CI: 0.65-0.74). CONCLUSION: In this large population-based study of children who underwent PSG for sleep disorder assessment, OSA diagnosis/treatment was associated with an improvement in some mental health indicators, such as fewer new mental healthcare encounters compared to no OSA, and lower odds of mental healthcare encounters compared to pre-OSA treatment.

Air pollution, weather and positive airway pressure treatment adherence in adults with sleep apnea: a retrospective community-based repeated-measures longitudinal study.

We assessed the relation between air pollution, weather, and adherence to positive airway pressure (PAP) therapy in a retrospective community-based repeated-measures study of adults with obstructive sleep apnea who purchased PAP devices from a registered provider between 2013 and 2017 (Ottawa, Ontario, Canada) and had at least one day of data. Daily PAP-derived data, air pollution, and weather databases were linked using postal code. The exposures were mean nocturnal (8:00 p.m. to 8:00 a.m.) (i) residential concentrations of nitrogen dioxide (NO2 ), fine particulate matter <=2.5 µm (PM2.5 ), ozone (O3 ), and Air Quality Health Index (AQHI), and (ii) temperature, relative humidity, and barometric pressure. Covariates in the main model were demographics, season, exposure year, and PAP therapy mode. We analysed 8148 adults (median age of 54 years and 61% men) and 2,071,588 days of data. Based on daily data, the median (interquartile range) daily PAP usage was 416 (323-487) min. Using mixed-effect regression analyses to incorporate daily data and clustering by individuals, we found a statistically significant decrease in adherence for increased levels of NO2 , PM2.5 , and AQHI. The largest effect was for NO2 : a decrease in daily PAP use while comparing the highest versus lowest quartiles (Qs) was 3.4 (95% confidence interval [CI] 2.8-3.9) min. Decreased PAP adherence was also associated with increased temperature (Q4 versus Q1: 2.6 [95% CI: 1.5-3.7] min) and decreased barometric pressure (Q1 versus Q4: 2.0 [95% CI 1.5-2.5] min). We observed modest but statistically significant acute effects of air pollution and weather on daily PAP adherence.

The relationship between the morningness-eveningness questionnaire and incident cancer: A historical clinical cohort study.

OBJECTIVE: We conducted a retrospective cohort study to explore the relationship between chronotype measured by the total Morningness-Eveningness Questionnaire (MEQ) score and incident cancer. METHODS: We used clinical and provincial health administrative data on consecutive adults who underwent a Level 1 Polysomnography (PSG) and completed the MEQ between 2010 and 2015 in an academic hospital (Ontario, Canada) and were cancer-free at baseline. Cancer status was derived from the Ontario Cancer Registry. Individuals were followed until death or March 31, 2020. We used multivariable Cox cause-specific regressions to address the research objective. RESULTS: Of 3,004 individuals, 1,781 were analyzed: a median age of 54 years (IQR: 40-64) and 838 (47.1%) men. The median total MEQ score was 63 (IQR: 55-69); 61 (3.4%) were classified as evening (≤41), 536 (30.1%) as intermediate (42-58), and 1,184 (66.5%) as morning chronotypes (≥59). Over a median of 7 years (IQR: 5-8), 120 (6.7%) developed cancer. A U-shape relationship was found between the total MEQ score and an increased hazard of incident cancer, controlling for PSG measures of sleep apnea severity and sleep architecture, demographics, and comorbidities. Compared to the median of 63.0, a total MEQ score greater or less than the median was associated with an increased hazard of incident cancer, with the largest effect for those with a total score ≥76 (e.g., HR of a MEQ total score of 78 vs. 63: 2.01, 95% CI: 1.09-3.71). CONCLUSION: The U-shaped curve may reflect deviations from a standard circadian tendency, which may stress biological systems and influence malignancy risk.

Resource Use and Costs of Indwelling Pleural Catheters vs Pleurodesis for Malignant Pleural Effusions: A Population-based Study.

RATIONALE: Malignant pleural effusions (MPE) are associated with significant health service use and healthcare costs, but the current evidence is limited. OBJECTIVES: To compare 12-month post-procedure: (1) health service utilization, and (2) healthcare costs following indwelling pleural catheter (IPC) insertion with at-home drainage performed by homecare nursing services, versus in-hospital chemical pleurodesis. METHODS: We performed a retrospective population-based study on a cohort of adults with MPE who underwent IPC insertion or chemical pleurodesis between January 1, 2015 and December 31, 2019 using provincial health administrative data (Ontario, Canada). Patients were followed from the procedure date until death or until 12-month post-procedure. Inverse probability of treatment weighting (IPTW) was performed to adjust for imbalances in baseline characteristics. Differences in length of stay (LOS), readmissions, emergency department visits, home care visits, and healthcare costs were estimated using weighted regression analysis. RESULTS: Of 5,752 included individuals, 4432 (77%) underwent IPC insertion and 1320 (23%) had pleurodesis. In the weighted sample, individuals who received an IPC had fewer inpatient days (12.4 days vs 16 days, standardized mean difference 0.229), but a higher proportion of subsequent admissions for empyema (2.7% vs 1.1%, p=0.0002) compared to those undergoing pleurodesis. IPC individuals received more hours of nursing home care (41 hours vs 21.1 hours, standardized mean difference 0.671) but overall had lower average healthcare costs ($40,179 vs $46,640 per patient, standardized mean difference 0.177) than those receiving pleurodesis. CONCLUSIONS: IPCs with home nursing drainage are associated with reduced health resource use compared to pleurodesis in adults with MPE even after controlling for important baseline and clinical characteristics. Given that both procedures have similar health outcomes, our findings support the ongoing promotion of IPCs to increase outpatient management of patients with MPEs. Primary source of funding: TOHAMO Innovation Fund grant.

Obstructive sleep apnea in those with idiopathic intracranial hypertension undergoing diagnostic in-laboratory polysomnography.

RATIONALE: The association of obstructive sleep apnea (OSA) with idiopathic intracranial hypertension (IIH) remains unclear, and few studies have used objective in-laboratory polysomnography (PSG) data. Thus, we used PSG data to examine the: 1) association between OSA, and its severity, with IIH and 2) sex differences in OSA severity in those with and without IIH. METHODS: We retrospectively analyzed diagnostic PSG data from January 2015 to August 2023 for patients who were diagnosed with IIH by a neuro-ophthalmologist using the modified Dandy criteria. We selected three age, sex, and body mass index (BMI) matched controls for each IIH patient. We examined potential associations of IIH with OSA using regression. Sex differences were analyzed using ANOVA. RESULTS: Of 3482 patients who underwent PSG, we analyzed 78 IIH patients (16 males) and 234 matched controls (48 males). Five (6.4 %) IIH and 39 (16.7 %) control patients had OSA, defined as AHI≥15. After adjusting for age, sex, BMI, and comorbidities, IIH was negatively associated with the presence of OSA (OR 0.29, 95%CI 0.10-0.87, p = 0.03). However, models that adjusted for acetazolamide use, with or without comorbidities, showed no significant relationship with OSA (OR 0.31, p = 0.20). Males with IIH had a significantly higher age (p = 0.020), OSA severity (p = 0.032), and arousal index (p = 0.046) compared to females with IIH. CONCLUSIONS: IIH treated with acetazolamide was not an independent risk factor for OSA presence or severity. The presence of IIH treated with acetazolamide likely does not warrant routine screening for OSA, but related risk factors may identify appropriate patients.

All Obstructive Sleep Apnea Events Are Not Created Equal: The Relationship between Event-related Hypoxemia and Physiologic Response.

Rationale: Obstructive sleep apnea (OSA) severity is typically assessed by the apnea-hypopnea index (AHI), a frequency-based metric that allocates equal weight to all respiratory events. However, more severe events may have a greater physiologic impact. Objectives: The purpose of this study was to determine whether the degree of event-related hypoxemia would be associated with the postevent physiologic response. Methods: Patients with OSA (AHI, ⩾5/h) from the multicenter Canadian Sleep and Circadian Network cohort were studied. Using mixed-effect linear regression, we examined associations between event-related hypoxic burden (HBev) assessed by the area under the event-related oxygen saturation recording with heart rate changes (ΔHRev), vasoconstriction (vasoconstriction burden [VCBev] assessed with photoplethysmography), and electroencephalographic responses (power ratio before and after events). Results: Polysomnographic recordings from 658 patients (median [interquartile range] age, 55.00 [45.00, 64.00] yr; AHI, 27.15 [14.90, 64.05] events/h; 42% female) were included in the analyses. HBev was associated with an increase in all physiologic responses after controlling for age, sex, body mass index, sleep stage, total sleep time, and study centers; for example, 1 standard deviation increase in HBev was associated with 0.21 [95% confidence interval, 0.2, 0.22], 0.08 [0.08, 0.09], and 0.22 [0.21, 0.23] standard deviation increases in ΔHRev, VCBev, and ß-power ratio, respectively. Conclusions: Increased event-related hypoxic burden was associated with greater responses across a broad range of physiologic signals. Future metrics that incorporate information about the variability of these physiologic responses may have promise in providing a more nuanced assessment of OSA severity.

Pandemic Effect on Healthcare Use and Death in Adults with Epilepsy: A Population Study.

OBJECTIVES: We conducted a population-based study using Ontario health administrative data to describe trends in healthcare utilization and mortality in adults with epilepsy during the first pandemic year (March 2020-March 2021) compared to historical data (2016-2019). We also investigated if changes in outpatient visits and diagnostic testing during the first pandemic year were associated with increased risk for hospitalizations, emergency department (ED) visits, or death. METHODS: Projected monthly visit rates (per 100,000 people) for outpatient visits, electroencephalography, magnetic resonance, computed tomography, all-cause ED visits, hospitalizations, and mortality were calculated based on historical data by fitting monthly time series autoregressive integrated moving-average models. Two-way interactions were calculated using Quasi-Poisson models. RESULTS: In adults with epilepsy during the first quarter of the pandemic, we demonstrated a reduction in all-cause outpatient visits, diagnostic testing, ED visits and hospitalizations, and a temporary increase in mortality (observed rates of 355.8 vs projected 308.8, 95% CI: 276.3-345.1). By the end of the year, outpatient visits increased (85,535.4 vs 76,620.6, 95% CI: 71,546.9-82,059.4), and most of the diagnostic test rates returned to the projected. The increase in the rate of all-cause mortality during the pandemic, compared to pre-pandemic, was greater during months with the lower frequency of diagnostic tests than months with higher frequency (interaction p-values <.0001). CONCLUSION: We described the impact of the pandemic on healthcare utilization and mortality in adults with epilepsy during the first year. We demonstrated that access to relevant diagnostic testing is likely important for this population while planning restrictions on non-urgent health services.

Scalable computational algorithms for geospatial COVID-19 spread using high performance computing.

A nonlinear partial differential equation (PDE) based compartmental model of COVID-19 provides a continuous trace of infection over space and time. Finer resolutions in the spatial discretization, the inclusion of additional model compartments and model stratifications based on clinically relevant categories contribute to an increase in the number of unknowns to the order of millions. We adopt a parallel scalable solver that permits faster solutions for these high fidelity models. The solver combines domain decomposition and algebraic multigrid preconditioners at multiple levels to achieve the desired strong and weak scalabilities. As a numerical illustration of this general methodology, a five-compartment susceptible-exposed-infected-recovered-deceased (SEIRD) model of COVID-19 is used to demonstrate the scalability and effectiveness of the proposed solver for a large geographical domain (Southern Ontario). It is possible to predict the infections for a period of three months for a system size of 186 million (using 3200 processes) within 12 hours saving months of computational effort needed for the conventional solvers.

Development of Multivariable Prediction Models for the Identification of Patients Admitted to Hospital with an Exacerbation of COPD and the Prediction of Risk of Readmission: A Retrospective Cohort Study using Electronic Medical Record Data.

BACKGROUND: Approximately 20% of patients who are discharged from hospital for an acute exacerbation of COPD (AECOPD) are readmitted within 30 days. To reduce this, it is important both to identify all individuals admitted with AECOPD and to predict those who are at higher risk for readmission. OBJECTIVES: To develop two clinical prediction models using data available in electronic medical records: 1) identifying patients admitted with AECOPD and 2) predicting 30-day readmission in patients discharged after AECOPD. METHODS: Two datasets were created using all admissions to General Internal Medicine from 2012 to 2018 at two hospitals: one cohort to identify AECOPD and a second cohort to predict 30-day readmissions. We fit and internally validated models with four algorithms. RESULTS: Of the 64,609 admissions, 3,620 (5.6%) were diagnosed with an AECOPD. Of those discharged, 518 (15.4%) had a readmission to hospital within 30 days. For identification of patients with a diagnosis of an AECOPD, the top-performing models were LASSO and a four-variable regression model that consisted of specific medications ordered within the first 72 hours of admission. For 30-day readmission prediction, a two-variable regression model was the top performing model consisting of number of COPD admissions in the previous year and the number of non-COPD admissions in the previous year. CONCLUSION: We generated clinical prediction models to identify AECOPDs during hospitalization and to predict 30-day readmissions after an acute exacerbation from a dataset derived from available EMR data. Further work is needed to improve and externally validate these models.

Impact of sleep chronotype on in-laboratory polysomnography parameters.

Morningness-eveningness preference, also known as chronotype, is the tendency for a person to sleep during certain hours of the day and is broadly categorised into morning and evening types. In-laboratory polysomnography (iPSG) is the gold-standard to assess sleep, however, an individual's chronotype is not accounted for in current protocols, which may confound collected sleep data. The objective of our study was to assess if chronotype had an association with sleep physiology. Patients who completed the diagnostic iPSG and the Morningness-Eveningness Questionnaire (MEQ), which categorises patients into morning type, neither or evening type, were assessed. Multivariable linear regression models were used to assess if chronotype was associated with sleep quality, duration, and physiology during iPSG. The study sample included 2612 patients (mean age of 53.6 years, 48% male) recruited during 2010-2015. Morning type, compared with neither type, was significantly associated with an increase in total sleep time and rapid eye movement (REM) sleep, and a decrease in sleep onset latency and the arousal index. Evening type, compared with neither type, was significantly associated with a decrease in total sleep time, sleep efficiency, and REM sleep, and an increase in sleep onset latency and wake after sleep onset. Additionally, iPSG lights out time was significantly different between the different chronotypes. Overall, a morningness chronotype was associated with favourable sleep quality and duration while an eveningness chronotype was associated with reduced sleep quality. Our study quantifies the association of chronotype with iPSG metrics and suggests that laboratory protocols should consider chronotype in their evaluations.

Physician benzodiazepine self-use prior to and during the COVID-19 pandemic in Ontario, Canada: a population-level cohort study.

OBJECTIVES: The aim of this study was to investigate physician benzodiazepine (BZD) self-use pre-COVID-19 pandemic and to examine changes in BZD self-use during the first year of the pandemic. DESIGN: Population-based retrospective cohort study using linked routinely collected administrative health data comparing the first year of the pandemic to the period before the pandemic. SETTING: Province of Ontario, Canada between March 2016 and March 2021. PARTICIPANTS: INTERVENTION: Onset of the COVID-19 pandemic in March 2020. OUTCOMES MEASURES: The primary outcome measure was the receipt of one or more prescriptions for BZD, which was captured via the Narcotics Monitoring System. RESULTS: In a cohort of 30 798 physicians (mean age 42, 47.8% women), we found that during the year before the pandemic, 4.4% of physicians had 1 or more BZD prescriptions. Older physicians (6.8% aged 50+ years), female physicians (5.1%) and physicians with a prior mental health (MH) diagnosis (12.4%) were more likely than younger (3.7% aged <50 years), male physicians (3.8%) and physicians without a prior MH diagnosis (2.9%) to have received 1 or more BZD prescriptions. The first year of the COVID-19 pandemic was associated with a 10.5% decrease (adjusted OR (aOR) 0.85, 95% CI: 0.80 to 0.91) in the number of physicians with 1 or more BZD prescriptions compared with the year before the pandemic. Female physicians were less likely to reduce BZD self-use (aORfemale=0.90, 95% CI: 0.83 to 0.98) compared with male physicians (aORmale=0.79, 95% CI: 0.72 to 0.87, pinteraction=0.046 during the pandemic. Physicians presenting with an incident MH visit had higher odds of filling a BZD prescription during COVID-19 compared with the prior year. CONCLUSIONS: Physicians' BZD prescriptions decreased during the first year of the COVID-19 pandemic in Ontario, Canada. These findings suggest that previously reported increases in mental distress and MH visits among physicians during the pandemic did not lead to greater self-use of BZDs.

Self-reported sleep disturbances among people who have had a stroke: a cross-sectional analysis.

BACKGROUND: Sleep disturbances and their potential association with stroke remains understudied at a population level. We sought to determine the prevalence of sleep disturbances among people who have effects of stroke compared with the general population. METHODS: We used data from people aged 18 years or older who responded to the sleep and chronic disease modules of the 2017-2018 cycle of the Canadian Community Health Survey (CCHS). We measured sleep disturbances by self-reports of having trouble staying awake most or all of the time; either short (< 5 h) or long (> 9 h) nightly sleep duration; having trouble going to or staying asleep most or all of the time; and never, rarely or sometimes having refreshing sleep. We used log-binomial and multinomial regression to investigate prevalence of sleep disturbances among respondents who reported effects of stroke compared with others, adjusting for confounding factors. RESULTS: We included 46 404 CCHS respondents, 682 of whom reported effects of stroke. The prevalence of sleep disturbances for those with effects of stroke was higher than among others in the sample with regard to trouble staying awake (13.0% v. 6.1%; adjusted relative risk [RR] 2.16, 95% confidence interval [CI] 1.59-2.94), short or long duration sleep (28.9% v. 10.0%; adjusted RR 1.93, 95% CI 1.57-2.38), trouble going to or staying asleep, (28.1% v. 17.6%; adjusted RR 1.53, 95% CI 1.28-1.83) and lack of refreshing sleep (41.1% v. 37.1%; adjusted RR 1.30, 95% CI 1.14-1.49). The prevalence of at least 1 reported measure of sleep disturbance was 61.6% among those with effects of stroke, compared with 48.2% among others (adjusted RR 1.28, 95% CI 1.18-1.40). INTERPRETATION: Self-report of having effects of stroke was associated with increased prevalence of sleep disturbances compared with the general population. Sleep disturbances were reported by a high proportion of respondents with effects of stroke, indicating the importance of screening for related disorders.

Polysomnographic Assessment of Sleep Disturbances in Cancer Development: A Historical Multicenter Clinical Cohort Study.

BACKGROUND: Many cellular processes are controlled by sleep. Therefore, alterations in sleep might be expected to stress biological systems that could influence malignancy risk. RESEARCH QUESTION: What is the association between polysomnographic measures of sleep disturbances and incident cancer, and what is the validity of cluster analysis in identifying polysomnography phenotypes? STUDY DESIGN AND METHODS: We conducted a retrospective multicenter cohort study using linked clinical and provincial health administrative data on consecutive adults free of cancer at baseline with polysomnography data collected between 1994 and 2017 in four academic hospitals in Ontario, Canada. Cancer status was derived from registry records. Polysomnography phenotypes were identified by k-means cluster analysis. A combination of validation statistics and distinguishing polysomnographic features was used to select clusters. Cox cause-specific regressions were used to assess the relationship between identified clusters and incident cancer. RESULTS: Among 29,907 individuals, 2,514 (8.4%) received a diagnosis of cancer over a median of 8.0 years (interquartile range, 4.2-13.5 years). Five clusters were identified: mild (mildly abnormal polysomnography findings), poor sleep, severe OSA or sleep fragmentation, severe desaturations, and periodic limb movements of sleep (PLMS). The associations between cancer and all clusters compared with the mild cluster were significant while controlling for clinic and year of polysomnography. When additionally controlling for age and sex, the effect remained significant only for PLMS (adjusted hazard ratio [aHR], 1.26; 95% CI, 1.06-1.50) and severe desaturations (aHR, 1.32; 95% CI, 1.04-1.66). Further controlling for confounders, the effect remained significant for PLMS, but was attenuated for severe desaturations. INTERPRETATION: In a large cohort, we confirmed the importance of polysomnographic phenotypes and highlighted the role that PLMS and oxygenation desaturation may play in cancer. Using this study's findings, we also developed an Excel (Microsoft) spreadsheet (polysomnography cluster classifier) that can be used to validate the identified clusters on new data or to identify which cluster a patient belongs to. TRIAL REGISTRY: ClinicalTrials.gov; Nos.: NCT03383354 and NCT03834792; URL: www. CLINICALTRIALS: gov.

Screening for Primary Aldosteronism Among Hypertensive Adults with Obstructive Sleep Apnea: A Retrospective Population-Based Study.

BACKGROUND: Hypertension plus obstructive sleep apnea (OSA) is recommended in some guidelines as an indication to screen for primary aldosteronism (PA), yet prior data has brought the validity of this recommendation into question. Given this context, it remains unknown whether this screening recommendation is being implemented into clinical practice. METHODS: We conducted a population-based retrospective cohort study of all adult Ontario (Canada) residents with hypertension plus OSA from 2009 to 2020 with follow-up through 2021 utilizing provincial health administrative data. We measured the proportion of individuals who underwent PA screening via the aldosterone-to-renin ratio by year. We further examined screening rates among patients with hypertension plus OSA by the presence of concurrent hypokalemia and resistant hypertension. Clinical predictors associated with screening were assessed via Cox regression modeling. RESULTS: The study cohort included 53,130 adults with both hypertension and OSA, of which only 634 (1.2%) underwent PA screening. Among patients with hypertension, OSA, and hypokalemia, the proportion of eligible patients screened increased to 2.8%. Among patients ≥65 years with hypertension, OSA, and prescription of ≥4 antihypertensive medications, the proportion of eligible patients screened was 1.8%. Older age was associated with a decreased likelihood of screening while hypokalemia and subspecialty care with internal medicine, cardiology, endocrinology, or nephrology were associated with an increased likelihood of screening. No associations with screening were identified with sex, rural residence, cardiovascular disease, diabetes, or respirology subspecialty care. CONCLUSIONS: The population-level uptake of the guideline recommendation to screen all patients with hypertension plus OSA for PA is exceedingly low.

Obstructive sleep apnea is associated with markers of cerebral small vessel disease in a dose-response manner: A systematic review and meta-analysis.

Cerebral small vessel disease manifests on neuroimaging as white matter hyperintensities, lacunes, cerebral microbleeds, perivascular spaces or subcortical infarcts and is a major contributor to dementia, stroke and incident death. We aimed to determine whether obstructive sleep apnea severity is associated cerebral small vessel disease. A systematic search was conducted for studies examining the association between obstructive sleep apnea and cerebral small vessel disease markers. A random-effects model was used to meta-analyze unadjusted odds ratios derived from event rates. The neuroimaging-derived measures of white matter hyperintensities, lacunes, and cerebral microbleeds were compared against increasing obstructive sleep apnea severity, as measured by apnea-hypopnea indices of <5, 5-15, ≥15 and ≥ 30. Thirty-two observational studies were included: ten reported effect sizes for white matter hyperintensities, nine for lacunes and three for cerebral microbleeds. Compared to patients without obstructive sleep apnea, the odds of possessing white matter hyperintensities were 1.7 [95% confidence interval 0.9-3.6] in mild, 3.9 [2.7-5.5] in moderate-severe and 4.3 [1.9-9.6] in severe obstructive sleep apnea. Moderate-severe obstructive sleep apnea was associated with a higher risk of lacunar infarcts. Obstructive sleep apnea had no association with cerebral microbleeds and an indeterminate association with perivascular spaces and subcortical infarcts due to insufficient data.