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BackgroundMany cellular processes are controlled by sleep. Therefore, alterations in sleep might be expected to stress biological systems that could influence malignancy risk.Research questionWhat 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 methodsWe 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.ResultsAmong 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.InterpretationIn 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 registryClinicalTrials.gov; Nos.: NCT03383354 and NCT03834792; URL: www.Clinicaltrialsgov.

Rationale: The evidence for an association between cancer survival and obstructive sleep apnea (OSA) remains underexplored. Objectives: To evaluate an association between markers of OSA severity (respiratory disturbances, hypoxemia, and sleep fragmentation) and cancer-related mortality in individuals with previously diagnosed cancer. Methods: We conducted a multicenter retrospective cohort study using linked clinical and provincial health administrative data on consecutive adults who underwent a diagnostic sleep study between 1994 and 2017 in four Canadian academic hospitals and were previously diagnosed with cancer through the Ontario Cancer Registry. Multivariable cause-specific Cox regressions were used to address the research objective. Results: We included 2,222 subjects. Over a median follow-up time of 5.6 years (interquartile range [IQR], 2.7-9.1 years), 261/2,222 (11.7%) individuals with prevalent cancer died from cancer-related causes, which accounted for 44.2% (261/590) of all-cause death. Controlling for age, sex, alcohol use disorder, prior heart failure, chronic obstructive pulmonary disease, hypertension, diabetes, treatment for OSA, clinic site, year of the sleep study, and time since the cancer diagnosis, measures of hypoxemia and sleep fragmentation, but not apnea-hypopnea index, were significantly associated with the cancer-specific mortality: percentage of time spent with arterial oxygen saturation (SaO2)

RationaleDespite the high prevalence of obstructive sleep apnea (OSA) and concurrent use of opioid therapy, no large-scale population studies have investigated whether opioid use and pre-existing OSA may interact synergistically to increase the risk of adverse health consequences. To address this knowledge gap, we conducted a retrospective cohort study using provincial health administrative data to evaluate whether the combined presence of opioid use and OSA increases the risk of adverse health consequences, such as mortality, hospitalizations, and emergency department (ED) visits; and if it does, whether this co-occurrence has synergistic clinical relevance.MethodsWe included all adults who underwent a diagnostic sleep study in Ontario, Canada, between 2013 and 2016. Individuals were considered exposed to opioids if they filled a prescription that overlapped with the date of their sleep study (Opioid+). Individuals with at least a 50% probability of having a diagnosis of moderate to severe OSA (OSA+) were identified using a previously externally validated case-ascertainment model. The primary outcome was all-cause mortality; secondary outcomes were all-cause or ischemic heart disease hospitalizations, all-cause ED visits, and motor vehicle collisions (MVC) requiring hospital or ED visit. We used multivariable Cox regression models to compare hazards between four mutually exclusive groups: (1) Opioid+ OSA+; (2) Opioid+ OSA-; (3) Opioid- OSA+, and (4) OSA- Opioid- (reference for comparison). Relative excess risks due to interaction (RERI) were calculated to test for additive interaction.ResultsOf 300,663 adults who underwent a sleep study, 15,713 (5.2%) were considered as Opioid+ and 128,351 (42.7%) as OSA+. Over a median of two years, 6,223 (2.1%) died from any cause. Regardless of OSA status, opioid use at the date of the sleep study was associated with an increased hazard for all-cause mortality with the greatest hazard associated with Opioid+ OSA- (adjusted hazard ratio [aHR]: 1.75, 95% CI 1.57-1.94), but not Opioid+ OSA+ (aHR: 1.14, 95% CI 1.02-1.27) as hypothesized. Regardless of OSA status, opioid use at the date of the sleep study was associated with an increased hazard for all secondary outcomes. Opioid+ OSA+ was associated with the greatest hazards of all-cause hospitalizations (aHR 1.55, 95% CI 1.49-1.61) and MVC (aHR of 1.39; 95% CI 1.09-1.77); however, no statistically significant synergistic effects were observed.ConclusionsAdults referred for sleep disorder assessment who used opioids had a significantly increased hazard of adverse health outcomes than those who did not, regardless of whether they had a high probability of moderate to severe OSA. The use of opioids and OSA was associated with the greatest hazard of all-cause hospitalizations and MVC requiring hospital or ED visit. The interaction of opioids and OSA did not confer a synergistic risk for poor outcomes.

BackgroundTo examine the association between the severity of obstructive sleep apnea (OSA) and nocturnal hypoxemia with incident cancer.MethodsThis was a multicenter retrospective clinical cohort study using linked clinical and provincial health administrative data on consecutive adults who underwent a diagnostic sleep study between 1994 and 2017 in four academic hospitals (Canada) who were free of cancer at baseline. Cancer status was derived from the Ontario Cancer Registry. Cox cause-specific regressions were utilized to address the objective and to calculate the 10-year absolute risk difference (ARD) in the marginal probability of incident cancer and the number needed to harm (NNH).ResultsOf 33,997 individuals considered, 33,711 with no missing OSA severity were included: median age, 50 years; 58% male; and 23% with severe OSA (apnea-hypopnea index >30). Of the 18,458 individuals with information on sleep time spent with oxygen saturation (SaO2) 30% of sleep with SaO2

Objective/backgroundEvidence on sex differences in the association between obstructive sleep apnea (OSA) and cardiovascular outcomes is limited and controversial. We conducted a historical cohort study to investigate this relationship.Patients/methodsClinical data on adults who underwent sleep study at a large urban academic hospital (Toronto, Canada) between 1994 and 2010 were linked to provincial health administrative data from 1991 to 2015. We fit Cox regressions to investigate the association between OSA severity and a cardiovascular composite outcome (all-cause mortality or hospitalization due to myocardial infarction, stroke, heart failure or atrial fibrillation), controlling for risk factors and stratifying by sex.ResultsA total of 10,149 subjects were included: median age of 49 years, 38% women. Over a median of 9.3 years, 1782 (18%) participants developed an outcome. The association between percentage of sleep time spent with oxygen saturation

Background: Individuals with chronic obstructive pulmonary disease (COPD) are often at risk for or have comorbid cardiovascular disease and are likely to die of cardiovascular-related causes. Objectives: To prioritize a list of research topics related to the diagnosis and management of patients with COPD and comorbid cardiovascular diseases (heart failure, atherosclerotic vascular disease, and atrial fibrillation) by summarizing existing evidence and using consensus-based methods. Methods: A literature search was performed. References were reviewed by committee co-chairs. An international, multidisciplinary committee, including a patient advocate, met virtually to review evidence and identify research topics. A modified Delphi approach was used to prioritize topics in real time on the basis of their potential for advancing the field. Results: Gaps spanned the translational science spectrum from basic science to implementation: 1) disease mechanisms; 2) epidemiology; 3) subphenotyping; 4) diagnosis and management; 5) clinical trials; 6) care delivery; 7) medication access, adherence, and side effects; 8) risk factor mitigation; 9) cardiac and pulmonary rehabilitation; and 10) health equity. Seventeen experts participated, and quorum was achieved for all votes (>80%). Of 17 topics, ≥70% agreement was achieved for 12 topics after two rounds of voting. The range of summative Likert scores was −15 to 25. The highest priority was "Conduct pragmatic clinical trials with patient-centered outcomes that collect both pulmonary and cardiac data elements." Health equity was identified as an important topic that should be embedded within all research. Conclusions: We propose a prioritized research agenda with the purpose of stimulating high-impact research that will hopefully improve outcomes among people with COPD and cardiovascular disease. [ABSTRACT FROM AUTHOR]

Rationale: A common strategy to reduce COPD readmissions is to encourage patient follow-up with a physician within 1 to 2 weeks of discharge, yet evidence confirming its benefit is lacking. We used a new study design called target randomized trial emulation to determine the impact of follow-up visit timing on patient outcomes. Methods: All Ontario residents aged 35 or older discharged from a COPD hospitalization were identified using health administrative data and randomly assigned to those who received and did not receive physician visit follow-up by within seven days. They were followed to all-cause emergency department visits, readmissions or death. Targeted randomized trial emulation was used to adjust for differences between the groups. COPD emergency department visits, readmissions or death was also considered. Results: There were 94,034 patients hospitalized with COPD, of whom 73.5% had a physician visit within 30 days of discharge. Adjusted hazard ratio for all-cause readmission, emergency department visits or death for people with a visit within seven days post discharge was 1.03 (95% Confidence Interval [CI]: 1.01–1.05) and remained around 1 for subsequent days; adjusted hazard ratio for the composite COPD events was 0.97 (95% CI 0.95–1.00) and remained significantly lower than 1 for subsequent days. Conclusion: While a physician visit after discharge was found to reduce COPD events, a specific time period when a physician visit was most beneficial was not found. This suggests that follow-up visits should not occur at a predetermined time but be based on factors such as anticipated medical need. [ABSTRACT FROM AUTHOR]

Background and Objective: Establishing an accurate and timely diagnosis of idiopathic pulmonary fibrosis (IPF) is essential for appropriate management and prognostication. In some cases, surgical lung biopsy (SLB) is performed but carries non‐negligible risk. The objective of this retrospective study was to determine if SLB is associated with accelerated lung function decline in patients with IPF using the Canadian Registry for Pulmonary Fibrosis. Methods: Linear mixed models and Cox proportional hazards regression models were used to compare decline in forced vital capacity (FVC)%, diffusion capacity of the lung (DLCO%) and risk of death or lung transplantation between SLB and non‐SLB patients. Adjustments were made for baseline age, sex, smoking history, antifibrotic use, and lung function. A similar analysis compared lung function changes 12 months pre‐ and post‐SLB. Results: A total of 81 SLB patients and 468 non‐SLB patients were included. In the SLB group, the post‐biopsy annual FVC% decline was 2.0% (±0.8) in unadjusted, and 2.1% (±0.8) in adjusted models. There was no difference in FVC% decline, DLCO% decline, or time to death or lung transplantation between the two groups, in adjusted or unadjusted models (all p‐values >0.07). In the pre‐post SLB group, no differences were identified in FVC% decline in unadjusted or adjusted models (p = 0.07 for both). Conclusion: No association between SLB and lung function decline or risk of death or lung transplantation was identified in this multi‐centre study of patients with IPF. [ABSTRACT FROM AUTHOR]

Background and Objective: Interstitial lung disease (ILD) can occur as a manifestation of rheumatoid arthritis (RA) at various times in the disease course. We aimed to identify factors associated with early versus late onset RA‐ILD and how the timing of RA‐ILD influenced surgical lung biopsy completion and mortality. Methods: We performed a retrospective observational study using health services data from Ontario, Canada. We identified RA cases between 2000 and 2020 using the Ontario Rheumatoid Arthritis Database. RA‐ILD diagnosis required repeat physician visits for ILD, with early RA‐ILD defined as within 1 year of RA diagnosis. We performed multivariable logistic regression to identify factors associated with early RA‐ILD and surgical lung biopsy completion, and multivariable cox‐proportional hazards regression to evaluate the association of early versus late RA‐ILD on all‐cause and RA‐ILD related mortality. Results: In total, we identified 3717 cases of RA‐ILD. Older age at RA diagnosis [OR 1.04 (95%CI 1.03–1.05), p < 0.0001], female sex [OR 1.16 (95%CI 1.01–1.35), p = 0.04] and immigrating to Ontario [OR 1.70 (95%CI 1.35–2.14), p < 0.0001] was associated with early RA‐ILD. Patients with early versus late RA‐ILD experienced similar odds of undergoing a surgical lung biopsy [OR 1.34 (95%CI 0.83–2.16), p = 0.23]. Early RA‐ILD was associated with increased all‐cause mortality [HR 1.17 (95%CI 1.07–1.29), p = 0.0009], primarily driven by an increase in RA‐ILD related mortality [HR 1.45 (95%CI 1.19–1.76), p = 0.0003]. Conclusion: Age at RA onset, female sex and immigration status are associated with early RA‐ILD. Patients with early RA‐ILD experience increased all‐cause and RA‐ILD related mortality after adjusting for demographics and comorbidities. We show that females, immigrants and patients diagnosed with RA at an older age, are at increased risk for early RA‐ILD (within 1‐year of RA diagnosis). Early RA‐ILD carries an increased risk for RA‐ILD related mortality, which may justify a more aggressive approach to disease monitoring and treatment. [ABSTRACT FROM AUTHOR]