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.

Sleep breathing disorder frequency, risk factors, and treatment among adults with cystic fibrosis.

BACKGROUND: Our understanding of the epidemiology of sleep breathing disorders among adults with cystic fibrosis (CF) is limited. Our purpose was to describe the frequency, risk factors and treatment of sleep breathing disorders among adults with CF. METHODS: This was a retrospective analysis of linked data from laboratory-based diagnostic polysomnography (PSG) undertaken at St. Michael's Hospital (Toronto, Canada) and the Canadian CF Registry. Adults (≥19 years old) with CF that underwent a diagnostic PSG at St. Michael's Hospital between 2002 and 2021 were included. Sleep breathing disorder frequency, risk factors, and treatment were described, using descriptive statistics and logistic regression. RESULTS: There were 42 patients included (33.3 % women and median age at diagnostic PSG was 34.7 years). Obstructive sleep apnea [OSA] was the most commonly observed sleep breathing disorder (found in 64.3 %), followed by sustained nocturnal hypoxemia (16.7 %), and sleep hypoventilation (9.5 %). Only 41 % of individuals with an elevated total apnea-hypopnea index were receiving positive airway pressure [PAP] therapy. Corticosteroid use (either oral or inhaled) was the only factor with a significant positive association with presence of any sleep breathing disorder (odds ratio 5.00, 95 % confidence interval 1.28-22.78). CONCLUSIONS: Among adults with CF, OSA occurs more commonly than previously appreciated and the majority of sleep breathing disorders were not being treated with PAP or supplemental oxygen. Management of sleep breathing disorders among adults with CF reflects a potentially important care gap, but further research is needed to determine the health impacts of treating sleep breathing disorders in CF.

An analysis of sex differences in pulmonary arteriovenous malformation presentation, complications and management in a large, multinational registry of patients with hereditary haemorrhagic telangiectasia.

This large, multinational, sex-based analysis among individuals with HHT showed that pulmonary AVM frequency, physical characteristics, presentation, complications and management do not generally significantly differ between males and females https://bit.ly/3TNLA6v.

Cannabis use and risks of respiratory and all-cause morbidity and mortality: a population-based, data-linkage, cohort study.

INTRODUCTION: Although cannabis is frequently used worldwide, its impact on respiratory health is characterised by controversy. OBJECTIVE: To evaluate the association between cannabis use and respiratory-related emergency room (ER) visits and hospitalisations. METHODS: A retrospective, population-based, cohort study was carried out, linking health survey and health administrative data for residents of Ontario, Canada, aged 12-65 years, between January 2009 and December 2015. Individuals self-reporting cannabis use within the past year were matched to control individuals (people who reported never using cannabis, or used cannabis only once, and more than 12 months ago) in upwards of a 1:3 ratio on 31 different variables, using propensity score matching methods. Respiratory-related and all-cause ER visits or hospitalisations, and all-cause mortality, were evaluated up to 12 months following the index date. RESULTS: We identified 35 114 individuals who had either used cannabis in the past year or were controls, of whom 6425 (18.3%) used cannabis in the past year. From this group, 4807 (74.8%) were propensity-score matched to 10 395 control individuals. In the propensity score matched cohort, there was no significant difference in odds of respiratory-related ER visit or hospitalisation between cannabis users and the control group (OR 0.91, 95% CI 0.77 to 1.09). Compared with control individuals, cannabis users had significantly increased odds of all-cause ER visit or hospitalisation (OR 1.22, 95% CI 1.13 to 1.31) and there was no significant difference with respect to all-cause mortality (OR 0.99, 95% CI 0.49 to 2.02). CONCLUSIONS: Although no significant association was observed between cannabis use and respiratory-related ER visits or hospitalisations, the risk of an equally important morbidity outcome, all-cause ER visit or hospitalisation, was significantly greater among cannabis users than among control individuals. Therefore, cannabis use is associated with increased risk for serious adverse health events and its recreational consumption is not benign.

A critical review of the respiratory benefits and harms of orally administered opioids for dyspnea management in COPD.

INTRODUCTION: Dyspnea occurring in chronic obstructive pulmonary disease (COPD) that is refractory to traditional management strategies is a common and challenging problem. Considerable attention has been paid to the off-label use of orally administered opioids as a pharmacotherapy option for refractory dyspnea in COPD. Multiple professional respiratory society guidelines express support for the application of oral opioids for this purpose. AREAS COVERED: This manuscript will critically review randomized controlled trials undertaken to date that evaluate the efficacy of oral opioids for dyspnea in COPD, as well as phase IV observational studies that examine for potential opioid-related respiratory harms in the COPD population (literature was searched on PubMed up to June 2021). COPD guideline recommendations relating to opioids for dyspnea will subsequently be critiqued. EXPERT OPINION: Opioid efficacy trials demonstrate at best a small improvement in dyspnea in limited numbers of individuals with COPD, whereas safety trials consistently show an increased risk of respiratory-related exacerbation, hospitalization and death in association with opioid use. In contrast to what is expressed in guidelines, the current body of evidence does not the support the wide application of opioids to manage refractory dyspnea among individuals with COPD, but instead, a highly selective and careful approach.

Weekly epistaxis duration as an indicator of epistaxis severity in hereditary hemorrhagic telangiectasia-Preliminary results from a randomized controlled trial.

OBJECTIVES: There is great interest in developing and studying novel therapies for epistaxis in hereditary hemorrhagic telangiectasia (HHT) given its associated morbidity and impact on patients' quality of life. Several recent randomized controlled trials (RCTs) have been negative, likely attributed to poorly characterized outcome measures. This study reported on and evaluated an epistaxis outcome measure, weekly epistaxis duration (WED) in an ongoing RCT, with the aim of better characterizing the measurement of epistaxis for clinical trials. MATERIALS AND METHODS: Patients were recruited to an ongoing phase II, double-blind, cross-over RCTs of oral doxycycline for HHT-associated epistaxis. Patients were included for the epistaxis measures analysis if they had already completed the initial 3-month run-in period, and had received treatment of either study drug doxycycline or placebo for a minimum of 6 months. The primary measure of interest was patient-reported outcome (PRO)-WED, captured from prospective daily diaries. Epistaxis severity score (ESS) was collected as a secondary outcome. RESULTS: Seven patients were included for analysis, with 98% completion of the daily diary. The average PRO-WED across all patients was 85.0 minutes, SD 93.2 at baseline, and 65.6 minutes, SD 59.5 during treatment/placebo. Coefficient of variance for PRO-WED at baseline and during treatment/placebo was 0.49, SD 0.1 and 0.58, SD 0.2, respectively. Statistically significant changes in the mean PRO-WED from baseline to treatment/placebo was noted in six patients (86%). Only two patients (29%) had a significant change in ESS, with both reporting decreased (improved) scores after treatment/placebo as compared to baseline. CONCLUSIONS: PRO-WED was a feasible clinical trials measure, was reasonably stable during baseline measurement, and appeared to be variable with treatment state, suggesting it may provide a sensitive clinical trials PRO in HHT.

Morbidity and mortality reduction associated with polysomnography testing in idiopathic pulmonary fibrosis: a population-based cohort study.

BACKGROUND: It is not well-known if diagnosing and treating sleep breathing disorders among individuals with idiopathic pulmonary fibrosis (IPF) improves health outcomes. We evaluated the association between receipt of laboratory-based polysomnography (which is the first step in the diagnosis and treatment of sleep breathing disorders in Ontario, Canada) and respiratory-related hospitalization and all-cause mortality among individuals with IPF. METHODS: We used a retrospective, population-based, cohort study design, analyzing health administrative data from Ontario, Canada, from 2007 to 2019. Individuals with IPF were identified using an algorithm based on health administrative codes previously developed by IPF experts. Propensity score matching was used to account for potential differences in 41 relevant covariates between individuals that underwent polysomnography (exposed) and individuals that did not undergo polysomnography (controls), in order minimize potential confounding. Respiratory-related hospitalization and all-cause mortality were evaluated up to 12 months after the index date. RESULTS: Out of 5044 individuals with IPF identified, 201 (4.0%) received polysomnography, and 189 (94.0%) were matched to an equal number of controls. Compared to controls, exposed individuals had significantly reduced rates of respiratory-related hospitalization (hazard ratio [HR] 0.43, 95% confidence interval [CI] 0.24-0.75), p = 0.003) and all-cause mortality (HR 0.49, 95% CI 0.30-0.80), p = 0.004). Significantly reduced rate of respiratory-related hospitalization (but not all-cause mortality) was also observed among those with > = 1 respiratory-related hospitalization (HR 0.38, 95% CI 0.15-0.99) and systemic corticosteroid receipt (HR 0.37, 95% CI 0.19-0.94) in the year prior to the index date, which reflect sicker subgroups of persons. CONCLUSIONS: Undergoing polysomnography was associated with significantly improved clinically-important health outcomes among individuals with IPF, highlighting the potential importance of incorporating this testing in IPF disease management.

Morbidity and mortality associated with prescription cannabinoid drug use in COPD.

INTRODUCTION: Respiratory-related morbidity and mortality were evaluated in relation to incident prescription oral synthetic cannabinoid (nabilone, dronabinol) use among older adults with chronic obstructive pulmonary disease (COPD). METHODS: This was a retrospective, population-based, data-linkage cohort study, analysing health administrative data from Ontario, Canada, from 2006 to 2016. We identified individuals aged 66 years and older with COPD, using a highly specific, validated algorithm, excluding individuals with malignancy and those receiving palliative care (n=185 876 after exclusions). An equivalent number (2106 in each group) of new cannabinoid users (defined as individuals dispensed either nabilone or dronabinol, with no dispensing for either drug in the year previous) and controls (defined as new users of a non-cannabinoid drug) were matched on 36 relevant covariates, using propensity scoring methods. Cox proportional hazard regression was used. RESULTS: Rate of hospitalisation for COPD or pneumonia was not significantly different between new cannabinoid users and controls (HR 0.87; 95% CI 0.61-1.24). However, significantly higher rates of all-cause mortality occurred among new cannabinoid users compared with controls (HR 1.64; 95% CI 1.14-2.39). Individuals receiving higher-dose cannabinoids relative to controls were observed to experience both increased rates of hospitalisation for COPD and pneumonia (HR 2.78; 95% CI 1.17-7.09) and all-cause mortality (HR 3.31; 95% CI 1.30-9.51). CONCLUSIONS: New cannabinoid use was associated with elevated rates of adverse outcomes among older adults with COPD. Although further research is needed to confirm these observations, our findings should be considered in decisions to use cannabinoids among older adults with COPD.

Predictors of Opioid-related Adverse Pulmonary Events among Older Adults with Chronic Obstructive Pulmonary Disease.

Rationale: Although opioids are frequently prescribed in chronic obstructive pulmonary disease (COPD), there is poor understanding regarding which individuals will experience pulmonary harm upon exposure.Objectives: We sought to identify patient characteristics and opioid drug properties predictive of opioid-related adverse pulmonary events among older adults with chronic COPD.Methods: A retrospective, population-based, cohort study design was used, analyzing Ontario heath administrative data. Individuals aged 66 years and older, with validated, physician-diagnosed COPD receiving a new opioid drug were included. Adverse pulmonary events (defined as an emergency room visit, hospitalization, or death related to either COPD or pneumonia) occurring within 30 days following new opioid receipt were considered. Multivariable-adjusted, cause-specific hazard modeling was used to identify predictors of adverse pulmonary events.Results: Out of 169,517 older adults with COPD receiving a new opioid, 4,861 (2.9%) experienced an adverse pulmonary event within 30 days. Factors independently predisposing to adverse pulmonary events included older age (≥85 yr old: hazard ratio [HR], 1.37; 95% confidence interval [CI], 1.26-1.49), long-term-care home residence (HR, 1.32; 95% CI, 1.21-1.44), severe COPD exacerbation within the preceding year (HR, 2.96; 95% CI, 2.77-3.17), comorbidities (including non-COPD lung disease [HR, 1.16; 95% CI, 1.09-1.23], congestive heart failure [HR, 1.22; 95% CI, 1.14-1.30], sleep disorder [HR, 1.22; 95% CI, 1.15-1.30], and dementia [HR, 1.14; 95% CI, 1.05-1.24]); other psychoactive medication receipt, including benzodiazepines (HR, 1.27; 95% CI, 1.19-1.35) and serotonergic antidepressants (HR, 1.10; 95% CI, 1.03-1.19), and receipt of an opioid-only agent (HR, 1.35; 95% CI, 1.26-1.46). Factors that independently protected from adverse pulmonary events included female sex (HR, 0.78; 95% CI, 0.73-0.82), surgery within the preceding year (HR, 0.70; 95% CI, 0.64-0.77), and musculoskeletal disease (HR, 0.75; 95% CI, 0.70-0.80). No significant associations were observed between adverse pulmonary events and opioid half-life duration or opioid daily dosage.Conclusions: Patient and opioid drug factors predictive of opioid-related adverse pulmonary events among older adults with COPD were identified, which may assist with safer opioid prescribing.

Reperfusion of Pulmonary Arteriovenous Malformations Following Embolotherapy: A Randomized Controlled Trial of Detachable Versus Pushable Coils.

PURPOSE: To compare 1 year post-embolization reperfusion rates in pulmonary arteriovenous malformations (PAVMs) treated with the 0.035″ Interlock™ Fibered IDC™ Occlusion System coils (IDC) (Boston Scientific, Marlborough, Massachusetts) versus 0.035″ Nester coils (Cook Medical Inc., Bloomington, Indiana). MATERIALS AND METHODS: A randomized controlled trial was performed randomizing individual PAVMs to treatment with IDC versus Nester coils at the largest hereditary hemorrhagic telangiectasia center in Canada. The primary outcome was CT evidence of reperfusion at 1 year. Secondary outcomes included periprocedural complications, fluoroscopy time and contrast volume. RESULTS: Our study was terminated prematurely due to slow recruitment and subsequent expiration of funding. A total of 46 PAVMs in 25 patients (64% female) were included in our study; 26 randomized to Nester coils and 20 randomized to IDC. One patient was lost to follow-up. At a mean follow-up of 421.2 ± 215.7 days, no significant difference in PAVM reperfusion was detected between Nester coils and IDC (0% vs. 5.6%, p > 0.05). No major periprocedural complications were noted in either group. Fluoroscopy time (Nester: 15.0 ± 11.8 min vs. IDC 16.0 ± 5.4 min, p > 0.05) and contrast volume (Nester: 80.3 ± 36.5 ml vs. IDC 87.3 ± 51.7 ml, p > 0.05) utilized did not differ between groups. CONCLUSION: No significant difference was detected in PAVM reperfusion rates, periprocedural complication rates, contrast volume utilization or fluoroscopy time following embolization with IDC and Nester coils.

Opioid utility for dyspnea in chronic obstructive pulmonary disease: a complicated and controversial story.

Chronic obstructive pulmonary disease (COPD) is common chronic respiratory disorder, predominantly caused by exposure to cigarette smoke or biomass fuels, and it usually affects older adults. Dyspnea in COPD that is unresponsive to traditional management is a challenging disease complication for both the patient and the health care professional. Off-label use of opioids has been advocated as a pharmacotherapy strategy for refractory dyspnea. However, negative respiratory outcomes are a potential concern with opioids drugs, especially among individuals with COPD. In this review, randomized controlled trials evaluating opioid efficacy among individuals with COPD are reviewed and critically analyzed, and data from observational drug safety studies is also presented. In summary, the evidence in support of using opioids for refractory dyspnea in COPD is minimal and weak, and there is mounting data demonstrating that opioids are associated with increased respiratory-related morbidity and mortality in this population. Therefore, current evidence does not support the broad application of opioids for refractory dyspnea among individuals with COPD. However, there may be subsets of individuals that experience modest improvement in dyspnea with opioids, and better understanding predictors and mechanisms of such opioid responsiveness should be a focus of future research endeavours.

Somatic Mutations in Vascular Malformations of Hereditary Hemorrhagic Telangiectasia Result in Bi-allelic Loss of ENG or ACVRL1.

Hereditary hemorrhagic telangiectasia (HHT) is a Mendelian disease characterized by vascular malformations (VMs) including visceral arteriovenous malformations and mucosal telangiectasia. HHT is caused by loss-of-function (LoF) mutations in one of three genes, ENG, ACVRL1, or SMAD4, and is inherited as an autosomal-dominant condition. Intriguingly, the constitutional mutation causing HHT is present throughout the body, yet the multiple VMs in individuals with HHT occur focally, rather than manifesting as a systemic vascular defect. This disconnect between genotype and phenotype suggests that a local event is necessary for the development of VMs. We investigated the hypothesis that local somatic mutations seed the formation HHT-related telangiectasia in a genetic two-hit mechanism. We identified low-frequency somatic mutations in 9/19 telangiectasia through the use of next-generation sequencing. We established phase for seven of nine samples, which confirms that the germline and somatic mutations in all seven samples exist in trans configuration; this is consistent with a genetic two-hit mechanism. These combined data suggest that bi-allelic loss of ENG or ACVRL1 may be a required event in the development of telangiectasia, and that rather than haploinsufficiency, VMs in HHT are caused by a Knudsonian two-hit mechanism.

Prescription Synthetic Oral Cannabinoid use Among Older Adults with Chronic Obstructive Pulmonary Disease: A Population-Based Cohort Study.

BACKGROUND: Synthetic oral cannabinoids (nabilone and dronabinol) may have adverse respiratory effects. Our purpose was to describe the scope, pattern, and patient characteristics associated with incident off-label synthetic oral cannabinoid use among older adults with chronic obstructive pulmonary disease (COPD) compared to older adults without COPD. METHODS: This was a retrospective, population-based, cohort study using Ontario, Canada, heath administrative data. Individuals aged 66 years or older were included, and physician-diagnosed COPD was identified using a previously validated, highly specific algorithm. Incident off-label oral cannabinoid use was examined between April 1, 2005 and March 31, 2015. Descriptive statistics were used to describe drug use patterns. Multiple logistic regression was used to identify patient characteristics associated with incident drug use. RESULTS: There were 172,282 older adults with COPD and 1,068,256 older adults without COPD identified between April 1, 2005 and March 31, 2015. Incident synthetic oral cannabinoid use during this period occurred with significantly greater (p < 0.001) frequency among older adults with COPD (0.6%) versus older adults without COPD (0.3%). Compared to those without COPD, older adults with COPD used synthetic cannabinoids for significantly longer durations and more frequently at higher doses. CONCLUSIONS: Although incident off-label oral cannabinoid use was relatively low among all older Ontarian adults, this drug class was used with greater frequency and more often in potentially concerning ways among older adults with COPD. These findings raise possible safety concerns, but further research on the respiratory safety of oral cannabinoids among individuals with COPD is needed.

Effectiveness and Safety of Inhaled Corticosteroids in Older Individuals with Chronic Obstructive Pulmonary Disease and/or Asthma. A Population Study.

Rationale: Inhaled corticosteroids (ICS) are established medications for the management of both asthma and chronic obstructive pulmonary disease (COPD), two common chronic airway diseases. However, there is still uncertainty with respect to their use in some cases, specifically in older adults with asthma, people with concurrent asthma and COPD, and some people with COPD (given the association of ICS with pneumonia).Objectives: To compare the effectiveness and safety of ICS in older adults with asthma, COPD, or features of both in a real-word setting.Methods: In this retrospective longitudinal population cohort study, individuals 66 years of age or older in Ontario, Canada, who met a validated case definition of physician-diagnosed COPD and/or asthma between 2003 and 2014 were followed until March 2015 through provincial health administrative data. Overlap in COPD and asthma diagnoses was permitted and stratified for in subgroup analyses. The exposure was new receipt of ICS. The primary effectiveness and safety outcomes were hospitalizations for obstructive lung disease (OLD) and hospitalizations for pneumonia, respectively. Propensity scores were used to adjust for confounders.Results: The study included 87,690 individuals with asthma (27% with concurrent COPD) and 150,593 individuals with COPD (25% with concurrent asthma). In terms of effectiveness, controlling for confounders, ICS was associated with fewer hospitalizations for OLD (hazard ratio [HR], 0.84; 95% confidence interval [CI], 0.79-0.88) in subjects with asthma alone, with concurrent COPD attenuating the benefit. A similar association was seen in subjects with COPD and concurrent asthma (HR, 0.88; 95% CI, 0.84-0.92), but not in those with COPD alone, where ICS receipt had little impact on hospitalizations. In terms of safety, ICS receipt was associated with a marginally increased risk of pneumonia hospitalizations in people with COPD and no asthma (HR, 1.03; 95% CI, 1.00-1.06), but not in the other groups.Conclusions: ICS was associated with fewer hospitalizations for OLD in older adults with asthma and concurrent asthma and COPD, but had little impact on OLD and pneumonia hospitalizations in those with COPD alone.

Benzodiazepine and opioid co-usage in the US population, 1999-2014: an exploratory analysis.

STUDY OBJECTIVES: The study objectives were to explore trends in prevalence of couse of benzodiazepine receptor modulators and opioids, and nonselective and selective (i.e. Z-drugs) benzodiazepine receptor modulators, in the United States, as well as risk factors for these drug utilization patterns. METHODS: This was a multiyear, cross-sectional, population-level study, using US health survey data. Data from eight National Health and Nutrition Examination Survey (NHANES) cycles were analyzed, from 1999-2000 until 2013-2014, with each survey cycle containing information on ~10 000 individuals. The main measure was prevalent prescription drug use within 30 days preceding survey administration. Drug usage was objectively confirmed for a large majority of participants though direct inspection of prescription bottles. RESULTS: The estimated prevalence of concurrent benzodiazepine receptor modulator and opioid use in the United States was 0.39% in 1999-2000 and 1.36% in 2013-2014, reflecting absolute and relative changes of +0.97% and +249%. The estimated prevalence of nonselective and selective benzodiazepine receptor modulator couse steadily rose in the United States from 0.05% in 1999-2000 to 0.47% in 2013-2014, reflecting absolute and relative increases of +0.42% and +840%. Independent risk factors for these two forms of psychoactive medication polypharmacy were identified. CONCLUSIONS: In this exploratory analysis, concurrent use of benzodiazepine receptor modulators and opioids, and nonselective and selective benzodiazepine receptor modulators, was found to have progressively risen in the United States. The progressive increases in these two forms of psychoactive medication polypharmacy are concerning, given that these drug use patterns are associated with increased risk for serious adverse outcomes.