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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.

With the rapid rise in cases of COVID-19 across the world, health systems face unprecedented challenges in the delivery of patient care. This includes constrained capacity for intensive care unit (...

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.

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.

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.

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.

IntroductionRespiratory-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).MethodsThis 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.ResultsRate 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).ConclusionsNew 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.

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.

Aims Diuretic drugs may theoretically improve respiratory health outcomes in chronic obstructive pulmonary disease (COPD) through several possible mechanisms, but they might also lead to respiratory harm. We evaluated the association of incident oral diuretic drug use with respiratory-related morbidity and mortality among older adults with COPD. Methods This was a population-based, retrospective cohort study using health administrative data from Ontario, Canada, for the period 2008–2013. We identified adults aged 66 years and older with nonpalliative COPD using a validated algorithm. Respiratory-related morbidity and mortality were evaluated within 30 days of incident oral diuretic drug use compared to nonuse using Cox proportional hazard regression and applying inverse probability of treatment weighting using the propensity score to minimize confounding. Results Out of 99 766 individuals aged 66 years and older with COPD identified, incident diuretic receipt occurred in 51.7%. Relative to controls, incident diuretic users had significantly increased rates for hospitalization for COPD or pneumonia [hazard ratio (HR) 1.22, 95% confidence interval (CI) 1.07–1.40], as well as more emergency room visits for COPD or pneumonia (HR 1.35, 95% CI 1.18–1.56), COPD or pneumonia-related mortality (HR 1.41; 95% CI 1.04–1.92) and all-cause mortality (HR 1.20, 95% CI 1.06–1.35). The increased respiratory-related morbidity and mortality observed were specifically as a result of loop diuretic use. Conclusions Incident diuretic drugs, and more specifically loop diuretics, were associated with increased rates of respiratory-related morbidity and mortality among older adults with nonpalliative COPD. Further studies are needed to determine if this association is causative or due to unresolved confounding.

We evaluated whether incident opioid drug use was associated with adverse cardiac events among older adults with chronic obstructive pulmonary disease (COPD). This was an exploratory, retrospective cohort study using health administrative data from Ontario, Canada, from 2008 to 2013. Using a validated algorithm, we identified adults aged 66 years and older with non-palliative COPD. Hazard ratios (HR) were estimated for adverse cardiac events within 30 days of incident opioid receipt compared to controls using inverse probability of treatment weighting using the propensity score. There were 134,408 community-dwelling individuals and 14,685 long-term care residents with COPD identified, 67.0 and 60.6% of whom received an incident opioid. Incident use of any opioid was associated with significantly decreased rates of emergency room (ER) visits and hospitalizations for congestive heart failure (CHF) among community-dwelling older adults (HR 0.84; 95% CI 0.73–0.97), but significantly increased rates of ischemic heart disease (IHD)-related mortality among long-term care residents (HR 2.15; 95% CI 1.50–3.09). In the community-dwelling group, users of more potent opioid-only agents without aspirin or acetaminophen combined had significantly increased rates of ER visits and hospitalizations for IHD (HR 1.38; 95% CI 1.08–1.77) and IHD-related mortality (HR 1.83; 95% CI 1.32–2.53). New opioid use was associated with elevated rates of IHD-related morbidity and mortality among older adults with COPD. Adverse cardiac events may need to be considered when administering new opioids to older adults with COPD, but further studies are required to establish if the observed associations are causal or related to residual confounding.

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). 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. 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. 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.

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. 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. 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

Hereditary Hemorrhagic Telangiectasia (HHT) is a Mendelian disease characterized by vascular malformations including visceral arteriovenous malformations and mucosal telangiectasia. HHT is caused by loss-of-function mutations in one of 3 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 vascular malformations in HHT patients 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 vascular malformations. 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 using high depth next-generation sequencing. We established phase for 7 of 9 samples using long-read sequencing, which confirm that the germline and somatic mutations in all 7 samples exist in trans configuration; consistent with a genetic two-hit mechanism. These combined data suggest that biallelic loss of ENG or ACVRL1 may be a required event in the development of telangiectasia, and that rather than haploinsufficiency, vascular malformations in HHT are caused by a Knudsonian two-hit mechanism.

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.

We evaluated risk of adverse respiratory outcomes associated with incident opioid use among older adults with chronic obstructive pulmonary diseases (COPD).This was a retrospective population-based cohort study using a validated algorithm applied to health administrative data to identify adults aged 66 years and older with COPD. Inverse probability of treatment weighting using the propensity score was used to estimate hazard ratios comparing adverse respiratory outcomes within 30 days of incident opioid use compared to controls.Incident opioid use was associated with significantly increased emergency room visits for COPD or pneumonia (HR 1.14, 95% CI 1.00–1.29; p=0.04), COPD or pneumonia-related mortality (HR 2.16, 95% CI 1.61–2.88; pIncident opioid use, and in particular use of the generally more potent opioid-only agents, was associated with increased risk for adverse respiratory outcomes, including respiratory-related mortality, among older adults with COPD. Potential adverse respiratory outcomes should be considered when prescribing new opioids in this population.

STUDY OBJECTIVES The purpose of this study was to examine whether or not insomnia symptoms were associated with measured dyslipidemia. METHODS This was a population-based multiyear cross-sectional study, using data from 2005-2008 United States National Health and Nutrition Examination Surveys. Survey participants ages 20 y and older self-reported the frequency of difficulty falling asleep, prolonged nocturnal awakening, and undesired early morning awakening over the preceding month. One-time venipuncture was performed and a low-density lipoprotein cholesterol (LDL-C) of ≥ 160 mg/ dL, triglycerides of ≥ 200 mg/dL, and a high-density lipoprotein cholesterol (HDL-C) of < 40 mg/dL denoted dyslipidemia. Descriptive statistics and multiple logistic regression were used. RESULTS Data on LDL-C, triglycerides, and HDL-C was available for 4,635, 4,757, and 9,798 individuals, respectively. There were no significant associations between having any insomnia symptom at least five times in the past month and high LDL-C (odds ratio [OR] 1.20, 95% confidence interval [CI] 0.92-1.55) or low HDL-C (OR 0.92, 95% CI 0.82-1.04) in unadjusted analyses, or with high triglycerides after adjusting for covariates (OR 1.03, 95% CI 0.78-1.37). Recipients of sleeping pills who also had insomnia symptoms had significantly increased adjusted odds of elevated LDL-C (OR 2.18, 95% CI 1.14-4.15). CONCLUSIONS Insomnia symptoms were generally not associated with dyslipidemia, but receipt of sleeping pills in the setting of insomnia was associated with elevated LDL-C. Further research is needed to confirm a possible link between sleeping pill use and dyslipidemia and to delineate if an association with atherosclerosis exists with specific types of sleeping pills or with all sedative medications more broadly.

Propensity score matching and stratification are methods that help minimise the risk of confounding and misattribution in observational studieshttp://ow.ly/DY0n30mrtQF

Aims The purpose of the present study was to describe the scope, pattern and patient characteristics associated with incident opioid use among older adults with chronic obstructive pulmonary disease (COPD). Methods This was a retrospective population-based cohort study using Ontario, Canada, healthcare administrative data. Study participants were individuals aged 66 years and older with physician-diagnosed COPD, identified using a validated algorithm, who were not receiving palliative care. We examined the incidence of oral opioid receipt between 1 April 2003 and 31 March 2012, as well as several patterns of incident opioid drug use. Results Among 107 109 community-dwelling and 16 207 long-term care resident older adults with COPD, 72 962 (68.1%) and 8811 (54.4%), respectively, received an incident opioid drug during the observation period. Among long-term care residents, multiple opioid dispensings (8.8%), dispensings for >30 days' duration (up to 19.8%), second dispensings (35–43%) and early refills (24.2%) were observed. Incident opioid dispensing was also observed to occur during COPD exacerbations (6.9% among all long-term care residents; 18.1% among long-term care residents with frequent exacerbations). These same patterns of incident opioid use occurred among community-dwelling individuals, but with relatively lower frequencies. Conclusions New opioid use was high among older adults with COPD. Potential safety concerns are raised by the degree and pattern of new opioid use, but further studies are needed to evaluate if adverse events are associated with opioid drug use in this older and respiratory-vulnerable population.

Our purpose was to evaluate the association of new benzodiazepine use relative to non-use with adverse clinical respiratory outcomes among older adults with chronic obstructive pulmonary disease (COPD). This was a retrospective population-based cohort study of Ontario, Canada, residents between 2003 and 2010. A validated algorithm was applied to health administrative data to identify adults aged 66 years and older with COPD. Relative risks (RRs) of several clinically important respiratory outcomes were examined within 30 days of incident benzodiazepine use compared with non-use, applying propensity score matching. New benzodiazepine users were at significantly higher risk for outpatient respiratory exacerbations (RR 1.45, 95% CI 1.36-1.54) and emergency room visits for COPD or pneumonia (RR 1.92, 95% CI 1.69-2.18) compared to non-users. Risk of hospitalisation for COPD or pneumonia was also increased in benzodiazepine users, but was nonsignificant (RR 1.09, 95% CI 1.00-1.20). There were no significant differences in intensive care unit admissions between the two groups and all-cause mortality was slightly lower among new versus non-users. Benzodiazepines were associated with increased risk for several serious adverse respiratory outcomes among older adults with COPD. The findings suggest that decisions to use benzodiazepines in older patients with COPD need to consider potential adverse respiratory outcomes.

Background Patients with chronic obstructive pulmonary disease (COPD) are more likely to be readmitted than patients with other chronic medical conditions, yet knowledge regarding such readmissions is limited. We aimed to determine factors associated with readmission within 30 days of a COPD hospitalization or death with an emphasis on examining aspects of socioeconomic status and specific comorbidities. Methods A population-based cohort study was conducted using health administrative data from Ontario, Canada. All hospitalizations for COPD between 2004 and 2014 were considered. The primary exposures were socioeconomic status as measured by residential instability (an ecologic variable), and comorbidities such as cardiovascular disease and cancer. Other domains of socioeconomic status were considered as secondary exposures. Logistic regression with generalized estimating equations was used to examine the effect of exposures, adjusting for other patient factors, on 30-day readmission or death. Results There were 126,013 patients contributing to 252,756 index COPD hospitalizations from 168 Ontario hospitals. Of these hospitalizations, 19.4% resulted in a readmission and 2.8% resulted in death within 30 days. After adjusting for other factors, readmissions or death were modestly more likely among people with the highest residential instability compared to the lowest (OR 1.05, 95% CI 1.01-1.09). Comorbidities such as cardiovascular disease and cancer, as well as other aspects of low socioeconomic status also increased readmission or death risk. Interpretation Socioeconomic status, measured in various ways, and many comorbidities predict 30-day readmission or death in patients hospitalized for COPD. Strategies that address these factors may help reduce readmissions and death.

The potential for respiratory-related harm needs to be considered when using opioid drugs in non-palliative COPD http://ow.ly/i5W03095MKV

Adverse respiratory outcomes are associated with incident opioid drug use among older adults with COPDhttp://ow.ly/kGTL304qEe5

Inhaled, long-acting anticholinergic medication (LAA), commonly used for moderate-to-severe chronic obstructive pulmonary disease (COPD), has been shown to decrease COPD hospitalizations, emergency department visits, and acute exacerbations but has also been associated with urinary tract infection (UTI) in a prior meta-analysis. The objective of this study was to verify if there was an association between LAA and UTI in older individuals with COPD. A population-based, real-world cohort study using health administrative data from Ontario, Canada was conducted. Incidence of UTI was compared between older people with physician-diagnosed COPD, who were new users of inhaled long-acting anticholinergics and new users of inhaled corticosteroids–a reference medication used in similar clinical settings that has no known association with UTI. Propensity score matching was used to minimize the effects of confounding. An overall association between LAA and various measures of UTI in older individuals was not found. However, in a priori defined stratified analyses, men newly initiated on LAA were 75% more likely to develop a UTI than men newly started on an inhaled corticosteroid (hazard ratio 1.75; 95% confidence interval 1.05–2.92). No significant association was seen in women. In conclusion, older men with COPD newly started on LAA are at increased risk of UTI. Men considering an inhaled LAA should be informed of this risk and, if they decide to take it, be provided with appropriate monitoring.

Purpose. There is no information on the change in prevalence of latent tuberculosis infection (LTBI) testing in the United States (US) following the introduction of the interferon gamma release assay (IGRA), a new and alternative diagnostic method for LTBI. The purpose of this study was to evaluate potential changes in the prevalence of LTBI testing in the US following the introduction of IGRA.Methods. This was a multiyear cross-sectional study using nationally representative data from the 1999-2000 and 2011-2012 US National Health and Nutrition Examination Surveys. Self-reported prevalence of LTBI testing was estimated among groups known to have increased LTBI risk. Descriptive statistics were used.Results. Compared to 1999-2000, significantly fewer individuals self-reported being tested for LTBI in 2011-2012 among Hispanic Americans (68.0% versus 60.7%,p<0.0001) and among those with comorbidities (74.7% versus 72.0%,p=0.02). There were also nonsignificant trends towards less self-reported LTBI testing in 2011-2012 versus 1999-2000 among household contacts of active TB cases, foreign-born individuals, and African Americans.Conclusions. Despite the introduction of IGRA, LTBI testing occurs less frequently in the US among vulnerable groups. Possibly inadequate targeted LTBI testing could result in increased active TB in the US in the future.

OBJECTIVE: To estimate the prevalence and determine the risk factors and health associations among individuals with combined chronic obstructive pulmonary disease and obesity.METHODS: Canadian national health survey data from 1994 to 2007 (n=650,000) were used. The presence of COPD was based on health professional-diagnosed self-report. The presence of obesity, defined by body mass index ≥30 kg/m2, was identified using self-reported and measured height and weight. Hospitalization, homecare use, physical activity assessments and socioeconomic data were all self-reported.RESULTS: In 2005, the prevalence of obesity in COPD (n=3470) and non-COPD (n=92,237) individuals was 24.6% and 17.1%, respectively (PCONCLUSIONS: The prevalence of obesity was higher in COPD, and exceeded that of the larger non-COPD group throughout the 13-year observation period. The presence of obesity in COPD was associated with significantly higher risk of severe activity limitation and increased health care utilization. The combination of obesity and COPD has major implications for health care delivery that has not been previously appreciated.

[See related article at [www.cmaj.ca/lookup/doi/10.1503/cmaj.160126][2]][2] A wide spectrum of neuropsychiatric symptoms may develop in people with dementia. These symptoms can cause distress to families and caregivers and are challenging for clinicians to manage. Symptoms range from physical

STUDY OBJECTIVES To estimate the prevalence of and identify sociodemographic risk factors for sedative medication use in the general Canadian population, and to examine the association between sedative medication use and body mass index (BMI). DESIGN Cross-sectional study SETTING Canadian population PARTICIPANTS Participants from the 1994-2003 Canadian national health surveys, the National Population Health Survey (NPHS) and the Canadian Community Health Survey (CCHS). For the 2003 CCHS, n = 134,072, ages 12-80+ years. INTERVENTIONS Not applicable MEASUREMENTS AND RESULTS The overall prevalence of sedative medication use in Canada in 2003 was 5.5%, having more than doubled since 1994. Notable rises in sedative medication use have occurred among men, non-elderly, and obese individuals. After adjusting for potential sociodemographic and health status confounders, including psychiatric comorbidities, the odds of sedative use were significantly greater among morbidly obese (BMI ≥ 35 kg/m(2)) men (OR = 1.89, 95%CI = 1.02-3.53) and underweight (BMI < 18.5 kg/m(2)) women (OR = 2.11, 95%CI = 1.26-3.53). CONCLUSIONS The use of sedative medications has substantially risen among the general Canadian population, and among particular population subgroups. The greater odds of sedative medication use found among morbidly obese men may reflect the presence of underlying obstructive sleep apnea, which may in turn serve to explain in part the known relationship between sedative medications and mortality. The increase in sedative medications coupled with their known adverse health associations raises potential public health concerns.

To the Editor: Tuberculosis guidelines identify individuals receiving the corticosteroid drug prednisone (or its equivalent) at a dose of >15 mg·day−1 for 2–4 weeks or more as a group at risk of tuberculosis if infected with Mycobacterium tuberculosis [1, 2]. There is an eight-fold increased risk of developing active tuberculosis with such drugs at this dose [3]. However, there is no information on the epidemiology of latent tuberculosis infection (LTBI), screening and treatment among oral corticosteroid users. Tuberculosis guidelines recommend using a threshold of ≥5 mm induration to identify latent infection among oral corticosteroid recipients [1, 2] but this recommendation is not evidence-based. The purpose of this study was to describe the prevalence, screening and treatment of LTBI among oral corticosteroid recipients in the USA. This was a cross-sectional study using US nationally representative, population-level data from the 1999–2000 National Health and Nutrition Examination Survey (NHANES). A description of the survey design and methodology appears elsewhere [4]. Self-reported medication receipt within the past month that required a prescription was collected by NHANES. Medication receipt was confirmed in 83.3% of participants through examiner inspection of prescription containers [5]. Survey participants who received any corticosteroid in an oral formulation within the past month were considered “recipients”. Survey participants who did not receive any oral corticosteroids within the past month were considered “nonrecipients”. Topical, inhaled or intra-articular corticosteroids were not included in this study. Information on total duration of corticosteroid receipt was collected but not dose. A single-step tuberculin skin test (TST) …

We evaluated the relationship between new selective serotonin reuptake inhibitor (SSRI) or serotonin–noradrenaline reuptake inhibitor (SNRI) drug use and respiratory-related morbidity and mortality among older adults with chronic obstructive pulmonary disease (COPD).This was a retrospective population-based cohort study using heath administrative data from Ontario, Canada. Individuals aged ≥66 years, with validated, physician-diagnosed COPD (n=131 718) were included. New SSRI/SNRI users were propensity score matched 1:1 to controls on 40 relevant covariates to minimise potential confounding.Among propensity score matched community-dwelling individuals, new SSRI/SNRI users compared to non-users had significantly higher rates of hospitalisation for COPD or pneumonia (hazard ratio (HR) 1.15, 95% CI 1.05–1.25), emergency room visits for COPD or pneumonia (HR 1.13, 95% CI 1.03–1.24), COPD or pneumonia-related mortality (HR 1.26, 95% CI 1.03–1.55) and all-cause mortality (HR 1.20, 95% CI 1.11–1.29). In addition, respiratory-specific and all-cause mortality rates were higher among long-term care home residents newly starting SSRI/SNRI drugs versus controls.New use of serotonergic antidepressants was associated with small, but significant, increases in rates of respiratory-related morbidity and mortality among older adults with COPD. Further research is needed to clarify if the observed associations are causal or instead reflect unresolved confounding.

Summary Background The purposes of this study were to estimate the prevalence of recent influenza vaccination, to identify sociodemographic risk factors and reasons for non-vaccination, and to examine the association between influenza vaccination and respiratory medication use, among individuals with asthma and COPD in Canada. Methods Data from the 2003 Statistics Canada Canadian Community Health Survey ( n =134,072, age 12–80+ years) were analyzed. All data were based on self-report. Results An estimated 36.3% and 47.9% of individuals with asthma and COPD, respectively, were immunized for influenza within the last year in 2003. These vaccination rates were relatively lower than those seen with other non-respiratory health conditions. Respondents thinking that influenza vaccination was not necessary was the most frequent reason cited for non-vaccination among individuals with asthma and COPD. Men, non-Ontarians, younger age groups, current smokers, and those without a family doctor were less likely to be vaccinated among individuals with asthma and COPD. After controlling for potential sociodemographic confounders, among individuals with asthma, those vaccinated for influenza had significantly greater odds of using inhalers/nebulizers (OR=1.8, 95% CI=1.3–2.4). No other significant medication use associations were observed among individuals with asthma and COPD. Conclusions Recent self-reported influenza vaccination rates among individuals with asthma and COPD were relatively low. Influenza vaccination was not associated with decreased respiratory medication use among individuals with asthma and COPD, suggesting that vaccination may not help prevent exacerbations. More research is needed to fully clarify the role of influenza vaccination in chronic respiratory disease, particularly asthma, to justify policies of mass-immunization.

Caring for individuals with advanced chronic obstructive pulmonary disease (COPD) with refractory breathlessness is undoubtedly challenging and I commend the authors for undertaking important and necessary research in this area. I did not write that opioids ‘should not be used’ in patients with advanced COPD.1 Based on the authors’ own data showing significantly increased all-cause mortality among individuals with advanced COPD receiving benzodiazepine and ‘high-dose’ opioids,2 I expressed that some caution should be displayed when prescribing these medications to these older, respiratory-vulnerable patients, …

New opioid drug use is associated with increased respiratory-related morbidity and mortality in nonpalliative COPDhttp://ow.ly/wRfb303k4Yl

OBJECTIVES: This study assesses the affordability of a nutritious diet for households in Toronto that are supported by welfare. METHODS: For three hypothetical households, welfare incomes were compared to the monthly costs for food, shelter, and other essential expenditures in Toronto. RESULTS: If households lived in market rental accommodation, average monthly incomes were insufficient to cover expenses for the single-person household and two-parent family, and barely adequate for the single-parent family considered in this study. However, the single-parent family’s actual income fell below expenses for six months of the year. For households with children, the relative inadequacy of welfare increased as children grew older. Living in rent-geared-to-income housing afforded substantial financial advantage, but the welfare income of single-person households was still insufficient to meet basic needs. INTERPRETATION: These findings indicate discrepancies between welfare incomes and costs of basic needs, which may explain the vulnerability of welfare recipients to food insecurity.

Patient and drug regimen selection important with opioid use in advanced COPD, given adverse respiratory event riskhttp://ow.ly/LNXJ30bPD6C

Non-selective benzodiazepines are a class of sedative and anxiolytic medication that are commonly prescribed. Physiology studies and animal studies suggest that non-selective benzodiazepines may adversely impact respiration through a variety of mechanisms. Several recent, well-designed, population-based observational studies confirm that benzodiazepine-related negative respiratory outcomes are a concern. In this article, the mechanisms and clinical evidence for non-selective benzodiazepine-related adverse respiratory outcomes, as well as the methodological issues relating to the evaluation of adverse drug effects are reviewed.

OBJECTIVE: To determine whether increasing frequency of insomnia symptoms is associated with increasing hypertension risk. METHOD: This was a large population-based multiyear cross-sectional study. Participants of the 2005-2008 National Health and Nutrition Examination Surveys responding to sleep quality questions were included (n = 12,643). Self-reported insomnia symptoms (ie, difficulty falling asleep, prolonged nocturnal awakening, or undesired early morning awakening, based on DSM-IV-TR, National Institutes of Health, and American Academy of Sleep Medicine criteria) over the past month with and without self-reported short sleep time (ie, < 6 hours) were categorized as 0, 1-4, 5-15, and 16-30 times in the past month. Outcomes included doctor-diagnosed self-reported hypertension made at any point in the past, self-reported current receipt of antihypertensive medications, and measured systolic and diastolic hypertension. RESULTS: While significant and increasing unadjusted odds of doctor-diagnosed hypertension and current antihypertensive medication receipt were found among individuals with increasing insomnia symptom frequency, these odds ratios (ORs) were for the most part rendered nonsignificant after controlling for covariates (eg, adjusted ORs and 95% confidence intervals [CIs] of current antihypertensive receipt for insomnia symptoms coupled with short sleep time: 1-4 times in the past month: 1.17, 0.78-1.76; 5-15 times in the past month: 1.60, 1.01-2.53; and 16-30 times in the past month: 1.41, 0.93-2.14). Even before controlling for covariates, there were generally no significant positive associations between objectively measured systolic and diastolic hypertension and insomnia symptoms regardless of symptom frequency (e.g., unadjusted ORs and 95% CIs of measured systolic hypertension for insomnia symptoms coupled with short sleep time: 1-4 times in the past month: 0.88, 0.53-1.47; 5-15 times in the past month: 1.16, 0.77-1.77; and 16-30 times in the past month: 1.30, 0.95-1.78). CONCLUSIONS: Insomnia symptoms, regardless of their frequency, are generally not significantly positively associated with hypertension. These results have important implications relating to screening and management of patients with insomnia symptoms.

Objective: To examine if the association with hypertension was different between individuals with and without insomnia symptoms. Methods: This was a population-based, multiyear, crosssectional study with data from the 2005–2008 United States National Health and Nutrition Examination Surveys (n ¼12643). Insomnia symptoms were considered if at least one of difficulty falling asleep, prolonged nocturnal awakening, or early morning awakening was reported, at least five times per month. Short sleep time (