Agreement of the modified Medical Research Council and New York Heart Association scales for assessing the impact of self-rated breathlessness in cardiopulmonary disease.

BACKGROUND: The functional impact of breathlessness is assessed using the modified Medical Research Council (mMRC) scale for chronic respiratory disease and with the New York Heart Association Functional Classification (NYHA) scale for heart failure. We evaluated agreement between the scales and their concurrent validity with other clinically relevant patient-reported outcomes in cardiorespiratory disease. METHODS: Outpatients with stable chronic respiratory disease or heart failure were recruited. Agreement between the mMRC and NYHA scales was analysed using Cramér's V and Kendall's tau B tests. Concurrent validity was evaluated using correlations with clinically relevant measures of breathlessness, anxiety, depression, and health-related quality of life. Analyses were conducted for all participants and separately in chronic obstructive pulmonary disease (COPD) and heart failure. RESULTS: In a total of 182 participants with cardiorespiratory disease, the agreement between the mMRC and NYHA scales was moderate (Cramér's V: 0.46; Kendall's tau B: 0.57) with similar results for COPD (Cramér's V: 0.46; Kendall's tau B: 0.66) and heart failure (Cramér's V: 0.46; Kendall's tau B: 0.67). In the total population, the scales correlated in similar ways to other patient-reported outcomes. CONCLUSION: In outpatients with cardiorespiratory disease, the mMRC and NYHA scales show moderate to strong correlations and similar associations with other patient-reported outcomes. This supports that the scales are comparable when assessing the impact of breathlessness on function and patient-reported outcomes.

Minimal Clinically Important Differences and Feasibility of Dyspnea-12 and the Multidimensional Dyspnea Profile in Cardiorespiratory Disease.

CONTEXT: Breathlessness is a cardinal symptom in cardiorespiratory disease and consists of multiple dimensions that can be measured using the instruments Dyspnea-12 (D12) and the Multidimensional Dyspnea Profile (MDP). OBJECTIVES: The objective of the study is to determine the minimal clinically important differences (MCIDs) of all D12 and MDP summary and subdomain scores as well as the instruments' feasibility in patients with cardiorespiratory disease. METHODS: Prospective multicenter cohort study of outpatients with diagnosed cardiorespiratory disease and breathlessness in daily life. D12 and MDP were assessed at baseline, after 30-90 minutes and two weeks. MCIDs were calculated using anchor-based and distributional methods for summary and subdomain scores. Feasibility was assessed as rate of missing data, help required, self-reported difficulty, and completion time. RESULTS: A total 182 outpatients (53.3% women) were included; main diagnoses were chronic obstructive pulmonary disease (COPD; 25%), asthma (21%), heart failure (19%), and idiopathic pulmonary fibrosis (19%). Anchor-based MCIDs were for D12 total score 2.83 (95% CI 1.99-3.66); D12 physical 1.81 (1.29-2.34); D12 affective 1.07 (0.64-1.49); MDP A1 unpleasantness 0.82 (0.56-1.08); MDP perception 4.63 (3.21-6.05), and MDP emotional score 2.37 (1.10-3.64). The estimates were consistent with small-to-moderate effect sizes using distributional analysis, and MCIDs were similar between COPD and non-COPD patients. The instruments were generally feasible and quick to use. CONCLUSION: D12 and MDP are responsive to change and feasible for use for assessing multidimensional breathlessness in outpatients with cardiorespiratory disease. MCIDs were determined for use as endpoints in clinical trials.

Respiratory outcomes after a 1-year treatment of obstructive sleep apnoea with bibloc versus monobloc oral appliances: a multicentre, randomized equivalence trial.

Objective: The benefit of bibloc over monobloc appliances in treating obstructive sleep apnoea (OSA) has not been evaluated in randomized trials. We hypothesized that these types of appliances would be equally effective.Material and methods: In this multicentre, randomized equivalence trial, patients with OSA received one type of bibloc or one type of monobloc treatment. At baseline, a 1-night polygraphy study was done, and this was repeated after 1 year. The outcome was any change in the apnoea-hypopnoea index (AHI) and the limits of equivalence between the two devices were set at ±5 AHI units.Results: Of 302 patients, 146 were randomly assigned to bibloc and 156 to monobloc appliances. In 88 and 104 patients, respectively, there were significant reductions in the AHI (p < .001) with a mean change of -16.7 (95% CI -19.4 to -14.1) in the bibloc and -11.8 (-14.9 to -8.7) in the monobloc groups. The proportions of responders defined as having an AHI <10 were 68% and 65% for the bibloc and monobloc groups, respectively. Treatment-related adverse events were mild, transient and the dropouts were more frequent in the bibloc group.Conclusions: Both types of treatments positively and significantly reduced respiratory disturbances, but at the 1-year follow-up, they were not significantly different in treating OSA, with a numerically greater reduction of the AHI value with the bibloc appliance. However, the higher proportion of treatment-related adverse events and higher proportion of dropouts among bibloc users should be balanced against the advantage of a greater reduction in the AHI.

Clinical validation of the Swedish version of Dyspnoea-12 instrument in outpatients with cardiorespiratory disease.

Introduction: Breathlessness is the cardinal symptom in both cardiac and respiratory diseases, and includes multiple dimensions. The multidimensional instrument Dyspnoea-12 has been developed to assess both physical and affective components of breathlessness. This study aimed to perform a clinical validation of the Swedish version of Dyspnoea-12 in outpatients with cardiorespiratory disease. Methods: Stable outpatients with cardiorespiratory disease and self-reported breathlessness in daily life were recruited from five Swedish centres. Assessments of Dyspnoea-12 were performed at baseline, after 30-90 min and after 2 weeks. Factor structure was tested using confirmatory factor analysis and internal consistency using Cronbach's alpha. Test-retest reliability was analysed using intraclass correlation coefficients (ICCs). Concurrent validity at baseline was evaluated by examining correlations with lung function and several instruments for the assessment of symptoms and health status. Results: In total, 182 patients were included: with the mean age of 69 years and 53% women. The main causes of breathlessness were chronic obstructive pulmonary disease (COPD; 25%), asthma (21%), heart failure (19%) and idiopathic pulmonary fibrosis (19%). Factor analysis confirmed the expected underlying two-component structure with two subdomains. The Dyspnoea-12 total score, physical subdomain score and affective subdomain scores showed high internal consistency (Cronbach's alpha 0.94, 0.84 and 0.80, respectively) and acceptable reliability after 2 weeks (ICC total scores 0.81, 0.79 and 0.73). Dyspnoea-12 showed concurrent validity with the instruments modified Medical Research Council scale, COPD Assessment Test, European Quality of Life-Five Dimensions-Five levels, the Functional Assessment of Chronic Illness Therapy-Fatigue, the Hospital Anxiety and Depression Scale, and with forced expiratory volume in 1 s in percentage of predicted value. The results were consistent across different cardiorespiratory conditions. Conclusion: The Dyspnoea-12 is a valid instrument for multidimensional assessment of breathlessness in Swedish patients with cardiorespiratory diseases.

Validation of the Swedish Multidimensional Dyspnea Profile (MDP) in outpatients with cardiorespiratory disease.

Introduction: Breathlessness is a cardinal symptom in cardiorespiratory disease. An instrument for measuring different aspects of breathlessness was recently developed, the Multidimensional Dyspnea Profile (MDP). This study aimed to validate the MDP in terms of the underlying factor structure, internal consistency, test-retest reliability and concurrent validity in Swedish outpatients with cardiorespiratory disease. Methods: Outpatients with stable cardiorespiratory disease and breathlessness in daily life were recruited. Factor structure of MDP was analysed using confirmatory factor analysis; internal consistency was analysed using Cronbach's alpha; and test-retest reliability was analysed using intraclass correlation coefficients (ICCs) for patients with unchanged breathlessness between assessments (baseline, after 30-90 min and 2 weeks). Concurrent validity was evaluated using correlations with validated scales of breathlessness, anxiety, depression and health-related quality of life. Results: In total, 182 outpatients with cardiorespiratory disease and breathlessness in daily life were included; 53.3% were women; main diagnoses were chronic obstructive pulmonary disease (24.7%), asthma (21.4%), heart failure (19.2%) and idiopathic pulmonary fibrosis (18.7%). The MDP total, immediate perception and emotional response scores, and individual item scores showed expected factor structure and acceptable measurement properties: internal consistency (Cronbach's alpha, range 0.80-0.93); test-retest reliability at 30-90 min and 2 weeks (ICC, range 0.67-0.91); and concurrent validity. There was no evidence of a learning effect. Findings were similar between diagnoses. Discussion: MDP is a valid instrument for multidimensional measurement of breathlessness in Swedish outpatients across cardiorespiratory diseases.

REgistry-based randomized controlled trial of treatment and Duration and mortality in long-term OXygen therapy (REDOX) study protocol.

OBJECTIVE: Long-term oxygen therapy (LTOT) during 15 h/day or more prolongs survival in patients with chronic obstructive pulmonary disease (COPD) and severe hypoxemia. No randomized controlled trial has evaluated the net effects (benefits or harms) from LTOT 24 h/day compared with 15 h/day or the effect in conditions other than COPD. We describe a multicenter, national, phase IV, non-superiority, registry-based, randomized controlled trial (R-RCT) of LTOT prescribed 24 h/day compared with 15 h/day. The primary endpoint is all-cause-mortality at 1 year. Secondary endpoints include cause-specific mortality, hospitalizations, health-related quality of life, symptoms, and outcomes in interstitial lung disease. METHODS/DESIGN: Patients qualifying for LTOT are randomized to LTOT 24 h/day versus 15 h/day during 12 months using the Swedish Register for Respiratory Failure (Swedevox). Planned sample size in this pragmatic study is 2126 randomized patients. Clinical follow-up and concurrent treatments are according to routine clinical practice. Mortality, hospitalizations, and incident diseases are assessed using national Swedish registries with expected complete follow-up. Patient-reported outcomes are assessed using postal questionnaire at 3 and 12 months. DISCUSSION: The R-RCT approach combines the advantages of a prospective randomized trial and large clinical national registries for enrollment, allocation, and data collection, with the aim of improving the evidence-based use of LTOT. TRIAL REGISTRATION: Clinical Trial registered with www.clinicaltrials.gov , Title: REgistry-based Treatment Duration and Mortality in Long-term OXygen Therapy (REDOX); ID: NCT03441204.

Use of bibloc and monobloc oral appliances in obstructive sleep apnoea: a multicentre, randomized, blinded, parallel-group equivalence trial.

Background: The clinical benefit of bibloc over monobloc appliances in treating obstructive sleep apnoea (OSA) has not been evaluated in randomized trials. We hypothesized that the two types of appliances are equally effective in treating OSA. Objective: To compare the efficacy of monobloc versus bibloc appliances in a short-term perspective. Patients and methods: In this multicentre, randomized, blinded, controlled, parallel-group equivalence trial, patients with OSA were randomly assigned to use either a bibloc or a monobloc appliance. One-night respiratory polygraphy without respiratory support was performed at baseline, and participants were re-examined with the appliance in place at short-term follow-up. The primary outcome was the change in the apnoea-hypopnea index (AHI). An independent person prepared a randomization list and sealed envelopes. Evaluating dentist and the biomedical analysts who evaluated the polygraphy were blinded to the choice of therapy. Results: Of 302 patients, 146 were randomly assigned to use the bibloc and 156 the monobloc device; 123 and 139 patients, respectively, were analysed as per protocol. The mean changes in AHI were -13.8 (95% confidence interval -16.1 to -11.5) in the bibloc group and -12.5 (-14.8 to -10.3) in the monobloc group. The difference of -1.3 (-4.5 to 1.9) was significant within the equivalence interval (P = 0.011; the greater of the two P values) and was confirmed by the intention-to-treat analysis (P = 0.001). The adverse events were of mild character and were experienced by similar percentages of patients in both groups (39 and 40 per cent for the bibloc and monobloc group, respectively). Limitations: The study shows short-term results with a median time from commencing treatment to the evaluation visit of 56 days and long-term data on efficacy and harm are needed to be fully conclusive. Conclusion: In a short-term perspective, both appliances were equivalent in terms of their positive effects for treating OSA and caused adverse events of similar magnitude. Trial registration: Registered with ClinicalTrials.gov (#NCT02148510).

Surgery for Chronic Otitis Media Causes Greater Taste Disturbance Than Surgery for Otosclerosis.

OBJECTIVES: Patients with otosclerosis more often complain about postoperative taste disturbance than patients with chronic otitis media, which seems paradoxical. We aim to investigate if and potentially why this seems to be the case, since the chorda tympani nerve (CTN) is thought to be severely traumatized less frequently during surgery in the former than in the latter. STUDY DESIGN: Prospective cohort study. SETTING: Department of Otorhinolaryngology at Hospital of Vastmanland, Vasteras, Sweden. PATIENTS: Sixty-five adults undergoing primary middle ear surgery were included. Thirty-seven were operated on for chronic suppurative otitis media with or without cholesteatoma (CSOM) and 28 for otosclerosis. INTERVENTIONS: Middle ear surgery due to otosclerosis or CSOM. Subjective and objective taste measurements and quality of life (QoL) questionnaire. MAIN OUTCOME MEASURES: Taste was assessed using electrogustometry (EGM) and the filter paper disc (FPD) method before and up to 1 year after surgery. Questionnaires on taste disturbance, including a visual analogue scale (VAS), and QoL were completed before and up to 1 year after surgery. RESULTS: Subjective taste disturbance anytime during the 1-year follow-up were reported by 62 and 46%, respectively. The difference in EGM 1 week after surgery compared with preoperative EGM was significantly greater among CSOM patients than otosclerosis. One year postoperatively, the difference is non-significant. CONCLUSION: Surgery for CSOM causes greater initial and more long-lasting taste disturbances as compared with surgery for otosclerosis. One-year postoperative taste normalizes for both CSOM and otosclerosis patients according to VAS and EGM measurements. No real change in QoL was seen 1-year postoperatively. LEVEL OF EVIDENCE: Level 2 evidence is prospective observational research with an experimental design.

Oxygen for breathlessness in patients with chronic obstructive pulmonary disease who do not qualify for home oxygen therapy.

BACKGROUND: Breathlessness is a cardinal symptom of chronic obstructive pulmonary disease (COPD). Long-term oxygen therapy (LTOT) is given to improve survival time in people with COPD and severe chronic hypoxaemia at rest. The efficacy of oxygen therapy for breathlessness and health-related quality of life (HRQOL) in people with COPD and mild or no hypoxaemia who do not meet the criteria for LTOT has not been established. OBJECTIVES: To determine the efficacy of oxygen versus air in mildly hypoxaemic or non-hypoxaemic patients with COPD in terms of (1) breathlessness; (2) HRQOL; (3) patient preference whether to continue therapy; and (4) oxygen-related adverse events. SEARCH METHODS: We searched the Cochrane Airways Group Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and Embase, to 12 July 2016, for randomised controlled trials (RCTs). We handsearched the reference lists of included articles. SELECTION CRITERIA: We included RCTs of the effects of non-invasive oxygen versus air on breathlessness, HRQOL or patient preference to continue therapy among people with COPD and mild or no hypoxaemia (partial pressure of oxygen (PaO2) > 7.3 kPa) who were not already receiving LTOT. Two review authors independently assessed articles for inclusion in the review. DATA COLLECTION AND ANALYSIS: Two review authors independently collected and analysed data. We assessed risk of bias by using the Cochrane 'Risk of bias tool'. We pooled effects recorded on different scales as standardised mean differences (SMDs) with 95% confidence intervals (CIs) using random-effects models. Lower SMDs indicated decreased breathlessness and reduced HRQOL. We performed subanalyses and sensitivity analyses and assessed the quality of evidence according to the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. MAIN RESULTS: Compared with the previous review, which was published in 2011, we included 14 additional studies (493 participants), excluded one study and included data for meta-analysis of HRQOL. In total, we included in this review 44 studies including 1195 participants, and we included 33 of these (901 participants)in the meta-analysis.We found that breathlessness during exercise or daily activities was reduced by oxygen compared with air (32 studies; 865 participants; SMD -0.34, 95% CI -0.48 to -0.21; I2 = 37%; low-quality evidence). This translates to a decrease in breathlessness of about 0.7 points on a 0 to 10 numerical rating scale. In contrast, we found no effect of short-burst oxygen given before exercise (four studies; 90 participants; SMD 0.01, 95% CI -0.26 to 0.28; I2 = 0%; low-quality evidence). Oxygen reduced breathlessness measured during exercise tests (25 studies; 442 participants; SMD -0.34, 95% CI -0.46 to -0.22; I2 = 29%; moderate-quality evidence), whereas evidence of an effect on breathlessness measured in daily life was limited (two studies; 274 participants; SMD -0.13, 95% CI, -0.37 to 0.11; I2 = 0%; low-quality evidence).Oxygen did not clearly affect HRQOL (five studies; 267 participants; SMD 0.10, 95% CI -0.06 to 0.26; I2 = 0%; low-quality evidence). Patient preference and adverse events could not be analysed owing to insufficient data. AUTHORS' CONCLUSIONS: We are moderately confident that oxygen can relieve breathlessness when given during exercise to mildly hypoxaemic and non-hypoxaemic people with chronic obstructive pulmonary disease who would not otherwise qualify for home oxygen therapy. Most evidence pertains to acute effects during exercise tests, and no evidence indicates that oxygen decreases breathlessness in the daily life setting. Findings show that oxygen does not affect health-related quality of life.

Long-Term Oxygen Therapy 24 vs 15 h/day and Mortality in Chronic Obstructive Pulmonary Disease.

Long-term oxygen therapy (LTOT) ≥ 15 h/day improves survival in hypoxemic chronic obstructive pulmonary disease (COPD). LTOT 24 h/day is often recommended but may pose an unnecessary burden with no clear survival benefit compared with LTOT 15 h/day. The aim was to test the hypothesis that LTOT 24 h/day decreases all-cause, respiratory, and cardiovascular mortality compared to LTOT 15 h/day in hypoxemic COPD. This was a prospective, observational, population-based study of COPD patients starting LTOT between October 1, 2005 and June 30, 2009 in Sweden. Overall and cause-specific mortality was analyzed using Cox and Fine-Gray regression, controlling for age, sex, prescribed oxygen dose, PaO2 (air), PaCO2 (air), Forced Expiratory Volume in one second (FEV1), WHO performance status, body mass index, comorbidity, and oral glucocorticoids. A total of 2,249 included patients were included with a median follow-up of 1.1 years (interquartile range, 0.6-2.1). 1,129 (50%) patients died and no patient was lost to follow-up. Higher LTOT duration analyzed as a continuous variable was not associated with any change in mortality rate (hazard ratio [HR] 1.00; (95% confidence interval [CI], 0.98 to 1.02) per 1 h/day increase above 15 h/day. LTOT exactly 24 h/day was prescribed in 539 (24%) patients and LTOT 15-16 h/day in 1,231 (55%) patients. Mortality was similar between the groups for all-cause, respiratory and cardiovascular mortality. In hypoxemic COPD, LTOT 24 h/day was not associated with a survival benefit compared with treatment 15-16 h/day. A design for a registry-based randomized trial (R-RCT) is proposed.

Cardiovascular and antacid treatment and mortality in oxygen-dependent pulmonary fibrosis: A population-based longitudinal study.

BACKGROUND AND OBJECTIVE: Severe idiopathic pulmonary fibrosis is associated with an increased risk of cardiovascular disease and gastro-oesophageal reflux, which may influence prognosis. We evaluated associations between cardiovascular and antacid medications, and mortality, in oxygen-dependent pulmonary fibrosis (PF) of unknown cause. METHODS: Prospective population-based study of adults starting long-term oxygen therapy (LTOT) for PF in Sweden 2005-2009. PF of unknown cause was defined by excluding patients with known or probable secondary PF. Time-dependent associations between medications and all-cause mortality were analysed using extended Cox regression, adjusting for potential confounders including age, sex, vital capacity, blood gases, body mass index, performance status, comorbidity and concurrent medications. RESULTS: Of 462 included patients, 329 (71%) died under observation. No patient was lost to follow-up. Angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (ACEI/ARB) were associated with reduced adjusted mortality (HR 0.63; 0.47-0.85) and antiplatelet drugs with increased mortality (HR 1.49; 1.11-2.00), largely driven by higher mortality in women. There were no associations with mortality for antacid treatments, ß-blockers, diuretics or statins. CONCLUSION: In oxygen-dependent PF, treatment with ACEI/ARB was associated with improved survival, antiplatelet drugs with decreased survival, whereas there was no association between antacid, ß-blocker, diuretic or statin treatment and survival.

The identification of complex interactions in epidemiology and toxicology: a simulation study of boosted regression trees.

BACKGROUND: There is a need to evaluate complex interaction effects on human health, such as those induced by mixtures of environmental contaminants. The usual approach is to formulate an additive statistical model and check for departures using product terms between the variables of interest. In this paper, we present an approach to search for interaction effects among several variables using boosted regression trees. METHODS: We simulate a continuous outcome from real data on 27 environmental contaminants, some of which are correlated, and test the method's ability to uncover the simulated interactions. The simulated outcome contains one four-way interaction, one non-linear effect and one interaction between a continuous variable and a binary variable. Four scenarios reflecting different strengths of association are simulated. We illustrate the method using real data. RESULTS: The method succeeded in identifying the true interactions in all scenarios except where the association was weakest. Some spurious interactions were also found, however. The method was also capable to identify interactions in the real data set. CONCLUSIONS: We conclude that boosted regression trees can be used to uncover complex interaction effects in epidemiological studies.

Hypo- and hypercapnia predict mortality in oxygen-dependent chronic obstructive pulmonary disease: a population-based prospective study.

BACKGROUND: The prognostic role of the arterial blood gas tension of carbon dioxide (PaCO2) in severe Chronic Obstructive Pulmonary Disease (COPD) remains unknown. The aim of this study was to estimate the association between PaCO2 and mortality in oxygen-dependent COPD. METHODS: National prospective study of patients starting long-term oxygen therapy (LTOT) for COPD in Sweden between October 1, 2005 and June 30, 2009, with all-cause mortality as endpoint. The association between PaCO2 while breathing air, PaCO2 (air), and mortality was estimated using Cox regression adjusted for age, sex, arterial blood gas tension of oxygen (PaO2), World Health Organization performance status, body mass index, comorbidity, and medications. RESULTS: Of 2,249 patients included, 1,129 (50%) died during a median 1.1 years (IQR 0.6-2.0 years) of observation. No patient was lost to follow-up. PaCO2 (air) independently predicted adjusted mortality (p < 0.001). The association with mortality was U-shaped, with the lowest mortality at approximately PaCO2 (air) 6.5 kPa and increased mortality at PaCO2 (air) below 5.0 kPa and above 7.0 kPa. CONCLUSION: In oxygen-dependent COPD, PaCO2 (air) is an independent prognostic factor with a U-shaped association with mortality.

Safety of benzodiazepines and opioids in very severe respiratory disease: national prospective study.

OBJECTIVE: To evaluate the safety of benzodiazepines and opioids in patients with very severe chronic obstructive pulmonary disease (COPD). DESIGN: Population based longitudinal consecutive cohort study. SETTING: Centres prescribing long term oxygen therapy in Sweden. PATIENTS: 2249 patients starting long term oxygen therapy for COPD in Sweden between 2005 and 2009 in the national Swedevox Register. MAIN OUTCOME MEASURES: Effects of benzodiazepines and opioids on rates of admission to hospital and mortality, adjusted for age, sex, arterial blood gases, body mass index (BMI), performance status, previous admissions, comorbidities, and concurrent drugs. RESULTS: 1681 (76%) patients were admitted to hospital, and 1129 (50%) died under observation. No patient was lost to follow-up. Benzodiazepines and opioids were not associated with increased admission: hazard ratio 0.98 (95% confidence interval, 0.87 to 1.10) and 0.98 (0.86 to 1.10), respectively. Benzodiazepines were associated with increased mortality (1.21, 1.05 to 1.39) with a dose response trend. Opioids also had a dose response relation with mortality: lower dose opioids (≤ 30 mg oral morphine equivalents a day) were not associated with increased mortality (1.03, 0.84 to 1.26) in contrast with higher dose opioids (1.21, 1.02 to 1.44). Concurrent benzodiazepines and opioids in lower doses were not associated with increased admissions (0.86, 0.53 to 1.42) or mortality (1.25, 0.78 to 1.99). Associations were not modified by being naive to the drugs or by hypercapnia. CONCLUSIONS: Lower dose opioids are not associated with increased admissions or deaths in patients with COPD and might be safe for symptom reduction in severe respiratory disease.

Do clinical factors explain persistent sex disparities in the use of acute reperfusion therapy in STEMI in Sweden and Canada?

AIMS: This study examined clinical factors associated with sex differences in the use of acute reperfusion therapy (fibrinolysis or primary percutaneous coronary intervention) in ST-elevation myocardial infarction (STEMI) patients, and the interaction between sex and these factors in Sweden and Canada. METHODS: Patients with STEMI in Sweden (n=32,676 from the Register of Information and Knowledge about Swedish Heart Intensive Care Admissions) were compared with similar patients in Canada (n=3375 from the Canadian Global Registry of Acute Coronary Events) for the period 2004-2008. RESULTS: Unadjusted vs. age-adjusted odds ratios (OR) for no reperfusion (women vs. men) were for Sweden 1.57 (95% CI 1.49-1.64) vs. 1.14 (95% CI 1.08-1.20), and for Canada 1.61 (95% CI 1.39-1.87) vs. OR 1.18 (95% CI 1.01-1.39). Sex differences persisted after multivariable adjustments (including prehospital delay, atypical symptoms, diabetes), factors for which no interaction with sex was found. Among women <60 years, adjusting for atypical symptoms in Canada and angiographic data in Sweden made the greatest contribution to explaining observed sex differences. CONCLUSIONS: In both countries, acute reperfusion therapy in STEMI was used less often in women than in men. Factors associated with these sex differences appear to differ between older and younger women. Targeted interventions are needed to optimize care for women with STEMI, as well as sex- and age-stratified reporting of quality indicators to assess their effectiveness.