Complications of ultrasound guided very small-bore chest drains for pleural effusions of different etiology.

Background: Small-bore chest drains are now the most common drains for treating pleural effusion (PE), but knowledge on complications is limited especially in malignant PE and empyema. We aimed to evaluate rate of complications of ultrasound guided small bore chest drains [6-10 French (F)] by PE etiology. Methods: Retrospective cohort study of 484 chest drains inserted in 330 adults in a Swedish department 2018-2020. Rate of complications (blockage, dislocation, infection, or misplacement) and repeat intervention (new drain within 2 weeks or surgery) was analyzed by effusion type (organ failure, parapneumonic, malignant, empyema, other, unknown), age, sex, seniority of radiologist, and bore size using multivariable logistic regression. Results: Most inserted drains (73.3%) were 6 F. The rate of repeat intervention was substantially higher in malignant PE [25.5%; adjusted odds ratio (aOR) 3.3; 95% confidence interval (CI): 1.6-6.8] and empyema (56.4%; aOR 11.9; 95% CI: 4.8-29.4) compared to other aetiologies (range, 9.5-17.8%). Surgery as complication occurred in empyema in 23.0% of cases (aOR 10.6; 95% CI: 1.4-79.4). The rate of repeat intervention in simple PE (parapneumonic or due to organ failure) was low (range, 9.5-12.5%). Conclusions: A single small-bore chest drain (6-10 F) was successful in the vast majority of simple PEs, but had high complication rates in empyema with frequent need of additional drains or surgery. These findings support use of larger drains and early consultation with a thoracic surgeon in empyema.

Severity of Airflow Obstruction Based on FEV1/FVC vs FEV1% of Predicted in the General US Population.

RATIONALE: According to GOLD, the ratio of FEV1/FVC is used to confirm airflow obstruction in COPD diagnosis, whereas FEV1% of predicted (FEV1%pred) is used for severity grading. STaging of Airflow obstruction by the FEV1/FVC Ratio (STAR) and its prediction of adverse outcomes has not been evaluated in general populations. OBJECTIVE: To compare the STAR (FEV1/FVC) versus GOLD (FEV1%pred) classification for the severity of airflow limitation in terms of exertional breathlessness and mortality in the general US population. METHODS: Severity stages according to STAR and GOLD were applied to the multi-ethnic National Health and Nutrition Examination Survey (NHANES) 2007-2012 survey including ages 18-80 years, using post-bronchodilatory FEV1/FVC<0.70 to define airflow obstruction in both staging systems. Prevalence of severity stages STAR 1-4 and GOLD 1-4 was calculated and associations with breathlessness and mortality were analyzed by multinomial logistic regression and Cox regression, respectively. RESULTS: STAR versus GOLD severity staging of airflow obstruction showed similar associations with breathlessness and all-cause mortality, regardless of ethnicity/race. In those with airflow obstruction, the correlation between the two classification systems was 0.461 (p<0.001). STAR reclassified 59% of GOLD stage 2 as having mild airflow obstruction (STAR 1). STAR 1 was more clearly differentiated from the non-obstructive compared to GOLD stage 1 in terms of both breathlessness and mortality. CONCLUSIONS: FEV1/FVC and FEV1%pred as measures of severity of airflow limitation show similar prediction of breathlessness and mortality in the adult US population across ethnicity groups. However, stage 1 differed more clearly from non-obstructive based on FEV1/FVC than FEV1%pred. This article is open access and distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).

Exertional breathlessness related to medical conditions in middle-aged people: the population-based SCAPIS study of more than 25,000 men and women.

BACKGROUND: Breathlessness is common in the population and can be related to a range of medical conditions. We aimed to evaluate the burden of breathlessness related to different medical conditions in a middle-aged population. METHODS: Cross-sectional analysis of the population-based Swedish CArdioPulmonary bioImage Study of adults aged 50-64 years. Breathlessness (modified Medical Research Council [mMRC] ≥ 2) was evaluated in relation to self-reported symptoms, stress, depression; physician-diagnosed conditions; measured body mass index (BMI), spirometry, venous haemoglobin concentration, coronary artery calcification and stenosis [computer tomography (CT) angiography], and pulmonary emphysema (high-resolution CT). For each condition, the prevalence and breathlessness population attributable fraction (PAF) were calculated, overall and by sex, smoking history, and presence/absence of self-reported cardiorespiratory disease. RESULTS: We included 25,948 people aged 57.5 ± [SD] 4.4; 51% women; 37% former and 12% current smokers; 43% overweight (BMI 25.0-29.9), 21% obese (BMI ≥ 30); 25% with respiratory disease, 14% depression, 9% cardiac disease, and 3% anemia. Breathlessness was present in 3.7%. Medical conditions most strongly related to the breathlessness prevalence were (PAF 95%CI): overweight and obesity (59.6-66.0%), stress (31.6-76.8%), respiratory disease (20.1-37.1%), depression (17.1-26.6%), cardiac disease (6.3-12.7%), anemia (0.8-3.3%), and peripheral arterial disease (0.3-0.8%). Stress was the main factor in women and current smokers. CONCLUSION: Breathlessness mainly relates to overweight/obesity and stress and to a lesser extent to comorbidities like respiratory, depressive, and cardiac disorders among middle-aged people in a high-income setting-supporting the importance of lifestyle interventions to reduce the burden of breathlessness in the population.

Low-Dose Morphine Does Not Cause Sleepiness in COPD: A Secondary Analysis of a Randomized Trial.

RATIONALE: Regular, low-dose, sustained-release morphine is frequently prescribed for persistent breathlessness in chronic obstructive pulmonary disease (COPD). However, effects on daytime sleepiness, perceived sleep quality and daytime function have not been rigorously investigated. OBJECTIVES: Determine the effects of regular, low-dose, sustained-release morphine on sleep parameters in COPD. METHODS: Pre-specified secondary analyses of validated sleep questionnaire data from a randomized trial of daily, low-dose, sustained -release morphine versus placebo over four weeks commencing at 8mg or 16mg/day with blinded up-titration over two weeks to a maximum of 32mg/day. Primary outcomes for these analyses were week-1 Epworth Sleepiness Scale (ESS) and Karolinska Sleepiness Scale (KSS) responses on morphine versus placebo. Secondary outcomes included Leeds Sleep Evaluation Questionnaire (LSEQ) scores (end of weeks 1 and 4), KSS and ESS beyond week-1 and associations between breathlessness, morphine, and questionnaire scores. MEASUREMENTS AND MAIN RESULTS: 156 people were randomized. Week-1 sleepiness scores were not different on morphine versus placebo (∆ESS [95%CI] versus placebo: 8mg group: -0.59 [-1.99, 0.81], p=0.41; 16mg group: -0.72 [-2.33, 0.9], p=0.38; ∆KSS versus placebo: 8mg group: 0.11 [-0.7, 0.9], p=0.78; 16mg group: -0.41 [-1.31, 0.49], p=0.37). This neutral effect persisted at later timepoints. In addition, participants who reported reduced breathlessness with morphine at 4 weeks also had improvement in LSEQ domain scores including perceived sleep quality and daytime function. CONCLUSIONS: Regular, low-dose morphine does not worsen sleepiness when used for breathlessness in COPD. Individual improvements in breathlessness with morphine may be related to improvements in sleep.

Factors most strongly associated with breathlessness in a population aged 50-64 years.

Background: Breathlessness is a troublesome and prevalent symptom in the population, but knowledge of related factors is scarce. The aim of this study was to identify the factors most strongly associated with breathlessness in the general population and to describe the shapes of the associations between the main factors and breathlessness. Methods: A cross-sectional analysis was carried out of the multicentre population-based Swedish CArdioPulmonary bioImage Study (SCAPIS) of adults aged 50 to 64 years. Breathlessness was defined as a modified Medical Research Council breathlessness rating ≥2. The machine learning algorithm extreme gradient boosting (XGBoost) was used to classify participants as either breathless or nonbreathless using 449 factors, including physiological measurements, blood samples, computed tomography cardiac and lung measurements, lifestyle, health conditions and socioeconomics. The strength of the associations between the factors and breathlessness were measured by SHapley Additive exPlanations (SHAP), with higher scores reflecting stronger associations. Results: A total of 28 730 participants (52% women) were included in the study. The strongest associated factors for breathlessness were (in order of magnitude): body mass index ( SHAP score 0.39), forced expiratory volume in 1 s (0.32), physical activity measured by accelerometery (0.27), sleep apnoea (0.22), diffusing lung capacity for carbon monoxide (0.21), self-reported physical activity (0.17), chest pain when hurrying (0.17), high-sensitivity C-reactive protein (0.17), recent weight change (0.14) and cough (0.13). Conclusion: This large population-based study of men and women aged 50-64 years identified the main factors related to breathlessness that may be prevented or amenable to public health interventions.

Abnormal Exertional Breathlessness on Cardiopulmonary Cycle Exercise Testing in Relation to Self-Reported and Physiological Responses in Chronic Airflow Limitation.

BACKGROUND: Exertional breathlessness is a cardinal symptom of cardiorespiratory disease. RESEARCH QUESTION: How does breathlessness abnormality, graded using normative reference equations during cardiopulmonary exercise testing (CPET), relate to self-reported and physiological responses in people with chronic airflow limitation (CAL)? STUDY DESIGN AND METHODS: An analysis was done of people aged ≥ 40 years with CAL undergoing CPET in the Canadian Cohort Obstructive Lung Disease study. Breathlessness intensity ratings (Borg CR10 scale [0-10 category-ratio scale for breathlessness intensity rating]) were evaluated in relation to power output (W), rate of oxygen uptake (V˙o2), and minute ventilation (V˙e) at peak exercise, using normative reference equations as follows: (1) probability of breathlessness normality (probability of having an equal or greater Borg CR10 rating among healthy; lower probability reflecting more severe breathlessness) and (2) presence of abnormal breathlessness (rating above the upper limit of normal). Associations with relevant participant-reported and physiologic outcomes were evaluated. RESULTS: We included 330 participants (44% women): mean ± SD age, 64 ± 10 years (range, 40-89 years); FEV1/FVC, 57.3% ± 8.2%; FEV1, 75.6% ± 17.9% predicted. Abnormally low exercise capacity (peak V˙o2 < lower limit of normal) was present in 26%. Relative to peak W, V˙o2, and V˙e, abnormally high breathlessness was present in 26%, 25%, and 18% of participants. For all equations, abnormally high exertional breathlessness was associated with worse lung function, exercise capacity, self-reported symptom burden, physical activity, and health-related quality of life; and greater physiological abnormalities during CPET. INTERPRETATION: Abnormal breathlessness graded using CPET normative reference equations was associated with worse clinical, physiological, and functional outcomes in people with CAL, supporting construct validity of abnormal exertional breathlessness.

Smoking and home oxygen therapy: a review and consensus statement from a multidisciplinary Swedish taskforce.

BACKGROUND: Home oxygen therapy (HOT) improves survival in patients with hypoxaemic chronic respiratory disease. Most patients evaluated for HOT are former or active smokers. Oxygen accelerates combustion and smoking may increase the risk of burn injuries and fire hazards; therefore, it is considered a contraindication for HOT in many countries. However, there is variability in the practices and policies regarding this matter. This multidisciplinary Swedish taskforce aimed to review the potential benefits and risks of smoking in relation to HOT, including medical, practical, legal and ethical considerations. METHODS: The taskforce of the Swedish Respiratory Society comprises 15 members across respiratory medicine, nursing, medical law and ethics. HOT effectiveness and adverse risks related to smoking, as well as practical, legal and ethical considerations, were reviewed, resulting in five general questions and four PICO (population-intervention-comparator-outcome) questions. The strength of each recommendation was rated according to the GRADE (grading of recommendation assessment, development and evaluation) methodology. RESULTS: General questions about the practical, legal and ethical aspects of HOT were discussed and summarised in the document. The PICO questions resulted in recommendations about assessment, management and follow-up of smoking when considering HOT, if HOT should be offered to people that meet the eligibility criteria but who continue to smoke, if a specific length of time of smoking cessation should be considered before assessing eligibility for HOT, and identification of areas for further research. CONCLUSIONS: Multiple factors need to be considered in the benefit/risk evaluation of HOT in active smokers. A systematic approach is suggested to guide healthcare professionals in evaluating HOT in relation to smoking.

Exercise Systolic Blood Pressure Response During Cycle Ergometry is Associated with Future Hypertension in Normotensive Individuals.

AIMS: We aimed to investigate the association between the exercise systolic blood pressure (SBP) response and future hypertension (HTN) in normotensive individuals referred for cycle ergometry, with special regard to reference exercise SBP values, and exercise capacity. METHODS: In this longitudinal cohort study, data from 14,428 exercise tests were cross-linked with Swedish national registries on diagnoses and medications. We excluded individuals with a baseline diagnosis of cardiovascular disease or HTN. The peak exercise SBP (SBPpeak) was recorded and compared to the upper limit of normal (ULN) derived from SBPpeak reference equations incorporating age, sex, resting SBP and exercise capacity. To evaluate the impact of exercise capacity, three SBP to work rate slopes (SBP/W-slopes), were calculated, relative to either supine or seated SBP at rest or to the first exercise SBP. Adjusted hazard ratios (HRadjusted [95% Confidence interval, CI]) for incident HTN during follow-up, in relation to SBP response metrics, were calculated. RESULTS: We included 3,895 normotensive individuals (49±14 years, 45% females) with maximal cycle ergometer tests. During follow-up (median 7.5 years) 22% developed HTN. Higher SBPpeak and SBPpeak>ULN were associated with incident HTN (HRadjusted 1.19 [1.14-1.23] per 10 mmHg, and 1.95 [1.54-2.47], respectively). All three SBP/W-slopes were positively associated to incident HTN, particularly the SBP/W-slope calculated as supine-to-peak SBP (HRadjusted 1.25 [1.19-1.31] per 1 mmHg/10W). CONCLUSION: Both SBPpeak>ULN based on reference values and high SBP/W-slopes were associated with incident HTN in normotensive individuals and should be considered in the evaluation of the cycle ergometry SBP response.

We examined the systolic blood pressure response during maximal bicycle exercise testing in individuals without hypertension or established cardiovascular disease, and found that: When applying reference values for peak systolic blood pressure during cycling exercise, accounting for age, sex, resting blood pressure and exercise capacity, exceeding the upper limit of normal was associated with twice as high relative risk of future hypertension, compared to having a peak systolic blood pressure within normal limits. A steep increase in exercise blood pressure in relation to the increase in work rate was also associated with future hypertension but did not always coincide with elevated peak systolic blood pressure.

The impact of regular, low-dose, sustained-release morphine for chronic breathlessness on caregiver burden: An exploratory analysis of the BEAMS trial.

BACKGROUND: Chronic breathlessness adversely impacts people with chronic obstructive pulmonary disease and their caregivers (family and friends), who may, in turn, experience significant burden due to their caregiving role. Sustained-release morphine may reduce chronic breathlessness in some patients, which may have an impact on caregivers' perceived burden. AIM: To explore the impact on caregiver burden of active treatment of people with chronic breathlessness (modified Medical Research Council (mMRC) ⩾ 3) and chronic obstructive pulmonary disease (COPD) with regular, low-dose, sustained-release morphine within a multi-site, double-blind, randomised, placebo-controlled trial. DESIGN: Exploratory analysis of self-reported caregiver burden at baseline and end of week 3 in a randomised, double-blind, placebo-controlled study. Caregiver measures included: demographics and perceived burden (Zarit Burden Interview 12-item short-form questionnaire). Patient measures included: worst breathlessness and FitBitR-measures. SETTING/PARTICIPANTS: All consenting caregivers of trial patient participants in a multi-site study recruiting from palliative care and respiratory services. RESULTS: Caregivers (n = 49; 59% women; median age 68 years [IQR 50-75]) reported median baseline caregiver burden 12 [IQR 5-17], with 53% reporting high burden (⩾13). Eighty-four percent of caregivers reported no change in burden. In people whose worst breathlessness improved, caregiver burden moved in the same direction, though the correlation was not significant (rs = 0.25, p = 0.17). Conversely, caregiver burden worsened as patients' minutes lightly active increased, with the correlation being significant (rs = 0.56, p = 0.04). CONCLUSIONS: Caregivers reported high levels of caregiver burden, but patients' response to treatment in terms of their symptom and function may influence change in caregiver burden over a three-week period.

Normative Reference Equations for Breathlessness Intensity during Incremental Cardiopulmonary Cycle Exercise Testing.

Rationale: Cardiopulmonary exercise testing (CPET) is the gold standard to evaluate exertional breathlessness, a common and disabling symptom. However, the interpretation of breathlessness responses to CPET is limited by a scarcity of normative data. Objectives: We aimed to develop normative reference equations for breathlessness intensity (Borg 0-10 category ratio) response in men and women aged ⩾40 years during CPET, in relation to power output (watts), oxygen uptake, and minute ventilation. Methods: Analysis of ostensibly healthy people aged ⩾40 years undergoing symptom-limited incremental cycle CPET (10 W/min) in the CanCOLD (Canadian Cohort Obstructive Lung Disease) study. Participants had smoking histories <5 pack-years and normal lung function and exercise capacity. The probability of each Borg 0-10 category ratio breathlessness intensity rating by power output, oxygen uptake, and minute ventilation (as an absolute or a relative value [percentage of predicted maximum]) was predicted using ordinal multinomial logistic regression. Model performance was evaluated by fit, calibration, and discrimination (C statistic) and externally validated in an independent sample (n = 86) of healthy Canadian adults. Results: We included 156 participants (43% women) from CanCOLD; the mean age was 65 (range, 42-91) years, and the mean body mass index was 26.3 (standard deviation, 3.8) kg/m2. Reference equations were developed for women and men separately, accounting for age and/or body mass. Model performance was high across all equations, including in the validation sample (C statistic for men = 0.81-0.92, C statistic for women = 0.81-0.96). Conclusions: Normative reference equations are provided to compare exertional breathlessness intensity ratings among individuals or groups and to identify and quantify abnormal breathlessness responses (scores greater than the upper limit of normal) during CPET.

Risk assessment of SWEN21 a suggested new dive table for the Swedish armed forces: bubble grades by ultrasonography.

Introduction: To develop the diving capacity in the Swedish armed forces the current air decompression tables are under revision. A new decompression table named SWEN21 has been created to have a projected risk level of 1% for decompression sickness (DCS) at the no stop limits. The aim of this study was to evaluate the safety of SWEN21 through the measurement of venous gas emboli (VGE) in a dive series. Methods: A total 154 dives were conducted by 47 divers in a hyperbaric wet chamber. As a proxy for DCS risk serial VGE measurements by echocardiography were conducted and graded according to the Eftedal-Brubakk scale. Measurements were done every 15 minutes for approximately 2 hours after each dive. Peak VGE grades for the different dive profiles were used in a Bayesian approach correlating VGE grade and risk of DCS. Symptoms of DCS were continually monitored. Results: The median (interquartile range) peak VGE grade after limb flexion for a majority of the time-depth combinations, and of SWEN21 as a whole, was 3 (3-4) with the exception of two decompression profiles which resulted in a grade of 3.5 (3-4) and 4 (4-4) respectively. The estimated risk of DCS in the Bayesian model varied between 4.7-11.1%. Three dives (2%) resulted in DCS. All symptoms resolved with hyperbaric oxygen treatment. Conclusions: This evaluation of the SWEN21 decompression table, using bubble formation measured with echocardiography, suggests that the risk of DCS may be higher than the projected 1%.

Measuring whole body inert gas wash-out.

Introduction: Quantifying inert gas wash-out is crucial to understanding the pathophysiology of decompression sickness. In this study, we developed a portable closed-circuit device for measuring inert gas wash-out and validated its precision and accuracy both with and without human subjects. Methods: We developed an exhalate monitor with sensors for volume, temperature, water vapor and oxygen. Inert gas volume was extrapolated from these inputs using the ideal gas law. The device's ability to detect volume differences while connected to a breathing machine was analysed by injecting a given gas volume eight times. One hundred and seventy-two coupled before-and-after measurements were then compared with a paired t-test. Drift in measured inert gas volume during unlabored breathing was evaluated in three subjects at rest using multilevel linear regression. A quasi-experimental cross-over study with the same subjects was conducted to evaluate the device's ability to detect inert gas changes in relation to diving interventions and simulate power. Results: The difference between the injected volume (1,996 ml) and the device's measured volume (1,986 ml) was -10 ml. The 95% confidence interval (CI) for the measured volume was 1,969 to 2,003 ml. Mean drift during a 43 min period of unlaboured breathing was -19 ml, (95% CI, -37 to -1). Our power simulation, based on a cross-over study design, determined a sample size of two subjects to detect a true mean difference of total inert gas wash-out volume of 100 ml. Conclusions: We present a portable device with acceptable precision and accuracy to measure inert gas wash-out differences that may be physiologically relevant in the pathophysiology of decompression sickness.

Which breathlessness dimensions associate most strongly with fatigue?-The population-based VASCOL study of elderly men.

BACKGROUND: Breathlessness and fatigue are common symptoms in older people. We aimed to evaluate how different breathlessness dimensions (overall intensity, unpleasantness, sensory descriptors, emotional responses) were associated with fatigue in elderly men. METHODS: This was a cross-sectional analysis of the population-based VAScular disease and Chronic Obstructive Lung Disease (VASCOL) study of 73-year old men. Breathlessness dimensions were assessed using the Dyspnoea-12 (D-12), Multidimensional Dyspnoea Profile (MDP), and the modified Medical Research Council (mMRC) scale. Fatigue was assessed using the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) questionnaire. Clinically relevant fatigue was defined as FACIT-F≤ 30 units. Scores were compared standardized as z-scores and analysed using linear regression, adjusted for body mass index, smoking, depression, cancer, sleep apnoea, prior cardiac surgery, respiratory and cardiovascular disease. RESULTS: Of 677 participants, 11.7% had clinically relevant fatigue. Higher breathlessness scores were associated with having worse fatigue; for D-12 total, -0.35 ([95% CI] -0.41 to -0.30) and for MDP A1, -0.24 (-0.30 to -0.18). Associations were similar across all the evaluated breathlessness dimensions even when adjusting for the potential confounders. CONCLUSION: Breathlessness assessed using D-12 and MDP was associated with worse fatigue in elderly men, similarly across different breathlessness dimensions.

The modified Medical Research Council scale misclassifies exertional breathlessness among people referred for exercise testing.

Background: Exertional breathlessness is a major symptom in cardiorespiratory disease and is often assessed using the modified Medical Research Council (mMRC) questionnaire. The mMRC might underestimate exertional breathlessness in people with impaired exercise capacity who have reduced their physical activity to avoid the symptom. We aimed to evaluate the ability of mMRC to detect abnormally high exertional breathlessness or abnormally low exercise capacity during incremental cycle exercise testing (IET). Methods: A secondary analysis of data from a randomised controlled trial of outpatients aged 18 years or older referred for IET was carried out. Participants completed the mMRC before IET. Abnormally high exertional breathlessness was defined as a breathlessness (Borg 0-10) intensity response more than the upper limit of normal. Abnormally low exercise capacity was defined using published reference equations. The sensitivity, specificity, accuracy and discriminative ability of each mMRC rating to detect each outcomewas calculated. Results: 92 participants were included; the mean age was 59 years, 61% were male, and 64% and 15% had mMRC 1 and ≥2, respectively. An mMRC ≥2 had the highest accuracy (71%) to detect abnormally high exertional breathlessness, with a specificity of 93% but a sensitivity of only 28%, failing to identify 72% of people with abnormally high exertional breathlessness. The accuracy, specificity and sensitivity for abnormally low exercise capacity was 64%, 88% and 19%, respectively. Conclusion: Among people referred for clinical exercise testing, the mMRC dyspnoea scale misclassified exertional breathlessness and exercise capacity assessed using cycle IET, with substantial underdetection. A mMRC dyspnoea rating of 0-1 does not preclude the presence of abnormally high exertional breathlessness or abnormally low exercise capacity.

Factors important for health-related quality of life in men and women: The population based SCAPIS study.

INTRODUCTION: Health-related quality of life (HRQoL) is essential for human wellbeing, influenced by a complex interplay of factors, and is reported lower in women than men. We aimed to evaluate which factors were the most important for HRQoL in a middle-aged general population. METHODS: This was a cross-sectional, multi-centre study of 29,212 men (48%) and women (52%) aged 50-64 in the general population in Sweden. Physical and mental HRQoL (0-100) was assessed using the Short Form 12 questionnaire, and association was evaluated for 356 variables including demographics, lifestyle, symptoms, physiological measurements, and health conditions. Using machine learning, each variable´s importance for HRQoL was measured by an importance score, comparable to effect size, and summarised in 54 factors, in men and women separately. RESULTS: Men and women had similar mean and standard deviation (SD) scores for physical HRQoL (53.4 [SD 8.1] vs 51.4 [9.7]) and mental HRQoL (37.1 [5.0] vs 37.3 [5.4]). The most important factors for physical HRQoL were (importance score) physical activity (40), employment (36), pain (33), sleep (33), and sense of control (26). The most important factors for mental HRQoL were sense of control (18), physical activity (12), depression (12), pain (6), and employment (5). CONCLUSIONS: The factors important for HRQoL identified by this study are likely to be amenable to interventions, and our findings can support prioritising interventions. The identified factors need to be a target even before middle-age to lay the foundation for long and happy lives.