Validity and Responsiveness of EQ-5D in Asthma: A Systematic Review and Meta-analysis.

OBJECTIVE: We aimed to synthesize the evidence on the construct validity and responsiveness of the EQ-5D and compare them with asthma-specific health-related quality-of-life scales, to guide further research and clinical applications in asthma. METHODS: We searched key databases from inception to 1 June, 2024 and used the COnsensus-based Standards for the Selection of Health Measurement Instruments (COSMIN) method to appraise the evidence. The effect size estimates were aggregated using the inverse variance method to evaluate the relative efficiency of EQ-5D measures against the Asthma Quality of Life Questionnaire (AQLQ) and/or its corresponding preference-based index, Asthma Quality of Life-5 Dimensions (AQL-5D). RESULTS: There were 493 tests (construct validity: 428; responsiveness: 65) drawn from 37 selected articles (validation: 7; clinical: 30). Overall, 78.4% and 76.9% of the a priori hypotheses for assessing construct validity (convergent validity: 56.4%; known groups: 88.5%) and responsiveness, respectively, were satisfied. The methodological quality was "very good" or "adequate" in 78.2% of construct validity tests and 92.3% of responsiveness tests. The pooled correlation coefficient between EQ-5D index and AQLQ total scores was 0.52 (95% confidence interval 0.43-0.59), and between EQ visual analog scale and AQLQ total scores was 0.53 (95% confidence interval 0.34-0.69). The Cohen's d ratios for the index, level sum scores, and visual analog scale compared to AQLQ were 0.56 (n = 27), 1.16 (n = 16), and 0.75 (n = 37). The EQ-5D index's Cohen's d ratio compared to AQL-5D was 0.49 (n = 5). The standardized response mean ratios for the index and visual analog scale compared to AQLQ were 0.26 (n = 11) and 0.63 (n = 9). CONCLUSIONS: The EQ-5D demonstrated overall good validity and responsiveness in the adult asthma population. However, a comparison against disease-specific instruments suggested scope for improvement in its psychometric performance for this population.

An Exploratory Study of Alternative Time Frames and Descriptors for EQ-5D-5L in Obstructive Airway Diseases Using Mixed Methods.

OBJECTIVES: EQ-5D-5L with its recall time of "today" may limit its ability to capture episodic symptoms and exacerbations in chronic obstructive airway diseases (OAD). We examined whether longer time frames and changing the intensity response scales to frequency scales could improve the measurement properties of EQ-5D-5L. METHODS: We used a mixed-method design starting with in-depth interviews with 20 patients and clinicians to elicit preferred time frames using concept elicitation techniques and content analyses. We then administered the top 4 preferred variants using 1- and 4-weeks' time frames with the original intensity or an alternative frequency response scale alongside EQ-5D-5L and St George Respiratory Questionnaire to OAD patients during 2 different visits. We compared the ceiling effects and construct validity by testing a priori hypotheses in relation to St George Respiratory Questionnaire and clinical outcomes via correlation and receiver operating characteristic (ROC) analyses, respectively. Follow-up patients were categorized into "better," "stable," and "worse" groups to assess reliability using intraclass correlation coefficient (ICC) or Cohen's Kappa (k) and responsiveness using ROC analysis. RESULTS: A total of 184 patients (mean [SD] age: 54[18]; female: 37.0%) completed baseline assessments. A total of 120 patients also completed follow-up assessments (mean [SD] interval: 2.8 [1.7] months). The ceilings were lower in the variants compared with EQ-5D-5L (P < .001). Reliability of the variants were comparable to or higher than EQ-5D-5L. The c-statistic values derived from ROC analyses of the variants were consistently higher than EQ-5D-5L. CONCLUSIONS: Use of longer time frames with the original intensity or the frequency response scales may improve EQ-5D-5L's psychometric properties in OAD patients.

Mandibular Advancement vs CPAP for Blood Pressure Reduction in Patients With Obstructive Sleep Apnea.

BACKGROUND: Hypertension guidelines recommend diagnosis and treatment of obstructive sleep apnea (OSA) in patients with hypertension. The mandibular advancement device (MAD) is an oral appliance therapy for patients who decline or cannot tolerate continuous positive airway pressure (CPAP). OBJECTIVES: We compared the relative effectiveness of MAD vs CPAP in reducing 24-hour ambulatory blood pressure (BP). METHODS: In an investigator-initiated, randomized, noninferiority trial (prespecified margin 1.5 mm Hg), 321 participants aged ≥40 years with hypertension and increased cardiovascular risk were recruited at 3 public hospitals for polysomnography. Of these, 220 participants with moderate-to-severe OSA (apnea-hypopnea index ≥15 events per hour) were randomized to either MAD or CPAP (1:1). The primary outcome was the difference between the 24-hour mean arterial BP at baseline and 6 months. RESULTS: Compared with baseline, the 24-hour mean arterial BP decreased by 2.5 mm Hg (P = 0.003) at 6 months in the MAD group, whereas no change was observed in the CPAP group (P = 0.374). The between-group difference was -1.6 mm Hg (95% CI: -3.51 to 0.24, noninferiority P < 0.001). The MAD group demonstrated a larger between-group reduction in all secondary ambulatory BP parameters compared with the CPAP group, with the most pronounced effects observed in the asleep BP parameters. Both the MAD and CPAP improved daytime sleepiness, with the between-group difference similar (P = 0.384). There were no between-group differences in cardiovascular biomarkers. CONCLUSIONS: MAD is noninferior to CPAP for reducing 24-hour mean arterial BP in participants with hypertension and increased cardiovascular risk. (Cardiosleep Research Program on Obstructive Sleep Apnea, Blood Pressure Control and Maladaptive Myocardial Remodeling-Non-inferiority Trial [CRESCENT]; NCT04119999).

Lived experience of patients with sleep apnea: a systematic synthesis of qualitative evidence.

BACKGROUND: Sleep apnea (SA) is a prevalent chronic disease with significant morbidity that negatively impacts a patient's perception of health and quality of life (QoL). OBJECTIVE: This review synthesized qualitative evidence on the experiences of patients living with SA to understand the disease's impacts on QoL. METHODS: We performed a systematic review of qualitative studies and searched eight electronic databases from inception dates to 22 September 2020. We analyzed the data using Sandelowski's proposed method of meta-synthesis, and applied Critical Appraisal Skills Program (CASP) and GRADE-Confidence in the Evidence from Reviews of Qualitative research (GRADE-CERQual) criteria to appraise the studies' qualities, and synthesized findings, respectively. RESULTS: Fourteen qualitative studies met the selection criteria. Four themes and 16 subthemes emerged: (1) sleep-related manifestations (n = 14) with four subthemes (sleep disruptors; sleepiness & napping; fatigue & low energy level; decreased cognition), (2) reduced psychological well-being and functioning (n = 14) with seven subthemes (anxiety & feeling vulnerable; hostility; sadness, sense of hopelessness & depression; embarrassment, shame & diminished self-concept; guilt & self-blame; maladaptive coping; self-stigma, (3) impaired physical and role functioning (n = 13) with three subthemes (reduced activities & routine disruption; reduced sexual activities & desire; reduced job performance & participation), (4) impaired social and relational functioning (n = 13) with two subthemes (strained interpersonal relationships; social isolation & loneliness). CONCLUSIONS: SA patients experienced sleep-disrupting symptoms and daytime sleepiness/fatigue which adversely impacted physical, psycho-cognitive, and social aspects of their lives in complex interactive ways. This understanding can help facilitate patient-centric care and develop comprehensive patient-reported measures to effect good health outcomes.

Obstructive sleep apnea during rapid eye movement sleep in patients after percutaneous coronary intervention: a multicenter study.

PURPOSE: Obstructive sleep apnea (OSA) during the rapid eye movement (REM) stage of the sleep cycle is associated with intense hypoxemia and cardiovascular instability. We characterized OSA during REM sleep in patients after percutaneous coronary intervention. METHODS: In this multicenter study, 204 patients who had undergone percutaneous coronary intervention in the prior 6 to 36 months were recruited for in-laboratory polysomnography. The primary measure was respiratory events during REM sleep. The patients were divided into 2 groups: (1) OSA during REM sleep (≥ 15 events/h) and (2) absence of OSA during REM sleep (< 15 events/h). RESULTS: Based on the overall apnea-hypopnea index ≥ 15, 148 patients (74.0%) had OSA. After excluding patients with failed polysomnography or REM sleep < 30 min, 163 patients formed the cohort for this analysis. OSA during REM sleep was diagnosed in 132 patients (81%). Compared with the patients without OSA during REM sleep, those with OSA during REM sleep had a higher body mass index (p = 0.003) and systolic blood pressure (p = 0.041), and a higher prevalence of diabetes mellitus (p = 0.029). Logistic regression analysis, including age, sex, diabetes mellitus, indication for percutaneous coronary intervention, and indication for multi-vessel percutaneous coronary intervention, showed that diabetes mellitus was the only independent predictor of OSA during REM sleep (odds ratio 2.83; 95% CI, 1.17 to 6.83; p = 0.021). CONCLUSION: In patients treated with percutaneous coronary intervention, there was a high prevalence of OSA during REM sleep. Diabetes mellitus was an independent predictor of OSA during REM sleep.

Screening and treatment of obstructive sleep apnea in acute coronary syndrome. A randomized clinical trial.

BACKGROUND: We evaluated the effects of sleep-study guided multidisciplinary therapy (SGMT) of obstructive sleep apnoea (OSA) in patients presenting with acute coronary syndrome. METHODS: Eligible patients were randomized into (1) SGMT, comprised a sleep study during the index admission and continuous positive airway pressure and behavioral therapy for those with at least mild OSA or (2) standard therapy. The primary end point was the change in the plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) level from baseline to the 7-month follow-up. RESULTS: A total of 159 patients completed the trial. Of the 70 patients randomized to SGMT, 21 (30%), 15 (22%) and 27 (39%) were diagnosed with mild, moderate and severe OSA, respectively. Continuous positive airway pressure and a positional pillow were prescribed to 57 (91%) and 6 (9%) patients with OSA. Although plasma NT-proBNP levels were lower after 7 months compared to the baseline, the levels did not differ significantly between the SGMT and standard therapy groups at baseline (579 ±â€¯1117 vs. 611 ±â€¯899 pg/dL, p = .851) or at 7 months (90 ±â€¯167 vs. 93 ±â€¯174 pg/dL, p = .996). The changes in NT-proBNP levels from baseline to 7 months were similar with SGMT and standard therapy (-489 vs. -518 pg/dL, p = .726). Similar findings were observed for the plasma ST2 and hs-CRP levels. CONCLUSIONS: OSA screening and multifaceted treatment during the sub-acute phase of acute coronary syndrome did not further reduce the levels of cardiovascular biomarkers when compared with standard therapy. CLINICAL TRIAL REGISTRATION: clinicaltrial.gov NCT02599298.

Prevalence of and factors associated with poor sleep quality and short sleep in a working population in Singapore.

OBJECTIVES: We aimed to examine the prevalence of poor sleep quality and short sleep and their associated factors in a working population in Singapore. DESIGN: This is a cross-sectional analysis. SETTING: Four companies in Singapore were included in this study. PARTICIPANTS: Participants included 464 full-time employees (aged ≥21 years). MEASUREMENTS: Self-reported sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI). Self-administered questionnaires were used to collect data on sociodemographic characteristics, health behaviours, medical history, chronotype, psychosocial factors, health-related quality of life (HRQoL) and occupational factors. Clinical measurements were performed using standard tools and protocols. Multivariate logistic regression was used to examine the factors associated with poor sleep quality (PSQI global score >5) and short sleep (<7 hours/night). RESULTS: The mean age was 39.0 (SD: 11.4) years, and 79.5% were men. The prevalence of poor sleep quality was 42.5%, and 66.2% were short sleepers. Nearly three-fourths (71.3%) had at least one of these two conditions. Age, Malay ethnicity (vs. Chinese), chronic conditions, poorer mental health, stress at home or work and shift work were positively associated, and mental component summary of the HRQoL scale and work years in the current company were negatively associated with poor sleep quality. Age, Malay and Indian ethnicities (vs. Chinese), longer dinner-to-bed time, snacking between dinner and bed time, and poorer mental health were positively associated with short sleep. CONCLUSIONS: Poor sleep quality and short sleep were highly common in this working population in Singapore. Workplace policies should include education and intervention programmes to promote better sleep hygiene.

Sleep study-guided multidisciplinary therapy (SGMT) for patients with acute coronary syndrome: Trial rationale and design.

Obstructive sleep apnea (OSA) is an emerging risk marker for acute coronary syndrome (ACS). This randomized trial aims to determine the effects of sleep study-guided multidisciplinary therapy (SGMT) comprising overnight sleep study, continuous positive airway pressure, and behavioral therapy for OSA during the subacute phase of ACS. We hypothesize that SGMT will reduce (1) the plasma levels of N-terminal pro brain natriuretic peptide and suppression of tumorigenicity 2; (2) the estimated 10-year risk of cardiovascular mortality as measured by the European Systematic Coronary Risk Evaluation (SCORE) algorithm; and (3) the cardiovascular event rate during a 3-year follow-up, compared with standard therapy. In the SGMT trial, 180 patients presenting with ACS will be randomly assigned to SGMT (n = 90) and standard therapy (n = 90) groups. Both groups will receive guideline-mandated treatment for ACS. Those assigned to SGMT will additionally undergo a sleep study and, if OSA is diagnosed, attend a multidisciplinary OSA clinic where they will receive personalized treatment including continuous positive airway pressure and behavioral/lifestyle counseling. The primary endpoint is the plasma N-terminal pro brain natriuretic peptide concentration at 7-month follow-up. This report presents the baseline characteristics of 117 patients (SGMT group: n =54; standard therapy group: n =63) who had been enrolled into the study as of August 31, 2017. The results of this trial will help us to understand whether active OSA diagnosis and treatment will improve the physiologic and clinical cardiovascular outcomes of this group of patients.

Sleep-disordered Breathing in Cardiac Rehabilitation: Prevalence, Predictors, and Influence on the Six-Minute Walk Test.

BACKGROUND: Identification of non-traditional risk factors is an important component of cardiac rehabilitation (CR). However, the prevalence and predictors of sleep-disordered breathing (SDB) and its influence on exercise performance in patients attending CR remain poorly described. METHODS: Patients enrolled in a national CR centre were eligible for a comprehensive SDB screening program. Screening questionnaires for SDB, overnight sleep study, and the 6-minute walk test (6MWT) were conducted. RESULTS: We recruited 332 patients (mean age 62±10 years, 62.4% male) attending CR for primary (29.2%) or secondary (70.8%) prevention, of which 209 successfully completed the overnight sleep study. Sleep-disordered breathing group patients (n=68, 32.5%) were older and had a higher body mass index (BMI) and neck and waist circumferences than the non-SDB group patients. After adjusting for neck and waist circumference, age (OR=1.06; 95% CI 1.02-1.10; p=0.001) and BMI (OR=1.19; 95% CI 1.10-1.30; p<0.001) remained independent predictors of SDB. A high risk of SDB based on the Berlin Questionnaire (43.4% versus 35.5%, p=0.277) or STOP-BANG questionnaire (63.2% versus 53.2%, p=0.170) and excessive daytime sleepiness (Epworth Sleepiness Scale >10, 23.9% versus 17.7%, p=0.297) were similar between the groups. The 6MWT scores were significantly lower in the SDB than non-SDB group (mean difference -32 m; 95% CI -57-7; p=0.013). The relationship was no longer significant after adjusting for age, sex, and waist circumference. CONCLUSION: Sleep-disordered breathing is prevalent in CR patients and is independently predicted by ageing and obesity. The association between SDB and poorer exercise performance may be explained by age, sex, and waist circumference.

Long-term continuous positive airway pressure therapy normalizes high exhaled nitric oxide levels in obstructive sleep apnea.

STUDY OBJECTIVES: Upper airway inflammation and oxidative stress have been implicated in the pathogenesis of obstructive sleep apnea (OSA) and may be linked to cardiovascular consequences. We prospectively examined fraction of exhaled nitric oxide (FENO), a surrogate marker of upper airway inflammation using a portable nitric oxide analyzer (NIOX MINO). DESIGN: In consecutive adult nonsmokers with suspected OSA, FENO was measured immediately before and after polysomnographic studies, and within 1-3 months following continuous positive airway pressure (CPAP) therapy. MEASUREMENT AND RESULTS: FENO levels were increased in the 75 patients with OSA compared to the 29 controls, both before sleep (13.4 ± 6.5 ppb vs. 6.5 ± 3.5; p < 0.001) and after sleep (19.0 ± 7.7 ppb vs. 6.9 ± 3.7; p < 0.001). Furthermore, in patients with OSA, FENO levels were significantly higher post-sleep than pre-sleep (19.0 ± 7.7 ppb vs. 13.4 ± 6.5; p < 0.001), while there was no significant overnight change in patients without OSA. The rise in FENO correlated with the apnea-hypopnea index (r = 0.65, p < 0.001), nadir oxygen saturation (r = 0.54, p < 0.001), and arousal index (r = 0.52, p < 0.001). Thirty-seven of these patients underwent CPAP titration and treatment. Successful titration was associated with a lower overnight increase in FENO (7.2 ± 3.3 vs. 11.0 ± 4.3, p = 0.02). FENO levels declined after 1-3 months of CPAP therapy (11.7 ± 4.4 ppb, p < 0.001). CONCLUSIONS: FENO levels are elevated in OSA, correlate with severity, and decrease after positive pressure therapy. This study supports the role of upper airway inflammation in OSA pathogenesis and a possible role for FENO in monitoring CPAP therapy.

The debate on CXR utilization and interpretation is only just beginning: a Pro/Con debate.

The CXR is the most commonly performed radiographic examination worldwide. Its ease of performance, apparent ease of interpretation and low radiation dose, alongside its great spatial resolution would suggest that it should be the first investigation performed in all patients presenting with thoracic disease. But, the advent of ever-improving multislice CT and increasing scanner availability has resulted in some patients being referred directly for scanning, bypassing the CXR. This has resulted in an inexorable rise in the number of scans performed, with an increase in patient radiation exposure and concerns among legislators and physicians that the number of scans needs to be regulated. A key role in the reduction of unnecessary scanning in patients with thoracic disease is the understanding of the place of the CXR, its ability to help in disease detection and monitoring, and its limitations.

Bronchial mucoepidermoid carcinoma.

We report a case of a minimally fluoro-2-deoxy-D-glucose avid bronchial mucoepidermoid tumor in a young male heavy smoker who presented with hemoptysis and a normal chest x-ray.