Mild obstructive sleep apnoea in females: post hoc analysis of the MERGE randomised controlled trial.

Background: A post hoc analysis of the MERGE trial was conducted, to investigate whether sex differences are evident at the mildest end of the disease spectrum, for symptoms associated with obstructive sleep apnoea (OSA) and the response to continuous positive airway pressure (CPAP) treatment. Methods: MERGE participants with mild OSA (apnoea-hypopnoea index 5-15 events·h-1; American Academy of Sleep Medicine 2012 criteria) were randomised to either CPAP plus standard care (sleep hygiene counselling) or standard care alone for 3 months. Quality of life (QoL) was measured by questionnaires completed before and after the 3 months. This post hoc analysis of participants of the MERGE trial compared the symptom presentation, and response to CPAP, between the sexes. Results: 233 patients were included; 71 (30%) were female. Females were more symptomatic at baseline in all QoL questionnaires. Specifically, females had lower 36-item Short-Form Health Survey (SF-36) Vitality scores (mean±sd 39.1±10.1 versus 44.8±10.3) and higher Epworth Sleepiness Scale (ESS) scores (mean±sd 11.0±4.2 versus 9.5±4.4). Both sexes experienced snoring, but more females reported fatigue and more males reported witnessed apnoeas. All symptoms improved with CPAP for both sexes; however, females had larger improvements in SF-36 Vitality scores, which was the primary outcome of the MERGE trial (mean change 9.4 (95% CI 6.8-12.0) versus 6.0 (95% CI 4.3-7.7); p=0.034), and ESS (mean change -4.1 (95% CI -5.1- -3.0) versus -2.5 (95% CI -3.1- -1.8); p=0.015), after adjustment for baseline scores and CPAP usage. Conclusions: Sex differences are apparent in patients with mild OSA. Females experience worse QoL symptoms than males at presentation to the sleep clinic; however, these improve significantly with CPAP treatment.

Efficacy of vibrotactile positional therapy devices on patients with positional obstructive sleep apnoea: a systematic review and meta-analysis.

INTRODUCTION: Vibrotactile positional therapy (PT) devices are a new treatment modality for positional obstructive sleep apnoea (POSA). This review aimed to determine the effect of vibrotactile PT on the Apnoea Hypopnoea Index (AHI) and the percentage of time spent in the supine position (%Tsupine) in patients with POSA, compared with baseline. Secondary aims were to investigate the effect on daytime sleepiness, quality of life and sleep quality. METHODS: A systematic review and meta-analysis was performed of randomised controlled trials (RCTs) and cohort studies that investigated the effect of vibrotactile PT in POSA patients. Searches were performed via MEDLINE, CENTRAL and Embase up to 29 October 2022. RESULTS: 1119 studies were identified, 18 studies met the inclusion criteria (10 RCTs, 8 cohort studies). The use of vibrotactile PT significantly reduced the AHI at follow-up compared with baseline (mean difference (95% CI) -9.19 events/hour (-11.68 to -6.70); p<0.00001). The mean %Tsupine was also significantly reduced (mean difference (95% CI) -32.79% (-38.75% to -26.83%); p<0.00001). The percentage changes in the AHI and %Tsupine were 43% and 70%, respectively. Secondary outcomes were daytime sleepiness, quality of life and sleep indices. These showed minimal change, although follow-up was short. CONCLUSION: Vibrotactile PT devices are effective in treating POSA; reducing both AHI and %Tsupine. The effect on sleep quality, daytime sleepiness and disease-specific quality of life was minimal. However, there were limited data and follow-up was often brief, meaning that further research is needed to determine the effect of vibrotactile PT on patient-centred outcomes. PROSPERO REGISTRATION NUMBER: CRD42020188617.

Reasons for Long-term Opioid Prescriptions After Guideline-directed Opioid Prescribing and Excess Opioid Pill Disposal.

OBJECTIVES: The aim of this study was to determine the frequency and reasons for long-term opioid prescriptions (rxs) after surgery in the setting of guideline-directed prescribing and a high rate of excess opioid disposal. BACKGROUND: Although previous studies have demonstrated that 5% to 10% of opioid-naïve patients prescribed opioids after surgery will receive long-term (3-12 months after surgery) opioid rxs, little is known about the reasons why long-term opioids are prescribed. METHODS: We studied 221 opioid-naïve surgical patients enrolled in a previously reported prospective clinical trial which used a patient-centric guideline for discharge opioid prescribing and achieved a high rate of excess opioid disposal. Patients were treated on a wide variety of services; 88% of individuals underwent cancer-related surgery. Long-term opioid rxs were identified using a Prescription Drug Monitoring Program search and reasons for rxs and opioid adverse events were ascertained by medical record review. We used a consensus definition for persistent opioid use: opioid rx 3 to 12 months after surgery and >60day supply. RESULTS: 15.3% (34/221) filled an opioid rx 3 to 12 months after surgery, with 5.4% and 12.2% filling an rx 3 to 6 and 6 to 12 months after surgery, respectively. The median opioid rx days supply per patient was 7, interquartile range 5 to 27, range 1 to 447 days. The reasons for long-term opioid rxs were: 51% new painful medical condition, 40% new surgery, 6% related to the index operation; only 1 patient on 1 occasion was given an opioid rx for a nonspecific reason. Five patients (2.3%) developed persistent opioid use, 2 due to pain from recurrent cancer, 2 for new medical conditions, and 1 for a chronic abscess. CONCLUSIONS: In a group of prospectively studied opioid-naïve surgical patients discharged with guideline-directed opioid rxs and who achieved high rates of excess opioid disposal, no patients became persistent opioid users solely as a result of the opioid rx given after their index surgery. Long-term opioid use did occur for other, well-defined, medical or surgical reasons.

Virtual consultations for patients with obstructive sleep apnoea: a systematic review and meta-analysis.

BACKGROUND: The coronavirus disease 2019 pandemic has accelerated the adoption of virtual care strategies for the management of patients with obstructive sleep apnoea/hypopnoea syndrome (OSAHS). RESEARCH QUESTION: What is the effectiveness of virtual consultations compared to in-person consultations for the management of continuous positive airway pressure (CPAP) therapy in adult patients with OSAHS? METHODS: A systematic review and meta-analysis (PROSPERO; CRD42022297532) based on six electronic databases plus manually selected journals was conducted in January 2022. Two researchers independently selected, quality appraised and extracted data. The co-primary outcomes were patient-reported sleepiness, assessed by the Epworth Sleepiness Scale (ESS), and reported cost-effectiveness. RESULTS: 12 studies (n=1823 adults) were included in the review. Seven studies (n=1089) were included in the meta-analysis which showed no difference in the magnitude of improvement in patient-reported sleepiness scores between virtual and in-person consultations (mean difference -0.39, 95% CI -1.38-0.60; p=0.4), although ESS scores improved in both groups. Virtual care strategies modestly increased CPAP therapy adherence and were found to be less costly than in-person care strategies in the three Spanish trials that reported cost-effectiveness. CONCLUSION: The findings of this review suggest that virtual care delivered by telephone or video consultations is as effective as in-person consultations for improving subjective sleepiness in patients with OSAHS treated with CPAP. This clinical management strategy may also improve CPAP adherence without increasing the costs, supporting its potential as a follow-up management strategy, where patients prefer this approach.

Diagnosis of Sleep Apnoea Using a Mandibular Monitor and Machine Learning Analysis: One-Night Agreement Compared to in-Home Polysomnography.

Background: The capacity to diagnose obstructive sleep apnoea (OSA) must be expanded to meet an estimated disease burden of nearly one billion people worldwide. Validated alternatives to the gold standard polysomnography (PSG) will improve access to testing and treatment. This study aimed to evaluate the diagnosis of OSA, using measurements of mandibular movement (MM) combined with automated machine learning analysis, compared to in-home PSG. Methods: 40 suspected OSA patients underwent single overnight in-home sleep testing with PSG (Nox A1, ResMed, Australia) and simultaneous MM monitoring (Sunrise, Sunrise SA, Belgium). PSG recordings were manually analysed by two expert sleep centres (Grenoble and London); MM analysis was automated. The Obstructive Respiratory Disturbance Index calculated from the MM monitoring (MM-ORDI) was compared to the PSG (PSG-ORDI) using intraclass correlation coefficient and Bland-Altman analysis. Receiver operating characteristic curves (ROC) were constructed to optimise the diagnostic performance of the MM monitor at different PSG-ORDI thresholds (5, 15, and 30 events/hour). Results: 31 patients were included in the analysis (58% men; mean (SD) age: 48 (15) years; BMI: 30.4 (7.6) kg/m2). Good agreement was observed between MM-ORDI and PSG-ORDI (median bias 0.00; 95% CI -23.25 to + 9.73 events/hour). However, for 15 patients with no or mild OSA, MM monitoring overestimated disease severity (PSG-ORDI < 5: MM-ORDI mean overestimation + 5.58 (95% CI + 2.03 to + 7.46) events/hour; PSG-ORDI > 5-15: MM-ORDI overestimation + 3.70 (95% CI -0.53 to + 18.32) events/hour). In 16 patients with moderate-severe OSA (n = 9 with PSG-ORDI 15-30 events/h and n = 7 with a PSG-ORD > 30 events/h), there was an underestimation (PSG-ORDI > 15: MM-ORDI underestimation -8.70 (95% CI -28.46 to + 4.01) events/hour). ROC optimal cut-off values for PSG-ORDI thresholds of 5, 15, 30 events/hour were: 9.53, 12.65 and 24.81 events/hour, respectively. These cut-off values yielded a sensitivity of 88, 100 and 79%, and a specificity of 100, 75, 96%. The positive predictive values were: 100, 80, 95% and the negative predictive values 89, 100, 82%, respectively. Conclusion: The diagnosis of OSA, using MM with machine learning analysis, is comparable to manually scored in-home PSG. Therefore, this novel monitor could be a convenient diagnostic tool that can easily be used in the patients' own home. Clinical Trial Registration: https://clinicaltrials.gov, identifier NCT04262557.

Nasal versus oronasal masks for home non-invasive ventilation in patients with chronic hypercapnia: a systematic review and individual participant data meta-analysis.

BACKGROUND: The optimal interface for the delivery of home non-invasive ventilation (NIV) to treat chronic respiratory failure has not yet been determined. The aim of this individual participant data (IPD) meta-analysis was to compare the effect of nasal and oronasal masks on treatment efficacy and adherence in patients with COPD and obesity hypoventilation syndrome (OHS). METHODS: We searched Medline and Cochrane Central Register of Controlled Trials for prospective randomised controlled trials (RCTs) of at least 1 month's duration, published between January 1994 and April 2019, that assessed NIV efficacy in patients with OHS and COPD. The main outcomes were diurnal PaCO2, PaO2 and NIV adherence (PROSPERO CRD42019132398). FINDINGS: Of 1576 articles identified, 34 RCTs met the inclusion criteria and IPD were obtained for 18. Ten RCTs were excluded because only one type of mask was used, or mask data were missing. Data from 8 RCTs, including 290 IPD, underwent meta-analysis. Oronasal masks were used in 86% of cases. There were no differences between oronasal and nasal masks for PaCO2 (0.61 mm Hg (95% CI -2.15 to 3.38); p=0.68), PaO2 (-0.00 mm Hg (95% CI -4.59 to 4.58); p=1) or NIV adherence (0·29 hour/day (95% CI -0.74 to 1.32); p=0.58). There was no interaction between the underlying pathology and the effect of mask type on any outcome. INTERPRETATION: Oronasal masks are the most used interface for the delivery of home NIV in patients with OHS and COPD; however, there is no difference in the efficacy or tolerance of oronasal or nasal masks.

Guidelines for Patient-CenteredOpioid Prescribing and Optimal FDA-Compliant Disposal of Excess Pills after Inpatient Operation: Prospective Clinical Trial.

BACKGROUND: To optimize responsible opioid prescribing after inpatient operation, we implemented a clinical trial with the following objectives: prospectively validate patient-centered opioid prescription guidelines and increase the FDA-compliant disposal rate of leftover opioid pills to higher than currently reported rates of 20% to 30%. STUDY DESIGN: We prospectively enrolled 229 patients admitted for 48 hours or longer after elective general, colorectal, urologic, gynecologic, or thoracic operation. At discharge, patients received a prescription for both nonopioid analgesics and opioids based on their opioid usage the day before discharge: if 0 oral morphine milligram equivalents (MME) were used, then five 5-mg oxycodone pill-equivalents were prescribed; if 1 to 29 MME were used, then fifteen 5-mg oxycodone pill-equivalents were prescribed; if 30 or more MME were used, then thirty 5-mg oxycodone pill-equivalents were prescribed. We considered patients' opioid pain medication needs to be satisfied if no opioid refills were obtained. To improve FDA-compliant disposal of leftover pills, we implemented patient education, convenient drop-box, reminder phone call, and questionnaire. RESULTS: Our opioid guideline satisfied 93% (213 of 229) of patients. Satisfaction was significantly higher in lower opioid usage groups (p = 0.001): 99% (99 of 100) in the 0 MME group, 90% (91 of 101) in the 1 to 29 MME group, and 82% (23 of 28) in the 30 or more MME group. Overall, 95% (217 of 229) of patients used nonopioid analgesics. Sixty percent (138 of 229) had leftover pills; 83% (114 of 138) disposed of them using an FDA-compliant method and 51% (58 of 114) used the convenient drop-box. Of 2,604 prescribed pills, only 187 (7%) were kept by patients. CONCLUSIONS: This clinical trial prospectively validated a patient-centered opioid discharge prescription guideline that satisfied 93% of patients. FDA-compliant disposal of excess pills was achieved in 83% of patients with easily actionable interventions.

Reducing Unnecessary Chest X-Ray Films After Thoracic Surgery: A Quality Improvement Initiative.

BACKGROUND: Previous work has identified that inpatient post-thoracic surgery chest x-ray films (CXR) are overutilized. METHODS: A three-phase rapid cycle quality improvement initiative was performed to reduce empiric post-thoracic surgery CXR use by 25% over 1 year. We adapted evidence-based guidelines and implemented "plan-do-study-act" (PDSA) cycle methodology. The PDSA cycles included (1) education with literature and preintervention statistics; (2) electronic medical record order-set modification; and (3) audit and feedback with monthly status reports. Each cycle lasted 3 months. Use of CXR was tracked in the post-anesthesia care unit and as a daily rate of non-post-anesthesia care unit CXRs. Cost data were estimated from Centers for Medicare & Medicaid Services fees. RESULTS: During the initiative, 292 thoracic surgery inpatients were monitored. Before intervention, 99% of patients (69 of 70) received a post-anesthesia care unit CXR, and the daily rate of other CXRs was 1.6. Overall, there was a significant reduction in CXR utilization (P < .001). Post-anesthesia care unit CXRs decreased by 42%, lowering to 89% (68 of 76) to 68% (50 of 74) to 57% (41 of 72) in PDSA cycles 1 through 3, respectively. The daily rate of other CXRs decreased by 38%, lowering to 1.4 to 1.3 to 1.0. Patient perioperative characteristics and health care quality measures were not different between cycles. After quality improvement implementation, cost savings were estimated to be at least $73,292 per year. CONCLUSIONS: Implementation of our quality improvement initiative safely and systematically reduced empiric CXR use after inpatient thoracic surgery. Results will be used in future quality improvement initiatives to reduce unnecessary postoperative testing.

Continuous positive airway pressure versus standard care for the treatment of people with mild obstructive sleep apnoea (MERGE): a multicentre, randomised controlled trial.

BACKGROUND: The evidence base for the treatment of mild obstructive sleep apnoea is limited and definitions of disease severity vary. The MERGE trial investigated the clinical effectiveness of continuous positive airway pressure in patients with mild obstructive sleep apnoea. METHODS: MERGE, a multicentre, parallel, randomised controlled trial enrolled patients (≥18 years to ≤80 years) with mild obstructive sleep apnoea (apnoea-hypopnoea index [AHI] ≥5 to ≤15 events per h using either AASM 2007 or AASM 2012 scoring criteria) from 11 UK sleep centres. Participants were assigned (1:1) to either 3 months of continuous positive airway pressure plus standard care (sleep counselling), or standard care alone, by computer-generated randomisation; neither participants nor researchers were blinded. The primary outcome was a change in the score on the Short Form-36 questionnaire vitality scale in the intention-to-treat population of patients with mild obstructive sleep apnoea diagnosed using the American Academy of Sleep Medicine 2012 scoring criteria. The study is registered with ClinicalTrials.gov, NCT02699463. FINDINGS: Between Nov 28, 2016 and Feb 12, 2019, 301 patients were recruited and randomised. 233 had mild obstructive sleep apnoea using AASM 2012 criteria and were included in the intention-to-treat analysis: 115 were allocated to receive continuous positive airway pressure and 118 to receive standard care. 209 (90%) of these participants completed the trial. The vitality score significantly increased with a treatment effect of a mean of 10·0 points (95% CI 7·2-12·8; p<0·0001) after 3 months of continuous positive airway pressure, compared with standard care alone (9·2 points [6·8 to 11·6] vs -0·8 points [-3·2 to 1·5]). Using the ANCOVA last-observation-carried-forward analysis, a more conservative estimate, the vitality score also significantly increased with a treatment effect of a mean of 7·5 points (95% CI 5·3 to 9·6; p<0·0001) after 3 months of continuous positive airway pressure, compared with standard care alone (7·5 points [6·0 to 9·0] vs 0·0 points [-1·5 to 1·5]). Three serious adverse events occurred (one allocated to the continuous positive airway pressure group) and all were unrelated to the intervention. INTERPRETATION: 3 months of treatment with continuous positive airway pressure improved the quality of life in patients with mild obstructive sleep apnoea. These results highlight the need for health-care professionals and providers to consider treatment for patients with mild obstructive sleep apnoea. FUNDING: ResMed Ltd.

Association of Decreased Postsurgical Opioid Prescribing With Patients' Satisfaction With Surgeons.

Importance: Opioid overdose is the leading cause of injury-related death in the United States. Several studies have shown that surgeons overprescribe opioids, and guidelines for appropriate opioid prescribing are available. Concern about patient-reported satisfaction scores may be a barrier to surgeons adopting guideline-directed prescribing. Objective: To determine whether decreased opioid prescribing is associated with a decrease in patient-reported satisfaction with their surgeon. Design, Setting, and Participants: Retrospective analysis of clinician satisfaction scores at Dartmouth-Hitchcock Medical Center obtained in 2 periods: 1 before (period A) and 1 after (period B) an educational intervention that resulted in decreased opioid prescribing. The analysis included 11 surgeons who performed 5 common outpatient general surgical operations on 996 patients. Data were analyzed between March and August 2018. Main Outcomes and Measures: Patient-reported overall satisfaction rating of the surgeon (scale, 0-10). This was collected by a nonstudy-related, routine general institutional survey of approximately 40% of all outpatient encounters. Results: Of the total number of patients, 67% were women (667 of 996), and the mean patient age was 58 years. Comparing period A with B, the proportion of patients prescribed opioids decreased from 90.2% (n = 367 of 407) to 72.8% (n = 429 of 589) (P < .001). The mean number of opioid pills per prescription decreased from 28.3 to 13.3 (P < .001) and significantly decreased for each of the 11 surgeons. One hundred five of 996 patients (10.5%) undergoing index operations responded to the survey. There was no difference in the mean clinician satisfaction ratings from period A vs B (9.70 vs 9.65; P = .69). During the study periods, 640 total surveys were collected referencing these surgeons (including outpatient encounters associated with operations other than the 5 index cases). There was no difference in the mean satisfaction ratings from period A vs period B (9.55 vs 9.59; P = .62). When individual clinicians were analyzed, none had a significant difference in overall satisfaction rating from period A vs period B. Conclusions and Relevance: Despite a marked decrease in the proportion of patients receiving opioids and in the number of pills prescribed, there was no significant change in clinician satisfaction ratings.

Association of the Use of a Mandatory Prescription Drug Monitoring Program With Prescribing Practices for Patients Undergoing Elective Surgery.

Importance: Most states have adopted the routine use of a prescription drug monitoring program (PDMP) to curb overprescribing of opioids. The American College of Surgeons promotes the use of these programs as a "guiding principle to curb the opioid epidemic." However, there is a paucity of data on the effects of the use of these programs for surgical patient populations. Objective: To determine the association of the mandatory use of a PDMP with the opioid prescribing practices for patients undergoing general surgery. Design, Setting, and Participants: A prospective observational cohort study was conducted at an academic hospital in New Hampshire among 1057 patients undergoing representative elective general surgical procedures from July 1, 2016, to June 30, 2017. Exposures: New state legislation mandated the use of a PDMP and opioid risk-assessment tool for all patients receiving an outpatient opioid prescription in New Hampshire beginning January 1, 2017. The electronic medical prescribing system was modified to facilitate and support compliance with the new requirements. Main Outcomes and Measures: Change in opioid prescribing practices after January 1, 2017, and time to complete PDMP requirements. Results: Among the 1057 patients (569 women [53.8%] and 488 men [46.2%]; mean [SD] age, 56.8 [15.4] years), the percentage of patients prescribed opioids after surgery did not decrease significantly (429 of 536 [80.0%] before the new requirements vs 401 of 521 [77.0%] after the requirements; P = .29). The mean number of opioid pills prescribed decreased from 30.8 to 24.0 (22.1%) in the 6 months prior to the mandatory PDMP requirement; the rate of decrease was actually less (from 22.8 to 21.9 pills [3.9%]) in the 6 months after the legislation. These new requirements did not identify any high-risk patients who subsequently were not prescribed opioids. The query and opioid abuse risk calculator together took a median time of 7 minutes (range, 2-17 minutes) to complete. Conclusions and Relevance: A mandatory PDMP query requirement was not significantly associated with the overall rate of opioid prescribing or the mean number of pills prescribed for patients undergoing general surgical procedures. In no cases was a high-risk patient identified, leading to avoidance of an opioid prescription. A PDMP can be a useful adjunct in certain settings, but this study found that it did not have the intended effect in a population undergoing elective surgical procedures. Legislative efforts to mandate PDMP use should be targeted to populations in which benefit can be demonstrated.

Guideline for Discharge Opioid Prescriptions after Inpatient General Surgical Procedures.

BACKGROUND: There is a paucity of data to inform appropriate opioid prescribing for patients who are discharged after a hospital admission for a surgical procedure. STUDY DESIGN: We studied 333 inpatients discharged to home after bariatric, benign foregut, liver, pancreas, ventral hernia, and colon surgery. Chronic opioid users or patients who had complications were excluded. Home opioid usage was quantified in 90% of the remaining patients by questionnaires and phone surveys. RESULTS: Eighty-five percent of patients were prescribed an opioid and 38% of prescribed opioid pills were taken. Fifteen opioid pills satisfied the opioid needs of 88% of patients discharged on postoperative day (POD) 1. For patients discharged after POD 1, in multivariate analysis, the number of opioid pills used at home was associated with the number taken the day before discharge (p < 0.0001) and patient age (p = 0.006), but not the type of surgery. Forty-one percent of patients took no opioids the day before discharge, 33% took 1 to 3, and 26% took more than 4 pills. Eighty-five percent of patients' home opioid requirements would be satisfied using the following guideline: if no opioid pills are taken the day before discharge, no prescription is needed; if 1 to 3 opioid pills are taken the day before discharge, then a prescription for 15 opioid pills is given at discharge; and if 4 or more pills are taken the day before discharge, then a prescription for 30 opioid pills is given at discharge. If these guidelines were used, the number of opioid pills prescribed would decrease by 40%. CONCLUSIONS: For patients admitted after surgical procedures, post-discharge opioid use is best predicted by usage the day before discharge. Use of this guideline could decrease opioid prescriptions substantially and effectively treat patients' pain.

Redefining Cut-Points for High Symptom Burden of the Global Initiative for Chronic Obstructive Lung Disease Classification in 18,577 Patients With Chronic Obstructive Pulmonary Disease.

BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) can be classified into groups A/C or B/D based on symptom intensity. Different threshold values for symptom questionnaires can result in misclassification and, in turn, different treatment recommendations. The primary aim was to find the best fitting cut-points for Global initiative for chronic Obstructive Lung Disease (GOLD) symptom measures, with an modified Medical Research Council dyspnea grade of 2 or higher as point of reference. METHODS: After a computerized search, data from 41 cohorts and whose authors agreed to provide data were pooled. COPD studies were eligible for analyses if they included, at least age, sex, postbronchodilator spirometry, modified Medical Research Council, and COPD Assessment Test (CAT) total scores. MAIN OUTCOMES: Receiver operating characteristic curves and the Youden index were used to determine the best calibration threshold for CAT, COPD Clinical Questionnaire, and St. Georges Respiratory Questionnaire total scores. Following, GOLD A/B/C/D frequencies were calculated based on current cut-points and the newly derived cut-points. FINDINGS: A total of 18,577 patients with COPD [72.0% male; mean age: 66.3 years (standard deviation 9.6)] were analyzed. Most patients had a moderate or severe degree of airflow limitation (GOLD spirometric grade 1, 10.9%; grade 2, 46.6%; grade 3, 32.4%; and grade 4, 10.3%). The best calibration threshold for CAT total score was 18 points, for COPD Clinical Questionnaire total score 1.9 points, and for St. Georges Respiratory Questionnaire total score 46.0 points. CONCLUSIONS: The application of these new cut-points would reclassify about one-third of the patients with COPD and, thus, would impact on individual disease management. Further validation in prospective studies of these new values are needed.

Randomized trial of 'intelligent' autotitrating ventilation versus standard pressure support non-invasive ventilation: impact on adherence and physiological outcomes.

BACKGROUND AND OBJECTIVE: Effective non-invasive ventilation (NIV) therapy is dependent on optimal ventilator settings to maximize clinical benefit and patient tolerance. Intelligent volume-assured pressure support (iVAPS) is a hybrid mode of servoventilation, providing constant automatic adjustment of pressure support (PS) to achieve a target ventilation determined by the patient's requirements. In a randomized crossover trial, we tested the hypothesis that iVAPS, with automated selection of ventilator settings, was non-inferior to standard PS ventilation, with settings determined by an experienced health-care professional, for controlling nocturnal hypoventilation in patients naive to NIV. METHODS: Eighteen patients referred to a ventilator clinic with chronic obstructive or restrictive lung disease and newly diagnosed nocturnal hypoventilation (10 male, median (interquartile range): age 54(41-61) years, mean daytime PaO2 9.25(8.59-10.31) kPa, -PaCO2 6.38(5.93-6.65) kPa were randomized to iVAPS and standard PS. Polysomnography with transcutaneous CO2 monitoring was performed at baseline and 1 month after each treatment period. Nightly hours of therapy were recorded by the ventilator. RESULTS: iVAPS delivered a lower median PS compared with standard PS (8.3(5.6-10.4) vs 10.0(9.0-11.4) cmH2 O; P = 0.001) for the same ventilatory outcome (mean overnight: SpO2 96(95-98) vs 96(93-97)%; P = 0.13 and PtcCO2 6.5(5.8-6.8) vs 6.2(5.8-6.9); P = 0.54). There was no difference in outcome between ventilator modes for spirometry, respiratory muscle strength, sleep quality, arousals or O2 desaturation index. Adherence was greater with iVAPS (5:40(4:42-6:49) vs 4:20(2:27-6:17) hh:mm/night; P = 0.004). CONCLUSIONS: iVAPS servoventilation with automation of ventilation settings is as effective as PS ventilation initiated by a skilled health-care professional in controlling nocturnal hypoventilation and produced better overnight adherence in patients naive to NIV.

Patent foramen ovale is not associated with hypoxemia in severe chronic obstructive pulmonary disease and does not impair exercise performance.

RATIONALE: Patent foramen ovale (PFO) may be disadvantageous in chronic obstructive pulmonary disease (COPD). It is unknown whether right-to-left shunting through PFO increases during exercise impairing exercise performance. OBJECTIVES: To determine whether (1) PFO prevalence is greater in hypoxemic versus less hypoxemic patients with COPD, (2) PFO is associated with clinically relevant impairment, and (3) right-to-left shunting increases during exercise and impairs exercise performance. METHODS: Patients with COPD and age-matched control subjects underwent contrast transthoracic echocardiography and transcranial Doppler to identify PFO. Patients with COPD with no shunt and patients with large PFO underwent cardiopulmonary exercise tests with contrast transcranial Doppler, esophageal, and gastric balloon catheters. MEASUREMENTS AND MAIN RESULTS: PFO prevalence was similar in 50 patients with COPD and 50 healthy control subjects (46% vs. 30%; P = 0.15). Large shunts were more common in patients with COPD (26% vs. 6%; P = 0.01). In an expanded COPD cohort, PFO prevalence was similar in 31 hypoxemic (Pao2 ≤ 7.3 kPa) and 63 less hypoxemic (Pao2 > 8.0 kPa) patients with COPD (39% vs. 52%; P = 0.27). Patients with intrapulmonary shunting had lower Pao2 than both patients with PFO and those with no right-to-left shunt (7.7 vs. 8.6 vs. 9.3 kPa, respectively; P = 0.002). Shunting significantly increased during exercise in patients with COPD with PFO. Endurance time at 60% Vo2max was 574 (178) seconds for patients with PFO and 534 (279) seconds for those without (P = ns). CONCLUSIONS: Hypoxemic patients with COPD do not have a higher prevalence of PFO. Patients with COPD with PFO do not perform less well either on a 6-minute walk or submaximal exercise testing despite increased right-to-left shunting during exercise.

Breathlessness and skeletal muscle weakness in patients undergoing lung health screening in primary care.

Earlier diagnosis of COPD is a major public health challenge as symptoms may be attributed to the normal consequences of aging. The optimum strategy for identifying patients with COPD remains to be determined. People aged 35 and over (n = 1896) on a GP practice register were randomised to either invitation or an opportunistic lung health check which included spirometry, quadriceps strength and MRC dyspnoea score. Then, 101 participants subsequently completed the General Practice Physical Activity Questionnaire. A total of 335 attended over a 15-week period; 156 were in the invitation group and 179 from the opportunist group. In 25 persons, spirometry was unsatisfactory or contraindicated. Spirometry was normal in 204(65.8%) and restrictive in 36(11.6%). 70(22.6%) had airflow obstruction, corresponding to Global Initiative for Chronic Lung Disease (GOLD) stages I-IV in 18(5.8%), 35(11.3%), 14(4.5%) and 3(1.0%), respectively. The opportunist group were significantly more likely to have airflow obstruction 30.1% vs 14.3% (p = 0.001). Breathlessness was reported commonly (40.5%) and quadriceps strength correlated significantly with MRC dyspnoea score independent of age, sex, pack-years smoked, fat-free mass and FEV(1) percent predicted. This relationship was also present in the subgroup of healthy participants (n = 143). 51.5% of participants screened were classified as "inactive" and this group were weaker and more breathless than those who were more active. Airflow obstruction was more common in those screened opportunistically. Breathlessness and inactivity are common in patients taking part in spirometry screening. Breathlessness is significantly associated with leg strength independent of spirometry and should be amenable to interventions to increase physical activity.

Lung function indices for predicting mortality in COPD.

Chronic obstructive pulmonary disease (COPD) is characterised by high morbidity and mortality. It remains unknown which aspect of lung function carries the most prognostic information and if simple spirometry is sufficient. Survival was assessed in COPD outpatients whose data had been added prospectively to a clinical audit database from the point of first full lung function testing including spirometry, lung volumes, gas transfer and arterial blood gases. Variables univariately associated with survival were entered into a multivariate Cox proportional hazard model. 604 patients were included (mean ± SD age 61.9 ± 9.7 years; forced expiratory volume in 1 s 37 ± 18.1% predicted; 62.9% males); 229 (37.9%) died during a median follow-up of 83 months. Median survival was 91.9 (95% CI 80.8-103) months with survival rates at 3 and 5 years 0.83 and 0.66, respectively. Carbon monoxide transfer factor % pred quartiles (best quartile (>51%): HR 0.33, 95% CI 0.172-0.639; and second quartile (51-37.3%): HR 0.52, 95% CI 0.322-0.825; versus lowest quartile (<27.9%)), age (HR 1.04, 95% CI 1.02-1.06) and arterial oxygen partial pressure (HR 0.85, 95% CI 0.77-0.94) were the only parameters independently associated with mortality. Measurement of gas transfer provides additional prognostic information compared to spirometry in patients under hospital follow-up and could be considered routinely.

Vitamin D and skeletal muscle strength and endurance in COPD.

It is not known whether vitamin D levels make a significant contribution to muscle dysfunction in chronic obstructive pulmonary disease (COPD). In 104 COPD patients (mean±sd forced expiratory volume in 1 s 44±22 % predicted) and 100 age- and sex-matched controls, serum 25-hydroxyvitamin D (25(OH)D), 1,25-dihydroxyvitamin D (1,25(OH)(2)D) and parathyroid hormone (PTH) levels were measured and related to quadriceps strength and endurance. In a subset of 26 patients and 13 controls, quadriceps biopsy was performed and mRNA expression of myogenic regulatory factors (mrf) and fibre-specific myosin heavy chains (MHC) was determined. COPD patients were weaker and less physically active than controls. 25(OH)D levels were similar in both groups (48.5±25.5 nmol·L(-1) COPD versus 55.4±28.3 nmol·L(-1) control, p=0.07) but PTH levels were significantly higher in patients (5.2±2.3 pmol·mL(-1) versus 4.4±2.0 pmol·L(-1), p=0.01). 1,25(OH)D was significantly correlated with strength in controls, but not in COPD patients and not with quadriceps endurance assessed using repetitive magnetic stimulation in COPD (n=35) or control (n=35) subjects. In controls, but not COPD patients, muscle biopsy analysis showed a negative relationship between 25(OH)D and MHCIIa expression (r(2)=0.5, p=0.01) and a positive relationship between mrf4 and MHCIIa expression (r(2)=0.5, p=0.009), and myogenic regulatory factor myf5 and MHCI expression (r(2)=0.72, p=0.004). In contrast with healthy controls, muscle strength is not associated with vitamin D levels in COPD, which may represent vitamin D resistance.

Respiratory muscle fatigue following exercise in patients with interstitial lung disease.

BACKGROUND: It is not known whether respiratory muscle fatigue occurs as a consequence of exercise in patients with interstitial lung disease (ILD) and, if so, to what extent it is related to changes in dynamic lung volumes. OBJECTIVES: To assess the development of respiratory muscle fatigue in patients with ILD and relate it to the respiratory pattern during exercise. METHODS: Sixteen ILD patients (11 women) performed incremental, symptom-limited cycle ergometry with inspiratory capacity manoeuvres used to measure changes in end-expiratory lung volume (EELV). Twitch transdia-phragmatic pressure (TwPdi) and twitch gastric pressure (TwT10Pga), in response to magnetic stimulation, were used to assess the development of fatigue. RESULTS: TwPdi did not differ significantly before and after exercise (21.8 ± 8 vs. 20.2 ± 8 cm H2O; p = 0.10), while TwT10Pga fell from 28.6 ± 18 to 25.2 ± 14 cm H2O (p = 0.02). EELV fell from 2.18 ± 0.65 to 1.91 ± 0.59 liters following exercise (p = 0.04). The fall in TwT10Pga correlated with peak oxygen uptake at peak of exercise (r = -0.52, p = 0.041), increase in heart rate (r = 0.53, p = 0.032) and with the decrease of EELV during exercise (r = 0.57, p = 0.021). Abdominal muscle fatiguers (n = 9, 56%), defined as having a ≥10% fall in TwT10Pga, had a fall in EELV of 22 ± 22% compared to 0.7 ± 8% in non-fatiguers (p = 0.016). CONCLUSION: Abdominal muscle fatigue develops during exercise in some ILD patients in association with increased expiratory muscle activity manifested by reduced EELV.

Singing classes for chronic obstructive pulmonary disease: a randomized controlled trial.

BACKGROUND: There is some evidence that singing lessons may be of benefit to patients with chronic obstructive pulmonary disease (COPD). It is not clear how much of this benefit is specific to singing and how much relates to the classes being a group activity that addresses social isolation. METHODS: Patients were randomised to either singing classes or a film club for eight weeks. Response was assessed quantitatively through health status questionnaires, measures of breathing control, exercise capacity and physical activity and qualitatively, through structured interviews with a clinical psychologist. RESULTS: The singing group (n=13 mean(SD) FEV1 44.4(14.4)% predicted) and film group (n=11 FEV1 63.5(25.5)%predicted) did not differ significantly at baseline. There was a significant difference between the response of the physical component score of the SF-36, favouring the singing group +12.9(19.0) vs -0.25(11.9) (p=0.02), but no difference in response of the mental component score of the SF-36, breathing control measures, exercise capacity or daily physical activity. In the qualitative element, positive effects on physical well-being were reported in the singing group but not the film group. CONCLUSION: Singing classes have an impact on health status distinct from that achieved simply by taking part in a group activity. TRIALS REGISTRATION: Registration Current Controlled Trials - ISRCTN17544114.