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STUDY OBJECTIVES: Excessive daytime sleepiness (EDS) is a treatment target for many patients with obstructive sleep apnea (OSA). We aimed to understand the prevalence, risk factors, and quality of life associated with EDS in a nonclinical, “real world” sample of patients with OSA. METHODS: Cross-sectional survey of patients with OSA participating in an online peer support community, assessing demographics, comorbidities, treatment, and quality of life. Differences in those with and without EDS (Epworth Sleepiness Scale > and ≤ 10) were assessed. RESULTS: The sample (n = 422) was 54.2% male, 65.9% were ≥ 55 years, and 43.3% reported sleeping ≤ 6 hours/night. EDS was identified among 31.0% of respondents and 51.7% reported sleepiness as a precipitating factor for seeking initial OSA treatment. EDS was more prevalent in individuals reporting asthma, insomnia symptoms, positive airway pressure (PAP) use less than 6 hours/night on ≥ 5 nights/week, or sleep duration < 6 hours/night. After adjusting for demographics and comorbidities, patients with EDS reported poorer mental and physical health and well-being, lower disease-specific functional status, more activity and work impairment, and more driving impairment (P values < .05). In the subsample (n = 265) with high PAP adherence, 26.0% reported EDS, and similar associations between EDS and outcomes were observed. CONCLUSIONS: These “real world” data suggest that patients seeking online OSA support experience a high prevalence of EDS, which was associated with poorer quality of life and worse functional status. Associations persisted among respondents with high self-reported PAP-therapy adherence, potentially driving these individuals to seek online support for sleepiness-related symptoms. CITATION: Wanberg LJ, Rottapel RE, Reid ML, et al. Prevalence of sleepiness and associations with quality of life in patients with sleep apnea in an online cohort. J Clin Sleep Med. 2021;17(12):2363–2372.

The sleep disruption experienced by patients admitted to hospital may have a negative effect on health but the nature and magnitude of the effect has not been conclusively outlined. The review was designed to examine the impact of sleep disruption associated with being a hospital inpatient, on short-term physical health outcomes in adult patients. Searches comprised journal databases, gray literature sources, and backward and forward citation searching. Two reviewers independently screened the records. Original studies of adult hospitalized patients' sleep were included if physical outcomes were also measured. Interventional studies were excluded. The methodological quality was assessed independently by 2 reviewers using CASP checklists. Sleep assessment measures and results, physical outcomes and contextual data were extracted. Results were synthesized according to frequently reported outcomes: delirium, pain intensity, physical strength, and respiratory function. A meta-analysis was not performed; studies were heterogeneous and reporting was limited. Of 9919 retrieved records, 26 published studies were included (published: 2001-2020). Risk of bias was moderately high. Confounding factors were poorly reported. Total sleep time was either normal or reduced. Sleep was disrupted: arousal indices were high (mean: 0 5-21/h); slow wave sleep proportions were limited. Subjective sleep quality was poor. The association between sleep reduction or disruption and short-term health outcomes was negative, mixed or equivocal and included increased delirium, higher pain intensity, poorer strength, and adverse respiratory function. The impact of sleep disruption on outcomes for hospitalized patients is not well defined.

Comorbidities in severe asthma are common and contribute to disease burden. The severe asthma phenotype and treatment response can be impacted by comorbid conditions. Real-world data on the use of mepolizumab in severe eosinophilic asthma (SEA) in the presence of comorbidities is needed to inform clinical practice.To investigate the impact of comorbid conditions on baseline phenotype in patients with SEA and assess the mepolizumab treatment effect by comorbidity status in SEA.Patients enrolled in the Australian Mepolizumab Registry (n=309) were classified into subgroups defined by the presence or absence of comorbidities, including nasal polyps, aspirin exacerbated airway disease, asthma-chronic obstructive pulmonary disease (COPD) overlap (ACO), fungal sensitisation and obesity. Patient baseline characteristics were compared, and the impacts of comorbidity on phenotype, identified by differences in patient age and/or baseline biomarker levels and/or asthma severity, were assessed. The mepolizumab treatment effects on clinical and biological outcomes at 12 months were assessed.Across comorbidity subgroups, mepolizumab reduced the rate of clinically significant exacerbations (range 47-77%), maintenance oral corticosteroid use (dose reduction 4.2-13.3 mg/day), and improved symptom control (Asthma Control Questionnaire-5 score 1.9-2.4 point reduction) and lung function (mean 3.4-9.3 post-bronchodilator percent predicted forced expiratory volume in 1s). Peripheral blood eosinophils were reduced (mean 480-780 cells/μL). Comorbidities (nasal polyps, obesity, ACO and fungal sensitisation) modified the baseline phenotype.Mepolizumab treatment is associated with comparable clinical improvements in in patients with SEA and comorbidities. Mepolizumab effectively minimizes the disease impact and corticosteroid burden in patients with SEA.

Background Clinicians are increasingly recognizing severe asthma patients in whom biologics and other add-on therapies lead to dramatic improvement. Currently, there is no agreed-upon super-responder (SR) definition. Objective To survey severe asthma experts using a modified Delphi process, to develop an international consensus-based definition of a severe asthma SR. Methods The Delphi panel was composed of 81 participants (94% specialist pulmonologists or allergists) from 24 countries and consisted of three iterative online voting rounds. Consensus on individual items, whether acceptance or rejection, required at least 70% agreement by panel members. Results Consensus was achieved that the SR definition should be based on improvement across three or more domains assessed over 12 months. Major SR criteria included exacerbation elimination, a large improvement in asthma control (two or more times the minimal clinically important difference), and cessation of maintenance of oral steroids (or weaning to adrenal insufficiency). Minor SR criteria were composed of a 75% exacerbation reduction, having well-controlled asthma, and 500 mL or greater improvement in FEV1. The SR definition requires improvement in at least two major criteria. In the future, the SR definition should be expanded to incorporate quality of life measures, although current tools can be difficult to implement in a clinical setting and further research is needed. Conclusions This international consensus-based definition of severe asthma SRs is an important prerequisite for better understanding SR prevalence, predictive factors, and the mechanisms involved. Further research is needed to understand the patient's perspective and to measure quality of life more precisely in SRs.

Background Little is known about the treatment burden experienced by patients with obstructive sleep apnoea (OSA) who use continuous positive airway pressure (CPAP) therapy. Participants 18 patients (33.3% males, mean age 59.7±11.8 years) with OSA who use CPAP therapy were interviewed. Methods Patients treated with CPAP for OSA at a tertiary hospital outpatient clinic in Sydney, Australia, were invited to participate in an interview in person or via phone. Semi-structured interviews were used to explore the treatment burden associated with using CPAP. The interviews were recorded, transcribed, and analysed using NVivo 12 qualitative analysis software. Results Four categories of OSA-specific treatment burden were identified: healthcare tasks, consequences of healthcare tasks, exacerbating and alleviating factors of treatment burden. Participants reported a significant burden associated with using CPAP, independently of how frequently they used their device. Common sources of their treatment burden included attending healthcare appointments, the financial cost of treatment, lifestyle changes, treatment-related side effects and general discomfort. Conclusions This study demonstrated that there is a significant treatment burden associated with the use of CPAP, and that treatment non-adherence is not the only consequence of treatment burden. Other consequences include relationship burden, stigma and financial burden. It is important for physicians to identify other negative impacts of treatment burden in order to optimise the patient experience.

Background: Patients with mild asthma represent a substantial proportion of the population with asthma, yet there are limited data on their true burden of disease. We aimed to describe the clinical and healthcare resource utilisation (HCRU) burden of physician-assessed mild asthma. Methods: Patients with mild asthma were included from the NOVEL observational longiTudinal studY (NOVELTY; NCT02760329), a global, 3-year, real-world prospective study of patients with asthma and/or chronic obstructive pulmonary disease from community practice (specialised and primary care). Diagnosis and severity were based on physician discretion. Clinical burden included physician-reported exacerbations and patient-reported measures. HCRU included inpatient and outpatient visits. Results: Overall, 2004 patients with mild asthma were included; 22.8% experienced >= 1 exacerbation in the previous 12 months, of whom 72.3% experienced >= 1 severe exacerbation. Of 625 exacerbations reported, 48.0% lasted >1 week, 27.7% were preceded by symptomatic worsening lasting >3 days, and 50.1% required oral corticosteroid treatment. Health status was moderately impacted (St George's Respiratory Questionnaire score: 23.5 [standard deviation +/- 17.9]). At baseline, 29.7% of patients had asthma symptoms that were not well controlled or very poorly controlled (Asthma Control Test score = 2 exacerbations in the previous year. In terms of HCRU, at least one unscheduled ambulatory visit for exacerbations was required by 9.5% of patients, including 9.2% requiring >= 1 emergency department visit and 1.1% requiring >= 1 hospital admission. Conclusions: In this global sample representing community practice, a significant proportion of patients with physician-assessed mild asthma had considerable clinical burden and HCRU.

As the COVID-19 pandemic has developed, concern for invasive fungal infections in critically ill COVID-19 patients with acute respiratory distress syndrome (ARDS) has emerged. We describe a clinical case of coronavirus disease (COVID-19) associated pulmonary aspergillus (CAPA) infection and acute respiratory distress syndrome (ARDS) with a good clinical outcome, in a previously well, non-immunocompromised Australian woman.

Objectives Motor neuron disease (MND) is a neurodegenerative disorder leading to functional decline and death. Multidisciplinary MND clinics provide an integrated approach to management and facilitate discussion on advanced care directives (ACDs). The study objectives are to analyse (1) the prevalence of ACD in our MND clinic, (2) the relationship between ACD and patient demographics and (3) the relationship between ACD decision-making and variables such as NIV, PEG, hospital admissions and location of death. Methods Using clinic records, all patients who attended the MND clinic in Liverpool Hospital between November 2014 and November 2019 were analysed. Data include MND subtypes, symptom onset to time of diagnosis, time of diagnosis to death, location and reason of death. ACD prevalence, non-invasive ventilation (NIV) and percutaneous endoscopic gastrostomy (PEG) requirements were analysed. Results There were 78 patients; M:F=1:1. 44 (56%) patients were limb onset, 28 (36%) bulbar onset, 4 primary lateral sclerosis and 2 flail limb syndrome presentations. 27% patients completed ACDs, while 32% patients declined ACDs. Patients born in Australia or in a majority English-speaking country were more likely to complete ACDs compared to those born in a non-English-speaking country. There was no significant correlation between ACD completion and age, gender, MND subtype, symptom duration, NIV, PEG feeding, location of death. Conclusion One-quarter of patients completed ACDs. ACDs did not correlate with patient age, gender, MND subtype and symptom duration or decision-making regarding NIV, PEG feeding or location of death. Further studies are needed to address factors influencing patients’ decisions regarding ACDs.

Due to an ongoing recent evolution in practice, sleep medicine as a discipline has been compelled to respond to the converging pressures to reduce costs, improve outcomes, and demonstrate value. Patient "researchers" are uniquely placed to participate in initiatives that address the specific needs and priorities of patients and facilitate the identification of interventions with high likelihood of acceptance by the "customer." To date, however, the "patient voice" largely has been lacking in processes affecting relevant policies and practice guidelines. In this Special Report, patient and research leaders of the Sleep Apnea Patient-Centered Outcomes Network (SAPCON), a national collaborative group of patients, researchers and clinicians working together to promote patient-centered comparative effectiveness research, discuss these interrelated challenges in the context of sleep apnea, and the role patients and patient-centered networks may play in informing evidence-based research designed to meet patient's needs. We first briefly discuss the challenges facing sleep medicine associated with costs, outcomes, and value. We then discuss the key role patients and patient-centered networks can play in efforts to design research to guide better sleep health care, and national support for such initiatives. Finally, we summarize some of the challenges in moving to a new paradigm of patient-researcher-clinician partnerships. By forging strong partnerships among patients, clinicians and researchers, networks such as SAPCON can serve as a living demonstration of how to achieve value in health care.

Study ObjectivesHome sleep apnea testing (HSAT) is increasingly used as an alternative to laboratory-based polysomnography (PSG) for the diagnosis of obstructive sleep apnea. Patient satisfaction with sleep testing performed at home or in the lab has been sparsely assessed, despite its potentially pivotal role in determining patients’ acceptance of sleep apnea treatment. We hypothesize that satisfaction in clinical practice may differ from what has been previously reported within the research setting.MethodsWe analyzed survey data including responses to questions regarding diagnostic sleep study type and sleep study experience satisfaction from 2563 sleep apnea patients enrolled in the Sleep Apnea Patient-Centered Outcomes Network.ResultsPatients (mean age 57 years; 54% male) who underwent in-lab PSG were more likely to be satisfied with their study experience than patients who had a HSAT (71% vs 60%; p < 0.01). Furthermore, the 38 per cent diminished odds of satisfaction in patients having HSAT (OR: 0.62; 95% CI: 0.49–0.77) persisted after adjustment for potential confounders (OR: 0.41, 95% CI; 0.27–0.63). Greater sleep apnea symptom burden and satisfaction with CPAP therapy were associated with greater study satisfaction. Effect modifications on study types by college degree education and tiredness as a study trigger were detected.ConclusionsPatients receiving care in the community who underwent PSG reported greater satisfaction with study experience than patients who underwent HSAT in contrast to findings from randomized controlled trials. Our findings, based on data from contemporary “real-world” settings, suggest that assumptions about the generalizability of early reports comparing in-lab PSG to home-based paradigms need to be revisited.

A 66-year-old woman with a background of chronic lymphocytic leukemia (CLL) was admitted to the hospital on several occasions with recurrent episodes of community-acquired pneumonia. Computed tomography and bronchoscopy revealed multiple obstructing endobronchial polyps. Post-obstructive pneumonia together with immunoglobulin G deficiency was considered the most likely cause of these recurrent infections. Bronchoscopy was performed for removal of the critically obstructing lesions. Histopathology revealed replacement of bronchial mucosa with CLL deposits. Despite a brief window of infection-free survival following therapy, she remained susceptible to pneumonia with further hospital admissions and eventually died from her disease.

We describe a patient with persisting fevers, a progressive pulmonary infiltrate, and high levels of serum lactate dehydrogenase. No underlying cause for these changes was found prior to her death despite extensive investigations. Postmortem tissue revealed invasive pulmonary aspergillosis and subsequent brain examination revealed vascular changes in keeping with intravascular large B-cell lymphoma (IVLBCL). On review, subtle yet extensive lymphomatous infiltrates involved the vasculature of multiple other organs, including the lungs. Aspergillosis is a relatively rare presenting feature of lymphoproliferative disorders, and IVLBCL is a rare subtype of diffuse large B-cell non-Hodgkin's lymphoma with, to our knowledge, very few case reports to date. Lymphoma should be considered in patients presenting with pneumonitis with bilateral lung infiltrates on imaging, with a high serum level of lactate dehydrogenase.

Background.Healthcare workers have an increased risk of latent tuberculosis infection (LTBI), but previous studies suggested that they might be reluctant to accept preventive tuberculosis (TB) treatment. We aimed to examine doctors’ and nurses’ experience of TB screening and to explore their attitudes towards preventive TB treatment.Methods.We conducted a survey among randomly selected healthcare workers at a tertiary hospital in Sydney, Australia, using a paper-based questionnaire.Results.A total of 1,304 questionnaires were distributed and 311 (24%) responses were received. The majority of hospital staff supported preventive TB treatment in health care workers with evidence of latent TB infection (LTBI) in general (74%, 164/223) and for them personally (81%, 198/244) while 80 and 53 healthcare workers respectively had no opinion on the topic. Staff working in respiratory medicine were significantly less likely to support preventive TB treatment in health care workers in general or for them personally if they would have evidence of LTBI compared to other specialties (p= 0.001). Only 13% (14/106) of respondents with evidence of LTBI indicated that they had been offered preventive TB treatment. Twenty-one percent (64/306) of respondents indicated that they did not know the difference between active and latent TB. Among staff who had undergone testing for LTBI, only 33% (75/230) felt adequately informed about the meaning of their test results.Discussion.Hospital staff in general had positive attitudes towards preventive TB treatment, but actual treatment rates were low and perceived knowledge about LTBI was insufficient among a significant proportion of staff. The gap between high support for preventive TB treatment among staff and low treatment rates needs to be addressed. Better education on the concept of LTBI and the meaning of screening test results is required.

Background This study examined potential risk factors of lymph node tuberculosis (LNTB), including phylogenetic lineages of Mycobacterium tuberculosis (MTB), in comparison to pulmonary tuberculosis (PTB) in a setting with an ethnically diverse population. Methods We conducted a case-control study at a major tuberculosis clinic in Sydney, Australia, which included all patients with peripheral LNTB seen at the clinic between 2000 and 2012. Controls were randomly selected patients with PTB seen at the same clinic during the study period. Epidemiological data were extracted from the hospital electronic database and medical records. Associations between LNTB and age, sex, ethnicity, comorbidities and phylogenetic lineages of MTB in comparison to PTB were examined using logistic regression in univariate and multivariate analyses. Results There were 212 cases with LNTB and 424 randomly selected controls with PTB. Among patients with LNTB, 74% were female and the mean age (standard deviation, SD) was 42 (16) years. Among patients with PTB, 43% were female and the mean age was 44 (22) years. Females, 45 to 64-year-olds and Southern Asians had an increased risk for LNTB (OR 3.13, 95% CI 2.10-4.67; OR 2.50, 95% CI 1.29-4.84; OR 3.95, 95% CI 1.54-10.12 respectively). Patients with diabetes were at a higher risk of PTB (OR 0.40, 95% CI 0.19 – 0.83 for LNTB). A subset analysis showed that patients infected with the East African Indian strain of MTB were more likely to develop LNTB (OR 10.07, 95% CI 2.37-42.77). Conclusions An increased risk for LNTB (but still lower rates than for PTB) was found among females, people aged 45 to 64 years and people born in Southern Asia. An increased risk for PTB was found among patients with diabetes. The East African Indian strain of MTB was significantly associated with a higher likelihood of LNTB compared to other MTB strains.

Objective: To test the B-cell antigen D8/17 as a marker of past rheumatic fever (RF) in a predominantly Aboriginal Australian population, and to evaluate technical modifications to allow its use in remote settings. Design and setting: Cross-sectional survey in a remote Aboriginal community, a regional tertiary referral hospital and a tertiary paediatric centre in Melbourne. Participants: 106 people, including three with acute RF, 38 with a history of past RF, 20 relatives of these people, and 45 healthy controls. Main outcome measure: D8/17 expression in B cells. Results: Blood was collected from each participant and the expression of D8/17 and CD19 in each sample was analysed by flow cytometry. The mean proportion of D8/17-positive B cells was 39.3% (SD, 11.8) in patients with previous RF, 22.5% (SD, 5.2) in first-degree relatives, 11.6% (SD, 7.2) in controls, and 83.7% (SD, 10.1) in patients with acute RF (analysis of variance test between means, P = 0.001). A cut-off of 22.1% of D8/17-positive B cells to indicate past RF yielded the highest percentage of correct results (95.4%). Delayed staining of whole blood (mean, 0.55 days; SD, 0.2) gave equivalent results to immediate staining, but the D8/17 assay on peripheral blood mononuclear cells was unreliable. Conclusions: The B-cell antigen D8/17 accurately identifies Australians with a past history of RF, and the assay is feasible in remote settings with access to facilities capable of performing D8/17 staining within half a day of sample collection.

Aim: To identify factors that affect rheumatic fever prophylaxis for remote-living Aboriginal patients, and to determine the proportion who received adequate prophylaxis. Design and setting: Interview (with analysis based on principles of grounded theory) of patients with a history of rheumatic fever or rheumatic heart disease and their relatives, and health service providers in a remote Aboriginal community; audit of benzathine penicillin coverage of patients with rheumatic heart disease. Participants: 15 patients with rheumatic heart disease or a history of rheumatic fever, 18 relatives and 18 health care workers. Results: Patients felt that the role of the clinic was not only to care for them physically, but that staff should also show nurturing holistic care to generate trust and treatment compliance. Differing expectations between patients and health care providers relating to the responsibility for care of patients absent from the community was a significant factor in patients missing injections. Neither a biomedical understanding of the disease nor a sense of taking responsibility for one's own health were clearly related to treatment uptake. Patients did not generally refuse injections, and 59% received adequate prophylaxis (> 75% of prescribed injections). Conclusion: In this Aboriginal community, concepts of being cared for and nurtured, MJA 2006; 184: 514–517 and belonging to a health service were important determinants of compliance.

It is unknown why only some individuals are susceptible to acute rheumatic fever (ARF). We investigated whether there are differences in the immune response, detectable by gene expression, between individuals who are susceptible to ARF and those who are not. Peripheral blood mononuclear cells (PBMCs) from 15 ARF-susceptible and 10 nonsusceptible (control) adults were stimulated with rheumatogenic (Rh+) group A streptococci (GAS) or nonrheumatogenic (Rh−) GAS. RNA from stimulated PBMCs from each subject was cohybridized with RNA from unstimulated PBMCs on oligonucleotide arrays to compare gene expression. Thirty-four genes were significantly differentially expressed between ARF-susceptible and control groups after stimulation with Rh+ GAS. A total of 982 genes were differentially expressed between Rh+ GAS- and Rh− GAS-stimulated samples from ARF-susceptible individuals. Thirteen genes were differentially expressed in the same direction (predominantly decreased) between the two study groups and between the two stimulation conditions, giving a strong indication of their involvement. Seven of these were immune response genes involved in cytotoxicity, chemotaxis, and apoptosis. There was variability in the degree of expression change between individuals. The high proportion of differentially expressed apoptotic and immune response genes supports the current model of autoimmune and cytokine dysregulation in ARF. This study also raises the possibility that a “failed” immune response, involving decreased expression of cytotoxic and apoptotic genes, contributes to the immunopathogenesis of ARF.

Superantigens (SAgs) from group A streptococcus (GAS) are potent T cell mitogens, and have been suggested to play a role in severe streptococcal disease. Neutralizing antibodies protect against SAg-mediated disease and their levels should therefore be inversely related to severe streptococcal infection. Neutralizing anti-SAg titers in patients with severe GAS infection and patients without disease were compared in two separate groups. The first group comprised patients with invasive GAS disease from New Zealand European, Maori, and Pacific Island descent. The second group comprised Aboriginal Australian individuals with rheumatic heart disease and/or a past history of acute rheumatic fever. Patients sera were tested for their ability to neutralize T cell mitogenicity of recombinant streptococcal SAgs as a measure of functional SAg-neutralizing antibody concentration. In both studies, no inverse correlation was observed between disease and the level of serum SAg-neutralizing activity. Notably, much higher levels of natural immunity to all streptococcal SAgs were found in New Zealand Maori, New Zealand Pacific Island, and Aboriginal Australian individuals, suggesting a high degree of natural exposure and seroconversion in these groups compared to the New Zealand European cohort. Levels of serum antibodies against SAgs could not be used to predict disease susceptibility in groups with existing high levels of SAg-neutralizing antibodies.