Obstructive Sleep Apnea is a Risk Factor for Incident COVID-19 Infection.

Cross-sectional studies suggest that obstructive sleep apnea (OSA) is a potential risk factor for incident COVID-19 infection, but longitudinal studies are lacking. In this study, two surveys from a large general population cohort, the COVID-19 Outbreak Public Evaluation (COPE) Initiative, undertaken 147 ± 58 days apart were analyzed to determine whether the pre-existing OSA was a risk factor for the incidence of COVID-19. Of the 24,803 respondents completing the initial survey, 14,950 were negative for COVID-19; data from the follow-up survey were available for 2,325 respondents. Those with incident COVID-19 infection had a slightly higher prevalence of OSA (14.3 vs. 11.5%, p=0.068). Stratification by treatment status revealed that those untreated for their OSA were at greater risk for developing COVID-19 infection (OSA Untreated, 14.2 vs. 7.4%, p≤0.05). In a logistic regression model adjusted for comorbidities, demographic and socioeconomic factors and the interaction between vaccination status and OSA, incident COVID-19 infection was 2.15 times more likely in those with untreated OSA (aOR: 2.15, 95% CI: 1.18-3.92, p≤0.05). Stratification by treatment status revealed only untreated OSA participants were at greater risk for COVID-19 (aOR: 3.21, 95% CI: 1.25-8.23, p≤0.05). The evidence from this study confirms untreated OSA as a risk factor for acquiring COVID-19 infection and highlights the importance of actively treating and managing OSA as a preventative mechanism against COVID-19 disease.

Consensus palliative care referral criteria for people with chronic obstructive pulmonary disease.

OBJECTIVE: People with advanced chronic obstructive pulmonary disease (COPD) have substantial palliative care needs, but uncertainty exists around appropriate identification of patients for palliative care referral.We conducted a Delphi study of international experts to identify consensus referral criteria for specialist outpatient palliative care for people with COPD. METHODS: Clinicians in the fields of respiratory medicine, palliative and primary care from five continents with expertise in respiratory medicine and palliative care rated 81 criteria over three Delphi rounds. Consensus was defined a priori as ≥70% agreement. A criterion was considered 'major' if experts endorsed meeting that criterion alone justified palliative care referral. RESULTS: Response rates from the 57 panellists were 86% (49), 84% (48) and 91% (52) over first, second and third rounds, respectively. Panellists reached consensus on 17 major criteria for specialist outpatient palliative care referral, categorised under: (1) 'Health service use and need for advanced respiratory therapies' (six criteria, eg, need for home non-invasive ventilation); (2) 'Presence of symptoms, psychosocial and decision-making needs' (eight criteria, eg, severe (7-10 on a 10 point scale) chronic breathlessness); and (3) 'Prognostic estimate and performance status' (three criteria, eg, physician-estimated life expectancy of 6 months or less). CONCLUSIONS: International experts evaluated 81 potential referral criteria, reaching consensus on 17 major criteria for referral to specialist outpatient palliative care for people with COPD. Evaluation of the feasibility of these criteria in practice is required to improve standardised palliative care delivery for people with COPD.

Development of a Multifaceted Program for Pharmacogenetics Adoption at an Academic Medical Center: Practical Considerations and Lessons Learned.

In 2019, Indiana University launched the Precision Health Initiative to enhance the institutional adoption of precision medicine, including pharmacogenetics (PGx) implementation, at university-affiliated practice sites across Indiana. The overarching goal of this PGx implementation program was to facilitate the sustainable adoption of genotype-guided prescribing into routine clinical care. To accomplish this goal, we pursued the following specific objectives: (i) to integrate PGx testing into existing healthcare system processes; (ii) to implement drug-gene pairs with high-level evidence and educate providers and pharmacists on established clinical management recommendations; (iii) to engage key stakeholders, including patients to optimize the return of results for PGx testing; (iv) to reduce health disparities through the targeted inclusion of underrepresented populations; (v) and to track third-party reimbursement. This tutorial details our multifaceted PGx implementation program, including descriptions of our interventions, the critical challenges faced, and the major program successes. By describing our experience, we aim to assist other clinical teams in achieving sustainable PGx implementation in their health systems.

Perinatal intervention strategies providing food with micronutrients to pregnant and breastfeeding women in low- and middle-income countries: A scoping review.

In resource-constrained settings, pregnant and breastfeeding women and girls (PBW/G) are particularly vulnerable to undernutrition. Micronutrient-fortified balanced energy protein (BEP) supplementation may be provided to boost maternal nutritional status and improve birth and infant outcomes. We conducted a scoping review of the published literature to determine the impact of BEP and other related nutrition interventions that provided fortified food or cash along with a minimum of 3 micronutrients on maternal, birth, and infant/child outcomes in low- and middle-income countries. We conducted a PubMed search using pre-defined keywords and controlled vocabulary search terms. All titles and abstracts were reviewed for eligibility by two independent reviewers, and data were extracted according to outcome type. We identified 149 eligible research articles that reported on a total of 21 trials and/or programme evaluations which assessed the health impact of one or more products (fortified lipid-based nutrient supplement [LNS, n = 12], fortified blended flours [n = 5], milk-based beverages [n = 2], and local food/snacks [n = 3]) that provided 118-750 kcal/day and varying levels of protein and micronutrients. Only one of these programme evaluations assessed the impact of the provision of cash and fortified food. Effects on maternal outcomes such as gestational weight gain and duration of gestation were promising but inconsistent. Birth outcomes were reported in 15 studies, and the effects on birthweight and birth length were generally positive. Seven studies demonstrated sustained benefits on infant and child growth out of the 15 studies that reported at least one of these outcomes, although data were sparse. Additional research is needed to investigate issues of dose, cost-effectiveness, and incorporation into multi-component interventions.

Sleep and long COVID: Preexisting sleep issues and the risk of PASC in a large general population using 3 different model definitions.

Study Objectives: Insomnia, poor sleep quality and extremes of sleep duration are associated with COVID-19 infection. This study assessed whether these factors are related to Post-Acute Sequelae of SARS-CoV-2 infection (PASC). Methods: Cross-sectional survey of a general population of 24,803 U.S. adults to determine the association of insomnia, poor sleep quality and sleep duration with PASC. Results: Prevalence rates of PASC among previously COVID-19 infected participants for three definitions of PASC were COPE (21.9%), NICE (38.9%) and RECOVER PASC Score (15.3%). PASC was associated with insomnia in all 3 models in fully adjusted models with adjusted odds ratios (aORs) and 95% confidence intervals (CI) ranging from 1.30 (95% CI: 1.11-1.52, p≤0.05, PASC Score) to 1.52 (95% CI: 1.34-1.71, p≤0.001, (NICE). Poor sleep quality was related to PASC in all models with aORs ranging from 1.77 (95% CI: 1.60-1.97, p≤0.001, NICE) to 2.00 (95% CI: 1.77-2.26, p≤0.001, COPE). Sleep <6 hours was associated with PASC with aORs between 1.59 (95% CI: 1.40-1.80, p≤0.001, PASC Score) to 1.70 (95% CI: 1.53-1.89, p≤0.001, COPE). Sleep ≥ 9 hours was not associated with PASC in any model. Although vaccination with COVID-19 booster decreased the likelihood of developing PASC, it did not attenuate associations between insomnia, poor sleep quality and short sleep duration with PASC in any of the models. Conclusions: Insomnia, poor sleep quality and short sleep duration are potential risk factors for PASC. Interventions to improve sleep may decrease the development of PASC.

Thoracic Society of Australia and New Zealand clinical practice guideline on adult home oxygen therapy.

This Thoracic Society of Australia and New Zealand Guideline on the provision of home oxygen therapy in adults updates a previous Guideline from 2015. The Guideline is based upon a systematic review and meta-analysis of literature to September 2022 and the strength of recommendations is based on GRADE methodology. Long-term oxygen therapy (LTOT) is recommended for its mortality benefit for patients with COPD and other chronic respiratory diseases who have consistent evidence of significant hypoxaemia at rest (PaO2 ≤ 55 mm Hg or PaO2 ≤59 mm Hg in the presence of hypoxaemic sequalae) while in a stable state. Evidence does not support the use of LTOT for patients with COPD who have moderate hypoxaemia or isolated nocturnal hypoxaemia. In the absence of hypoxaemia, there is no evidence that oxygen provides greater palliation of breathlessness than air. Evidence does not support the use of supplemental oxygen therapy during pulmonary rehabilitation in those with COPD and exertional desaturation but normal resting arterial blood gases. Both positive and negative effects of LTOT have been described, including on quality of life. Education about how and when to use oxygen therapy in order to maximize its benefits, including the use of different delivery devices, expectations and limitations of therapy and information about hazards and risks associated with its use are key when embarking upon this treatment.

Mandatory large-scale food fortification programmes can reduce the estimated prevalence of inadequate zinc intake by up to 50% globally.

Large-scale food fortification (LSFF) can increase dietary micronutrient intake and improve micronutrient status. Here we used food balance sheet data from the Food and Agriculture Organization of the United Nations to estimate current country-specific prevalences of inadequate zinc intake. We assessed the potential effects of improving existing LSFF programmes for cereal grains or implementing new programmes in 40 countries where zinc deficiency is a potential public health problem. Accounting for LSFF programmes as currently implemented, 15% of the global population (1.13 billion individuals) is estimated to have inadequate zinc intake. In countries where zinc deficiency is a potential public health problem, the implementation of high-quality mandatory LSFF programmes that include zinc as a fortificant would substantially increase the availability of zinc in the national food supply, reducing the estimated prevalence of inadequate zinc intake by up to 50% globally. Investments in strong LSFF programmes could have a substantial impact on population zinc status.

Control of dermatomyositis skin disease activity lags behind control of muscles disease activity during the early treatment stages of classic dermatomyositis: A retrospective, single-centre study.

This study aimed to retrospectively identify differences in relative control of cutaneous and muscular disease activity in adult dermatomyositis (DM) patients at a single, tertiary care centre following initiation of diagnosis and treatment. Our results demonstrated a significantly lower complete treatment response rate of skin disease compared to muscular disease at 6-months and persistent but not statistically significant lower skin disease response at 12 months. These results suggest DM skin disease activity may be more refractory to treatment than muscle disease activity, especially in the early disease phase.

SABINA + Hong Kong: a territory wide study of prescribing trends and outcomes associated with the use of short-acting ß2 agonists in the Chinese population.

BACKGROUND: Excessive use of short-acting ß2 agonists (SABA) in patients with asthma continues to be a notable concern due to its link to higher mortality rates. Global relevance of SABA overuse in asthma management cannot be understated, it poses significant health risk to patients with asthma and imposes burden on healthcare systems. This study, as part of global SABINA progamme, aimed to describe the prescribing patterns and clinical outcomes associated with SABA use in the Chinese population. METHODS: Retrospective cohort study was conducted using anonymized electronic healthcare records of Clinical Data Analysis and Reporting System (CDARS) from Hong Kong Hospital Authority (HA). Patients newly diagnosed with asthma between 2011 and 2018 and aged ≥12 years were included, stratified by SABA use (≤2, 3-6, 7-10, or ≥11 canisters/year) during one-year baseline period since asthma diagnosis date. Patients were followed up from one-year post-index until earliest censoring of events: outcome occurrence and end of study period (31 December 2020). Cox proportional regression and negative binomial regression were used to estimate the mortality risk and frequency of hospital admissions associated with SABA use respectively, after adjusting for age, sex, Charlson Comorbidity Index (CCI), and inhaled corticosteroid (ICS) dose. Outcomes include all-cause, asthma-related, and respiratory-related mortality, frequency of hospital admissions for any cause, and frequency of hospital admissions due to asthma. RESULTS: 17,782 patients with asthma (mean age 46.7 years, 40.8% male) were included and 59.1% of patients were overusing SABA (≥ 3 canisters per year). Each patient was prescribed a median of 5.61 SABA canisters/year. SABA overuse during baseline period was associated with higher all-cause mortality risk compared to patients with ≤2 canisters/year. Association was dose-dependent, highest risk in those used ≥11 canisters/year (adjusted hazard ratio: 1.42, 95% CI: 1.13, 1.79) and 3-6 canisters/year (adjusted hazard ratio: 1.22, 95% CI: 1.00, 1.50). Higher SABA prescription volume associated with increased frequency of hospital admissions with greatest risk observed in 7-10 canisters/year subgroup (adjusted rate ratio: 4.81, 95% CI: 3.66, 6.37). CONCLUSIONS: SABA overuse is prevalent and is associated with increased all-cause mortality risk and frequency of hospital admissions among the patients with asthma in Hong Kong.

Association of Chronotype and Shiftwork With COVID-19 Infection.

OBJECTIVE: This study assesses whether chronotype is related to COVID-19 infection and whether there is an interaction with shift work. Methods: This study used a cross-sectional survey of 19,821 U.S. adults. Results: COVID-19 infection occurred in 40% of participants, 32.6% morning and 17.2% evening chronotypes. After adjusting for demographic and socioeconomic factors, shift/remote work, sleep duration, and comorbidities, morning chronotype was associated with a higher (adjusted odds ratio [aOR]: 1.15, 95% CI: 1.10-1.21) and evening chronotype with a lower (aOR: 0.82, 95% CI: 0.78-0.87) prevalence of COVID-19 infection in comparison to an intermediate chronotype. Working exclusively night shifts was not associated with higher prevalence of COVID-19. Morning chronotype and working some evening shifts was associated with the highest prevalence of previous COVID-19 infection (aOR: 1.87, 95% CI: 1.28-2.74). Conclusion: Morning chronotype and working a mixture of shifts increase risk of COVID-19 infection.

Venous blood gases in the assessment of respiratory failure in patients undergoing sleep studies: a randomized study.

STUDY OBJECTIVES: Venous blood gases (VBGs) are not consistently considered suitable surrogates for arterial blood gases (ABGs) in assessing acute respiratory failure due to variable measurement error. The physiological stability of patients with chronic ventilatory failure may lead to improved agreement in this setting. METHODS: Adults requiring ABGs for sleep or ventilation titration studies had VBGs drawn before or after each ABG, in a randomized order. Veno-arterial correlation and agreement were examined for carbon dioxide tension (PCO2), pH, oxygen tension (PO2), and oxygen saturation (SO2). RESULTS: We analyzed 115 VBG-ABG pairs from 61 patients. Arterial and venous measures were correlated (P < .05) for PCO2 (r = .84) and pH (r = .72), but not for PO2 or SO2. Adjusted mean veno-arterial differences (95% limits of agreement) were +5.0 mmHg (-4.4 to +14.4) for PCO2; -0.02 (-0.09 to +0.04) for pH; -34.3 mmHg (-78.5 to +10.0) for PO2; and -23.9% (-61.3 to +13.5) for SO2. VBGs obtained from the dorsal hand demonstrated a lower mean PCO2 veno-arterial difference (P < .01). A venous PCO2 threshold of ≥ 45.8 mmHg was > 95% sensitive for arterial hypercapnia, so measurements below this can exclude the diagnosis without an ABG. A venous PCO2 threshold of ≥ 53.7 mmHg was > 95% specific for arterial hypercapnia, so such readings can be assumed diagnostic. The area under the receiver operating characteristic curve of 0.91 indicated high discriminatory capacity. CONCLUSIONS: A venous PCO2 < 45.8 mmHg or ≥ 53.7 mmHg would exclude or diagnose hypercapnia, respectively, in patients referred for sleep studies, but VBGs are poor surrogates for ABGs where precision is important. CLINICAL TRIAL REGISTRATION: Registry: Australian New Zealand Clinical Trials Register; Name: A comparison of arterial and blood gas analyses in sleep studies; URL: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=372717; Identifier: ACTRN12617000562370. CITATION: Lindstrom SJ, McDonald CF, Howard ME, et al. Venous blood gases in the assessment of respiratory failure in patients undergoing sleep studies: a randomized study. J Clin Sleep Med. 2024;20(8):1259-1266.

Association of Obstructive Sleep Apnea with Post-Acute Sequelae of SARS-CoV-2 Infection.

BACKGROUND: Obstructive sleep apnea is associated with COVID-19 infection. Less clear is whether obstructive sleep apnea is a risk factor for the development of post-acute sequelae of SARS-CoV-2 infection (PASC). STUDY DESIGN: Cross-sectional survey of a general population of 24,803 US adults to determine the association of obstructive sleep apnea with PASC. RESULTS: COVID-19 infection occurred in 10,324 (41.6%) participants. Prevalence of persistent (>3 months post infection) putative PASC-related physical and mental health symptoms ranged from 6.5% (peripheral edema) to 19.6% (nervous/anxious). In logistic regression models, obstructive sleep apnea was associated with all putative PASC-related symptoms with the highest adjusted odds ratios being fever (2.053) and nervous/anxious (1.939). In 4 logistic regression models of overall PASC derived from elastic net regression, obstructive sleep apnea was associated with PASC (range of adjusted odds ratios: 1.934-2.071); this association was mitigated in those with treated obstructive sleep apnea. In the best fitting overall model requiring ≥3 symptoms, PASC prevalence was 21.9%. CONCLUSION: In a general population sample, obstructive sleep apnea is associated with the development of PASC-related symptoms and a global definition of PASC. Treated obstructive sleep apnea mitigates the latter risk. The presence of 3 or more PASC symptoms may be useful in identifying cases and for future research.

Effectiveness and Respiratory Adverse Events Following Inactivated and mRNA COVID-19 Vaccines in Patients with COPD and Asthma: A Chinese Population-Based Study.

INTRODUCTION: Effectiveness and respiratory adverse events following coronavirus disease-2019 (COVID-19) vaccines have not been well investigated in Chinese patients with chronic obstructive pulmonary disease (COPD) and asthma. METHODS: Using electronic health care records in Hong Kong, we included adults with COPD or asthma or both and hospitalised for severe respiratory exacerbation in a self-controlled case series (SCCS) study between 23/02/2021 and 30/11/2022. Conditional Poisson regression models were used to estimate the incidence of outcomes within exposure periods (28 days after each dose) compared with baseline periods. Cox proportional hazard models evaluated vaccine effectiveness (VE) against COVID-related mortality, hospitalisation, and severe complications, including admission to intensive care units or ventilatory support. The VE assessment was based on vaccine types and the number of doses. RESULTS: In the SCCS, 343 CoronaVac recipients and 212 BNT162b2 recipients were included. No increased risk of outcomes was observed within the exposure periods. In the cohort study, 108,423 and 83,323 patients received ≥ 2 doses of CoronaVac and BNT162b2, respectively. The VE (95% CI) against COVID-related mortality, hospitalisation, and severe complications after two-dose CoronaVac was 77% (74-80%), 18% (6-23%), and 29% (12-43%), respectively, while for the two-dose regimen of BNT162b2, it was 92% (91-94%), 33% (30-37%), and 57% (45-66%), respectively. Higher VE against COVID-related mortality, hospitalisation, and severe complications was found for the three-dose regimen of CoronaVac (94%, 40%, and 71%) and BNT162b2 (98%, 65%, and 83%). Administering a fourth dose of either vaccine showed additional reductions in COVID-related outcomes. CONCLUSIONS: Among people with COPD and asthma, the COVID-19 vaccines CoronaVac and BNT162b2 did not increase severe exacerbations and achieved moderate-to-high effectiveness against COVID-related outcomes. COVID-19 vaccination remains essential and should be encouraged to protect this vulnerable population in future epidemic waves.

Vulnerability to environmental and climatic health provocations among women and men hospitalized with chronic heart disease: insights from the RESILIENCE TRIAL cohort.

AIMS: We aimed to recruit a representative cohort of women and men with multi-morbid chronic heart disease as part of a trial testing an innovative, nurse-co-ordinated, multi-faceted intervention to lower rehospitalization and death by addressing areas of vulnerability to external challenges to their health. METHODS AND RESULTS: The prospective, randomized open, blinded end-point RESILIENCE Trial recruited 203 hospital inpatients (mean age 75.7 ± 10.2 years) of whom 51% were women and 94% had combined coronary artery disease, heart failure, and/or atrial fibrillation. Levels of concurrent multi-morbidity were high (mean Charlson Index of Comorbidity Score 6.5 ± 2.7), and 8.9% had at least mild frailty according to the Rockwood Clinical Frailty Scale. Including the index admission, 19-20% of women and men had a pre-existing pattern of seasonally linked hospitalization (seasonality). Detailed phenotyping revealed that 48% of women and 40% of men had ≥3 physiological factors, and 15% of women and 16% of men had ≥3 behavioural factors likely to increase their vulnerability to external provocations to their health. Overall, 61-62% of women and men had ≥4 combined factors indicative of such vulnerability. Additional factors such as reliance on the public health system (63 vs. 49%), lower education (30 vs. 14%), and living alone (48 vs. 29%) were more prevalent in women. CONCLUSION: We successfully recruited women and men with multi-morbid chronic heart disease and bio-behavioural indicators of vulnerability to external provocations to their health. Once completed, the RESILIENCE TRIAL will provide important insights on the impact of addressing such vulnerability (promoting resilience) on subsequent health outcomes. REGISTRATION: ClinicalTrials.org: NCT04614428.

Protocol summary and statistical analysis plan for the low oxygen intervention for cardiac arrest injury limitation (LOGICAL) trial.

Background: The effect of conservative vs. liberal oxygen therapy on outcomes of intensive care unit (ICU) patients with hypoxic ischaemic encephalopathy (HIE) is uncertain and will be evaluated in the Low Oxygen Intervention for Cardiac Arrest injury Limitation (LOGICAL) trial. Objective: The objective of this study was to summarise the protocol and statistical analysis plans for the LOGICAL trial. Design setting and participants: LOGICAL is a randomised clinical trial in adults in the ICU who are comatose with suspected HIE (i.e., those who have not obeyed commands following return of spontaneous circulation after a cardiac arrest where there is clinical concern about possible brain damage). The LOGICAL trial will include 1400 participants and is being conducted as a substudy of the Mega Randomised registry trial comparing conservative vs. liberal oxygenation targets in adults receiving unplanned invasive mechanical ventilation in the ICU (Mega-ROX). Main outcome measures: The primary outcome is survival with favourable neurological function at 180 days after randomisation as measured with the Extended Glasgow Outcome Scale (GOS-E). A favourable neurological outcome will be defined as a GOS-E score of lower moderate disability or better (i.e. a GOS-E score of 5-8). Secondary outcomes include survival time, day 180 mortality, duration of invasive mechanical ventilation, ICU length of stay, hospital length of stay, the proportion of patients discharged home, quality of life assessed at day 180 using the EQ-5D-5L, and cognitive function assessed at day 180 using the Montreal Cognitive Assessment (MoCA-blind). Conclusions: The LOGICAL trial will provide reliable data on the impact of conservative vs. liberal oxygen therapy in ICU patients with suspected HIE following resuscitation from a cardiac arrest. Prepublication of the LOGICAL protocol and statistical analysis plan prior to trial conclusion will reduce the potential for outcome-reporting or analysis bias. Trial registration: Australian and New Zealand Clinical Trials Registry (ACTRN12621000518864).