Comparing performance of primary care clinicians in the interpretation of SPIROmetry with or without Artificial Intelligence Decision support software (SPIRO-AID): a protocol for a randomised controlled trial.

INTRODUCTION: Spirometry is a point-of-care lung function test that helps support the diagnosis and monitoring of chronic lung disease. The quality and interpretation accuracy of spirometry is variable in primary care. This study aims to evaluate whether artificial intelligence (AI) decision support software improves the performance of primary care clinicians in the interpretation of spirometry, against reference standard (expert interpretation). METHODS AND ANALYSIS: A parallel, two-group, statistician-blinded, randomised controlled trial of primary care clinicians in the UK, who refer for, or interpret, spirometry. People with specialist training in respiratory medicine to consultant level were excluded. A minimum target of 228 primary care clinician participants will be randomised with a 1:1 allocation to assess fifty de-identified, real-world patient spirometry sessions through an online platform either with (intervention group) or without (control group) AI decision support software report. Outcomes will cover primary care clinicians' spirometry interpretation performance including measures of technical quality assessment, spirometry pattern recognition and diagnostic prediction, compared with reference standard. Clinicians' self-rated confidence in spirometry interpretation will also be evaluated. The primary outcome is the proportion of the 50 spirometry sessions where the participant's preferred diagnosis matches the reference diagnosis. Unpaired t-tests and analysis of covariance will be used to estimate the difference in primary outcome between intervention and control groups. ETHICS AND DISSEMINATION: This study has been reviewed and given favourable opinion by Health Research Authority Wales (reference: 22/HRA/5023). Results will be submitted for publication in peer-reviewed journals, presented at relevant national and international conferences, disseminated through social media, patient and public routes and directly shared with stakeholders. TRIAL REGISTRATION NUMBER: NCT05933694.

Spirometry services in England post-pandemic and the potential role of AI support software: a qualitative study of challenges and opportunities.

BACKGROUND: Spirometry services to diagnose and monitor lung disease in primary care were identified as a priority in the NHS Long Term Plan, and are restarting post-COVID-19 pandemic in England; however, evidence regarding best practice is limited. AIM: To explore perspectives on spirometry provision in primary care, and the potential for artificial intelligence (AI) decision support software to aid quality and interpretation. DESIGN AND SETTING: Semi-structured interviews with stakeholders in spirometry services across England. METHOD: Participants were recruited by snowball sampling. Interviews explored the pre- pandemic delivery of spirometry, restarting of services, and perceptions of the role of AI. Transcripts were analysed thematically. RESULTS: In total, 28 participants (mean years' clinical experience = 21.6 [standard deviation 9.4, range 3-40]) were interviewed between April and June 2022. Participants included clinicians (n = 25) and commissioners (n = 3); eight held regional and/or national respiratory network advisory roles. Four themes were identified: 1) historical challenges in provision of spirometry services; 2) inequity in post- pandemic spirometry provision and challenges to restarting spirometry in primary care; 3) future delivery closer to patients' homes by appropriately trained staff; and 4) the potential for AI to have supportive roles in spirometry. CONCLUSION: Stakeholders highlighted historic challenges and the damaging effects of the pandemic contributing to inequity in provision of spirometry, which must be addressed. Overall, stakeholders were positive about the potential of AI to support clinicians in quality assessment and interpretation of spirometry. However, it was evident that validation of the software must be sufficiently robust for clinicians and healthcare commissioners to have trust in the process.

"It's like a forgotten issue sometimes ": Qualitative study of individuals living and caring for people with chronic breathlessness.

INTRODUCTION: This study aims to explore the perspectives of patients and carers with chronic breathlessness on current provision of care, care expectations, and self-management needs to develop relevant health services and resources to improve clinical outcomes. METHODS: In-depth semistructured interviews were conducted on patients living with chronic breathlessness and carers. RESULTS: Thirteen patients (cardiac, respiratory, and noncardiorespiratory) and two carers were interviewed (mean age 57 years, 47% female, median duration with breathlessness 5 years). Four main themes were identified: (1) living with breathlessness, (2) diagnosis delays, misdiagnosis, and knowledge gaps, (3) beyond curing disease: symptom relief and improving quality of life, and (4) self-management and limited support for it. CONCLUSION: Breathlessness has a high personal impact but remains a neglected condition in Australia. Patients suffer from lack of personal, community, and provider awareness, discontinuity of care, and too few clinical and self-management options.

Management of chronic breathlessness in primary care: what do GPs, non-GP specialists, and allied health professionals think?

BACKGROUND: To explore the perspectives of GPs, non-GP specialists, and allied health professionals on the role of primary care in diagnosing and managing chronic breathlessness, the barriers faced, and the resources needed to optimise care of patients with chronic breathlessness. METHODS: This was a qualitative study involving focus group discussions that included 35GPs, non-GP specialists, and allied health professionals. Topics explored included: (1) views on the role of primary care in diagnosing and managing chronic breathlessness; (2) barriers to optimal assessment in primary care; and (3) facilitators to further optimise the care of patients with chronic breathlessness. RESULTS: All participants considered that primary care has a central role to play in the assessment and management of chronic breathlessness, but greater access to referral services, suitable funding structures, and upskilling on the use of diagnostic tests such as spirometry and electrocardiography are required for this to be realised. Both GPs and non-GP specialists described great potential for developing better linkages, including new ways of referral and online consultations, greater ease of referral to allied health services, even if conducted virtually, for patients with functional causes of breathlessness. Participants identified a need to develop integrated breathlessness clinics for patients referred by GPs, which would ensure patients receive optimal care in the shortest possible time frame. CONCLUSIONS: GPs are crucial to achieving optimal care for breathless patients, especially given the multifactorial and multimorbid nature of breathlessness; however, there are significant gaps in services and resources at present that limit their ability to perform this role.

Clinical, technical, and implementation characteristics of real-world health applications using FHIR.

Objective: Understanding the current state of real-world Fast Healthcare Interoperability Resources (FHIR) applications (apps) will benefit biomedical research and clinical care and facilitate advancement of the standard. This study aimed to provide a preliminary assessment of these apps' clinical, technical, and implementation characteristics. Materials and Methods: We searched public repositories for potentially eligible FHIR apps and surveyed app implementers and other stakeholders. Results: Of the 112 apps surveyed, most focused on clinical care (74) or research (45); were implemented across multiple sites (56); and used SMART-on-FHIR (55) and FHIR version R4 (69). Apps were primarily stand-alone web-based (67) or electronic health record (EHR)-embedded (51), although 49 were not listed in an EHR app gallery. Discussion: Though limited in scope, our results show FHIR apps encompass various domains and characteristics. Conclusion: As FHIR use expands, this study-one of the first to characterize FHIR apps at large-highlights the need for systematic, comprehensive methods to assess their characteristics.

Qualitative validation of the modified Medical Research Council (mMRC) dyspnoea scale as a patient-reported measure of breathlessness severity.

INTRODUCTION: The modified Medical Research Council (mMRC) dyspnoea scale is a measure of breathlessness severity recommended by guidelines and utilised as an inclusion criterion or endpoint for clinical trials. No studies have been conducted to validate the categorical descriptors against the dyspnoea severity grade. METHODS: This study utilised cognitive interviews (Think Aloud method) to assess the content validity of the mMRC scale among 16 participants (13 with cardiac/respiratory disease). Participants were recruited to achieve representation across a variety of demographic factors. Interviews were conducted remotely via video conferencing and participants were presented with all 5 mMRC descriptors on screen in random order then asked to rank the statements "in order from the best breathing to the worst breathing". RESULTS: Mean age of participants was 57 years (range 22-84 years). Eleven had multimorbidity (≥2 comorbidities) including COPD, asthma, lung cancer, lung infection, interstitial lung disease, heart failure, depression, and anxiety. Length of time with breathlessness ranged between 2 weeks and >25 years. The median rank of the mMRC grade descriptors was concordant for mMRC grades 0, 1 and 4 but not grades 2 and 3. Even so, substantial heterogeneity was found in the distribution of responses for mMRC grade 0. CONCLUSION: Our study found substantial heterogeneity in participant grading of the mMRC descriptors, particularly for grades 0, 2 and 3, indicating that mMRC might not be a good discriminator of difference or change in dyspnoea severity. This study demonstrates the importance of content validation even for long-established PROs like mMRC.

Efficacy of self-management mobile applications for patients with breathlessness: Systematic review and quality assessment of publicly available applications.

INTRODUCTION: Apps can play a role in self-management of symptoms such as breathlessness. This systematic review aims to evaluate the clinical efficacy of breathlessness apps and assess the quality of those publicly available. METHODS: The full protocol for this systematic review is available on PROSPERO (CRD42021246277). Studies published between January 2010 to 2022 were obtained from six academic databases and included if they evaluated apps that offered breathlessness education and personalised feedback. Outcomes of interest included change in breathlessness and quality of life. Additionally, quality assessment was conducted on apps addressing breathlessness publicly available from Google Play, iOS app store, and regulatory agency libraries. RESULTS: A total of 2774 records were screened and 16 studies included in the systematic review. Disease groups addressed were chronic obstructive pulmonary disease, asthma, fibrotic lung disease, lung cancer, and heart failure. Use of mobile apps was found to result in clinical benefit especially when utilised for longer periods of time. For publicly available apps, a total of 776 apps were screened and 6 apps included. The mean quality rating using the Mobile App Rating Scale was 3.43 out of 5. Most apps were found to have good functionality and aesthetics; however, they were lacking in their quality of information and engagement. CONCLUSION: This review suggests that apps may provide clinical benefit to patients with breathlessness and can support clinical practice. However, few of those researched are available for public use and those accessible publicly were lacking in quality and compliance with m-Health best practices.

A systematic review on the effectiveness and impact of clinical decision support systems for breathlessness.

Breathlessness is a common presenting symptom in practice. This systematic review aimed to evaluate the impact of CDSS on breathlessness and associated diseases in real-world clinical settings. Studies published between 1 January 2000 to 10 September 2021 were systematically obtained from 14 electronic research databases including CENTRAL, Embase, Pubmed, and clinical trial registries. Main outcomes of interest were patient health outcomes, provider use, diagnostic concordance, economic evaluation, and unintended consequences. The review protocol was prospectively registered in PROSPERO (CRD42020163141). A total of 4294 records were screened and 37 studies included of which 30 were RCTs. Twenty studies were in primary care, 13 in hospital outpatient/emergency department (ED), and the remainder mixed. Study duration ranged from 2 weeks to 5 years. Most were adults (58%). Five CDSS were focused on assessment, one on assessment and management, and the rest on disease-specific management. Most studies were disease-specific, predominantly focused on asthma (17 studies), COPD (2 studies), or asthma and COPD (3 studies). CDSS for COPD, heart failure, and asthma in adults reported clinical benefits such as reduced exacerbations, improved quality of life, improved patient-reported outcomes or reduced mortality. Studies identified low usage as the main barrier to effectiveness. Clinicians identified dissonance between CDSS recommendations and real-world practice as a major barrier. This review identified potential benefits of CDSS implementation in primary care and outpatient services for adults with heart failure, COPD, and asthma in improving diagnosis, compliance with guideline recommendations, promotion of non-pharmacological interventions, and improved clinical outcomes including mortality.

A Design Thinking Approach to Developing a Clinical Decision Support System for Breathlessness in Primary Care.

Clinical decision support systems (CDSS) have the potential to support guideline implementation and bridge the research translation chasm. However, clinician barriers to uptake remain strongly reported in previous studies. This study aims to utilise a design thinking approach to develop a CDSS for breathlessness in primary care. A low fidelity mockup was developed based on an exploratory focus group to elucidate clinician needs and assess responses to key features. The low fidelity prototype was then developed and tested through two rounds of Think-Aloud testing. Post each Think-Aloud, changes were made and split-run (A/B) testing conducted in the second round in response to user interface concerns raised in the first round. Overall, GPs find the CDSS to be a useful addition to their breathlessness assessment and are open to its use. This study showed that utilising a design thinking and practice-oriented approach with rapid usability testing, it was possible to gain crucial insight in a more rapid and cost effective way.

Systematic review of effectiveness and quality assessment of patient education materials and decision aids for breathlessness.

BACKGROUND: Around 10% of adults suffer from clinically significant breathlessness. High quality and actionable patient education materials (PEMs) and patient decision aids (PDAs) have an important role for shared decision making and patient self-management. OBJECTIVE: To systematically assess the effectiveness of patient education materials (PEMs) and patient decision aids (PDAs) on clinical outcomes. Secondly, to assess the quality of PEMs and PDAs for breathlessness that are accessible online. METHODS: A systematic review of PEM or PDA intervention for breathlessness published between 1 January 2010 and November 2020 was conducted. An environmental scan and quality assessment of publicly available PEMs and PDAs was also conducted. RESULTS: Out of 2985 records, five studies were eligible for inclusion in this systematic review. Results of two randomised controlled trials suggest potential effectiveness of PEMs to improve patient reported outcomes and reduce healthcare utilization. In the environmental scan, 88 materials were included. Minimum reading age for most was high (Grade 10) and PEMs scored an average of 87% for understandability and 67% for actionability. Based on the DISCERN tool only 10 were classified as high quality. CONCLUSION: There is a paucity of evidence on the effectiveness of PEMs and PDAs for improvement in breathlessness. There is a need to develop higher quality PEMs for breathlessness.

Applications of nanoparticles in cardiovascular imaging and therapeutics.

Cardiovascular disease (CVD) is a major health problem afflicting millions of people worldwide. Early detection methods are lacking, and current therapies have significant limitations. Recently, there has been a surge in the number of studies investigating the utilisation of nanoparticles in cardiovascular imaging and therapy. With respect to cardiovascular imaging, previous studies have looked at the role of nanoparticles in thrombus formation, angiogenesis, blood pool and stem cell imaging. Whereas, with respect to therapy, nanoparticles have been studied for delivering drugs and nucleic acids, specifically to the site of interest; in the context of cardiac regeneration; and its potential in refining current therapy guidelines for CVD management. This review aims to extensively summarise the studies that have been conducted investigating the role of nanoparticles in different aspects of cardiovascular imaging and therapy.

Assessment and diagnosis of chronic dyspnoea: a literature review.

Dyspnoea or breathlessness is a common presenting symptom among patients attending primary care services. This review aimed to determine whether there are clinical tools that can be incorporated into a clinical decision support system for primary care for efficient and accurate diagnosis of causes of chronic dyspnoea. We searched MEDLINE, EMBASE and Google Scholar for all literature published between 1946 and 2020. Studies that evaluated a clinical algorithm for assessment of chronic dyspnoea in patients of any age group presenting to physicians with chronic dyspnoea were included. We identified 326 abstracts, 55 papers were reviewed, and eight included. A total 2026 patients aged between 20-80 years were included, 60% were women. The duration of dyspnoea was three weeks to 25 years. All studies undertook a stepwise or algorithmic approach to the assessment of dyspnoea. The results indicate that following history taking and physical examination, the first stage should include simply performed tests such as pulse oximetry, spirometry, and electrocardiography. If the patient remains undiagnosed, the second stage includes investigations such as chest x-ray, thyroid function tests, full blood count and NT-proBNP. In the third stage patients are referred for more advanced tests such as echocardiogram and thoracic CT. If dyspnoea remains unexplained, the fourth stage of assessment will require secondary care referral for more advanced diagnostic testing such as exercise tests. Utilising this proposed stepwise approach is expected to ascertain a cause for dyspnoea for 35% of the patients in stage 1, 83% by stage 3 and >90% of patients by stage 4.

Asthma and risk of infection, hospitalization, ICU admission and mortality from COVID-19: Systematic review and meta-analysis.

OBJECTIVE: As COVID-19 spreads across the world, there are concerns that people with asthma are at a higher risk of acquiring the disease, or of poorer outcomes. This systematic review aimed to summarize evidence on the risk of infection, severe illness and death from COVID-19 in people with asthma. DATA SOURCES AND STUDY SELECTION: A comprehensive search of electronic databases including preprint repositories and WHO COVID-19 database was conducted (until 26 May 2020). Studies reporting COVID-19 in people with asthma were included. For binary outcomes, we performed Sidik-Jonkman random effects meta-analysis. We explored quantitative heterogeneity by subgroup analyses, meta regression and evaluating the I2 statistic. RESULTS: Fifty-seven studies with an overall sample size of 587 280 were included. The prevalence of asthma among those infected with COVID-19 was 7.46% (95% CI = 6.25-8.67). Non-severe asthma was more common than severe asthma (9.61% vs. 4.13%). Pooled analysis showed a 14% risk ratio reduction in acquiring COVID-19 (95% CI = 0.80-0.94; p < 0.0001) and 13% reduction in hospitalization with COVID-19 (95% CI = 0.77-0.99, p = 0.03) for people with asthma compared with those without. There was no significant difference in the combined risk of requiring admission to ICU and/or receiving mechanical ventilation for people with asthma (RR = 0.87 95% CI = 0.94-1.37; p = 0.19) and risk of death from COVID-19 (RR = 0.87; 95% CI = 0.68-1.10; p = 0.25). CONCLUSION: The findings from this study suggest that the prevalence of people with asthma among COVID-19 patients is similar to the global prevalence of asthma. The overall findings suggest that people with asthma have a lower risk than those without asthma for acquiring COVID-19 and have similar clinical outcomes.

Asthma and COVID-19 risk: a systematic review and meta-analysis.

BACKGROUND: Individual case series and cohort studies have reported conflicting results in people with asthma on the vulnerability to and risk of mortality from coronavirus disease 2019 (COVID-19). RESEARCH QUESTION: Are people with asthma at a higher risk of being infected or hospitalised or poorer clinical outcomes from COVID-19? METHODS: A systematic review and meta-analysis based on five main databases including the World Health Organization COVID-19 database between 1 December 2019 and 11 July 2021 on studies with a control (non-asthma) group was conducted. Prevalence and risk ratios were pooled using Sidik-Jonkman random-effects meta-analyses. FINDINGS: 51 studies with an 8.08% (95% CI 6.87-9.30%) pooled prevalence of people with asthma among COVID-19 positive cases. The risk ratios were 0.83 (95% CI 0.73-0.95, p=0.01) for acquiring COVID-19; 1.18 (95% CI 0.98-1.42, p=0.08) for hospitalisation; 1.21 (95% CI 0.97-1.51, p=0.09) for intensive care unit (ICU) admission; 1.06 (95% CI 0.82-1.36, p=0.65) for ventilator use; and 0.94 (95% CI 0.76-1.17, p=0.58) for mortality for people with asthma. Subgroup analyses by continent revealed a significant difference in risk of acquiring COVID-19, ICU admission, ventilator use and death between the continents. INTERPRETATION: The risk of being infected with severe acute respiratory syndrome coronavirus 2 was reduced compared to the non-asthma group. No statistically significant differences in hospitalisation, ICU admission and ventilator use were found between groups. Subgroup analyses showed significant differences in outcomes from COVID-19 between America, Europe and Asia. Additional studies are required to confirm this risk profile, particularly in Africa and South America, where few studies originate.

Co-Designing a Primary Care Breathlessness Decision Support System: General Practitioners Requirements Analysis, Workflow Assessment and Prototype Development.

Clinical decision support systems (CDSS) have been shown in a variety of diseases to lead to improvements in care. The aim of this study is to design a CDSS to assist GPs to assess and manage breathlessness, a highly prevalent symptom in practice. A focus group is conducted to explore the needs of general practitioners (GPs), assess current workflow to identify points for intervention and develop early prototypes for testing. Five GPs took part in the focus group elucidating 248 relevant data points which were then qualitatively analyzed using the Technology Acceptance Model as the theoretical framework. In general, there was a positive attitude towards the use of CDSS for breathlessness with various proposed features from the participants. Twelve high level workflow steps were identified with 5 as key points for intervention. Several proposed features such as reporting likelihood of causes of breathlessness in a patient, link with evidence-based recommendations, integration with clinical notes and patient education materials were translated into a prototype. Mixed-method studies are planned to assess its usability to inform subsequent iterations of the CDSS development.

Targeting ageing and preventing organ degeneration with metformin.

BACKGROUND: Ageing is characterized by a decline in cognitive and bodily functions. Metformin, the most commonly prescribed antidiabetic agent today, has proved to be able to modulate oxidative stress, several inflammatory pathways and cellular senescence to promote anti-ageing. This review aims to explore and summarize the effects of metformin on ageing. RESULTS: Metformin, a longstanding treatment for diabetes, has been shown to increase lifespan in both vertebrate and mammalian models. This pleiotropic effect is hypothesized to mimic calorie restriction, a currently proven means of slowing ageing, by decreasing insulin and insulin-like growth factor (IGF)-1 levels and improving insulin sensitivity. However, studies have shown that metformin is also able to target several other ageing pathways, thereby inhibiting mammalian target of rapamycin (mTOR), increasing AMPK activity and improving DNA repair. Clinical studies, such as those supported by the UK Clinical Practice Research Datalink service, have reported that diabetes patients treated with metformin live longer than patients without diabetes. Metformin use can also reduce type 2 diabetes mellitus (T2DM) incidence among those at risk, lower cancer incidence, and improve cognitive function, cardiovascular disease (CVD) risk factors and atherosclerosis. CONCLUSION: Various studies have found that metformin can target several nutrient-sensing, anti-ageing and immune pathways, leading to reductions in oxidative stress, inflammation and DNA damage as well as providing effects similar to those of calorie restriction. However, further trials are still needed to confirm these findings.

Evidence Review and Practice Recommendation on the Material, Design, and Maintenance of Cloth Masks.

Despite numerous masking recommendations from public health agencies, including the World Health Organization, editorials, and commentaries providing support for this notion, none had examined different homemade masks or demonstrated that perhaps not all cloth masks are the same. This article aims to provide evidence-based recommendations on cloth-mask materials, its design, and, importantly, its maintenance. Articles were obtained from PubMed and preprint servers up to June 10, 2020. Current evidence suggests that filtration effectiveness can range from 3% to 95%. Multiple layer (hybrid) homemade masks made from a combination of high density 100% cotton and materials with electrostatic charge would be more effective than one made from a single material. Mask fit greatly affects filtration efficiency, and adding an overhead knot or nylon overlay potentially provides the best fit for cloth masks. There is a paucity of evidence for masks maintenance as most studies are in the laboratory setting; however, switching every 4 hours as in medical masks and stored in dedicated containers while awaiting disinfection is recommended. Outside of these recommendations to improve the effectiveness of cloth masks to reduce infection transmission, there is a need for countries to set up independent testing labs for homemade masks made based on locally available materials. This can use existing occupational health laboratories usually used for accrediting masks and respirators.

Pooled Testing for Expanding COVID-19 Mass Surveillance.

Diagnostic testing to identify patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) plays a key role to control the coronavirus disease (COVID-19) pandemic. While several countries have implemented the use of diagnostic testing in a massive scale as a cornerstone for infection control and surveillance, other countries affected by the pandemic are hampered by its limited testing capacity. Pooled testing was first introduced in the 1940s and is now used for screening in blood banks. Testing is done by pooling multiple individual samples together. Only in the case of a positive pool test would individual samples of the pool be tested, thus substantially reducing the number of tests needed. Several studies regarding their use for SARS CoV-2 have been done in the United States, Israel, and Germany. Studies have shown that an individual positive sample can still be detected in pools of up to 32 samples, and possibly even 64 samples, provided that additional polymerase chain reaction (PCR) amplification cycles are conducted with a sensitivity of 96%. Simulation studies to determine optimal pool size and pooling techniques have also been conducted. Based on these studies, pooled testing is shown to be able to detect positive samples with sufficient accuracy and can easily be used with existing equipment and personnel for population-wide screening.