Recommendations for asthma monitoring in children: A PeARL document endorsed by APAPARI, EAACI, INTERASMA, REG, and WAO.

Monitoring is a major component of asthma management in children. Regular monitoring allows for diagnosis confirmation, treatment optimization, and natural history review. Numerous factors that may affect disease activity and patient well-being need to be monitored: response and adherence to treatment, disease control, disease progression, comorbidities, quality of life, medication side-effects, allergen and irritant exposures, diet and more. However, the prioritization of such factors and the selection of relevant assessment tools is an unmet need. Furthermore, rapidly developing technologies promise new opportunities for closer, or even "real-time," monitoring between visits. Following an approach that included needs assessment, evidence appraisal, and Delphi consensus, the PeARL Think Tank, in collaboration with major international professional and patient organizations, has developed a set of 24 recommendations on pediatric asthma monitoring, to support healthcare professionals in decision-making and care pathway design.

Climate-conscious inhaler prescribing for family physicians.

OBJECTIVE: To provide family physicians with prescribing and diagnostic strategies that can reduce carbon emissions associated with inhalers. SOURCES OF INFORMATION: This review is based on the authors' experience developing the climate-conscious inhaler prescribing playbooks and courses for CASCADES (Creating a Sustainable Canadian Health System in a Climate Crisis). The approach was refined through patient and provider feedback since the first playbook was published in 2021. PubMed was also searched for relevant publications on inhaler use, asthma management, and chronic obstructive pulmonary disease (COPD) management. Current asthma and COPD guidelines were also reviewed. MAIN MESSAGE: There is growing acknowledgment of the substantial impact that inhalers have on climate emissions generated by the health sector. Recent surveys indicate that most Canadian patients care about climate change and would be willing to opt for less carbon-intensive treatment and care delivery options where available. Beyond inhaler choice, there are many opportunities to address the climate impacts of respiratory care and enhance quality of care. Working with patients to ensure they are using the right medications in the right ways will produce both carbon savings and better health outcomes. The climate crisis can therefore serve as a catalyst for improving treatment of patients with respiratory conditions. Family physicians may reduce carbon emissions associated with inhalers by reducing unnecessary inhaler prescribing; ensuring patients' control of asthma and COPD is optimized; considering whether a more sustainable inhaler may be appropriate; optimizing dosing technique to reduce emissions and waste; and disposing of inhalers appropriately if possible. CONCLUSION: Family physicians may reduce carbon emissions associated with inhalers through the following strategies: confirming diagnosis, controlling disease, considering inhaler type, optimizing dosing technique, and encouraging appropriate disposal.

Canadian Health Care Professionals' Familiarity with Chronic Cough Guidelines and Experiences with Diagnosis and Management: A Cross-Sectional Survey.

INTRODUCTION: Educational programs on chronic cough may improve patient care, but little is known about how Canadian physicians manage this common debilitating condition. We aimed to investigate Canadian physicians' perceptions, attitudes, and knowledge of chronic cough. METHODS: We administered a 10-min anonymous, online, cross-sectional survey to 3321 Canadian physicians in the Leger Opinion Panel who managed adult patients with chronic cough and had been in practice for > 2 years. RESULTS: Between July 30 and September 22, 2021, 179 physicians (101 general practitioners [GPs] and 78 specialists [25 allergists, 28 respirologists, and 25 ear/nose/throat specialists]) completed the survey (response rate: 5.4%). In a month, GPs saw a mean of 27 patients with chronic cough, whereas specialists saw 46. About one-third of physicians appropriately identified a duration of > 8 weeks as the definition for chronic cough. Many physicians reported not using international chronic cough management guidelines. Patient referrals and care pathways varied considerably, and patients frequently experienced lost to follow-up. While physicians endorsed nasal and inhaled corticosteroids as common treatments for chronic cough, they rarely used other guideline-recommended treatments. Both GPs and specialists expressed high interest in education on chronic cough. CONCLUSION: This survey of Canadian physicians demonstrates low uptake of recent advances in chronic cough diagnosis, disease categorization, and pharmacologic management. Canadian physicians also report unfamiliarity with guideline-recommended therapies, including centrally acting neuromodulators for refractory or unexplained chronic cough. This data highlights the need for educational programs and collaborative care models on chronic cough in primary and specialist care.

For UW Health, Health Plan Ownership Provides Financial Stability.

For health systems seeking a path forward and upward in a value-based environment, ownership of a health plan can yield many positives, including a chance to drive value-based care, financial margin improvement, and opportunities for rewarding partnerships. However, being both a payer and a provider-a "payvider"-can make extraordinary demands on both the health system and health plan. Developing this hybrid business has been a learning experience for UW Health, an academic medical center that, like others in academic healthcare, was built on a fee-for-service model. Today, UW Health is a majority owner of what has become the state's largest provider-owned health plan. As illustrated here, health plan ownership is not for every system. The burdens are heavy. But for UW Health, it is an important component of both mission and margin.

COPD Population in US Primary Care: Data From the Optimum Patient Care DARTNet Research Database and the Advancing the Patient Experience in COPD Registry.

PURPOSE: To describe demographic and clinical characteristics of chronic obstructive pulmonary disease patients managed in US primary care. METHODS: This was an observational registry study using data from the Chronic Obstructive Pulmonary Disease (COPD) Optimum Patient Care DARTNet Research Database from which the Advancing the Patient Experience COPD registry is derived. Registry patients were aged ≥35 years at diagnosis. Electronic health record data were collected from both registries, supplemented with patient-reported information/outcomes from the Advancing the Patient Experience registry from 5 primary care groups in Texas, Ohio, Colorado, New York, and North Carolina (June 2019 through November 2020). RESULTS: Of 17,192 patients included, 1,354 were also in the Advancing the Patient Experience registry. Patients were predominantly female (56%; 9,689/17,192), White (64%; 9,732/15,225), current/ex-smokers (80%; 13,784/17,192), and overweight/obese (69%; 11,628/16,849). The most commonly prescribed maintenance treatments were inhaled corticosteroid with a long-acting ß2-agonist (30%) and inhaled corticosteroid with a long-acting muscarinic antagonist (27%). Although 3% (565/17,192) of patitents were untreated, 9% (1,587/17,192) were on short-acting bronchodilator monotherapy, and 4% (756/17,192) were on inhaled corticosteroid monotherapy. Despite treatment, 38% (6,579/17,192) of patients experienced 1 or more exacerbations in the last 12 months. These findings were mirrored in the Advancing Patient Experience registry with many patients reporting high or very high impact of disease on their health (43%; 580/1,322), a breathlessness score 2 or more (45%; 588/1,315), and 1 or more exacerbation in the last 12 months (50%; 646/1,294). CONCLUSIONS: Our findings highlight the high exacerbation, symptom, and treatment burdens experienced by COPD patients managed in US primary care, and the need for more real-life effectiveness trials to support decision making at the primary care level.

Unsupervised probabilistic models for sequential Electronic Health Records.

We develop an unsupervised probabilistic model for heterogeneous Electronic Health Record (EHR) data. Utilizing a mixture model formulation, our approach directly models sequences of arbitrary length, such as medications and laboratory results. This allows for subgrouping and incorporation of the dynamics underlying heterogeneous data types. The model consists of a layered set of latent variables that encode underlying structure in the data. These variables represent subject subgroups at the top layer, and unobserved states for sequences in the second layer. We train this model on episodic data from subjects receiving medical care in the Kaiser Permanente Northern California integrated healthcare delivery system. The resulting properties of the trained model generate novel insight from these complex and multifaceted data. In addition, we show how the model can be used to analyze sequences that contribute to assessment of mortality likelihood.

Continuous-time probabilistic models for longitudinal electronic health records.

Analysis of longitudinal Electronic Health Record (EHR) data is an important goal for precision medicine. Difficulty in applying Machine Learning (ML) methods, either predictive or unsupervised, stems in part from the heterogeneity and irregular sampling of EHR data. We present an unsupervised probabilistic model that captures nonlinear relationships between variables over continuous-time. This method works with arbitrary sampling patterns and captures the joint probability distribution between variable measurements and the time intervals between them. Inference algorithms are derived that can be used to evaluate the likelihood of future using under a trained model. As an example, we consider data from the United States Veterans Health Administration (VHA) in the areas of diabetes and depression. Likelihood ratio maps are produced showing the likelihood of risk for moderate-severe vs minimal depression as measured by the Patient Health Questionnaire-9 (PHQ-9).

A real-life comparative effectiveness study into the addition of antibiotics to the management of asthma exacerbations in primary care.

BACKGROUND: Asthma exacerbations are major contributors to asthma morbidity and mortality. They are usually managed with bronchodilators and oral corticosteroids (OCS), but clinical trial evidence suggests that antibiotics could be beneficial. We aimed to assess whether treatment of asthma exacerbations with antibiotics in addition to OCS improved outcomes in larger, more representative routine-care populations. METHOD: A retrospective comparative effectiveness study into managing asthma exacerbations with OCS alone versus OCS plus antibiotics was conducted using the Optimum Patient Care Research Database. The dataset included 28 637 patients; following propensity score matching 20 024 adults and 4184 children were analysed. RESULTS: Antibiotics in addition to OCS were prescribed for the treatment of asthma exacerbations in 45% of adults and 32% of children. Compared to OCS alone, OCS plus antibiotics was associated with reduced risk of having an asthma/wheeze consultation in the following 2 weeks (children hazard ratio (HR) 0.84 (95% CI 0.73-0.96), p=0.012; adults HR 0.86 (95% CI 0.81-0.91), p<0.001), but an increase in risk of a further OCS prescription for a new/ongoing exacerbation within 6 weeks in adults (HR 1.11 (95% CI 1.01-1.21), p=0.030), but not children. Penicillins, but not macrolides, were associated with a reduction in the odds of a subsequent asthma/wheeze consultation compared to OCS alone, in both adults and children. CONCLUSION: Antibiotics were frequently prescribed in relation to asthma exacerbations, contrary to guideline recommendations. Overall, the routine addition of antibiotics to OCS in the management of asthma exacerbations appeared to confer little clinical benefit, especially when considering the risks of antibiotic overuse.

Reducing the hidden burden of severe asthma: recognition and referrals from primary practice.

Since their introduction many decades ago, systemic corticosteroids have become a mainstay treatment for asthma. Despite being a highly effective therapy, corticosteroids can cause significant adverse effects in patients. This results in a "double hit" for some patients as they suffer the burden of disease as well as the burden of treatment-induced morbidity.This article aims to raise awareness of the potential, harmful side effects of prolonged or repeated exposure to systemic corticosteroids in asthma. It also highlights the importance of referral of the appropriate patients with asthma from primary care for specialist assessment once other considerations such as adherence, inhaler technique and co-morbidity have been evaluated. We propose a simple decision step that may help busy primary care physicians and general practitioners to identify patients who could benefit from specialist assessment.Our decision step suggests that a patient with asthma should be reviewed at least once by an asthma specialist if he/she (i) has received ≥2 courses of oral corticosteroids in the previous year; asthma remains uncontrolled despite good adherence and inhaler technique; or (ii) has attended an emergency department or was hospitalized for asthma care.Such referral could facilitate wider access to diagnostic tools, in-depth assessment of confounding comorbidities, and non-corticosteroid-based therapies as needed, which may be unavailable in primary practice.

Accessing Highly Oriented Two-Dimensional Perovskite Films via Solvent-Vapor Annealing for Efficient and Stable Solar Cells.

Accessing vertical orientation of two-dimensional (2D) perovskite films is key to achieving high-performance solar cells with these materials. Herein, we report on solvent-vapor annealing (SVA) as a general postdeposition strategy to induce strong vertical orientation across broad classes of 2D perovskite films. We do not observe any local compositional drifts that would result in impure phases during SVA. Instead, our experiments point to solvent vapor plasticizing 2D perovskite films and facilitating their surface-induced reorientation and concomitant grain growth, which enhance out-of-plane charge transport. Solar cells with SVA 2D perovskites exhibit superior efficiency and stability compared to their untreated analogs. With a certified efficiency of (18.00 ± 0.30) %, our SVA (BDA)(Cs0.1FA0.9)4Pb5I16 solar cell boasts the highest efficiency among all solar cells with 2D perovskites (n ≤ 5) reported so far.

A comparison of tiotropium, long-acting ß2-agonists and leukotriene receptor antagonists on lung function and exacerbations in paediatric patients with asthma.

Diagnosing and treating asthma in paediatric patients remains challenging, with many children and adolescents remaining uncontrolled despite treatment. Selecting the most appropriate pharmacological treatment to add onto inhaled corticosteroids (ICS) in children and adolescents with asthma who remain symptomatic despite ICS can be difficult. This literature review compares the efficacy and safety of long-acting ß2-agonists (LABAs), leukotriene receptor antagonists (LTRAs) and long-acting muscarinic antagonists (LAMAs) as add-on treatment to ICS in children and adolescents aged 4-17 years.A literature search identified a total of 29 studies that met the inclusion criteria, including 21 randomised controlled trials (RCTs) of LABAs versus placebo, two RCTs of LAMAs (tiotropium) versus placebo, and four RCTs of LTRA (montelukast), all as add-on to ICS. In these studies, tiotropium and LABAs provided greater improvements in lung function than LTRAs, when compared with placebo as add-on to ICS. Although exacerbation data were difficult to interpret, tiotropium reduced the risk of exacerbations requiring oral corticosteroids when added to ICS, with or without additional controllers. LABAs and LTRAs had a comparable risk of asthma exacerbations with placebo when added to ICS. When adverse events (AEs) or serious AEs were analysed, LABAs, montelukast and tiotropium had a comparable safety profile with placebo.In conclusion, this literature review provides an up-to-date overview of the efficacy and safety of LABAs, LTRAs and LAMAs as add-on to ICS in children and adolescents with asthma. Overall, tiotropium and LABAs have similar efficacy, and provide greater improvements in lung function than montelukast as add-on to ICS. All three controller options have comparable safety profiles.

Azetidine-based selective glycine transporter-1 (GlyT1) inhibitors with memory enhancing properties.

A strategy to conformationally restrain a series of GlyT1 inhibitors identified potent analogs that exhibited slowly interconverting rotational isomers. Further studies to address this concern led to a series of azetidine-based inhibitors. Compound 26 was able to elevate CSF glycine levels in vivo and demonstrated potency comparable to Bitopertin in an in vivo rat receptor occupancy study. Compound 26 was subsequently shown to enhance memory in a Novel Object Recognition (NOR) behavioral study after a single dose of 0.03 mg/kg, and in a contextual fear conditioning (cFC) study after four QD doses of 0.01-0.03 mg/kg.

Opportunities to diagnose fibrotic lung diseases in routine care: A primary care cohort study.

BACKGROUND AND OBJECTIVE: Temporal trends of healthcare use in the period before a diagnosis of pulmonary fibrosis are poorly understood. We investigated trends in respiratory symptoms and LR HRU in the 10 years prior to diagnosis. METHODS: We analysed a primary care clinical cohort database (UK OPCRD) and assessed patients aged ≥40 years who had an electronically coded diagnosis of pulmonary fibrosis between 2005 and 2015 and a minimum 2 years of continuous medical records prior to diagnosis. Exclusion criteria consisted of electronic codes for recognized causes of pulmonary fibrosis such as CTD, sarcoidosis or EAA. RESULTS: Data for 2223 patients were assessed. Over the 10 years prior to diagnosis of pulmonary fibrosis, there was a progressive increase in HRU across multiple LR-related domains. Five years before diagnosis, 18% of patients had multiple healthcare contacts for LR complaints; this increased to 79% in the year before diagnosis, with 38% of patients having five or more healthcare contacts. CONCLUSION: There are opportunities to diagnose pulmonary fibrosis at an earlier stage; research into case-finding algorithms and strategies to educate primary care physicians is required.

The Electronic Asthma Management System (eAMS) improves primary care asthma management.

A high prevalence of suboptimal asthma control is attributable to known evidence-practice gaps. We developed a computerised clinical decision support system (the Electronic Asthma Management System (eAMS)) to address major care gaps and sought to measure its impact on care in adults with asthma.This was a 2-year interrupted time-series study of usual care (year 1) versus eAMS (year 2) at three Canadian primary care sites. We included asthma patients aged ≥16 years receiving an asthma medication within the last 12 months. The eAMS consisted of a touch tablet patient questionnaire completed in the waiting room, with real-time data processing producing electronic medical record-integrated clinician decision support.Action plan delivery (primary outcome) improved from zero out of 412 (0%) to 79 out of 443 (17.8%) eligible patients (absolute increase 0.18 (95% CI 0.14-0.22)). Time-series analysis indicated a 30.5% increase in physician visits with action plan delivery with the intervention (p<0.0001). Assessment of asthma control level increased from 173 out of 3497 (4.9%) to 849 out of 3062 (27.7%) eligible visits (adjusted OR 8.62 (95% CI 5.14-12.45)). Clinicians escalated controller therapy in 108 out of 3422 (3.2%) baseline visits versus 126 out of 3240 (3.9%) intervention visits (p=0.12). At baseline, a short-acting ß-agonist alone was added in 62 visits and a controller added in 54 visits; with the intervention, this occurred in 33 and 229 visits, respectively (p<0.001).The eAMS improved asthma quality of care in real-world primary care settings. Strategies to further increase clinician uptake and a randomised controlled trial to assess impact on patient outcomes are now required.

Patient preferences for a touch screen tablet-based asthma questionnaire.

OBJECTIVE: Assessment of asthma control and provision of asthma action plans are seldom performed in practice, partly due to limited time for physicians to ascertain required information. A patient-facing electronic asthma questionnaire could facilitate information collection. We sought to design a touch-tablet asthma questionnaire for use in the clinic waiting room and to describe patient preferences for the content of such a questionnaire. METHODS: We created a questionnaire prototype based on best evidence and employed rapid-cycle design (semi-structured focus group testing; analysis; corresponding modifications and re-testing) with asthma patients aged ≥16 years. We analyzed transcripts using deductive and inductive content analysis. Quantitative measures included Likert-scale questions and questionnaire completion times. RESULTS: There were 20 participants across five focus groups (15/20 (75%) female, age 49.1 ± 15.6 years). Content-related themes included: 1) comprehensibility (language) (how questionnaire language affected ease and accuracy of comprehension) and b) information collection (issues arising during information collection in the following identified subthemes: personal asthma symptoms and triggers; asthma control; asthma medications and contact information). Average questionnaire completion time was 11.7 ± 5.9 min. Summative Likert scale responses suggested high levels of question comprehension and confidence with responses. CONCLUSIONS: Our analysis provides novel insight about how best to formulate and present asthma-related content in an electronic questionnaire. Such questionnaires might facilitate quality improvement by improving efficiency of data collection, enabling better assessment of asthma control and medication adherence, and personalization of asthma action plans. Future studies should measure real-world uptake of such a questionnaire and impact on care.

New evidence-based tool to guide the creation of asthma action plans for adults.

OBJECTIVE: To improve the use of asthma action plans (AAPs) among primary care physicians. SOURCES OF INFORMATION: In a 2017 article, recent asthma guidelines and adult studies (January 2010 to March 2016) addressing acute loss of asthma control were reviewed to develop an evidence-based tool to help guide physicians in creating AAPs to maximize adherence and minimize errors. Evidence supporting the effects of AAPs is level I. Evidence supporting the recommendations in the tool ranges from level I to consensus. MAIN MESSAGE: A lack of knowledge about and training in creating appropriate AAP content is an important barrier to the use of AAPs, as is the fact that instructions provided by asthma guidelines are often difficult to integrate into real-world practice. In order to address these issues, a freely accessible, practical, evidence-based tool has recently been created, addressing both the knowledge and the practical barriers to AAP creation. This tool has been formatted as a printable bedside chart for the point of care, but could also be integrated into a computerized electronic decision support system in the future. CONCLUSION: Asthma action plans, in conjunction with asthma education and regular follow-up, can improve patients' symptoms and quality of life and reduce hospitalization. This novel point-of-care tool provides practical advice on how to complete AAPs to improve patients' asthma self-management.

Vaccine strategies for prevention of community-acquired pneumonia in Canada: Who would benefit most from pneumococcal immunization?

OBJECTIVE: To describe the burden of pneumococcal disease and associated risk factors in the Canadian adult population, delineate available pneumococcal vaccines and associated efficacy and effectiveness data, and review current pneumococcal vaccine recommendations and community-acquired pneumonia (CAP) prevention strategies in Canada. QUALITY OF EVIDENCE: Pneumococcal vaccination guidelines from the Canadian National Advisory Committee on Immunization in 2013 and 2016 constitute level III evidence for CAP prevention in the Canadian adult population. MAIN MESSAGE: It is recommended that immunosuppressed adults of all ages receive the 13-valent pneumococcal conjugate vaccine (PCV13) (grades A and B recommendations). In 2016, the National Advisory Committee on Immunization also recommended that all adults aged 65 years and older receive PCV13 (grade A recommendation) on an individual basis, followed by the 23-valent pneumococcal polysaccharide vaccine (grade B recommendation). This update is based on a large clinical study that demonstrated PCV13 efficacy against vaccine-type CAP in this population. CONCLUSION: Physicians should focus on improving pneumococcal vaccination rates among adults, which remain low. Vaccination with PCV13 should also be considered for adults with chronic conditions, whose baseline risk is often higher than that for healthy individuals aged 65 years and older.

Internet Use by Gynecologic Oncology Patients and Its Relationship with Anxiety.

This study describes the use of the Internet for health information research by patients attending a gynecologic oncology practice and examines the association between its use and anxiety. A self-administered survey assessed patients' demographic information and Internet use. The Hospital Anxiety and Depression Scale (HADS) and the State-Trait Anxiety Inventory (STAI) were administered concurrently. Of 212 patients who consented to the study, 98 (46%) had an appointment because of a cancer diagnosis. Of 199 respondents, 91 (46%) reported searching the Internet for information about their condition. Internet searching was unassociated with race/ethnicity and positively associated with education level, annual household income, and married/partnered civil status. Only 16% of the patients reported that a health-care provider recommended use of the Internet for research. Comparing patients who used the Internet for research with those who did not, the STAI state and trait anxiety scores were similar. The HADS anxiety subscale score was higher for those who used the Internet versus those who did not, which suggests heightened anxiety. Internet use for research is common in gynecologic oncology patients, and its use is associated with increased anxiety. Physicians can use this medium to educate patients about their disease, build trust, and alleviate fear.

An evidence-based, point-of-care tool to guide completion of asthma action plans in practice.

Asthma action plans (AAPs) reduce healthcare utilisation, improve quality of life and are recommended across guidelines. However, fewer than 25% of patients receive an AAP, partly due to prescribers' inability to complete "yellow zone" instructions (how to intensify therapy for acute loss of control). We sought to review best evidence to develop a practical, evidence-based tool to facilitate yellow zone guidance in adults.We reviewed recent asthma guidelines and adult studies addressing acute loss of asthma control (January 2010 to March 2016). We developed evidence-based rules for yellow zone therapy and operational guidelines to maximise adherence and minimise errors.We reviewed three guidelines and 11 manuscripts (2486 abstracts screened). Recommendations were comparable but some areas lacked guidance. For 15/43 asthma regimens, the commonly recommended four- to five-fold yellow zone inhaled corticosteroid dose increase was problematic due to regulatory dose limits. We identified evidence-based alternatives for 8/15 regimens. Operational guidance included increasing to a maximum of four inhalations while maintaining baseline inhaler frequency and device in the yellow zone.We developed a practical implementation tool to facilitate AAP delivery at the point of care, addressing existing gaps and uncertainties. Our tool should be implemented as part of a multifaceted approach to augment AAP usage.

Testosterone Therapy on Active Surveillance and Following Definitive Treatment for Prostate Cancer.

PURPOSE OF REVIEW: Previously considered an absolute contraindication, the use of testosterone therapy in men with prostate cancer has undergone an important paradigm shift. Recent data has changed the way we approach the treatment of testosterone deficiency in men with prostate cancer. In the current review, we summarize and analyze the literature surrounding effects of testosterone therapy on patients being treated in an active surveillance protocol as well as following definitive treatment for prostate cancer. RECENT FINDINGS: The conventional notion that defined the relationship between increasing testosterone and prostate cancer growth was based on limited studies and anecdotal case reports. Contemporary evidence suggests testosterone therapy in men with testosterone deficiency does not increase prostate cancer risk or the chances of more aggressive disease at prostate cancer diagnosis. Although the studies are limited, men who received testosterone therapy for localized disease did not have higher rates of recurrences or worse clinical outcomes. Current review of the literature has not identified adverse progression events for patients receiving testosterone therapy while on active surveillance/watchful waiting or definitive therapies. The importance of negative effects of testosterone deficiency on health and health-related quality of life measures has pushed urologists to re-evaluate the role testosterone plays in prostate cancer. This led to a paradigm shift that testosterone therapy might in fact be a viable option for a select group of men with testosterone deficiency and a concurrent diagnosis of prostate cancer.