Interventions to improve inhaler technique for people with asthma.

BACKGROUND: Asthma is a common chronic disease worldwide. Inhalers are often prescribed to help control asthma symptoms, improve quality of life and reduce the risk of exacerbations or flare-ups. However, evidence suggests that many people with asthma do not use their inhaler correctly. It is therefore important to evaluate whether interventions aimed specifically at improving technique are effective and safe, and whether use of these interventions translates into improved clinical outcomes. OBJECTIVES: To assess the impact of interventions to improve inhaler technique on clinical outcomes and safety in adults and children with asthma. SEARCH METHODS: We searched the Cochrane Airways Trials Register, which contains records compiled from multiple electronic and handsearched resources. We also searched trial registries and reference lists of primary studies. We conducted the most recent search on 23 November 2016. SELECTION CRITERIA: We included studies comparing a group of adults or children with asthma receiving an inhaler technique intervention versus a group receiving a control or alternative intervention. We included parallel and cluster-randomised trials of any duration conducted in any setting, and planned to include only the first phase of any cross-over trials identified. We included studies reported as full-text articles, those published as abstracts only and unpublished data. DATA COLLECTION AND ANALYSIS: Two review authors screened the search results for eligible studies. We extracted outcome data, assessed risk of bias in duplicate and resolved discrepancies by involving another review author. We grouped studies making similar comparisons by consensus (e.g. all those comparing enhanced inhaler technique education vs usual care) and conducted meta-analyses only if treatments, participants and the underlying clinical question were similar enough for pooling to make sense. We analysed dichotomous data as odds ratios, and continuous data as mean differences or standardised mean differences, all with random-effects models. We described skewed data narratively. We graded the results and presented evidence in 'Summary of findings' tables for each comparison. Primary outcomes were inhaler technique, asthma control and exacerbations requiring at least oral corticosteroids (OCS). MAIN RESULTS: This review includes 29 parallel randomised controlled trials (RCTs) (n = 2210), although not all reported relevant or useable data. All participants had asthma, and follow-up ranged from 2 to 26 weeks. Most studies were at low or unclear risk of selection and attrition biases and at high risk for biases associated with blinding. We considered most of the evidence to be of low quality owing to these biases and to imprecision in the estimates of effect.We classified studies into three comparisons: enhanced face-to-face training session(s), multi-media-delivered inhaler training (e.g. DVD, computer app or game) and technique feedback devices. Differences between interventions, populations and outcome measures limited quantitative analyses, particularly for exacerbations, adverse events, unscheduled visits to a healthcare provider and absenteeism from work or school.Enhanced inhaler technique education and multi-media training improved technique in most studies immediately after the intervention and at follow-up, although the variety of checklists used meant that this was difficult to assess reliably. For both adults and children, how and when inhaler technique was assessed appeared to affect whether inhaler technique improved and by how much.Analyses of the numbers of people who demonstrated correct or 'good enough' technique were generally more useful than checklist scores. Adult studies of enhanced education showed benefit when this metric was used at 2 to 26 weeks' follow-up (odds ratio (OR) 5.00, 95% confidence interval (CI) 1.83 to 13.65; 258 participants; three studies; 31 per 100 with correct technique in the control group compared with 69 (95% CI 45 to 86) in the education group; moderate-quality evidence). A similar result was seen in studies looking at feedback devices at four weeks' follow-up (OR 4.80, 95% CI 1.87 to 12.33; 97 participants; one study; 51 per 100 with correct technique in the control group compared with 83 (95% CI 66 to 93) in the feedback group; low-quality evidence). However, the benefit of multi-media training for adults even immediately after the intervention was uncertain (OR 2.15, 95% CI 0.84 to 5.50; 164 participants; two studies; I² = 49%; 30 per 100 in the control group with correct technique compared with 47 (95% CI 26 to 70) in the multi-media group; moderate-quality evidence). Evidence tended to be less clear for children, usually because results were based on fewer and smaller studies.Some studies did not report exacerbations in a way that allowed meta-analysis; others provided inconclusive results. Inhaler technique interventions provided some benefit for asthma control and quality of life but generally did not lead to consistent or important clinical benefits for adults or children. Confidence intervals included no difference or did not reach a threshold that could be considered clinically important. Responder analyses sometimes showed improvement among more people in the intervention groups, even though the mean difference between groups was small. We found no evidence about harms. AUTHORS' CONCLUSIONS: Although interventions to improve inhaler technique may work in some circumstances, the variety of interventions and measurement methods used hampered our ability to perform meta-analyses and led to low to moderate confidence in our findings. Most included studies did not report important improvement in clinical outcomes. Guidelines consistently recommend that clinicians check regularly the inhaler technique of their patients; what is not clear is how clinicians can most effectively intervene if they find a patient's technique to be inadequate, and whether such interventions will have a discernible impact on clinical outcomes

Immunomodulatory drugs in sepsis: a systematic review and meta-analysis

\ua9 2024 The Authors. Anaesthesia published by John Wiley & Sons Ltd on behalf of Association of Anaesthetists. Dysregulation of the host immune response has a central role in the pathophysiology of sepsis. There has been much interest in immunomodulatory drugs as potential therapeutic adjuncts in sepsis. We conducted a systematic review and meta-analysis of randomised controlled trials evaluating the safety and clinical effectiveness of immunomodulatory drugs as adjuncts to standard care in the treatment of adults with sepsis. Our primary outcomes were serious adverse events and all-cause mortality. Fifty-six unique, eligible randomised controlled trials were identified, assessing a range of interventions including cytokine inhibitors; anti-inflammatories; immune cell stimulators; platelet pathway inhibitors; and complement inhibitors. At 1-month follow-up, the use of cytokine inhibitors was associated with a decreased risk of serious adverse events, based on 11 studies involving 7138 patients (RR (95%CI) 0.95 (0.90–1.00), I2 = 0%). The only immunomodulatory drugs associated with an increased risk of serious adverse events were toll-like receptor 4 antagonists (RR (95%CI) 1.18 (1.04–1.34), I2 = 0% (two trials, 567 patients)). Based on 18 randomised controlled trials, involving 11,075 patients, cytokine inhibitors reduced 1-month mortality (RR (95%CI) 0.88 (0.78–0.98), I2 = 57%). Mortality reduction was also shown in the subgroup of 13 randomised controlled trials that evaluated anti-tumour necrosis factor α interventions (RR (95%CI) 0.93 (0.87–0.99), I2 = 0%). Anti-inflammatory drugs had the largest apparent effect on mortality at 2 months at any dose (two trials, 228 patients, RR (95%CI) 0.64 (0.51–0.80), I2 = 0%) and at 3 months at any dose (three trials involving 277 patients, RR (95%CI) 0.67 (0.55–0.81), I2 = 0%). These data indicate that, except for toll-like receptor 4 antagonists, there is no evidence of safety concerns for the use of immunomodulatory drugs in sepsis, and they may show some short-term mortality benefit for selected drugs

Inhaled Corticosteroids Particle Size and Risk of Hospitalization Due to Exacerbations and All-Cause Mortality in Patients with Chronic Obstructive Pulmonary Disease. A Nationwide Cohort Study

Christian Kjer Heerfordt,1 Christian Rønn,1 Josefin Eklöf,1 Pradeesh Sivapalan,1 Zitta Barrella Harboe,2,3 Charlotte Hyldgaard,4 Andreas Fløe,5 Alexander G Mathioudakis,6,7 Mats Christian Højbjerg Lassen,8 Tor Biering-Sørensen,8,9 Jens-Ulrik Stæhr Jensen1,3,10 1Section of Respiratory Medicine, Department of Medicine, Copenhagen University Hospital Herlev and Gentofte, Hellerup, Denmark; 2 Department of Respiratory Medicine and Infectious Diseases, Copenhagen University Hospital, North Zealand, Hillerød, Denmark; 3Department of Clinical Medicine Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; 4Diagnostic Centre, University Research Clinic for Innovative Patient Pathways, Silkeborg Regional Hospital, Silkeborg, Denmark; 5Department of Respiratory Diseases and Allergy, Aarhus University Hospital, Aarhus, Denmark; 6Division of Immunology, Immunity to Infection and Respiratory Medicine, School of Biological Sciences, The University of Manchester, Manchester, UK; 7North West Lung Centre, Wythenshawe Hospital, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK; 8Department of Cardiology, Herlev & Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark; 9Faculty of Biomedical Sciences, Copenhagen University, Copenhagen, Denmark; 10PERSIMUNE & CHIP: Department of Infectious Diseases, Rigshospitalet, University of Copenhagen, Copenhagen, DenmarkCorrespondence: Jens-Ulrik Stæhr Jensen, Email [email protected]: Extra-fine particle inhaled corticosteroids (ICS) improve peripheral airway distribution, but their effect on risk of exacerbations and all-cause mortality in patients with chronic obstructive pulmonary disease (COPD) is unclear.Methods: This observational cohort study compares patients with COPD who received extra-fine particle ICS to those who received standard particle size ICS from 2010 to 2017 while followed in outpatient clinics. The primary outcome was the time to a COPD exacerbation that required hospitalization, with all-cause mortality as a secondary outcome. Data were analyzed using an adjusted Cox proportional hazards model and a competing risk analysis. Two predefined subgroup analyses of patients treated with pressurised metered dose inhalers (pMDIs) and patients with a previous exacerbation history, was carried out. Lastly, we created a propensity score matched cohort as a sensitivity analysis.Results: Of the 40,489 patients included, 38,802 (95.8%) received stand particle size ICS and 1,687 (4.2%) received extra-fine particle ICS. In total 7,058 were hospitalized with a COPD exacerbation, and 4,346 died. No significant protective effect of extra-fine particle ICS against hospitalization due to COPD exacerbations (HR 0.93, 95% CI 0.82– 1.05, p=0.23) or all-cause mortality (HR 1.00, 95% CI 0.85– 1.17, p=0.99) was found when compared to standard particle size ICS. However, in the subgroup analysis of patients treated with pMDIs, extra-fine particle ICS was associated with reduction in risk of exacerbations (HR 0.72, 95% CI 0.63– 0.82, p< 0.001) and all-cause mortality (HR 0.72, 95% CI 0.61– 0.86, p< 0.001).Conclusion: The administration of extra-fine particle ICS was not associated with reduced risk of exacerbations or all-cause mortality in our primary analysis. A subgroup consisting of patients treated with pMDIs suggested potential protective benefits.Keywords: COPD, Inhaled Corticosteroids, Particle size, COPD exacerbation

Core outcome set for the management of acute exacerbations of chronic obstructive pulmonary disease: the COS-AECOPD ERS Task Force study protocol.

Randomised controlled trials (RCTs) on the management of COPD exacerbations evaluate heterogeneous outcomes, often omitting those that are clinically important and patient relevant. This limits their usability and comparability. A core outcome set (COS) is a consensus-based minimum set of clinically important outcomes that should be evaluated in all RCTs in specific areas of health care. We present the study protocol of the COS-AECOPD ERS Task Force, aiming to develop a COS for COPD exacerbation management, that could remedy these limitations. For the development of this COS we follow standard methodology recommended by the COMET initiative. A comprehensive list of outcomes is assembled through a methodological systematic review of the outcomes reported in relevant RCTs. Qualitative research with patients with COPD will also be conducted, aiming to identify additional outcomes that may be important to patients, but are not currently addressed in clinical research studies. Prioritisation of the core outcomes will be facilitated through an extensive, multi-stakeholder Delphi survey with a global reach. Selection will be finalised in an international, multi-stakeholder meeting. For every core outcome, we will recommend a specific measurement instrument and standardised time points for evaluation. Selection of instruments will be based on evidence-informed consensus. Our work will improve the quality, usability and comparability of future RCTs on the management of COPD exacerbations and, ultimately, the care of patients with COPD. Multi-stakeholder engagement and societal support by the European Respiratory Society will raise awareness and promote implementation of the COS

Predictors of treatment REsponse to inhaled corticosteroids (ICS) in Chronic Obstructive pulmonary disease: randomised controlled trials individual participant Data re-Evaluation-protocol of the ICS-RECODE individual participant data meta-analysis

Introduction Inhaled corticosteroids (ICS) can improve clinical outcomes in patients with chronic obstructive pulmonary disease (COPD) and eosinophilic airway inflammation, but they also increase the risk of side effects like pneumonia. Blood eosinophils guide ICS use, though evidence is limited. The predictors of treatment REsponse to ICS in COPD: a randomised controlled trials (RCTs) individual participant Data re-Evaluation (ICS-RECODE) research programme will leverage data from large RCTs to identify patients who benefit most from ICS with minimal risk. This protocol details an individual participant data (IPD) meta-analysis, assessing ICS safety, efficacy and treatment×covariate interactions to identify predictors of treatment response. Methods and analysis This meta-analysis will adhere to Cochrane, IPD handbook and Grading of Recommendations Assessment, Development and Evaluation (GRADE) guidance. We will conduct a two-stage IPD meta-analysis of RCTs evaluating the addition of ICS to maintenance COPD treatments. Only RCTs with at least 500 participants across all eligible arms will be included, to allow for treatment×covariate interaction evaluation. Primary outcomes are severe and moderate or severe exacerbation rates; secondary outcomes assess both safety and efficacy. Data from each RCT will be reanalysed using rigorous, consistent statistical methods. Treatment×covariate interactions will be assessed at the RCT level. Trial treatment effects and the coefficients of treatment×covariate interaction analyses will be pooled using random effects model meta-analysis. Risk of bias will be appraised using RoB-2 informed by IPD, and certainty of evidence will be assessed with GRADE and the Instrument to assess the Credibility of Effect Modification Analyses. The ICS-RECODE IPD meta-analysis will make use of the best available data to define evidence-based, precision medicine approaches for ICS use in COPD. Ethics and dissemination The Health Research Authority approved the ICS-RECODE study, exempting it from ethics review (HRA UK, Reference: 24/HRA/0460). Our findings will be published in peer-reviewed journals and shared with the scientific and broader stakeholder communities. PROSPERO registration number CRD42024508286

ERS/EAACI statement on adherence to international adult asthma guidelines

Guidelines aim to standardise and optimise asthma diagnosis and management. Nevertheless, adherence to guidelines is suboptimal and may vary across different healthcare professional (HCP) groups. Further to these concerns, this European Respiratory Society (ERS)/European Academy of Allergy and Clinical Immunology (EAACI) statement aims to: 1) evaluate the understanding of and adherence to international asthma guidelines by HCPs of different specialties via an international online survey; and 2) assess strategies focused at improving implementation of guideline-recommended interventions, and compare process and clinical outcomes in patients managed by HCPs of different specialties via systematic reviews. The online survey identified discrepancies between HCPs of different specialties which may be due to poor dissemination or lack of knowledge of the guidelines but also a reflection of the adaptations made in different clinical settings, based on available resources. The systematic reviews demonstrated that multifaceted quality improvement initiatives addressing multiple challenges to guidelines adherence are most effective in improving guidelines adherence. Differences in outcomes between patients managed by generalists or specialists should be further evaluated. Guidelines need to consider the heterogeneity of real-life settings for asthma management and tailor their recommendations accordingly. Continuous, multifaceted quality improvement processes are required to optimise and maintain guidelines adherence. Validated referral pathways for uncontrolled asthma or uncertain diagnosis are needed

GRADE Guidelines 30: the GRADE approach to assessing the certainty of modeled evidence—An overview in the context of health decision-making

Objectives: The objective of the study is to present the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) conceptual approach to the assessment of certainty of evidence from modeling studies (i.e., certainty associated with model outputs). / Study Design and Setting: Expert consultations and an international multidisciplinary workshop informed development of a conceptual approach to assessing the certainty of evidence from models within the context of systematic reviews, health technology assessments, and health care decisions. The discussions also clarified selected concepts and terminology used in the GRADE approach and by the modeling community. Feedback from experts in a broad range of modeling and health care disciplines addressed the content validity of the approach. / Results: Workshop participants agreed that the domains determining the certainty of evidence previously identified in the GRADE approach (risk of bias, indirectness, inconsistency, imprecision, reporting bias, magnitude of an effect, dose–response relation, and the direction of residual confounding) also apply when assessing the certainty of evidence from models. The assessment depends on the nature of model inputs and the model itself and on whether one is evaluating evidence from a single model or multiple models. We propose a framework for selecting the best available evidence from models: 1) developing de novo, a model specific to the situation of interest, 2) identifying an existing model, the outputs of which provide the highest certainty evidence for the situation of interest, either “off-the-shelf” or after adaptation, and 3) using outputs from multiple models. We also present a summary of preferred terminology to facilitate communication among modeling and health care disciplines. / Conclusion: This conceptual GRADE approach provides a framework for using evidence from models in health decision-making and the assessment of certainty of evidence from a model or models. The GRADE Working Group and the modeling community are currently developing the detailed methods and related guidance for assessing specific domains determining the certainty of evidence from models across health care–related disciplines (e.g., therapeutic decision-making, toxicology, environmental health, and health economics)

GRADE Guidelines 30: The GRADE Approach to Assessing the Certainty of Modelled Evidence - an Overview in the Context of Health Decision-making.

OBJECTIVES: To present the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) conceptual approach to the assessment of certainty of evidence from modelling studies (i.e. certainty associated with model outputs). STUDY DESIGN AND SETTING: Expert consultations and, an international multi-disciplinary workshop informed development of a conceptual approach to assessing the certainty of evidence from models within the context of systematic reviews, health technology assessments, and health care decisions. The discussions also clarified selected concepts and terminology used in the GRADE approach and by the modelling community. Feedback from experts in a broad range of modelling and health care disciplines addressed the content validity of the approach. RESULTS: Workshop participants agreed, that the domains determining the certainty of evidence previously identified in the GRADE approach (risk of bias, indirectness, inconsistency, imprecision, reporting bias, magnitude of an effect, dose-response relation, and the direction of residual confounding) also apply when of assessing the certainty of evidence from models. The assessment depends on the nature of model inputs and the model itself and on whether one is evaluating evidence from a single model or multiple models. We propose a framework for selecting the best available evidence from models: 1) developing de novo a model specific to the situation of interest, 2) identifying an existing model the outputs of which provide the highest certainty evidence for the situation of interest, either "off the shelf" or after adaptation, and 3) using outputs from multiple models. We also present a summary of preferred terminology to facilitate communication among modelling and health care disciplines. CONCLUSIONS: This conceptual GRADE approach provides a framework for using evidence from models in health decision making and the assessment of certainty of evidence from a model or models. The GRADE Working Group and the modelling community are currently developing the detailed methods and related guidance for assessing specific domains determining the certainty of evidence from models across health care-related disciplines (e.g. therapeutic decision-making, toxicology, environmental health, health economics)

Patient Safety in Internal Medicine

AbstractHospital Internal Medicine (IM) is the branch of medicine that deals with the diagnosis and non-surgical treatment of diseases, providing the comprehensive care in the office and in the hospital, managing both common and complex illnesses of adolescents, adults, and the elderly. IM is a key ward for Health National Services. In Italy, for example, about 17.3% of acute patients are discharged from the IM departments. After the epidemiological transition to chronic/degenerative diseases, patients admitted to hospital are often poly-pathological and so requiring a global approach as in IM. As such transition was not associated—with rare exceptions—to hospital re-organization of beds and workforce, IM wards are often overcrowded, burdened by off-wards patients and subjected to high turnover and discharge pressure. All these factors contribute to amplify some traditional clinical risks for patients and health operators. The aim of our review is to describe several potential errors and their prevention strategies, which should be implemented by physicians, nurses, and other healthcare professionals working in IM wards

Global, regional, and national incidence and mortality burden of non-COVID-19 lower respiratory infections and aetiologies, 1990-2021: a systematic analysis from the Global Burden of Disease Study 2021

Background Lower respiratory infections (LRIs) are a major global contributor to morbidity and mortality. In 2020–21, non-pharmaceutical interventions associated with the COVID-19 pandemic reduced not only the transmission of SARS-CoV-2, but also the transmission of other LRI pathogens. Tracking LRI incidence and mortality, as well as the pathogens responsible, can guide health-system responses and funding priorities to reduce future burden. We present estimates from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 of the burden of non-COVID-19 LRIs and corresponding aetiologies from 1990 to 2021, inclusive of pandemic effects on the incidence and mortality of select respiratory viruses, globally, regionally, and for 204 countries and territories. Methods We estimated mortality, incidence, and aetiology attribution for LRI, defined by the GBD as pneumonia or bronchiolitis, not inclusive of COVID-19. We analysed 26 259 site-years of mortality data using the Cause of Death Ensemble model to estimate LRI mortality rates. We analysed all available age-specific and sex-specific data sources, including published literature identified by a systematic review, as well as household surveys, hospital admissions, health insurance claims, and LRI mortality estimates, to generate internally consistent estimates of incidence and prevalence using DisMod-MR 2.1. For aetiology estimation, we analysed multiple causes of death, vital registration, hospital discharge, microbial laboratory, and literature data using a network analysis model to produce the proportion of LRI deaths and episodes attributable to the following pathogens: Acinetobacter baumannii, Chlamydia spp, Enterobacter spp, Escherichia coli, fungi, group B streptococcus, Haemophilus influenzae, influenza viruses, Klebsiella pneumoniae, Legionella spp, Mycoplasma spp, polymicrobial infections, Pseudomonas aeruginosa, respiratory syncytial virus (RSV), Staphylococcus aureus, Streptococcus pneumoniae, and other viruses (ie, the aggregate of all viruses studied except influenza and RSV), as well as a residual category of other bacterial pathogens. Findings Globally, in 2021, we estimated 344 million (95% uncertainty interval [UI] 325–364) incident episodes of LRI, or 4350 episodes (4120–4610) per 100 000 population, and 2·18 million deaths (1·98–2·36), or 27·7 deaths (25·1–29·9) per 100 000. 502 000 deaths (406 000–611 000) were in children younger than 5 years, among which 254 000 deaths (197 000–320 000) occurred in countries with a low Socio-demographic Index. Of the 18 modelled pathogen categories in 2021, S pneumoniae was responsible for the highest proportions of LRI episodes and deaths, with an estimated 97·9 million (92·1–104·0) episodes and 505 000 deaths (454 000–555 000) globally. The pathogens responsible for the second and third highest episode counts globally were other viral aetiologies (46·4 million [43·6–49·3] episodes) and Mycoplasma spp (25·3 million [23·5–27·2]), while those responsible for the second and third highest death counts were S aureus (424 000 [380 000–459 000]) and K pneumoniae (176 000 [158 000–194 000]). From 1990 to 2019, the global all-age non-COVID-19 LRI mortality rate declined by 41·7% (35·9–46·9), from 56·5 deaths (51·3–61·9) to 32·9 deaths (29·9–35·4) per 100 000. From 2019 to 2021, during the COVID-19 pandemic and implementation of associated non-pharmaceutical interventions, we estimated a 16·0% (13·1–18·6) decline in the global all-age non-COVID-19 LRI mortality rate, largely accounted for by a 71·8% (63·8–78·9) decline in the number of influenza deaths and a 66·7% (56·6–75·3) decline in the number of RSV deaths. Interpretation Substantial progress has been made in reducing LRI mortality, but the burden remains high, especially in low-income and middle-income countries. During the COVID-19 pandemic, with its associated non-pharmaceutical interventions, global incident LRI cases and mortality attributable to influenza and RSV declined substantially. Expanding access to health-care services and vaccines, including S pneumoniae, H influenzae type B, and novel RSV vaccines, along with new low-cost interventions against S aureus, could mitigate the LRI burden and prevent transmission of LRI-causing pathogens