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BACKGROUND: Mucociliary clearance (MCC) is critical to lung health and is impaired in many diseases. The path of MCC may have an important impact on clearance but has never been rigorously studied. The objective of this study is to assess the three-dimensional path of human tracheal MCC in disease and health. METHODS: Tracheal MCC was imaged in 12 ex-smokers, 3 non-smokers (1 opportunistically imaged during acute influenza and repeated after recovery) and 5 individuals with primary ciliary dyskinesia (PCD). Radiolabelled macroaggregated albumin droplets were injected into the trachea via the cricothyroid membrane. Droplet movement was tracked via scintigraphy, the path of movement mapped and helical and axial models of tracheal MCC were compared. MEASUREMENTS AND MAIN RESULTS: In 5/5 participants with PCD and 1 healthy participant with acute influenza, radiolabelled albumin coated the trachea and did not move. In all others (15/15), mucus coalesced into globules. Globule movement was negligible in 3 ex-smokers, but in all others (12/15) ascended the trachea in a helical path. Median cephalad tracheal MCC was 2.7 mm/min ex-smokers vs 8.4 mm/min non-smokers (p=0.02) and correlated strongly to helical angle (r=0.92 (p=0.00002); median 18o ex-smokers, 47o non-smokers (p=0.036)), but not to actual speed on helical path (r=0.26 (p=0.46); median 13.6 mm/min ex-smokers vs 13.9 mm/min non-smokers (p=1.0)). CONCLUSION: For the first time, we show that human tracheal MCC is helical, and impairment in ex-smokers is often caused by flattened helical transit, not slower movement. Our methodology provides a simple method to map tracheal MCC and speed in vivo.
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Depuración Mucociliar , Tráquea , Humanos , Depuración Mucociliar/fisiología , Tráquea/diagnóstico por imagen , Masculino , Femenino , Adulto , Persona de Mediana Edad , Moco/metabolismo , Trastornos de la Motilidad Ciliar/diagnóstico por imagen , Fumar/efectos adversos , Anciano , Adulto JovenRESUMEN
BACKGROUND: Cardiopulmonary dysfunction is a complex process with a broad range of etiologies. Investigations performed either at rest or those that only assess the function of a single organ (heart or lungs) are often insufficient. A simultaneous cardiopulmonary exercise test with stress echocardiography is a new approach to assessing cardiopulmonary dysfunction as it provides anatomical and functional imaging simultaneously while under increasing stress. To date, the application of cardiopulmonary exercise test-stress echocardiography (CPET-SE) has been broad and without structure, and its effect on patient outcomes is unclear. OBJECTIVE: The objective of this scoping review is to explore and analyze the evidence regarding the role of simultaneous CPET-SE in investigating cardiopulmonary dysfunction in outpatients. It will include any published study in which adult (older than or equal to 18 years of age) patients have completed a CPET-SE for the investigation of cardiopulmonary dysfunction. METHODS: This review will follow the Arksey and O'Malley framework, supported by the Joanna Briggs Institute methodology for scoping reviews. It will use the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews) checklist. Data sources will include MEDLINE, Scopus, Embase, and Cochrane (including reviews, trials, and protocols) electronic databases, with no date range defined. The search will be limited to the English language with no restrictions regarding pathology. Secondary references of the included sources will also be assessed by a hand search for suitability. A 2-person title-abstract screen and data charting process will be used. Independent experts will be used for consultation including an academic librarian and clinicians. The Covidence software will be used for article screening. RESULTS: This scoping review will provide a unified and detailed description of the applications of CPET-SE in investigating cardiopulmonary dysfunction. This will provide a platform for future research harnessing this investigatory method. The results will be presented in both tabular and graphical formats to ensure clarity. The results of this scoping review will be submitted to a relevant peer-reviewed academic journal for publication. CONCLUSIONS: The CPET-SE is a powerful tool for investigating cardiopulmonary dysfunction but remains in its infancy with a patchwork approach to indications, data reporting, and interpretation. This scoping review will unify the literature and provide a platform for future researchers and the development of a comprehensive application guideline. TRIAL REGISTRATION: Open Science Framework; https://osf.io/98r3e. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/52076.
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BACKGROUND: Structural lung changes seen on computed tomography (CT) scans in persons with primary ciliary dyskinesia (pwPCD) are currently described using cystic fibrosis (CF) derived scoring systems. Recent work has shown structural changes and frequencies that are unique to PCD, indicating the need for a unique PCD-derived scoring system. METHODS: Chest CT scans from 30 pwPCD, were described for structural changes including bronchiectasis, bronchial wall thickening, mucous plugging, atelectasis, air trapping, and interlobar septal thickening and, additionally, changes previously described as being frequent in pwPCD including extensive tree-in-bud pattern of mucous plugging, bronchoceles or nodules, thickening of interlobar and interlobular septa and whole lobe atelectasis. Based on these findings a novel and unique scoring system, the Specific PCD Evaluation by CT (SPEC) score was constructed. Scans were then re-scored using the SPEC score and results compared to corresponding measurements of lung function to assess structure-function correlation. RESULTS: Total SPEC scores ranged from 0 to 60 (max possible score 90). There was a strong negative correlation between the SPEC score (SPEC) and forced vital capacity (FVC), forced expiratory volume over 1 s (FEV1 ) and FEV1 /FVC ratio (-r = .784, -.865, -.872 respectively). CONCLUSIONS: Using PCD-derived data we describe the construct of a PCD-specific score for assessing lung structural damage on CT scans, the SPEC score. A strong correlation between the SPEC score and PFT variables was identified. The SPEC score holds the potential for describing longitudinal changes in CT scans and assessing the efficacy of interventive therapies in patients with PCD.
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Bronquiectasia , Trastornos de la Motilidad Ciliar , Atelectasia Pulmonar , Humanos , Pulmón , Tomografía Computarizada por Rayos X/métodos , Volumen Espiratorio Forzado , Trastornos de la Motilidad Ciliar/diagnóstico por imagenRESUMEN
Purpose: Medication adherence is crucial for achieving clinical goals. Medication adherence drivers and behaviors were explored across multiple conditions, countries, and medication schedules/modalities to develop a conceptual model of medication adherence, which could later be used to support development of a patient-reported outcome (PRO) measure of adherence. Patients and Methods: Targeted review of qualitative literature identified important medication adherence concepts. Fifty-seven qualitative concept elicitation interviews were conducted (USA n=21, Spain n=18, Germany n=18). Participants were prescribed medication for: hypertension (n=9), asthma (n=8), multiple myeloma (n=8), psoriasis (n=8), diabetes (n=7), depression (n=7), multiple sclerosis (n=7), and/or schizophrenia (n=6). Thematic analysis of verbatim transcripts was performed. Expert clinicians (n=3) provided input throughout. Results: Nine qualitative articles were selected for review from 2168 screened abstracts. Forty-two medication adherence concepts were reported and grouped into 10 domains. Eight forms of medication adherence were reported during interviews, along with 27 drivers of non-adherence, all of which were incorporated into a conceptual model. Participants reported skipping medication doses (n=36/57; 63.2%) or taking medication later in the day than prescribed (n=29/57; 50.9%). Common drivers of non-adherence included forgetfulness (n=35/57; 61.4%), being out of the usual routine (n=31/57; 54.4%) and being busy (n=22/57; 38.6%). US participants were more likely to report non-adherence due to low perceived efficacy (n=6/21, 28.6%) and cost (n=5/21, 23.8%) than German (n=1/18, 5.6%; n=0/18, 0.0%) or Spanish (n=2/18, 11.1%; n=1/18, 5.6%) participants. Conclusion: Findings highlight the diverse forms and drivers of medication non-adherence, informing the development of a comprehensive conceptual model of medication adherence. The conceptual model builds on and advances previous models of medication adherence and can be used by healthcare professionals to understand and interpret barriers to medication adherence and how best to support patients in taking their medication as intended.
Medication adherence is the extent to which a patient takes their medication as prescribed. This paper describes a literature review and concept elicitation interviews to identify forms and drivers of medication adherence across a diverse sample of participants. Forms of non-adherence identified included: deviating from the prescription, skipping a dose, taking a different amount, and taking medication at a different time. Behaviours and drivers can vary by condition, treatment modality, and dosing schedule.This research highlights the variation in the prevalence of medication non-adherence, and the different forms and drivers of non-adherence, based on individuals' demographic and clinical characteristics. The conceptual model developed advances previous models of medication adherence and may support healthcare professionals in the management of patients and how they can be supported to take medication as intended. The research ultimately informed the development of the Adelphi Adherence Questionnaire (ADAQ©), a novel generic patient-reported outcome measure.
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People with neuroendocrine neoplasms (NENs) face a multitude of challenges, including delayed diagnosis, low awareness of the cancer among healthcare professionals and limited access to multidisciplinary care and expert centres. We have developed the first patient care pathway for people living with NENs in England to guide disease management and help overcome these barriers. The pathway was developed in two phases. First, a pragmatic review of the literature was conducted, which was used to develop a draft patient care pathway. Second, the draft pathway was then updated following semi-structured interviews with carefully selected expert stakeholders. After each phase, the pathway was discussed among a multidisciplinary, expert advisory group (which comprised the authors and the Deputy Chief Operating Officer, West Suffolk NHS Foundation Trust), who reached a consensus on the ideal care pathway. This article presents the outputs of this research. The pathway identified key barriers to care and highlighted how these may be addressed, with many of the findings relevant to the rest of the UK and international audiences. NENs are increasing in incidence and prevalence in England, compounding pre-existing inequities in diagnosis and disease management. Effective integration of this pathway within NHS England will help achieve optimal, equitable care provision for all people with NENs, and should be feasible within the existing expert multidisciplinary teams across the country.
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Vías Clínicas , Tumores Neuroendocrinos , Humanos , Consenso , Tumores Neuroendocrinos/diagnóstico , Tumores Neuroendocrinos/epidemiología , Tumores Neuroendocrinos/terapiaRESUMEN
INTRODUCTION: Bronchiectasis is a worldwide chronic lung disorder where exacerbations are common. It affects people of all ages, but especially Indigenous populations in high-income nations. Despite being a major contributor to chronic lung disease, there are no licensed therapies for bronchiectasis and there remain relatively few randomised controlled trials (RCTs) conducted in children and adults. Our RCT will address some of these unmet needs by evaluating whether the novel mucoactive agent, erdosteine, has a therapeutic role in children and adults with bronchiectasis.Our primary aim is to determine in children and adults aged 2-49 years with bronchiectasis whether regular erdosteine over a 12-month period reduces acute respiratory exacerbations compared with placebo. Our primary hypothesis is that people with bronchiectasis who regularly use erdosteine will have fewer exacerbations than those receiving placebo.Our secondary aims are to determine the effect of the trial medications on quality of life (QoL) and other clinical outcomes (exacerbation duration, time-to-next exacerbation, hospitalisations, lung function, adverse events). We will also assess the cost-effectiveness of the intervention. METHODS AND ANALYSIS: We are undertaking an international multicentre, double-blind, placebo-RCT to evaluate whether 12 months of erdosteine is beneficial for children and adults with bronchiectasis. We will recruit 194 children and adults with bronchiectasis to a parallel, superiority RCT at eight sites across Australia, Malaysia and Philippines. Our primary endpoint is the rate of exacerbations over 12 months. Our main secondary outcomes are QoL, exacerbation duration, time-to-next exacerbation, hospitalisations and lung function. ETHICS AND DISSEMINATION: The Human Research Ethics Committees (HREC) of Children's Health Queensland (for all Australian sites), University of Malaya Medical Centre (Malaysia) and St. Luke's Medical Centre (Philippines) approved the study. We will publish the results and share the outcomes with the academic and medical community, funding and relevant patient organisations. TRIAL REGISTRATION NUMBER: ACTRN12621000315819.
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Bronquiectasia , Expectorantes , Estudios Multicéntricos como Asunto , Calidad de Vida , Tioglicolatos , Tiofenos , Adolescente , Adulto , Niño , Preescolar , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven , Bronquiectasia/tratamiento farmacológico , Progresión de la Enfermedad , Método Doble Ciego , Expectorantes/uso terapéutico , Ensayos Clínicos Controlados Aleatorios como Asunto , Tioglicolatos/uso terapéutico , Tiofenos/uso terapéutico , Resultado del TratamientoRESUMEN
Background: Consistent use of reliable and clinically appropriate outcome measures is a priority for clinical trials, with clear definitions to allow comparability. We aimed to develop a core outcome set (COS) for pulmonary disease interventions in primary ciliary dyskinesia (PCD). Methods: A multidisciplinary international PCD expert panel was set up. A list of outcomes was created based on published literature. Using a modified three-round e-Delphi technique, the panel was asked to decide on relevant end-points related to pulmonary disease interventions and how they should be reported. First, inclusion of an outcome in the COS was determined. Second, the minimum information that should be reported per outcome. The third round finalised statements. Consensus was defined as ≥80% agreement among experts. Results: During the first round, experts reached consensus on four out of 24 outcomes to be included in the COS. Five additional outcomes were discussed in subsequent rounds for their use in different subsettings. Consensus on standardised methods of reporting for the COS was reached. Spirometry, health-related quality-of-life scores, microbiology and exacerbations were included in the final COS. Conclusion: This expert consensus resulted in a COS for clinical trials on pulmonary health among people with PCD.
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Traducido del documento mimeografiado WHO/HEP/3,1 oct. 1953
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Educación en Salud , Escuelas de Salud Pública , Medicina , Curriculum , Capacitación en Servicio , Medicina Preventiva , Estados UnidosRESUMEN
Publicado en ingles en la OPS, American Journal of Public Health , jun. 1947