RESUMO
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.
RESUMO
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.
Assuntos
Bronquiectasia , Expectorantes , Estudos Multicêntricos como Assunto , Qualidade de Vida , Tioglicolatos , Tiofenos , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Bronquiectasia/tratamento farmacológico , Progressão da Doença , Método Duplo-Cego , Expectorantes/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Tioglicolatos/uso terapêutico , Tiofenos/uso terapêutico , Resultado do TratamentoRESUMO
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.
Assuntos
Procedimentos Clínicos , Tumores Neuroendócrinos , Humanos , Consenso , Tumores Neuroendócrinos/diagnóstico , Tumores Neuroendócrinos/epidemiologia , Tumores Neuroendócrinos/terapiaRESUMO
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.
Assuntos
Depuração Mucociliar , Traqueia , Humanos , Depuração Mucociliar/fisiologia , Traqueia/diagnóstico por imagem , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Muco/metabolismo , Transtornos da Motilidade Ciliar/diagnóstico por imagem , Fumar/efeitos adversos , Idoso , Adulto JovemRESUMO
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.
RESUMO
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.
RESUMO
AIM: Lung cancer is the leading cause of cancer-related deaths in Australia with poor long-term survival outcomes. Stage III non-small cell lung cancer (NSCLC) is a highly heterogenous group with diverse tumor characteristics and multiple, possible treatment options. We present retrospective data on patient characteristics, treatment patterns, and long-term outcomes in stage III NSCLC patients treated at a single cancer center in New South Wales, Australia. METHODS: Stage III NSCLC patients were identified from the 'Nepean Cancer Research Biobank'. Patient demographics, cancer-related information, and long-term follow-up data were collected and analyzed. RESULTS: A total of 88 patients were eligible for analysis with 61% of them diagnosed as stage IIIA, 35% IIIB, and 4% IIIC. Induction chemotherapy was administered in 20% of the patients. Overall, 48% of the study population underwent surgery, and 38% underwent concurrent chemoradiotherapy (CCRT). Both median progression-free survival and overall survival (OS) were superior in stage IIIA patients in comparison to stage IIIB (and IIIC) patients (22 vs. 11 months, p = .018; and 58 vs. 19 months, p = .048, respectively). Patients who were younger (<65 years old), good Eastern Cooperative Oncology Group performance status (ECOG PS <2), and females had better prognosis on univariate analysis. There was a nonstatistically significant trend toward better median OS with CCRT in comparison to surgery (58 vs. 37 months, p = .87). CONCLUSIONS: Long-term outcomes remain poor, and hence better treatment strategies are urgently needed in stage III NSCLC. Equally, more robust, prospective studies would help delineate the optimal treatment modality in these patients.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Feminino , Humanos , Idoso , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/patologia , Estudos Retrospectivos , Estudos Prospectivos , Estadiamento de Neoplasias , QuimiorradioterapiaRESUMO
All-solid-state lithium metal batteries can address crucial challenges regarding insufficient battery cycling life and energy density. The demonstration of long-cycling dendrite-free all-solid-state lithium metal batteries requires precise tailoring of lithium-ion transport of solid-state electrolytes (SSEs). In this work, a proof of concept is reported for precise tailoring of lithium-ion transport of a halide SSE, Li3InCl6, including intragranular (within grains) but also intergranular (between grains) lithium-ion transport. Lithium-ion migration tailoring mechanism in crystals is developed by unexpected enhanced Li, In, and Cl vacancy populations and lower energy barrier for hopping. The lithium-ion transport tailoring mechanism between the grains is determined by the elimination of voids between grains and the formation of unexpected supersonic conducting grain boundaries, boosting the lithium dendrite suppression ability of SSE. Due to boosted lithium-ion conduction and dendrite-suppression ability, the all-solid-state lithium metal batteries coupled with Ni-rich LiNi0.83Co0.12Mn0.05O2 cathodes and lithium metal anodes demonstrate breakthroughs in electrochemical performance by achieving extremely long cycling life at a high current density of 0.5 C (2000 cycles, 93.7% capacity retention). This concept of precise tailoring of lithium-ion transport provides a cost, time, and energy efficient solution to conquer the remaining challenges in all-solid-state lithium-metal batteries for fast developing electric vehicle markets.
RESUMO
OBJECTIVE: Right ventricular dysfunction (RVD) is common in the critically ill. To date studies exploring RVD sequelae have had heterogenous definitions and diagnostic methods, with limited follow-up. Additionally much literature has been pathology specific, limiting applicability to the general critically unwell patient. METHOD AND STUDY DESIGN: We conducted a systematic review and meta-analysis to evaluate the impact of RVD diagnosed with transthoracic echocardiography (TTE) on long-term mortality in unselected critically unwell patients compared to those without RVD. A systematic search of EMBASE, Medline and Cochrane was performed from inception to March 2022. All RVD definitions using TTE were included. Patients were those admitted to a critical or intensive care unit, irrespective of disease processes. Long-term mortality was defined as all-cause mortality occurring at least 30 days after hospital admission. A priori subgroup analyses included disease specific and delayed mortality (death after hospital discharge/after the 30th day from hospital admission) in patients with RVD. A random effects model analysis was performed with the Dersimionian and Laird inverse variance method to generate effect estimates. RESULTS: Of 5985 studies, 123 underwent full text review with 16 included (n = 3196). 1258 patients had RVD. 19 unique RVD criteria were identified. The odds ratio (OR) for long term mortality with RVD was 2.92 (95% CI 1.92-4.54, I2 76.4%) compared to no RVD. The direction and extent was similar for cardiac and COVID19 subgroups. Isolated RVD showed an increased risk of delayed mortality when compared to isolated left/biventricular dysfunction (OR 2.01, 95% CI 1.05-3.86, I2 46.8%). CONCLUSION: RVD, irrespective of cause, is associated with increased long term mortality in the critically ill. Future studies should be aimed at understanding the pathophysiological mechanisms by which this occurs. Commonly used echocardiographic definitions of RVD show significant heterogeneity across studies, which contributes to uncertainty within this dataset.
Assuntos
Disfunção Ventricular Direita , Humanos , Disfunção Ventricular Direita/diagnóstico por imagem , Estado Terminal , Ecocardiografia , Unidades de Terapia IntensivaRESUMO
Rationale: Inhaled granulocyte-macrophage colony-stimulating factor (GM-CSF) has been proposed as a potential immunomodulatory treatment for nontuberculous mycobacterial (NTM) infection.Objectives: This open-label, noncomparative pilot trial investigated the efficacy and safety of inhaled GM-CSF (molgramostim nebulizer solution) in patients with predominantly treatment-refractory pulmonary NTM infection (Mycobacterium avium complex [MAC] and M. abscessus [MABS]), either in combination with ongoing guideline-based therapy (GBT) or as monotherapy in patients who had stopped GBT because of lack of efficacy or intolerability.Methods: Thirty-two adult patients with refractory NTM infection (MAC, n = 24; MABS, n = 8) were recruited into two cohorts: those with (n = 16) and without (n = 16) ongoing GBT. Nebulized molgramostim 300 µg/d was administered over 48 weeks. Sputum cultures and smears and clinical assessments (6-min-walk distance, symptom scores, Quality of Life-Bronchiectasis Questionnaire score, and body weight) were collected every 4 weeks during treatment and 12 weeks after the end of treatment. The primary endpoint was sputum culture conversion, defined as three consecutive monthly negative cultures during the treatment period.Results: Eight patients (25%) achieved culture conversion on treatment (seven [29.2%] patients with MAC infection, one [12.5%] patient with MABS infection); in four patients, this was durable after the end of treatment. Of the 24 patients with MAC infection, an additional 4 patients had a partial response, converting from smear positive at baseline to smear negative at the end of treatment, and time to positivity in liquid culture media increased. Two of these patients sustained negative cultures from the end of treatment. Other clinical endpoints were unchanged. Serious adverse events were mainly pulmonary exacerbations or worsening NTM infection. Three deaths, not treatment related, were reported.Conclusions: In this population of patients with severe NTM disease, molgramostim was safe and well tolerated. Sputum culture conversion rates for patients with MAC infection (29.2%) were greater than reported for similar refractory MAC cohorts managed with GBT alone. Less benefit was seen for MABS infection. No serious safety concerns were identified. Further evaluation in a larger cohort is warranted.Clinical trial registered with www.clinicaltrials.gov (NCT03421743).
Assuntos
Infecções por Mycobacterium não Tuberculosas , Infecção por Mycobacterium avium-intracellulare , Adulto , Humanos , Fator Estimulador de Colônias de Granulócitos e Macrófagos/uso terapêutico , Projetos Piloto , Qualidade de Vida , Infecções por Mycobacterium não Tuberculosas/epidemiologia , Infecção por Mycobacterium avium-intracellulare/tratamento farmacológico , Complexo Mycobacterium avium , Micobactérias não Tuberculosas , Proteínas RecombinantesRESUMO
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.
Assuntos
Bronquiectasia , Transtornos da Motilidade Ciliar , Atelectasia Pulmonar , Humanos , Pulmão , Tomografia Computadorizada por Raios X/métodos , Volume Expiratório Forçado , Transtornos da Motilidade Ciliar/diagnóstico por imagemRESUMO
INTRODUCTION: The relationship of acute right heart dysfunction (RHD) with long-term cardiopulmonary dysfunction and its' associated morbidity has not been clearly elucidated. We propose a prospective, observational study to assess the natural history of acute RHD using a combination of imaging, functional and qualitative assessment methods, including the recently described combination of simultaneous maximal effort cardiopulmonary exercise testing and stress echocardiography. METHODS AND ANALYSIS: We propose a single-centre study of patients ≥18 years admitted to either the intensive care or respiratory close observation units with RHD on transthoracic echocardiography (TTE). Participants will undergo a repeat TTE ~72 hours after the initial study, with a final TTE performed prior to discharge in patients who have a prolonged (>1 week) stay. Inpatient clinical, biochemical and therapeutic indices will be collected contemporaneously. At ~6 months postdischarge, participants will undergo evaluation with validated symptom assessment tools (Dyspnoea-12 and PAH-SYMPACT Questionnaires) and a combined maximal effort cardiopulmonary exercise test and stress echocardiogram. This study is an observational, hypothesis-generating study with a recruitment target of 100 patients established based on typical admission rates of the relevant hospital departments. Measures of central tendency and dispersion will be used to describe the cohort. Inferential statistics will be used to compare the two a priori defined groups of those whose RHD had resolved prior to hospital discharge and those whose dysfunction persisted at time of discharge. ETHICS AND DISSEMINATION: This study has received ethics approval from the local ethics committee (Nepean and Blue Mountains Local Health District approval, project 2021/ETH12111). Written informed consent will be sought from all patients prior to recruitment. The results will be submitted for publication in a relevant peer-reviewed journal and presented at an appropriate national/international conference. STUDY REGISTRATION: Australian New Zealand Clinical Trials Registry, ANZCTR12623000309684.
Assuntos
Assistência ao Convalescente , Alta do Paciente , Humanos , Estudos Prospectivos , Austrália , Ecocardiografia , Estudos Observacionais como AssuntoRESUMO
The oxygen storage capacity of ceria-based catalytic materials is influenced by their size, morphology, and surface structure, which can be tuned using surfactant-mediated synthesis. In particular, the cuboidal morphology exposes the most reactive surfaces; however, when the capping agent is removed, the nanocubes can agglomerate and limit the available reactive surface. Here, we study ceria nanocubes, lanthanum-doped ceria nanocubes, and ceria nanocubes embedded inside a highly porous silica aerogel by high-energy resolution fluorescence detection-X-ray absorption near edge spectroscopy at the Ce L3 edge. In situ measurements showed an increased reversibility of redox cycles in ceria nanocubes when embedded in the aerogel, demonstrating enhanced reactivity due to the retention of reactive surfaces. These aerogel nanocomposites show greater improvement in the redox capacity and increased thermal stability of this catalytic material compared to the surfactant-capped nanocubes. Ex situ measurements were also performed to study the effect of lanthanum doping on the cerium oxidation state in the nanocubes, indicating a higher proportion of Ce4+ compared to that of the undoped ceria nanocubes.
RESUMO
BACKGROUND: Patient and health system costs for treating multidrug-resistant tuberculosis (MDR-TB) remain high even after treatment duration was shortened. Many patients do not finish treatment, contributing to increased transmission and antimicrobial resistance. A restructure of health services, that is more patient-centred has the potential to reduce costs and increase trust and patient satisfaction. The aim of the study is to investigate how costs would change in the delivery of MDR-TB care in Ethiopia under patient-centred and hybrid approaches compared to the current standard-of-care. METHODS: We used published data, collected from 2017 to 2020 as part of the Standard Treatment Regimen of Anti-Tuberculosis Drugs for Patients with MDR-TB (STREAM) trial, to populate a discrete event simulation (DES) model. The model was developed to represent the key characteristics of patients' clinical pathways following each of the three treatment delivery strategies. To the pathways of 1000 patients generated by the DES model we applied relevant patient cost data derived from the STREAM trial. Costs are calculated for treating patients using a 9-month MDR-TB treatment and are presented in 2021 United States dollars (USD). RESULTS: The patient-centred and hybrid strategies are less costly than the standard-of-care, from both a health system (by USD 219 for patient-centred and USD 276 for the hybrid strategy) and patient perspective when patients do not have a guardian (by USD 389 for patient-centred and USD 152 for the hybrid strategy). Changes in indirect costs, staff costs, transport costs, inpatient stay costs or changes in directly-observed-treatment frequency or hospitalisation duration for standard-of-care did not change our results. CONCLUSION: Our findings show that patient-centred and hybrid strategies for delivering MDR-TB treatment cost less than standard-of-care and provide critical evidence that there is scope for such strategies to be implemented in routine care. These results should be used inform country-level decisions on how MDR-TB is delivered and also the design of future implementation trials.
Assuntos
Tuberculose Resistente a Múltiplos Medicamentos , Humanos , Etiópia , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Antituberculosos/uso terapêutico , Hospitalização , Custos e Análise de CustoRESUMO
Ball-milling and harsh manufacturing processes often generate crystal disorder which have practical implications on the physical and chemical stabilities of solid drugs during subsequent storage, transport, and handling. The impact of the physical state of solid drugs, containing different degrees/levels of crystal disorder, on their autoxidative stability under storage has not been widely investigated. This study investigates the impact of differing degrees of crystal disorder on the autoxidation of Mifepristone (MFP) to develop a predictive (semi-empirical) stability model. Crystalline MFP was subjected to different durations of ambient ball milling, and the resulting disorder/ amorphous content was quantified using a partial least square (PLS) regression model based on Raman spectroscopy data. Samples of MFP milled to generate varying levels of disorder were subjected to a range of (accelerated) stability conditions, and periodically sampled to examine their recrystallization and degradation extents. Crystallinity was monitored by Raman spectroscopy, and the degradation was evaluated by liquid chromatography. The analyses of milled samples demonstrated a competition between recrystallization and degradation via autoxidation of MFP, to different extents depending on stability conditions/exposure time. The degradation kinetics were analyzed by accounting for the preceding amorphous content, and fitted with a diffusion model. An extended Arrhenius equation was used to predict the degradation of stored samples under long-term (25°C/60% RH) and accelerated (40°C/75% RH, 50°C/75% RH) stability conditions. This study highlights the utility of such a predictive stability model for identifying the autoxidative instability in non-crystalline/partially crystalline MFP, owing to the degradation of the amorphous phases. This study is particularly useful for identifying drug-product instability by leveraging the concept of material sciences.
Assuntos
Ciência dos Materiais , Mifepristona , Cristalização , Estabilidade de Medicamentos , Varredura Diferencial de CalorimetriaRESUMO
This position statement, updated from the 2015 guidelines for managing Australian and New Zealand children/adolescents and adults with chronic suppurative lung disease (CSLD) and bronchiectasis, resulted from systematic literature searches by a multi-disciplinary team that included consumers. The main statements are: Diagnose CSLD and bronchiectasis early; this requires awareness of bronchiectasis symptoms and its co-existence with other respiratory diseases (e.g., asthma, chronic obstructive pulmonary disease). Confirm bronchiectasis with a chest computed-tomography scan, using age-appropriate protocols and criteria in children. Undertake a baseline panel of investigations. Assess baseline severity, and health impact, and develop individualized management plans that include a multi-disciplinary approach and coordinated care between healthcare providers. Employ intensive treatment to improve symptom control, reduce exacerbation frequency, preserve lung function, optimize quality-of-life and enhance survival. In children, treatment also aims to optimize lung growth and, when possible, reverse bronchiectasis. Individualize airway clearance techniques (ACTs) taught by respiratory physiotherapists, encourage regular exercise, optimize nutrition, avoid air pollutants and administer vaccines following national schedules. Treat exacerbations with 14-day antibiotic courses based upon lower airway culture results, local antibiotic susceptibility patterns, clinical severity and patient tolerance. Patients with severe exacerbations and/or not responding to outpatient therapy are hospitalized for further treatments, including intravenous antibiotics and intensive ACTs. Eradicate Pseudomonas aeruginosa when newly detected in lower airway cultures. Individualize therapy for long-term antibiotics, inhaled corticosteroids, bronchodilators and mucoactive agents. Ensure ongoing care with 6-monthly monitoring for complications and co-morbidities. Undertake optimal care of under-served peoples, and despite its challenges, delivering best-practice treatment remains the overriding aim.
Assuntos
Bronquiectasia , Pneumopatias , Criança , Humanos , Adulto , Adolescente , Nova Zelândia , Austrália , Bronquiectasia/terapia , Bronquiectasia/tratamento farmacológico , Pneumopatias/tratamento farmacológico , Antibacterianos/uso terapêuticoRESUMO
INTRODUCTION: Pulmonary rehabilitation is recommended for people with bronchiectasis. Various education topics are included in these programmes, but the content is largely guided by the needs of people with other respiratory conditions. OBJECTIVES: With the education topics applicable to people with bronchiectasis unclear, we aimed to explore the perspective of adults with this condition on relevant educational topics in a pulmonary rehabilitation context. METHODS: Participants from the Australian Bronchiectasis Registry were invited to undertake a semi-structured interview. Interview transcripts were coded independently, with themes established by consensus (two researchers). RESULTS: Twenty-one people participated. The major themes were greater clarity on the underlying cause of bronchiectasis and prognosis. Most sought knowledge about self-management strategies and treatments to address extra-pulmonary symptoms. Participants requested more information on physiotherapy options and the role of exercise and physical activity outside of pulmonary rehabilitation. Preferences were mixed for the education delivery model. CONCLUSIONS: We have identified unmet educational topics of interest for people with bronchiectasis. Our study provides a framework for education topics desired by adults with bronchiectasis within a pulmonary rehabilitation setting. The topics identified will guide development of an education curriculum for pulmonary rehabilitation that is more fit-for-purpose for people with bronchiectasis.
Assuntos
Bronquiectasia , Doenças Respiratórias , Adulto , Humanos , Austrália/epidemiologia , Exercício Físico , Modalidades de Fisioterapia , Qualidade de VidaRESUMO
Bronchiectasis is emerging as a global health issue, and this is reflected by a series of registries that were established worldwide [...].