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7. Thiazolidinediones inhibit airway smooth muscle release of the chemokine CXCL10: in vitro comparison with current asthma therapies

Author

Seidel Petra, Alkhouri Hatem, Lalor Daniel J, Burgess Janette K, Armour Carol L, and Hughes J

Subjects
Mast cell chemoattractant, Glucocorticoids, Long-acting β2-agonists, Salmeterol, Fluticasone, Ciglitazone, Rosiglitazone, Diseases of the respiratory system, RC705-779
Abstract

Abstract Background Activated mast cells are present within airway smooth muscle (ASM) bundles in eosinophilic asthma. ASM production of the chemokine CXCL10 plays a role in their recruitment. Thus the effects of glucocorticoids (fluticasone, budesonide), long-acting β2-agonists (salmeterol, formoterol) and thiazolidinediones (ciglitazone, rosiglitazone) on CXCL10 production by ASM cells (ASMC) from people with and without asthma were investigated in vitro. Methods Confluent serum-deprived cells were treated with the agents before and during cytokine stimulation for 0-24 h. CXCL10 protein/mRNA, IκB-α levels and p65 activity were measured using ELISA, RT PCR, immunoblotting and p65 activity assays respectively. Data were analysed using ANOVA followed by Fisher’s post-hoc test. Results Fluticasone and/or salmeterol at 1 and 100 nM inhibited CXCL10 release induced by IL-1β and TNF-α, but not IFNγ or all three cytokines (cytomix). The latter was also not affected by budesonide and formoterol. In asthmatic ASMC low salmeterol, but not formoterol, concentrations increased cytomix-induced CXCL10 release and at 0.01 nM enhanced NF-κB activity. Salmeterol 0.1nM together with fluticasone 0.1 and 10 nM still increased CXCL10 release. The thiazolidinediones ciglitazone and rosiglitazone (at 25 and 100 μM) inhibited cytomix-induced CXCL10 release but these inhibitory effects were not prevented by the PPAR-g antagonist GW9662. Ciglitazone did not affect early NF-κB activity and CXCL10 mRNA production. Conclusions Thus the thiazolidinediones inhibited asthmatic ASMC CXCL10 release under conditions when common asthma therapies were ineffective or enhanced it. They may provide an alternative strategy to reduce mast cell-ASM interactions and restore normal airway physiology in asthma.

Published
2012
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8. Experiences of community pharmacists involved in the delivery of a specialist asthma service in Australia

Author

Emmerton Lynne M, Smith Lorraine, LeMay Kate S, Krass Ines, Saini Bandana, Bosnic-Anticevich Sinthia Z, Reddel Helen K, Burton Deborah L, Stewart Kay, and Armour Carol L

Subjects
Pharmacy, Asthma, Disease management service, Experiences, Feedback, Public aspects of medicine, RA1-1270
Abstract

Abstract Background The role of community pharmacists in disease state management has been mooted for some years. Despite a number of trials of disease state management services, there is scant literature into the engagement of, and with, pharmacists in such trials. This paper reports pharmacists’ feedback as providers of a Pharmacy Asthma Management Service (PAMS), a trial coordinated across four academic research centres in Australia in 2009. We also propose recommendations for optimal involvement of pharmacists in academic research. Methods Feedback about the pharmacists’ experiences was sought via their participation in either a focus group or telephone interview (for those unable to attend their scheduled focus group) at one of three time points. A semi-structured interview guide focused discussion on the pharmacists’ training to provide the asthma service, their interactions with health professionals and patients as per the service protocol, and the future for this type of service. Focus groups were facilitated by two researchers, and the individual interviews were shared between three researchers, with data transcribed verbatim and analysed manually. Results Of 93 pharmacists who provided the PAMS, 25 were involved in a focus group and seven via telephone interview. All pharmacists approached agreed to provide feedback. In general, the pharmacists engaged with both the service and research components, and embraced their roles as innovators in the trial of a new service. Some experienced challenges in the recruitment of patients into the service and the amount of research-related documentation, and collaborative patient-centred relationships with GPs require further attention. Specific service components, such as the spirometry, were well received by the pharmacists and their patients. Professional rewards included satisfaction from their enhanced practice, and pharmacists largely envisaged a future for the service. Conclusions The PAMS provided pharmacists an opportunity to become involved in an innovative service delivery model, supported by the researchers, yet trained and empowered to implement the clinical service throughout the trial period and beyond. The balance between support and independence appeared crucial in the pharmacists’ engagement with the trial. Their feedback was overwhelmingly positive, while useful suggestions were identified for future academic trials.

Published
2012
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11. An exploration of clinical interventions provided by pharmacists within a complex asthma service

Author

Lemay, Kate S., Saini, Bandana, Bosnic-Anticevich, Sinthia, Smith, Lorraine, Stewart, Kay, Emmerton, Lynne, Burton, Deborah L., Krass, Ines, and Armour, Carol L.

Subjects
Farmacéuticos, Práctica Basada en la Evidencia Practice, Pharmaceutical Services, Evidence-Based Practice, Australia, Pharmacists, Asthma, Asma, Servicios Farmacéuticos
Abstract

Background: Pharmacists in Australia are accessible health care professionals, and their provision of clinical pharmacy interventions in a range of areas has been proven to improve patient outcomes. Individual clinical pharmacy interventions in the area of asthma management have been very successful. An understanding of the nature of these interventions will inform future pharmacy services. What we do not know is when pharmacists provide a complex asthma service, what elements of that service (interventions) they choose to deliver. Objective: To explore the scope and frequency of asthma-related clinical interventions provided by pharmacists to patients in an evidence-based complex asthma service. Methods: Pharmacists from 4 states/territories of Australia were trained in asthma management. People with asthma had 3 or 4 visits to the pharmacy. Guided by a structured patient file, the pharmacist assessed the patient´s asthma and management and provided interventions where and when considered appropriate, based on their clinical decision making skills. The interventions were recorded in a checklist in the patient file. They were then analysed descriptively and thematically. Results: Pharmacists provided 22,909 clinical pharmacy interventions over the service to 570 patients (398 of whom completed the service). The most frequently delivered interventions were in the themes "Education on asthma", "Addressing trigger factors", "Medications - safe and effective use" and "Explore patient perspectives". The patients had a high and ongoing need for interventions. Pharmacists selected interventions based on their assessment of perceived need then revisited and reinforced these interventions. Conclusion: Pharmacists identified a number of areas in which patients required interventions to assist with their asthma management. Many of these were perceived to require continuing reinforcement over the duration of the service. Pharmacists were able to use their clinical judgement to assess patients and provide clinical pharmacy interventions across a range of asthma management needs. Antecedentes: Los farmacéuticos en Australia son profesionales de la salud accesibles y su prestación de intervenciones de farmacia clínica ha demostrado mejorar los resultados de salud de los pacientes en un conjunto de áreas. Las intervenciones de farmacia clínica en asma han demostrado ser de gran éxito. La comprensión de la naturaleza de estas intervenciones informará para los futuros servicios farmacéuticos. Lo que no sabemos es, cuando los farmacéuticos proporcionan un servicio complejo de asma, que elementos del servicio (intervenciones) eligen realizar. Objetivo: Explorar el ámbito y la frecuencia de las intervenciones clínicas en asma proporcionadas por farmacéuticos a pacientes en un servicio complejo de asma basado en la evidencia. Métodos: Se entrenó en el manejo del asma a farmacéuticos de 4 estados/territorios de Australia. La gente con asma visitaba 3 o 4 veces la farmacia. Guiado por un registro estructurado del paciente, el farmacéutico evaluaba el asma y el manejo y las intervenciones realizadas cuando y donde consideraba necesario, basándose en sus habilidades de toma de decisión clínica. Se registraban las intervenciones en un check-list en la historia del paciente. Se analizaron descriptiva y temáticamente. Resultados: Los farmacéuticos proporcionaron 22.909 intervenciones de farmacia clínica en el servicio a 570 pacientes (de los que 398 completaron el servicio). Las intervenciones más frecuentemente realizadas estaban en los temas "Educación sobre asma", "Manejando factores desencadenantes", "Medicación - uso seguro y efectivo" y "Explorar las perspectivas del paciente". Los pacientes presentaban una gran y continuada necesidad de intervenciones. Los farmacéuticos seleccionaron las intervenciones basándose en su juicio de la necesidad percibida y después revisaron y reforzaron esas intervenciones. Conclusión: Los farmacéutico identificaron varias áreas en las que los pacientes necesitaban intervenciones para ayudarles en su manejo del asma. Muchas de estas requirieron refuerzo continuo durante la prestación del servicio. Los farmacéuticos fueron capaces de utilizar su juicio clínico para evaluar pacientes y proporcionar intervenciones de farmacia clínica en un amplio abanico de necesidades de manejo del asma.

Published
2015

12. Using scenarios to test the appropriateness of pharmacist prescribing in asthma management

Author

Hanna, Tamer, Bajorek, Beata, Lemay, Kate, and Armour, Carol L.

Subjects
Patient Simulation, Práctica Profesional, Professional Role, Simulación de Pacientes, Recetas, Servicios de Farmacia Comunitaria, Australia, Professional Practice, Community Pharmacy Services, Papel Profesional, Drug Prescriptions, Asma
Abstract

Objective: To explore the potential for community pharmacist prescribing in terms of usefulness, pharmacists' confidence, and appropriateness, in the context of asthma management. Methods: Twenty community pharmacists were recruited using convenience sampling from a group of trained practitioners who had already delivered asthma services. These pharmacists were asked to complete a scenario-based questionnaire (9 scenarios) modelled on information from real patients. Pharmacist interventions were independently reviewed and rated on their appropriateness according to the Respiratory Therapeutic Guidelines (TG) by three expert researchers. Results: In seven of nine scenarios (78%), the most common prescribing intervention made by pharmacists agreed with TG recommendations. Although the prescribing intervention was appropriate in the majority of cases, the execution of such interventions was not in line with guidelines (i.e. dosage or frequency) in the majority of scenarios. Due to this, only 47% (76/162) of the interventions overall were considered appropriate. However, pharmacists were deemed to be often following common clinical practice for asthma prescribing. Therefore 81% (132/162) of prescribing interventions were consistent with clinical practice, which is often not guideline driven, indicating a need for specific training in prescribing according to guidelines. Pharmacists reported that they were confident in making prescribing interventions and that this would be very useful in their management of the patients in the scenarios. Conclusion: Community pharmacists may be able to prescribe asthma medications appropriately to help achieve good outcomes for their patients. However, further training in the guidelines for prescribing are required if pharmacists are to support asthma management in this way. Objetivo: Explorar el potencial de prescripción de los farmacéuticos comunitarios en términos de utilidad, confianza de los farmacéuticos, y adecuación en el contexto del manejo del asma. Métodos: Se reclutó a 20 farmacéuticos comunitarios mediante un muestreo de conveniencia de entre un grupo de facultativos entrenados que ya habían proporcionado servicios en asma. Se pidió a estos farmacéuticos que completasen un cuestionario basado en escenarios (9 escenarios) diseñados a partir de información de pacientes reales. Las intervenciones farmacéuticas fueron revisadas independientemente por 3 investigadores expertos y evaluada su adecuación de acuerdo con las Guías Terapéuticas Respiratorias (TG). Resultados: En 7 de los 9 escenarios (78%) la intervención prescriptora más frecuente de los farmacéuticos estaba de acuerdo con las recomendaciones de las TG. Aunque la intervención prescriptora era apropiada en la mayoría de los casos, la ejecución de esas intervenciones no estaba en línea con las guías (i.e. dosis o frecuencia) en la mayoría de los escenarios. Debido a esto, sólo el 47% (76/162) del total de las intervenciones fueron consideradas apropiadas. Sin embargo, se consideró que los farmacéuticos seguían con frecuencia la práctica clínica común de prescripción en asma. Por tanto, el 81% (136/162) de las intervenciones prescriptivas fueron considerados consistente con la práctica clínica, que a menudo no está basada en las guías. Los farmacéuticos informaron que estaban confiados en la realización de intervenciones de prescripción y que esto sería muy útil en su manejo de los pacientes en los escenarios. Concusión: Los farmacéuticos comunitarios pueden ser capaces de prescribir medicación para el asma adecuadamente para ayudar a conseguir buenos resultados a sus pacientes. Sin embargo, se requiere más formación sobre las guías de prescripción, si los farmacéuticos desean apoyar el manejo del asma de esta manera.

Published
2014

13. The role of community pharmacists in screening and subsequent management of chronic respiratory diseases: a systematic review

Author

Fathima, Mariam, Naik-Panvelkar, Pradnya, Saini, Bandana, and Armour, Carol L.

Subjects
Lung Diseases, Rastreo Masivo, Enfermedades Pulmonares Obstructivas, Práctica Profesional, Outcome Assessment (Health Care), Professional Role, Obstructive, Mass Screening, Professional Practice, Community Pharmacy Services, Evaluación de Procesos y Resultados (Atención de Salud), Rol Profesional, Servicios de Farmacia comunitaria
Abstract

Objective: The purpose of this review was to evaluate the role of community pharmacists in provision of screening with/without subsequent management of undiagnosed chronic obstructive pulmonary disease (COPD) and uncontrolled asthma. Methods: An extensive literature search using four databases (ie. Medline, PubMed, International Pharmaceutical Abstracts (IPA) and Scopus) with search terms pharmacy, screening, asthma or COPD was conducted. Searches were limited to the years 2003-2013, those in English and those reporting research with humans. Data retrieval, analysis and result presentation employed a scoping review method. Results: Seventeen articles met the inclusion/exclusion criteria, of which fifteen studies were based on people with asthma and two were based on people with COPD. Only seven asthma studies and one COPD study involved screening followed by subsequent management. More than half of the people screened were found to be poorly controlled and up to 62% of people were identified at high risk for COPD by community pharmacists. The studies varied in the method and type of asthma control assessment/screening, the type of intervention provided and the outcomes measured. The limitations of the reviewed studies included varying definitions of asthma control, different study methodologies, and the lack of long-term follow-up. While many different methods were used for risk assessment and management services by the pharmacists, all the studies demonstrated that community pharmacists were capable of identifying people with poorly controlled asthma and undiagnosed COPD and providing them with suitable interventions. Conclusion: The literature review identified that community pharmacists can play an effective role in screening of people with poorly controlled asthma and undiagnosed COPD along with delivering management interventions. However, there is very little literature available on screening for these chronic respiratory conditions. Future research should focus on development of patient care delivery model incorporating a screening protocol followed by targeted management interventions delivered by the community pharmacist. Objetivo: El propósito de esta revisión fue evaluar el papel de los farmacéuticos comunitarios en la provisión de rastreos con/sin posterior manejo de enfermedad pulmonar obstructiva crónica (EPOC) no diagnosticada y asma no controlada. Métodos: Se realizó una extensiva búsqueda bibliográfica usando cuatro bases de datos (ie. Medline, PubMed, International Pharmaceutical Abstracts (IPA) and Scopus) con términos de búsqueda farmacia, rastreo, asma o EPOC. Las búsquedas se limitaron a los años 2003-2013, a las escritas en inglés, y a las que comunicaban investigación en seres humanos. La recuperación, y análisis de datos y la presentación de resultados se realizaron mediante un método de determinación del alcance. Resultados: 17 artículos cumplieron los criterios de inclusión/exclusión, de los cuales, 15 eran de personas con asma y 2 con EPOC. Sólo 7 de los estudios de asma y uno de los de EPOC envolvían rastreos seguidos del consiguiente manejo. Más de la mitad de las personas rastreadas estaban pobremente controladas y hasta un 62% de las personas fueron identificadas como en alto riesgo de EPOC por los farmacéuticos. Los estudios variaban en el método y tipo de evaluación/rastreo del control de asma, el tipo de intervención realizada y los resultados medidos. Las limitaciones de los estudios revisados incluyeron la diversidad de definiciones de control de asma, las diferentes metodologías de estudio, y la falta de seguimiento a largo plazo. Aunque se utilizaron muchos métodos diferentes de evaluación del riesgo y de servicios de manejo de la enfermedad por los farmacéuticos, todos los estudios demostraron que los farmacéuticos comunitarios eran capaces de identificar personas con asma pobremente controlada y EPOC no diagnosticada y de realizar con ellos las intervenciones apropiadas. Conclusión: La revisión de la literatura identifico que los farmacéuticos comunitarios pueden jugar un papel efectivo en el rastreo de personas con asma pobremente controlado y EPOC no diagnosticada así como realizarles las intervenciones de manejo. Sin embargo, hay muy poca literatura disponible sobre el rastreo de estas enfermedades respiratorias crónicas. La investigación futura debería centrarse en el desarrollo de modelos de atención a pacientes que incorporen un protocolo de rastreo seguido de intervenciones de manejo de la enfermedad proporcionadas por los farmacéuticos comunitarios.

Published
2013

24. Measurement of consumer preference for treatments used to induce labour: a willingness‐to‐pay approach

Author

Taylor, Susan J. and Armour, Carol L.

Subjects
Original Articles
Abstract

AIM: The purpose of the study was to assess the acceptability to consumers of two methods of induction of labour using a willingness-to-pay (WTP) approach. The methods compared were amniotomy plus oxytocin and prostaglandin E2 vaginal gel, followed by oxytocin if necessary. METHODS: A description of each method was presented, in questionnaire format, to pregnant women attending a public hospital ante-natal clinic. Women were asked to choose one of the two treatments, then give a valuation in dollar terms for both their preferred treatment and the alternative. RESULTS: It was found that 73.7% of patients preferred gel. The mean maximum WTP for amniotomy plus oxytocin was Aus$133 while that for gel was Aus$178 (P=0.0001). Those who chose amniotomy plus oxytocin were WTP 90% more for their preferred treatment compared with the alternative (Aus$180 vs. Aus$95). Similarly, those who preferred gel were WTP 90% more for their preferred treatment compared with the alternative (Aus$222 vs. Aus$119). CONCLUSION: Consumers were able to assess drug information provided on the two therapies, make an informed choice and to value that choice. Information obtained in this way, combined with information on costs, could be used in policy decision-making.

Published
2000

26. People with insomnia: experiences with sedative hypnotics and risk perception.

Author

Cheung, Janet M. Y., Bartlett, Delwyn J., Armour, Carol L., Ellis, Jason G., and Saini, Bandana

Subjects
ALCOHOL drinking, DRUG labeling, INSOMNIA, INTERVIEWING, RESEARCH methodology, QUESTIONNAIRES, DATA analysis software
Abstract

Background: Sedative hypnotics form an important part of managing insomnia and are recommended for short‐term use. It is standard practice for clinicians to inform the patient to use medications only ‘when required’, but the use of these medications is often chronic. Little is known about the impact of standard labelling/instructions on promoting appropriate medication use for managing insomnia. Objective: To explore patient medication‐taking beliefs, experiences and behavioural practices relating to the use of pharmacological/complementary sleep aids for insomnia. Setting and Participants: Specialist sleep/psychology clinics and the general community in Sydney, Australia. Method: Semi‐structured interviews were conducted with 51 people with insomnia using a schedule of questions to gauge their experiences, beliefs and current practices relating to insomnia medication use. Interviews were audio‐recorded, transcribed verbatim and subjected to Framework Analysis to identify emergent themes. Results: Participants held distinctive views about the safety and efficacy of complementary and pharmacological agents but do not intuitively turn to medications to resolve their sleep complaint. Medication use was affirmed through tangible medication‐taking cues due to the ambivalence in current instructions and labelling. Practices such as dosage modification, medication substitution and delaying medication use might be important drivers for psychological dependence. Conclusion: Current labelling and instructions do not necessarily promote the quality use of sedative hypnotics due to the variability in patient interpretations. Clarifying the timing, quantity and frequency of medication administration as well as insomnia symptom recognition would play a significant role in optimizing the role of pharmacotherapy in the management of insomnia. [ABSTRACT FROM AUTHOR]

Published
2016
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37. Checklists for Powder Inhaler Technique: A Review and Recommendations.

Author

Basheti, Iman A., Bosnic-Anticevich, Sinthia Z., Armour, Carol L., and Reddel, Helen K.

Subjects
MEDICAL information storage & retrieval systems, MEDLINE, ONLINE information services, HEALTH outcome assessment, RESPIRATORY diseases, RESPIRATORY therapy equipment, SYSTEMATIC reviews, TREATMENT effectiveness
Abstract

Turbuhaler and Diskus are commonly used powder inhaler devices for patients with respiratory disease. Their effectiveness is limited in part by a patient’s ability to use them correctly. This has led to numerous studies being conducted over the last decade to assess the correct use of these devices by patients and health care professionals. These studies have generally used device-specific checklists to assess technique, this being the most feasible and accessible method for assessment. However, divergence between the checklists and scoring systems for the same device in different studies makes direct comparison of results difficult and at times inappropriate. Little evidence is available to assess the relative importance of different criteria; however, brief patient training based on specific inhaler technique checklists leads to significant improvement in asthma outcomes. This paper reviews common checklists and scoring systems used for Turbuhaler and Diskus, discusses the problem of heterogeneity between different checklists, and finally recommends suitable checklists and scoring systems for these devices based on the literature and previous findings. Only when similar checklists are used across different research studies will accurate comparisons and meta-analysis be possible. [ABSTRACT FROM AUTHOR]

Published
2014
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39. Th1 cytokine-induced syndecan-4 shedding by airway smooth muscle cells is dependent on mitogen-activated protein kinases.

Author

Xiahui Tan, Khalil, Najwa, Tesarik, Candice, Vanapalli, Karunasri, Yaputra, Viki, Alkhouri, Hatem, Oliver, Brian G. G., Armour, Carol L., and Hughes, J. Margaret

Abstract

In asthma, airway smooth muscle (ASM) chemokine secretion can induce mast cell recruitment into the airways. The functions of the mast cell chemoattractant CXCL10, and other chemokines, are regulated by binding to heparan sulphates such as syndecan-4. This study is the first demonstration that airway smooth muscle cells (ASMC) from people with and without asthma express and shed syndecan-4 under basal conditions. Syndecan-4 shedding was enhanced by stimulation for 24 h with the Th1 cytokines interleukin-1;β (IL-1β) or tumor necrosis factor-α (TNF-α), but not interferon-γ (IFNγ), nor the Th2 cytokines IL-4 and IL-13. ASMC stimulation with IL-1β, TNF-α, and IFNγ (cytomix) induced the highest level of syndecan-4 shedding. Nonasthmatic and asthmatic ASM cell-associated syndecan-4 protein expression was also increased by TNF-α or cytomix at 4-8 h, with the highest levels detected in cytomix-stimulated asthmatic cells. Cell-associated syndecan-4 levels were decreased by 24 h, whereas shedding remained elevated at 24 h, consistent with newly synthesized syndecan-4 being shed. Inhibition of ASMC matrix metalloproteinase-2 did not prevent syndecan-4 shedding, whereas inhibition of ERK MAPK activation reduced shedding from cytomix-stimulated ASMC. Although ERK inhibition had no effect on syndecan-4 mRNA levels stimulated by cytomix, it did cause an increase in cell-associated syndecan-4 levels, consistent with the shedding being inhibited. In conclusion, ASMC produce and shed syndecan-4 and although this is increased by the Th1 cytokines, the MAPK ERK only regulates shedding. ASMC syndecan-4 production during Th1 inflammatory conditions may regulate chemokine activity and mast cell recruitment to the ASM in asthma. [ABSTRACT FROM AUTHOR]

Published
2012
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40. Patient perceptions of treatment delivery platforms for cognitive behavioral therapy for insomnia

Author

Bandana Saini, Janet M Y Cheung, Tracey-Lea Laba, Delwyn J. Bartlett, Carol L. Armour, Cheung, Janet M Y, Bartlett, Delwyn J, Armour, Carol L, Laba, Tracey-Lea, and Saini, Bandana

Subjects
Adult, Male, medicine.medical_treatment, insomnia, Neuroscience (miscellaneous), Psychological intervention, Medicine (miscellaneous), Cognitive behavioral therapy for insomnia, behavioral disciplines and activities, Task (project management), 03 medical and health sciences, 0302 clinical medicine, Sleep Initiation and Maintenance Disorders, mental disorders, Insomnia, medicine, Humans, Medical education, Neurology & Neurosurgery, Cognitive Behavioral Therapy, business.industry, delivery formats, Cognitive behavioral therapy, Schedule (workplace), Mood, Treatment Outcome, behavoral therapy, 030228 respiratory system, The Internet, Perception, Female, Neurology (clinical), Psychology (miscellaneous), medicine.symptom, business, 030217 neurology & neurosurgery, Clinical psychology
Abstract

© 2018, © 2018 Taylor & Francis Group, LLC. Objective: Stepped care has given rise to the proliferation of abbreviated CBT-I programs and delivery formats. This includes interventions delivered by allied health professionals and those delivered electronically through the Internet. This article aims to explore patient perceptions between electronic and face-to-face (FTF) delivery platforms for (abbreviated) CBT-I. Participants: Patients with insomnia from specialist sleep or psychology clinics and those from the general community in Sydney, Australia. Method: Semistructured interviews were conducted with patients with insomnia, guided by a schedule of questions and a choice task to explore patient perceptions of the different CBT-I treatment delivery platforms (e.g., perceived advantages and disadvantages or willingness to engage with either platform). Interviews were transcribed verbatim and analyzed using Framework Analysis. Participants also completed a battery of clinical mood and insomnia measures. Results: Fifty-one interviews were conducted with patients with insomnia from specialist sleep or psychology clinics (n = 22) and the general community (n = 29). Synthesis of the qualitative data set revealed three themes pertinent to the patients’ perspective toward electronic and FTF CBT-I delivery: Concepts of Efficacy, Concerns About Treatment, and Treatment on My Terms. Participants’ choice to engage with either platform was also informed by diverse factors including perceived efficacy of treatment, personal commitments, lifestyle, and beliefs about sleep and insomnia. Conclusion: Clarifying patient treatment priorities and allaying potential concerns about engaging with an electronic treatment platform represent important steps for disseminating eCBT-I into mainstream practice.

Published
2019

41. Patient Preferences for Managing Insomnia: A Discrete Choice Experiment

Author

Bandana Saini, Janet M Y Cheung, Tracey-Lea Laba, Delwyn J. Bartlett, Carol L. Armour, Cheung, Janet MY, Bartlett, Delwyn J, Armour, Carol L, Saini, Bandana, and Laba, Tracey-Lea

Subjects
Adult, Male, insomnia, Decision Making, MEDLINE, Sample (statistics), treatment outcomes, Choice Behavior, Health administration, 03 medical and health sciences, 0302 clinical medicine, Sleep Initiation and Maintenance Disorders, Surveys and Questionnaires, Insomnia, Medicine, Humans, 030212 general & internal medicine, 11 Medical and Health Sciences, Multinomial logistic regression, Health economics, business.industry, long-term sleep benefits, Patient Preference, Middle Aged, Preference, Logistic Models, Female, Onset of action, medicine.symptom, business, 030217 neurology & neurosurgery, Clinical psychology
Abstract

BACKGROUND: Despite the rapid development of effective treatments, both pharmacological and non-pharmacological, insomnia management remains suboptimal at the practice interface. Patient preferences play a critical role in influencing treatment outcomes. However, there is currently a mismatch between patient preferences and clinician recommendations, partly perpetuated by a limited understanding of the patients' decision-making process. OBJECTIVES: The aim of our study was to empirically quantify patient preferences for treatment attributes common to both pharmacological and non-pharmacological insomnia treatments. METHOD: An efficient dual-response discrete choice experiment was conducted to evaluate patient treatment preferences for managing insomnia. The sample included 205 patients with self-reported insomnia and an Insomnia Severity Index ≥ 14. Participants were presented with two unlabelled hypothetical scenarios with an opt-out option across 12 choice sets. Data were analyzed using a mixed multinomial logit model to investigate the influence of five attributes (i.e. time, onset of action, maintainability of improved sleep, length of treatment, and monthly cost) on treatment preferences. RESULTS: Treatments were preferentially viewed if they conferred long-term sleep benefits (p

Published
2018

42. Asthmatic airway smooth muscle CXCL10 production: mitogen-activated protein kinase JNK involvement.

Author

Alrashdan YA, Alkhouri H, Chen E, Lalor DJ, Poniris M, Henness S, Brightling CE, Burgess JK, Armour CL, Ammit AJ, and Hughes JM

Subjects
Asthma immunology, Asthma pathology, Cell Movement drug effects, Chemokine CXCL10 immunology, Gene Expression drug effects, Humans, Interferon-gamma pharmacology, Interleukin-1beta pharmacology, MAP Kinase Kinase 4 genetics, MAP Kinase Kinase 4 metabolism, Mast Cells drug effects, Mast Cells immunology, Mast Cells pathology, Muscle, Smooth immunology, Muscle, Smooth metabolism, Myocytes, Smooth Muscle drug effects, Myocytes, Smooth Muscle immunology, NF-kappa B genetics, NF-kappa B metabolism, Phosphorylation, Protein Kinase Inhibitors pharmacology, RNA, Messenger biosynthesis, Respiratory System immunology, Respiratory System metabolism, Tumor Necrosis Factor-alpha pharmacology, p38 Mitogen-Activated Protein Kinases genetics, p38 Mitogen-Activated Protein Kinases metabolism, Asthma metabolism, Chemokine CXCL10 biosynthesis, Mast Cells metabolism, Myocytes, Smooth Muscle metabolism, Signal Transduction drug effects
Abstract

CXCL10 (IP10) is involved in mast cell migration to airway smooth muscle (ASM) bundles in asthma. We aimed to investigate the role of cytokine-induced MAPK activation in CXCL10 production by ASM cells from people with and without asthma. Confluent growth-arrested ASM cells were treated with inhibitors of the MAPKs ERK, p38, and JNK and transcription factor NF-κB, or vehicle, and stimulated with IL-1β, TNF-α, or IFN-γ, alone or combined (cytomix). CXCL10 mRNA and protein, JNK, NF-κB p65 phosphorylation, and Iκ-Bα protein degradation were assessed using real-time PCR, ELISA, and immunoblotting, respectively. Cytomix, IL-1β, and TNF-α induced CXCL10 mRNA expression more rapidly in asthmatic than nonasthmatic ASM cells. IL-1β and/or TNF-α combined with IFN-γ synergistically increased asthmatic ASM cell CXCL10 release. Inhibitor effects were similar in asthmatic and nonasthmatic cells, but cytomix-induced release was least affected, with only JNK and NF-κB inhibitors halving it. Notably, JNK phosphorylation was markedly less in asthmatic compared with nonasthmatic cells. However, in both, the JNK inhibitor SP600125 reduced JNK phosphorylation and CXCL10 mRNA levels but did not affect CXCL10 mRNA stability or Iκ-Bα degradation. Together, the JNK and NF-κB inhibitors completely inhibited their CXCL10 release. We concluded that, in asthmatic compared with nonasthmatic ASM cells, JNK activation was reduced and CXCL10 gene expression was more rapid following cytomix stimulation. However, in both, JNK activation did not regulate early events leading to NF-κB activation. Thus JNK and NF-κB provide independent therapeutic targets for limiting CXCL10 production and mast cell migration to the ASM in asthma.

Published
2012
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43. Th1 cytokine-induced syndecan-4 shedding by airway smooth muscle cells is dependent on mitogen-activated protein kinases.

Author

Tan X, Khalil N, Tesarik C, Vanapalli K, Yaputra V, Alkhouri H, Oliver BG, Armour CL, and Hughes JM

Subjects
Adult, Aged, Airway Remodeling, Asthma, Cells, Cultured, Extracellular Signal-Regulated MAP Kinases antagonists & inhibitors, Female, Humans, Interferon-gamma metabolism, Interferon-gamma pharmacology, Interleukin-1beta metabolism, Interleukin-1beta pharmacology, JNK Mitogen-Activated Protein Kinases antagonists & inhibitors, JNK Mitogen-Activated Protein Kinases metabolism, MAP Kinase Signaling System drug effects, Male, Matrix Metalloproteinase 2 metabolism, Matrix Metalloproteinase Inhibitors, Middle Aged, Muscle, Smooth metabolism, RNA, Messenger genetics, RNA, Messenger metabolism, Th1 Cells metabolism, Tumor Necrosis Factor-alpha metabolism, Tumor Necrosis Factor-alpha pharmacology, Young Adult, Extracellular Signal-Regulated MAP Kinases metabolism, Lung metabolism, Myocytes, Smooth Muscle metabolism, Syndecan-4 metabolism, Th1 Cells immunology
Abstract

In asthma, airway smooth muscle (ASM) chemokine secretion can induce mast cell recruitment into the airways. The functions of the mast cell chemoattractant CXCL10, and other chemokines, are regulated by binding to heparan sulphates such as syndecan-4. This study is the first demonstration that airway smooth muscle cells (ASMC) from people with and without asthma express and shed syndecan-4 under basal conditions. Syndecan-4 shedding was enhanced by stimulation for 24 h with the Th1 cytokines interleukin-1β (IL-1β) or tumor necrosis factor-α (TNF-α), but not interferon-γ (IFNγ), nor the Th2 cytokines IL-4 and IL-13. ASMC stimulation with IL-1β, TNF-α, and IFNγ (cytomix) induced the highest level of syndecan-4 shedding. Nonasthmatic and asthmatic ASM cell-associated syndecan-4 protein expression was also increased by TNF-α or cytomix at 4-8 h, with the highest levels detected in cytomix-stimulated asthmatic cells. Cell-associated syndecan-4 levels were decreased by 24 h, whereas shedding remained elevated at 24 h, consistent with newly synthesized syndecan-4 being shed. Inhibition of ASMC matrix metalloproteinase-2 did not prevent syndecan-4 shedding, whereas inhibition of ERK MAPK activation reduced shedding from cytomix-stimulated ASMC. Although ERK inhibition had no effect on syndecan-4 mRNA levels stimulated by cytomix, it did cause an increase in cell-associated syndecan-4 levels, consistent with the shedding being inhibited. In conclusion, ASMC produce and shed syndecan-4 and although this is increased by the Th1 cytokines, the MAPK ERK only regulates shedding. ASMC syndecan-4 production during Th1 inflammatory conditions may regulate chemokine activity and mast cell recruitment to the ASM in asthma.

Published
2012
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44. IL-17A acts via p38 MAPK to increase stability of TNF-alpha-induced IL-8 mRNA in human ASM.

Author

Henness S, van Thoor E, Ge Q, Armour CL, Hughes JM, and Ammit AJ

Subjects
Bronchi blood supply, Humans, Interleukin-17 pharmacology, Interleukin-8 metabolism, Lung Neoplasms pathology, Lung Neoplasms surgery, Pulmonary Circulation drug effects, Interleukin-17 physiology, Interleukin-8 genetics, Pulmonary Circulation physiology, RNA, Messenger genetics, Tumor Necrosis Factor-alpha pharmacology, p38 Mitogen-Activated Protein Kinases metabolism
Abstract

Human airway smooth muscle (ASM) plays an immunomodulatory role in asthma. Recently, IL-17A has become of increasing interest in asthma, being found at elevated levels in asthmatic airways and emerging as playing an important role in airway neutrophilia. IL-17A predominantly exerts its neutrophil orchestrating role indirectly via the induction of cytokines by resident airway structural cells. Here, we perform an in vitro study to show that although IL-17A did not induce secretion of the CXC chemokine IL-8 from ASM cells, IL-17A significantly potentiates TNF-alpha-induced IL-8 protein secretion and gene expression in a concentration- and time-dependent manner (P < 0.05). Levels of IL-8 protein produced after 24 h of incubation with TNF-alpha were enhanced 2.7-fold in the presence of IL-17A, and conditioned media significantly enhanced neutrophil chemotaxis in vitro. As IL-17A had no effect on the activity of NF-kappaB, a key transcriptional regulator of IL-8 gene expression, we then examined whether IL-17A acts at the posttranscriptional level. We found that IL-17A significantly augmented TNF-alpha-induced IL-8 mRNA stability. Interestingly, this enhanced stability occurred via a p38 MAPK-dependent pathway. The decay of IL-8 mRNA transcripts proceeded at a significantly faster rate when cells were pretreated with the p38 MAPK inhibitor SB-203580 (-0.05763 +/- 0.01964, t(1/2) = 12.0 h), compared with vehicle (-0.01030 +/- 0.007963, t(1/2) = 67.3 h) [results are expressed as decay constant (means +/- SE) and half-life (t(1/2) in h): P < 0.05]. Collectively, these results demonstrate that IL-17A amplifies the synthetic function of ASM cells, acting via a p38 MAPK-dependent posttranscriptional pathway to augment TNF-alpha-induced secretion of the potent neutrophil chemoattractant IL-8 from ASM cells.

Published
2006
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