Standardized exercise training is feasible, safe, and effective in pulmonary arterial and chronic thromboembolic pulmonary hypertension: results from a large European multicentre randomized controlled trial.

AIMS: This prospective, randomized, controlled, multicentre study aimed to evaluate efficacy and safety of exercise training in patients with pulmonary arterial (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH). METHODS AND RESULTS: For the first time a specialized PAH/CTEPH rehabilitation programme was implemented in 11 centres across 10 European countries. Out of 129 enrolled patients, 116 patients (58 vs. 58 randomized into a training or usual care control group) on disease-targeted medication completed the study [85 female; mean age 53.6 ± 12.5 years; mean pulmonary arterial pressure 46.6 ± 15.1 mmHg; World Health Organization (WHO) functional class II 53%, III 46%; PAH n = 98; CTEPH n = 18]. Patients of the training group performed a standardized in-hospital rehabilitation with mean duration of 25 days [95% confidence interval (CI) 17-33 days], which was continued at home. The primary endpoint, change of 6-min walking distance, significantly improved by 34.1 ± 8.3 m in the training compared with the control group (95% CI, 18-51 m; P < 0.0001). Exercise training was feasible, safe, and well-tolerated. Secondary endpoints showed improvements in quality of life (short-form health survey 36 mental health 7.3 ± 2.5, P = 0.004), WHO-functional class (training vs. control: improvement 9:1, worsening 4:3; χ2P = 0.027) and peak oxygen consumption (0.9 ± 0.5 mL/min/kg, P = 0.048) compared with the control group. CONCLUSION: This is the first multicentre and so far the largest randomized, controlled study on feasibility, safety, and efficacy of exercise training as add-on to medical therapy in PAH and CTEPH. Within this study, a standardized specialized training programme with in-hospital start was successfully established in 10 European countries.

ERS statement on exercise training and rehabilitation in patients with severe chronic pulmonary hypertension.

Objectives of this European Respiratory Society task force were to summarise current studies, to develop strategies for future research and to increase availability and awareness of exercise training for pulmonary hypertension (PH) patients.An evidence-based approach with clinical expertise of the task force members, based on both literature search and face-to-face meetings was conducted. The statement summarises current knowledge and open questions regarding clinical effects of exercise training in PH, training modalities, implementation strategies and pathophysiological mechanisms.In studies (784 PH patients in total, including six randomised controlled trials, three controlled trials, 10 prospective cohort studies and four meta-analyses), exercise training has been shown to improve exercise capacity, muscular function, quality of life and possibly right ventricular function and pulmonary haemodynamics. Nevertheless, further studies are needed to confirm these data, to investigate the impact on risk profiles and to identify the most advantageous training methodology and underlying pathophysiological mechanisms.As exercise training appears to be effective, cost-efficient and safe, but is scarcely reimbursed, support from healthcare institutions, commissioners of healthcare and research funding institutions is greatly needed. There is a strong need to establish specialised rehabilitation programmes for PH patients to enhance patient access to this treatment intervention.

Social deprivation and prognosis in Scottish patients with pulmonary arterial hypertension.

Several demographic and clinical factors have prognostic significance in idiopathic pulmonary arterial hypertension (IPAH). Studies in China and the USA have suggested an association between low socioeconomic status and reduced survival. The impact of social deprivation on IPAH survival in the UK is not known.280 patients with IPAH and hereditary PAH (HPAH) attending the Scottish Pulmonary Vascular Unit (Glasgow, UK) were assigned to social deprivation quintiles using the Scottish Index of Multiple Deprivation database. The association between survival and social deprivation quintile was assessed using Cox proportional hazards regression analysis.The distribution of IPAH/HPAH patients was more socially deprived than would be expected based on Scottish citizenry as a whole (Chi-squared 16.16, p=0.003), suggesting referral and access to care is not impeded by socioeconomic status. Univariate analysis demonstrated no significant association between social deprivation and survival (p=0.81), and this association failed to reach significance with inclusion of time, sex and age as covariates in the model (p=0.23). There were no statistically significant correlations between social deprivation and baseline clinical variables of prognostic importance except for age, sex and quality of life.Social deprivation is not a significant referral barrier or prognostic factor for IPAH and HPAH in Scotland.

Medical Therapies for the Treatment of Pulmonary Arterial Hypertension: How Do We Choose?

Significant advances have been made in the management of pulmonary arterial hypertension (PAH) in the past decade. There is a greater understanding of the disease process, more robust markers of prognostication and a wider range of disease-targeted therapies, with three classes of drug therapy now established. This has resulted in improved prognosis and quality of life but has also increased the complexity in making treatment decisions. To utilise these pharmacotherapies to their best potential, several factors need to be considered. This article will discuss how best to initiate and escalate PAH therapy on an individual patient basis by discussing current pharmacotherapies available, specific patient factors and determining treatment response and prognosis at diagnosis and during follow-up.

Implementing a self-management intervention for people with a chronic compensable musculoskeletal injury in a workers compensation context: a process evaluation.

PURPOSE: Determining factors critical for an intervention's success, specifically for whom and under what circumstances, is necessary if interventions are to be effectively targeted and efficiently implemented. This paper describes a process evaluation undertaken to assess the implementation of a novel self-management (SM) intervention developed for those with a chronic compensable work-related musculoskeletal disorder seeking to return to work. METHODS: The process evaluation, assessing the 'Self-Management for Return to Work' intervention, examined data from program leader evaluations, telephone interviews with stakeholders (injured worker participants, vocational rehabilitation consultant program leaders and compensation insurance regulators), post-intervention focus group session feedback, attendance lists and researcher notes. RESULTS: The evaluation identified several challenges and barriers associated with conducting research within the VR environment and with the characteristics of those targeted i.e., injured workers with a chronic compensable condition. These issues were primary contributing factors to the modifications to the randomised controlled trial methodology and the trial's premature cessation. CONCLUSIONS: Despite the difficulties encountered, high stakeholder acceptability suggests that the concept and theory underlying the targeted SM intervention were not flawed, though there is room for further tailoring to both the program method and its timing. The results of this process evaluation provide a useful platform for others considering the implementation of interventions within the vocational rehabilitation context or with individuals with chronic, compensated injuries.

Digital asthma self-management interventions: a systematic review.

BACKGROUND: Many people with asthma tolerate symptoms and lifestyle limitations unnecessarily by not utilizing proven therapies. Better support for self-management is known to improve asthma control, and increasingly the Internet and other digital media are being used to deliver that support. OBJECTIVE: Our goal was to summarize current knowledge, evidenced through existing systematic reviews, of the effectiveness and implementation of digital self-management support for adults and children with asthma and to examine what features help or hinder the use of these programs. METHODS: A comprehensive search strategy combined 3 facets of search terms: (1) online technology, (2) asthma, and (3) self-management/behavior change/patient experience. We undertook searches of 14 databases, and reference and citation searching. We included qualitative and quantitative systematic reviews about online or computerized interventions facilitating self-management. Title, abstract, full paper screening, and quality appraisal were performed by two researchers independently. Data extraction was undertaken using standardized forms. RESULTS: A total of 3810 unique papers were identified. Twenty-nine systematic reviews met inclusion criteria: the majority were from the United States (n=12), the rest from United Kingdom (n=6), Canada (n=3), Portugal (n=2), and Australia, France, Spain, Norway, Taiwan, and Greece (1 each). Only 10 systematic reviews fulfilled pre-determined quality standards, describing 19 clinical trials. Interventions were heterogeneous: duration of interventions ranging from single use, to 24-hour access for 12 months, and incorporating varying degrees of health professional involvement. Dropout rates ranged from 5-23%. Four RCTs were aimed at adults (overall range 3-65 years). Participants were inadequately described: socioeconomic status 0/19, ethnicity 6/19, and gender 15/19. No qualitative systematic reviews were included. Meta-analysis was not attempted due to heterogeneity and inadequate information provision within reviews. There was no evidence of harm from digital interventions. All RCTs that examined knowledge (n=2) and activity limitation (n=2) showed improvement in the intervention group. Digital interventions improved markers of self care (5/6), quality of life (4/7), and medication use (2/3). Effects on symptoms (6/12) and school absences (2/4) were equivocal, with no evidence of overall benefits on lung function (2/6), or health service use (2/15). No specific data on economic analyses were provided. Intervention descriptions were generally brief making it impossible to identify which specific "ingredients" of interventions contribute most to improving outcomes. CONCLUSIONS: Digital self-management interventions show promise, with evidence of beneficial effects on some outcomes. There is no evidence about utility in those over 65 years and no information about socioeconomic status of participants, making understanding the "reach" of such interventions difficult. Digital interventions are poorly described within reviews, with insufficient information about barriers and facilitators to their uptake and utilization. To address these gaps, a detailed quantitative systematic review of digital asthma interventions and an examination of the primary qualitative literature are warranted, as well as greater emphasis on economic analysis within trials.

Mortality risk factors during the 1918-1919 influenza pandemic in the Australian army.

BACKGROUND: Understanding the risk of mortality during the 1918-1919 influenza pandemic could inform preparations for a future pandemic. METHODS: Prospectively collected demographic, hospitalization, and death data from all individuals who served in the Australian Imperial Force from 1914 through 1919 in Europe and the Middle East were abstracted from archived records. Analyses were conducted to determine mortality risk factors. RESULTS: Hospitalization with a respiratory illness during the spring-summer of 1918 protected soldiers from death (odds ratio, 0.37 [95% confidence interval, 0.25-0.53]; P < .001) but not from hospitalization during the fall-winter of 1918-1919. During the fall-winter of 1918-1919, there was a strong inverse relationship between risk of dying of pneumonia-influenza and time in military service. The pneumonia-influenza death rate among men who enlisted in 1918 (6.33 deaths per 100 person-years) was 9 times higher than that among the 1917 enlistment cohort (0.72 deaths per 100 person-years) and >14 times higher than that among the 1916 cohort (0.43 deaths per 100 person-years), 1915 cohort (0.29 deaths per 100 person-years), and 1914 cohort (0.28 deaths per 100 person-years). CONCLUSION: There was a strong inverse relationship between length of service in the Australian Imperial Force and mortality risk from pneumonia-influenza during the fall-winter of 1918-1919. The protective effect of increased service likely reflected increased acquired immunity to influenza viruses and endemic bacterial strains that caused secondary pneumonia and most of the deaths during the 1918-1919 influenza pandemic.

Does self-management for return to work increase the effectiveness of vocational rehabilitation for chronic compensated musculoskeletal disorders? Protocol for a randomised controlled trial.

BACKGROUND: Musculoskeletal disorders are common and costly disorders to workers compensation and motor accident insurance systems and are a leading contributor to the burden of ill-health. In Australia, vocational rehabilitation is provided to workers to assist them to stay in, or return to work. Self-management training may be an innovative addition to improve health and employment outcomes from vocational rehabilitation. METHODS/DESIGN: The research plan contains mixed methodology consisting of a single blind randomised controlled trial, an economic evaluation and qualitative research. Participants (n = 366) are volunteers with compensated musculoskeletal disorders of 3 months to 3 years in duration who were working at the time of the injury/onset of the chronic disorder. The trial tests the effectiveness of usual vocational rehabilitation plus the Chronic Disease Self-Management Program (CDSMP) to which two additional and newly-developed modules have been added, against vocational rehabilitation alone (control) The modules added to the CDSMP focus on how to navigate through compensation systems and manage the return to work process, and aim to be relevant to those in a vocational rehabilitation setting.The primary outcome of this study is readiness for return to work which will be evaluated using the Readiness for Return-to-Work scale. Secondary outcomes include return to work status, health efficacy (heiQ questionnaire) and general health status (SF-12v2(R) Health Survey). Measures will be taken at baseline, immediately post-intervention and at 6- and 12- months post-intervention by an independent assessor. An economic evaluation will compare the costs and outcomes between the intervention and control groups in terms of cost-effectiveness and a partial cost-benefit or cost analysis. The impact of the intervention will also be evaluated qualitatively, in terms of its acceptability to stakeholders. DISCUSSION: This article describes the protocol for a single blind randomised controlled trial with a one year follow-up. The results will provide evidence for the addition or not of self-management training within vocational rehabilitation for chronic compensated musculoskeletal disorders. TRIAL REGISTRATION: Australia and New Zealand Clinical Trials Registry ACTRN12609000843257.

Australian military primary care practitioners do not believe clinical practice guidelines are needed for postdeployment medically unexplained symptoms.

In Australia, little research has been undertaken on the development of clinical practice guidelines (CPGs) to assist with the impact of postdeployment ill-health including medically unexplained symptoms (MUS) and it has been unclear whether such a development is desired by Australian primary care practitioners. In response an empirical investigation into the perceptions and experiences of 24 medical officers from the Australian military with regard to postdeployment ill-health, medically unexplained symptoms, and the potential development of CPGs in this area was undertaken. The analysis suggests that although MUS are accepted as common in general practice they are not perceived by practitioners to be as prevalent in the Australian Defense Forces. Although the medical officers do not perceive clinical practice guidelines as the best tool for managing MUS, there was interest in the development of practical tools to assist in the diagnosis of medically unexplained symptoms. The response by practitioners is of critical importance for the potential implementation of clinical practice guidelines in this area.

Compensation and wellness: a conflict for veterans' health.

In Australia greater attention is being given to health determinants, and the dominance of treatment in health policy and budgets is giving away some ground to prevention, health promotion, rehabilitation and disability management. This creates a dilemma for compensation systems: should the inclusion criteria be broadened to match the new thinking or should a narrower definition of "disease, injury or death" be retained? This issue is explored in the context of war syndromes among veterans. While veterans experience symptoms more frequently and more severely than military and community controls, their patterns of symptoms are not unique. Current compensation and benefit programs can create iatrogenic effects. It is concluded that compensation systems should be kept as safety nets while resources are provided to improve the capacity of primary health care caregivers, community organisations and veterans with war syndromes and their families to better deal with these problems. Adapting compensation systems to promote wellness through self-management health partnerships is one way of directing resources to individuals and their families. Action research at the community level with veterans, their families, their organisations, primary health care organisations, policy makers and researchers would allow this sector to work out the best way to apply existing efficacious tools to these modern health problems.

Validation of impedance cardiography in pulmonary arterial hypertension.

BACKGROUND: Non-invasive methods of measuring cardiac output are highly desirable in pulmonary arterial hypertension (PAH). We therefore sought to validate impedance cardiography (ICG) against thermodilution (TD) and cardiac magnetic resonance (CMR) in the measurement of cardiac output in patients under investigation for PAH. METHODS: A prospective, cross-sectional study was performed to compare single-point measurements of cardiac output obtained by impedance cardiography (COICG ) technology (PhysioFlow® ) with (i) contemporaneous TD measurements (COTD ) at rest and steady-state exercise during right heart catheterization and (ii) CMR measurements (COCMR ) at rest obtained within 72 h. RESULTS: Paired COICG and COTD measurements were obtained in 25 subjects at rest and 16 subjects at exercise. COCMR measurements were obtained in 16 subjects at rest. There was unsatisfactory correlation and agreement between COICG and COTD at rest (r = 0·42, P = 0·035; bias: 1·21 l min-1 , 95% CI: -2·33 to 4·75 l min-1 ) and exercise (r = .65, P = .007; bias: 1·41 l min-1 ; 95% CI: -3·99 to 6·81 l min-1 ) and in the change in COICG and COTD from rest to exercise (r = 0·53, P = 0·033; bias: 0·76 l min-1 , 95% CI: -3·74 to 5·26 l min-1 ). There was also a lack of correlation and unsatisfactory agreement between resting COICG and COCMR (r = 0·38, P = 0·1; bias: 1·40 l min-1 , 95% CI: -2·48 to 5·28 l min-1 ). In contrast, there was close correlation and agreement between resting COTD and COCMR (r = 0·87, P<0·001; bias: -0·16 l min-1 , 95% CI: -1·97 to 1·65). CONCLUSIONS: In a representative population of patients under investigation for PAH, ICG showed insufficient qualitative and quantitative value in the measurement of resting and exercise cardiac output when compared with TD and CMR.

The inhibitory profile of Ibudilast against the human phosphodiesterase enzyme family.

Ibudilast is widely used in Japan to treat ischemic stroke and bronchial asthma. Its mode of action is through the inhibition of cyclic nucleotide phosphodiesterases (PDEs). Growing evidence suggests this compound has utility in a range of neurological conditions linked to its ability to elevate cellular cyclic nucleotide concentrations, however limited data exists on Ibudilast's action on individual PDE families. We therefore used an extensive panel of human PDE enzymes to define the PDE inhibitory profile of this compound. Ibudilast preferentially inhibits PDE3A, PDE4, PDE10 and PDE11 with lesser inhibition of a number of other families. The significance of these findings is discussed in relation to Ibudilast's observed effects on certain disease states.

The effect of selective phosphodiesterase inhibitors, alone and in combination, on a murine model of allergic asthma.

BACKGROUND: The anti-inflammatory effects of the selective phosphodiesterase (PDE) inhibitors cilostazol (PDE 3), RO 20-1724 (PDE 4) and sildenafil (PDE 5) were examined in a murine model of allergic asthma. These compounds were used alone and in combination to determine any potential synergism, with dexamethasone included as a positive control. METHODS: Control and ovalbumin sensitised Balb/C mice were administered orally with each of the possible combinations of drugs at a dose of 3 mg/Kg for 10 days. RESULTS: When used alone, RO 20-1724 significantly reduced eosinophil influx into lungs and lowered tumour necrosis factor-alpha, interleukin-4 and interleukin-5 levels in the bronchoalveolar lavage fluid when compared to untreated mice. Treatment with cilostazol or sildenafil did not significantly inhibit any markers of inflammation measured. Combining any of these PDE inhibitors produced no additive or synergistic effects. Indeed, the anti-inflammatory effects of RO 20-1724 were attenuated by co-administration of either cilostazol or sildenafil. CONCLUSIONS: These results suggest that concurrent treatment with a PDE 3 and/or PDE 5 inhibitor will reduce the anti-inflammatory effectiveness of a PDE 4 inhibitor.

Assessment of revised recruitment standards for asthma in the Australian Defence Force.

OBJECTIVE: To assess the impact of relaxed asthma recruitment standards adopted by the Australian Defence Force in 2007. METHODS: A retrospective audit was conducted on clinical and administrative data for recruits, with and without mild asthma, in their first year of service. RESULTS: There was no evidence that mild asthmatics experienced worse outcomes than nonasthmatic recruits. Mild asthmatics had fewer illnesses and restricted duty days and were less costly compared to other recruits. There was no difference in the rate of discharge (attrition) between those with and without mild asthma. CONCLUSIONS: The revised recruitment standards for asthma in the Australian Defence Force have not resulted in unanticipated medical or administrative costs to the organization. Health and administrative outcomes differed little between mild asthmatics and nonasthmatic recruits in their first 12 months of service.

Spouses of military members' experiences and insights: qualitative analysis of responses to an open-ended question in a survey of health and wellbeing.

INTRODUCTION: There are few studies on the experiences of spouses of military members, with most focused on adverse impacts of deployment. Responses to an open-ended question in a survey of spouses' health and wellbeing enabled access to perceptions and insights on a broad range of topics. The objective of this investigation was to examine how respondents used the open-ended question and what they discussed, in aim of informing support service agencies and spouses of military members. METHODS: Thematic analysis was conducted on responses to the open-ended question. Descriptive analysis was performed on the demographics, military member characteristics and self-reported health of respondents and non-respondents to the open-ended question. FINDINGS: Over a quarter (28.5%) of the 1,332 survey participants answered the open-ended question, with respondents having a significantly higher level of education than non-respondents. Respondents expressed negative and positive experiences and insights on military life, provided personal information, commented on the survey, and qualified their responses to closed-ended questions. Topics included 'inadequate support', 'deployment impacts', 'suggestions for supporting agencies', 'appraisal of experiences' and 'coping strategies'. CONCLUSIONS: This investigation uncovered issues of importance to spouses of military members that were not included or identified in a quantitative study. The findings provide a platform from which to explore these issues further, particularly the impact of military life on the non-serving spouse's career. The findings also provide support agencies with evidence to strengthen their services and they give spouses an opportunity to reflect on their own and others' feelings and evaluations of military life.

Relationship between "purulent bronchitis" in military populations in Europe prior to 1918 and the 1918-1919 influenza pandemic.

Purulent bronchitis was a distinctive and apparently new lethal respiratory infection in British and American soldiers during the First World War. Mortality records suggest that purulent bronchitis caused localized outbreaks in the midst of a broad epidemic wave of lethal respiratory illness in 1916-1917. Probable purulent bronchitis deaths in the Australian Army showed an epidemic wave that moved from France to England. Purulent bronchitis may have been the clinical expression of infection with a novel influenza virus which also could have been a direct precursor of the 1918 pandemic strain.

Low but highly variable mortality among nurses and physicians during the influenza pandemic of 1918-1919.

BACKGROUND: During the 1918-1919 influenza pandemic, nurses and physicians were intensively exposed to the pandemic A/H1N1 strain. There are few published summaries of the mortality experiences of nurses and physicians during the pandemic. METHODS: Mortality records from U.S. and British Armies during the First World War and obituary notices in national medical association journals were reviewed to ascertain death notices of nurses and physicians likely to have died of influenza. RESULTS: Illness-related mortality among U.S. military nurses (1·05%) was one and one-half times higher than among U.S. medical officers (0·68%), nearly two times higher than among British medical officers (0·55%), and nine times higher than among British nurses (0·12%). Among U.S. nursing officers, mortality was approximately twice as high among those assigned in the United States than in Europe. Among civilian physicians, mortality during the influenza pandemic was markedly increased in Canada, New Zealand, South Africa and the United States but not Australia. CONCLUSIONS: During the 1918 pandemic, mortality among nurses and physicians was relatively low compared to their patients and significantly varied across locations and settings. Medical-care providers (particularly U.S. nursing officers) who were new to their assignments when pandemic-related epidemics occurred may have had higher risk of influenza-related mortality because of occupational exposures to bacterial respiratory pathogens that they had not previously encountered.