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In pulmonary tuberculosis (PTB), morbidity during treatment and residual pulmonary disability can be under-estimated. Among adults with smear-positive PTB at an outpatient clinic in Papua, Indonesia, we assessed morbidity at baseline and during treatment, and 6-month residual disability, by measuring functional capacity (six-minute walk test [6MWT] and pulmonary function), quality of life (St George's Respiratory Questionnaire [SGRQ]) and Adverse Events ([AE]: new symptoms not present at outset). Results were compared with findings in locally-recruited volunteers. 200 PTB patients and 40 volunteers were enrolled. 6WMT was 497m (interquartile range 460-529) in controls versus 408m (IQR 346-450) in PTB patients at baseline (p<0.0001) and 470m (IQR 418-515) in PTB patients after 6 months (p=0.02 versus controls). SGRQ total score was 0 units (IQR 0-2.9) in controls, versus 36.9 (27.4-52.8) in PTB patients at baseline (p<0.0001) and 4.3 (1.7-8.8) by 6 months (p<0.0001). Mean percentage of predicted FEV1 was 92% (standard deviation 19.9) in controls, versus 63% (19.4) in PTB patients at baseline (p<0.0001) and 71% (17.5) by 6 months (p<0.0001). After 6 months, 27% of TB patients still had at least moderate-severe pulmonary function impairment, and 57% still had respiratory symptoms, despite most achieving 'successful' treatment outcomes, and reporting good quality of life. More-advanced disease at baseline (longer illness duration, worse baseline X-ray) and HIV positivity predicted residual disability. AE at any time during treatment were common: itch 59%, arthralgia 58%, headache 40%, nausea 33%, vomiting 16%. We found high 6-month residual pulmonary disability and high AE rates. Although PTB treatment is highly successful, the extent of morbidity during treatment and residual impairment could be overlooked if not specifically sought. Calculations of PTB-related burden of disease should acknowledge that TB-related morbidity does not stop at 6 months. Early case detection and treatment are key in minimising residual impairment.

Vitamin D (vitD) and L-arginine have important antimycobacterial effects in humans. Adjunctive therapy with these agents has the potential to improve outcomes in active tuberculosis (TB). In a 4-arm randomised, double-blind, placebo-controlled factorial trial in adults with smear-positive pulmonary tuberculosis (PTB) in Timika, Indonesia, we tested the effect of oral adjunctive vitD 50,000 IU 4-weekly or matching placebo, and L-arginine 6.0 g daily or matching placebo, for 8 weeks, on proportions of participants with negative 4-week sputum culture, and on an 8-week clinical score (weight, FEV1, cough, sputum, haemoptysis). All participants with available endpoints were included in analyses according to the study arm to which they were originally assigned. Adults with new smear-positive PTB were eligible. The trial was registered at ClinicalTrials.gov NCT00677339. 200 participants were enrolled, less than the intended sample size: 50 received L-arginine + active vitD, 49 received L-arginine + placebo vit D, 51 received placebo L-arginine + active vitD and 50 received placebo L-arginine + placebo vitD. According to the factorial model, 99 people received arginine, 101 placebo arginine, 101 vitamin D, 99 placebo vitamin D. Results for the primary endpoints were available in 155 (4-week culture) and 167 (clinical score) participants. Sputum culture conversion was achieved by week 4 in 48/76 (63%) participants in the active L-arginine versus 48/79 (61%) in placebo L-arginine arms (risk difference -3%, 95% CI -19 to 13%), and in 44/75 (59%) in the active vitD versus 52/80 (65%) in the placebo vitD arms (risk difference 7%, 95% CI -9 to 22%). The mean clinical outcome score also did not differ between study arms. There were no effects of the interventions on adverse event rates including hypercalcaemia, or other secondary outcomes. Neither vitD nor L-arginine supplementation, at the doses administered and with the power attained, affected TB outcomes. ClinicalTrials.gov. Registry number: NCT00677339.

Background Chronic respiratory diseases, such as chronic obstructive pulmonary disease (COPD), disproportionately impact the Aboriginal and Torres Strait Islander population of Australia. Aboriginal Community Controlled Health Services (ACCHSs) are primary care services, established to provide healthcare in culturally safe environments for Aboriginal people. There is little information about the respiratory services for people with chronic respiratory diseases provided by ACCHSs. Aim To describe current provision of respiratory services of ACCHSs based in New South Wales (NSW), with a focus on identifying barriers and facilitators to providing pulmonary rehabilitation. Methods A researcher-administered survey was conducted via Zoom plus a follow-up email to collect client and health workforce data. Participants were NSW-based ACCHSs, members of the Aboriginal Health and Medical Research Council (AH&MRC). Exclusions were ACCHSs that only delivered drug and alcohol rehabilitation, housing or employment services. The survey collected information related to client numbers, smoking history, COPD diagnoses, health workforce, and respiratory services with a focus on pulmonary rehabilitation programs. Results Forty-one ACCHSs were invited to participate and 18 (44%) completed the survey. Most provided respiratory care, although variation existed in service scope and delivery. The main respiratory services provided were smoking cessation (100%), spirometry (89%) and respiratory clinics (33%). Most ACCHSs (78%), reported some access to respiratory physicians. No ACCHSs provided pulmonary rehabilitation. Main barriers included staff shortages, lack of staff training, financial constraints and lack of space. Several ACCHSs expressed interest in providing a pulmonary rehabilitation program, if appropriate resourcing was available. Ten ACCHS (56%) reported that Aboriginal clients would not access mainstream public health services for pulmonary rehabilitation. Barriers to accessing these externally available pulmonary rehabilitation programs included transportation issues, cultural considerations and geographical location. Conclusions ACCHSs are delivering respiratory services for Aboriginal people living with chronic respiratory diseases within constrained infrastructure and resources. Additional funding is required to improve access to best practice care for Aboriginal people living with COPD including culturally safe, evidence-based and accessible pulmonary rehabilitation programs.

Background Despite the high incidence of chronic obstructive pulmonary disease (COPD) in Aboriginal communities in Australia, Aboriginal Health Workers (AHWs) have limited knowledge about effective management. Aim To evaluate an online education program, co-designed with AHWs and exercise physiologists (EPs) or physiotherapists (PTs), to increase knowledge about COPD and its management. Methods AHWs and EPs from four Aboriginal Community Controlled Health Services (ACCHS) were recruited. An Aboriginal researcher and a physiotherapist experienced in COPD management and pulmonary rehabilitation (PR) delivered seven online education sessions. These sessions used co-design principles and an Aboriginal pedagogy framework ‘8 Ways of learning’, which incorporates Aboriginal protocols and perspectives to realign teaching techniques and strengthen learning outcomes. Topics covered were: How the lungs work; What is COPD; Medications and how to use inhalers and COPD Action Plans; Why exercise is important; Managing breathlessness; Healthy eating; Managing anxiety and depression. After each session, AHWs with support from EPs, co-designed education ‘yarning’ resources using Aboriginal ways of learning to ensure topics were culturally safe for the local Aboriginal community and practiced delivering this at the following session. At the end of the program participants completed an anonymous online survey (5-point Likert scale) to assess satisfaction, and a semi-structured interview about their experience of the online education. Results Of the 12 participants, 11 completed the survey (7 AHWs, 4 EPs). Most (90%) participants strongly agreed or agreed that the online sessions increased knowledge and skills they needed to support Aboriginal patients with COPD. All (100%) participants felt: their cultural perspectives and opinions were valued and that they were encouraged to include cultural knowledge. Most (91%) reported that delivering their own co-designed yarning scripts during the online sessions improved their understanding of the topics. Eleven participants completed semi-structured interviews about participating in online education to co-design Aboriginal ‘yarning’ resources. Themes identified were: revealing the Aboriginal lung health landscape; participating in online learning; structuring the online education sessions; co-designing with the facilitators. Conclusions Online education using co-design and 8 Ways of learning was rated highly by AHWs and EPs for improving COPD knowledge and valuing cultural perspectives. The use of co-design principles supported the cultural adaptation of COPD resources for Aboriginal people with COPD. Trial registration PROSPERO (registration number: CRD42019111405).

Background. The mechanisms underlying lung injury in vivax malaria are not well understood. Inflammatory responses to Plasmodium falciparum and P. vivax, to our knowledge, have not previously been compared at an organ level. Methods. Respiratory symptoms and physiological aspects were measured longitudinally in Indonesian adults with uncomplicated vivax (n=50) and falciparum (n=50) malaria. Normal values were derived from 109 control subjects. Gas transfer was partitioned into its alveolar-capillary membrane (DM) and pulmonary capillary vascular (VC) components, to characterize the site and timing of impaired gas transfer. Results. Mean baseline VC volume was significantly reduced in vivax and falciparum malaria, improving with treatment in each species. Baseline DM function was not impaired in either species. The progressive deterioration in DM function after treatment was statistically significant in vivax malaria but not in uncomplicated falciparum malaria. Oxygen saturation deteriorated after treatment in vivax but improved in falciparum malaria. Conclusions. The baseline reduction in VC volume but not in DM function suggests encroachment on VC volume by parasitized erythrocytes and suggests that P. vivax-infected erythrocytes may sequester within the pulmonary microvasculature. Progressive alveolar-capillary dysfunction after treatment of vivax malaria is consistent with a greater inflammatory response to a given parasite burden in P. vivax relative to that in P. falciparum.

Background Strong evidence exists for the benefits of pulmonary rehabilitation (PR) for people with chronic obstructive pulmonary disease (COPD), however the availability of culturally safe PR for Aboriginal and Torres Strait Islander (Indigenous) Peoples is limited. The study aims to determine whether PR can be implemented within Aboriginal Community Controlled Health Services (ACCHS) to improve outcomes for Indigenous people with COPD. Methods Multi-centre cohort study using participatory action research guided by the Knowledge-to-Action Framework. ACCHS supportive of enhancing services for chronic lung disease will be recruited. Aboriginal Health Workers (AHW) and the exercise physiologist (EP) or physiotherapist (PT) within these ACCHS will attend a workshop aimed at increasing knowledge and skills related to management of COPD and the provision of PR. Indigenous people with COPD will be invited to attend an 8-week, twice weekly, supervised PR program. Outcomes: AHW, EP/PT knowledge, skills and confidence in the assessment and management of COPD will be measured before and immediately after the BE WELL workshop and at 3, 6 and 12 months using a survey. PR participant measures will be exercise capacity (6-minute walk test (6MWT), health-related quality of life and health status at commencement and completion of an 8-week PR program. Secondary outcomes will include: number, length and cost of hospitalisations for a COPD exacerbation in 12-months prior and 12-months post PR; local contextual factors influencing implementation of PR; specific respiratory services provided by ACCHS to manage COPD prior to project commencement and at project completion. Repeated measures ANOVA will be used to evaluate changes in knowledge and confidence over time of AHWs and EP/PTs. Paired t-tests will be used to evaluate change in patient outcomes from pre- to post-PR. Number of hospital admissions in the 12 months before and after the PR will be compared using unpaired t-tests. Discussion Pulmonary rehabilitation is an essential component of best-practice management of COPD and is recommended in COPD guidelines. Indigenous peoples have limited access to culturally safe PR programs. This study will evaluate whether PR can be implemented within ACCHS and improve outcomes for Indigenous people with COPD. Trial registration Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12617001337369, Registered 2nd September 2017 https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=373585&isClinicalTrial=False

Background and Objectives: The objectives of this study were to identify and validate a screening tool to detect malnutrition among Indigenous and non-Indigenous Australian patients. Methods and Study Design: This study included medical patients admitted into three regional hospitals in Australia. A literature review was undertaken of current screening tools before the Malnutrition Screening Tool (MST) and the newly developed Adult Nutrition Tool (ANT) were used to validate a screening tool for use among participants against the Subjective Global Assessment (SGA) tool. The sensitivity and specificity of both the MST and ANT were determined for all study participants as well as according to participants' Indigenous status. Results: A total of 608 participants were enrolled into the study, of whom 271 (44.6%) were Indigenous. The area under the curve (AUC) when utilising ANT was higher in all participants compared to the MST (0.90, 95% CI 0.88-0.92 versus 0.81, 95% CI 0.77-0.84, p<0.001). The AUC was also significantly higher for Indigenous participants when utilising ANT compared to the MST (0.88, 95% CI 0.84-0.92 versus 0.78, 95% CI 0.73-0.83, p<0.001). An ANT >=2 demonstrated superior sensitivity for both Indigenous and non-Indigenous participants (96.0%, 95% CI 92.8-98.7%) than the MST (84.0%, 95% CI 78.9-88.3) but with inferior specificity (59.5%, 95% CI 54.2-64.6) than the MST (70.7%, 95% CI 65.7-75.3). Conclusions: The ANT is both a valid and accurate tool for Indigenous and non-Indigenous Australian patients. Further research is required to validate ANT to aide in the detection of malnutrition in other clinical settings.

ObjectiveTo further the understanding of the factors influencing outcome following rheumatic heart disease (RHD) related mitral valve surgery, which globally remains an important cause of heart disease and a particular problem in Indigenous Australians.MethodsThe Australian Cardiac Surgery Database was utilised to assess outcomes following mitral valve repair and replacement for RHD and non-RHD valve disease. The association with aetiology, demographics, comorbidities, preoperative status and operative procedure was evaluated.ResultsMitral valve repairs and replacements undertaken in Australia were analysed from 119 and 1078 RHD surgical procedures and 3279 and 2400 non-RHD procedures, respectively. RHD mitral valve repair, compared with replacement, resulted in a slightly shorter hospital stay and more reoperation for valve dysfunction, but no difference in 30-day survival. In unadjusted survival analysis to 5 years, RHD mitral valve repair and replacement were no different (HR 0.86, 95% CI 0.4 to 1.7), non-RHD repair was superior to replacement (HR 1.7, 95% CI 1.4 to 2.0), RHD and non-RHD repair were no different (HR 0.9, 95% CI 0.5 to 1.7), and RHD replacement was superior to non-RHD (HR 1.5, 95% CI 1.2 to 1.9). None of these differences persisted in adjusted analyses and there was no difference in long-term survival for Indigenous Australians.ConclusionIn this large prospective cohort study we have demonstrated that adjusted long-term survival following RHD mitral valve repair surgery in Australia is no different to replacement and no different to non-RHD. Interpretation of valve surgery outcome requires careful consideration of patient factors that may also influence survival.

BackgroundIn patients with severe malaria, acute respiratory distress syndrome usually develops after the start of drug treatment and is a major cause of death. Its pathogenesis is not well understood MethodsRespiratory symptom, spirometry, and gas transfer analyses were performed longitudinally in adults in Papua, Indonesia, with uncomplicated (n=50) and severe (n=30) falciparum malaria; normal values were derived from 109 control subjects. Gas transfer was partitioned into its alveolar-capillary membrane (DM) and pulmonary vascular (Vc) components, to characterize the site of impaired gas transfer ResultsCough was frequent in both patients with uncomplicated malaria (50%) and those with severe malaria (30%) and resolved by day 14. Reduced midexpiratory flow indicated obstruction of the small airways. Gas transfer was significantly impaired in patients with severe malaria. DM was reduced in patients with severe malaria but not in those with uncomplicated malaria and only returned to normal levels after 2 weeks. In patients with uncomplicated malaria, Vc was reduced at presentation but improved thereafter. In patients with severe malaria, Vc decreased with treatment and was lowest at day 7 ConclusionsOur results suggest that pulmonary vascular occlusion occurs in both patients with uncomplicated malaria and those with severe malaria, likely from sequestration of both red blood cells (RBCs) and white blood cells. There was also impaired alveolar-capillary membrane function in patients with severe malaria but not in those with uncomplicated malaria. Persistent impairment long after clearance of parasitized RBCs suggests prolonged posttreatment inflammatory alveolar-capillary injury

BackgroundThe grading of radiological severity in clinical trials in tuberculosis (TB) remains unstandardised. The aim of this study was to generate and validate a numerical score for grading chest x-ray (CXR) severity and predicting response to treatment in adults with smear-positive pulmonary TB.MethodsAt a TB clinic in Papua, Indonesia, serial CXRs were performed at diagnosis, 2 and 6 months in 115 adults with smear-positive pulmonary TB. Radiographic findings predictive of 2-month sputum microscopy status were used to generate a score. The validity of the score was then assessed in a second data set of 139 comparable adults with TB, recruited 4 years later at the same site. Relationships between the CXR score and other measures of TB severity were examined.ResultsThe estimated proportion of lung affected and presence of cavitation, but not cavity size or other radiological findings, significantly predicted outcome and were combined to derive a score given by percentage of lung affected plus 40 if cavitation was present. As well as predicting 2-month outcome, scores were significantly associated with sputum smear grade at diagnosis (p<0.001), body mass index, lung function, haemoglobin, exercise tolerance and quality of life (p<0.02 for each). In the validation data set, baseline CXR score predicted 2-month smear status significantly more accurately than did the proportion of lung affected alone. In both data sets, CXR scores decreased over time (p<0.001).ConclusionThis simple, validated method for grading CXR severity in adults with smear-positive pulmonary TB correlates with baseline clinical and microbiological severity and response to treatment, and is suitable for use in clinical trials.