Predictors of unfavourable treatment outcome in patients diagnosed with drug-resistant tuberculosis in the Torres Strait / Papua New Guinea border region

Drug-resistant tuberculosis (DR-TB) is an ongoing challenge in the Torres Strait Islands (TSI) / Papua New Guinea (PNG) border region. Treatment success rates have historically been poor for patients diagnosed with DR-TB, leading to increased transmission. This study aimed to identify variables associated with unfavourable outcome in patients diagnosed with DR-TB to inform programmatic improvements. A retrospective study of all DR-TB cases who presented to Australian health facilities in the Torres Strait between 1 March 2000 and 31 March 2020 was performed. This time period covers four distinct TB programmatic approaches which reflect Australian and Queensland Government decisions on TB management in this remote region. Univariate and multivariate predictors of unfavourable outcome were analysed. Unfavourable outcome was defined as lost to follow up, treatment failure and death. Successful outcome was defined as cure and treatment completion. In total, 133 patients with resistance to at least one TB drug were identified. The vast majority (123/133; 92%) of DR-TB patients had pulmonary involvement; and of these, 41% (50/123) had both pulmonary and extrapulmonary TB. Unfavourable outcomes were observed in 29% (39/133) of patients. Patients living with human immunodeficiency virus, renal disease or diabetes (4/133; 4/133; 3/133) had an increased frequency of unfavourable outcome (p <0.05), but the numbers were small. Among all 133 DR-TB patients, 41% had a low lymphocyte count, which was significantly associated with unfavourable outcome (p <0.05). We noted a 50% increase in successful outcomes achieved in the 2016–2020 programmatic period, compared to earlier periods (OR 5.3, 95% Confidence Interval [1.3, 20.4]). Being a close contact of a known TB case was associated with improved outcome. While DR-TB treatment outcomes have improved over time, enhanced surveillance for DR-TB, better cross border collaboration and consistent diagnosis and management of comorbidities and other risk factors should further improve patient care and outcomes

Critical Consideration of Tuberculosis Management of Papua New Guinea Nationals and Cross-Border Health Issues in the Remote Torres Strait Islands, Australia

The international border between Australia and Papua New Guinea (PNG) serves as a gateway for the delivery of primary and tertiary healthcare for PNG patients presenting to Australian health facilities with presumptive tuberculosis (TB). An audit of all PNG nationals with presumptive TB who presented to clinics in the Torres Strait between 2016 and 2019 was conducted to evaluate outcomes for PNG patients and to consider the consistency and equity of decision-making regarding aeromedical evacuation. We also reviewed the current aeromedical retrieval policy and the outcomes of patients referred back to Daru General Hospital in PNG. During the study period, 213 PNG nationals presented with presumptive TB to primary health centres (PHC) in the Torres Strait. In total, 44 (21%) patients were medically evacuated to Australian hospitals; 26 met the evacuation criteria of whom 3 died, and 18 did not meet the criteria of whom 1 died. A further 22 patients who met the medical evacuation criteria into Australia were referred to Daru General Hospital of whom 2 died and 10 were lost to follow-up. The cross-border movement of people from PNG into Australia is associated with an emergent duty of care. Ongoing monitoring and evaluation of patient outcomes are necessary for transparency and justice

Tuberculosis in the Torres Strait: the lady doth test too much

Introduction: Smear-positive pulmonary tuberculosis (PTB) requires rapid diagnosis and treatment to prevent ongoing transmission. Collection of two sputum specimens is considered the minimum requirement for the diagnosis of PTB but current guidelines in the Torres Strait Islands, Australia, recommend three sputum specimens; this frequently delays treatment initiation. Methods: A retrospective study was performed to ascertain the diagnostic yield of sputum specimens collected in the Torres Strait Islands. The study assessed demographics and characteristics of all PTB cases diagnosed between 2000 and 2018, and assessed the diagnostic yield in 143 patients from whom at least three sputum specimens had been collected prior to treatment commencement. Incremental and cumulative yield was calculated for each sputum specimen. Data were further analysed using binary logistic regression to examine the association between selected characteristics and a smear-positive acid-fast bacilli (AFB) result. Results: Overall, AFB was detected from the first or second sputum specimen in 97 of 101 PTB cases that were sputum smear positive. A smear-positive result was more common (odds ratio 2.84, 95% confidence interval 1.08–7.46) for Papua New Guinea nationals compared to Australian born patients. Of the 429 samples collected, 76 (18%) were of poor quality and the association between poor quality specimens and smear-negative results was significant (p<0.01). Among sputum smear-negative cases, 5/42= (12%) had three consecutive poor quality specimens. The most common collection modality in adults was voluntary expectoration; done in 391/429 (91%) of all specimens collected. Alternative specimen collection methods were mainly used in children; induced sputum 1/429 (0.2%), gastric aspirate 26/429 (6%) and nasopharyngeal aspirate 7/429 (1.6%). Errors with labelling, packaging and transportation occurred in 44 specimens from 15 patients. Conclusion: Two good quality specimens ensure adequate diagnostic yield for PTB and a third specimen should only be collected from patients with two negative specimens who have persistent symptoms. Ideally, decentralised Xpert Ultra® should be the frontline diagnostic test in remote settings, especially in settings like the Torres Strait Islands with high rates of drugresistant TB

Profit and loss analysis for an intensive care unit (ICU) in Japan: a tool for strategic management

BACKGROUND: Accurate cost estimate and a profit and loss analysis are necessary for health care practice. We performed an actual financial analysis for an intensive care unit (ICU) of a university hospital in Japan, and tried to discuss the health care policy and resource allocation decisions that have an impact on critical intensive care. METHODS: The costs were estimated by a department level activity based costing method, and the profit and loss analysis was based on a break-even point analysis. The data used included the monthly number of patients, the revenue, and the direct and indirect costs of the ICU in 2003. RESULTS: The results of this analysis showed that the total costs of US$2,678,052 of the ICU were mainly incurred due to direct costs of 88.8$ 2,295,044. However, it was determined that the ICU required at least 1,986 patient days within one fiscal year based on a break-even point analysis. As a result, an annual deficit of US$ 383,008 has occurred in the ICU. CONCLUSION: These methods are useful for determining the profits or losses for the ICU practice, and how to evaluate and to improve it. In this study, the results indicate that most ICUs in Japanese hospitals may not be profitable at the present time. As a result, in order to increase the income to make up for this deficit, an increase of 437 patient days in the ICU in one fiscal year is needed, and the number of patients admitted to the ICU should thus be increased without increasing the number of beds or staff members. Increasing the number of patients referred from cooperating hospitals and clinics therefore appears to be the best strategy for achieving these goals

The efficacy of antihypertensiye drugs in chronic intermittent hypoxia conditions

The authors would like to thank the Portuguese Fundacao para a Ciencia e a Tecnologia (FCT) and CEDOC (Chronic Diseases Research Centre, Lisbon, Portugal). Lucilia N. Diogo is supported by an FCT fellowship (SFRH/BD/48335/2008; PTDC/SAU-TOX/112264/2009).Sleep apnea/hypopnea disorders include centrally originated diseases and obstructive sleep apnea (OSA). This last condition is renowned as a frequent secondary cause of hypertension (HT). The mechanisms involved in the pathogenesis of HT can be summarized in relation to two main pathways: sympathetic nervous system stimulation mediated mainly by activation of carotid body (CB) chemoreflexes and/or asphyxia, and, by no means the least important, the systemic effects of chronic intermittent hypoxia (CIH). The use of animal models has revealed that CIH is the critical stimulus underlying sympathetic activity and hypertension, and that this effect requires the presence of functional arterial chemoreceptors, which are hyperactive in CIH. These models of CIH mimic the HT observed in humans and allow the study of CIH independently without the mechanical obstruction component. The effect of continuous positive airway pressure (CRAP), the gold standard treatment for OSA patients, to reduce blood pressure seems to be modest and concomitant antihypertensive therapy is still required. We focus this review on the efficacy of pharmacological interventions to revert HT associated with CIH conditions in both animal models and humans. First, we explore the experimental animal models, developed to mimic HT related to CIH, which have been used to investigate the effect of antihypertensive drugs (AHDs). Second, we review what is known about drug efficacy to reverse HT induced by CIH in animals. Moreover, findings in humans with OSA are cited to demonstrate the lack of strong evidence for the establishment of a first-line antihypertensive regimen for these patients. Indeed, specific therapeutic guidelines for the pharmacological treatment of HT in these patients are still lacking. Finally, we discuss the future perspectives concerning the non-pharmacological and pharmacological management of this particular type of HT.publishersversionpublishe

Cost-effectiveness and resource implications of aggressive action on tuberculosis in China, India, and South Africa: a combined analysis of nine models.

BACKGROUND: The post-2015 End TB Strategy sets global targets of reducing tuberculosis incidence by 50% and mortality by 75% by 2025. We aimed to assess resource requirements and cost-effectiveness of strategies to achieve these targets in China, India, and South Africa. METHODS: We examined intervention scenarios developed in consultation with country stakeholders, which scaled up existing interventions to high but feasible coverage by 2025. Nine independent modelling groups collaborated to estimate policy outcomes, and we estimated the cost of each scenario by synthesising service use estimates, empirical cost data, and expert opinion on implementation strategies. We estimated health effects (ie, disability-adjusted life-years averted) and resource implications for 2016-35, including patient-incurred costs. To assess resource requirements and cost-effectiveness, we compared scenarios with a base case representing continued current practice. FINDINGS: Incremental tuberculosis service costs differed by scenario and country, and in some cases they more than doubled existing funding needs. In general, expansion of tuberculosis services substantially reduced patient-incurred costs and, in India and China, produced net cost savings for most interventions under a societal perspective. In all three countries, expansion of access to care produced substantial health gains. Compared with current practice and conventional cost-effectiveness thresholds, most intervention approaches seemed highly cost-effective. INTERPRETATION: Expansion of tuberculosis services seems cost-effective for high-burden countries and could generate substantial health and economic benefits for patients, although substantial new funding would be required. Further work to determine the optimal intervention mix for each country is necessary. FUNDING: Bill & Melinda Gates Foundation

Emerging technologies for the production of renewable liquid transport fuels from biomass sources enriched in plant cell walls

Plant cell walls are composed predominantly of cellulose, a range of non-cellulosic polysaccharides and lignin. The walls account for a large proportion not only of crop residues such as wheat straw and sugarcane bagasse, but also of residues of the timber industry and specialist grasses and other plants being grown specifically for biofuel production. The polysaccharide components of plant cell walls have long been recognized as an extraordinarily large source of fermentable sugars that might be used for the production of bioethanol and other renewable liquid transport fuels. Estimates place annual plant cellulose production from captured light energy in the order of hundreds of billions of tons. Lignin is synthesized in the same order of magnitude and, as a very large polymer of phenylpropanoid residues, lignin is also an abundant, high energy macromolecule. However, one of the major functions of these cell wall constituents in plants is to provide the extreme tensile and compressive strengths that enable plants to resist the forces of gravity and a broad range of other mechanical forces. Over millions of years these wall constituents have evolved under natural selection to generate extremely tough and resilient biomaterials. The rapid degradation of these tough cell wall composites to fermentable sugars is therefore a difficult task and has significantly slowed the development of a viable lignocellulose-based biofuels industry. However, good progress has been made in overcoming this so-called recalcitrance of lignocellulosic feedstocks for the biofuels industry, through modifications to the lignocellulose itself, innovative pre-treatments of the biomass, improved enzymes and the development of superior yeasts and other microorganisms for the fermentation process. Nevertheless, it has been argued that bioethanol might not be the best or only biofuel that can be generated from lignocellulosic biomass sources and that hydrocarbons with intrinsically higher energy densities might be produced using emerging and continuous flow systems that are capable of converting a broad range of plant and other biomasses to bio-oils through so-called 'agnostic' technologies such as hydrothermal liquefaction. Continued attention to regulatory frameworks and ongoing government support will be required for the next phase of development of internationally viable biofuels industries.Hwei-Ting Tan, Kendall R. Corbin and Geoffrey B. Finche

Advances in Electronic-Nose Technologies Developed for Biomedical Applications

The research and development of new electronic-nose applications in the biomedical field has accelerated at a phenomenal rate over the past 25 years. Many innovative e-nose technologies have provided solutions and applications to a wide variety of complex biomedical and healthcare problems. The purposes of this review are to present a comprehensive analysis of past and recent biomedical research findings and developments of electronic-nose sensor technologies, and to identify current and future potential e-nose applications that will continue to advance the effectiveness and efficiency of biomedical treatments and healthcare services for many years. An abundance of electronic-nose applications has been developed for a variety of healthcare sectors including diagnostics, immunology, pathology, patient recovery, pharmacology, physical therapy, physiology, preventative medicine, remote healthcare, and wound and graft healing. Specific biomedical e-nose applications range from uses in biochemical testing, blood-compatibility evaluations, disease diagnoses, and drug delivery to monitoring of metabolic levels, organ dysfunctions, and patient conditions through telemedicine. This paper summarizes the major electronic-nose technologies developed for healthcare and biomedical applications since the late 1980s when electronic aroma detection technologies were first recognized to be potentially useful in providing effective solutions to problems in the healthcare industry