Providing palliative care closer to home: a retrospective analysis from a remote Australian hospital.

BACKGROUND: Rural and remote patients have reduced access to palliative care, often resulting in inter-hospital transfers and death a long way from home and family. Katherine Hospital (KH), a 50-bed hospital services a population with high Aboriginality who experience this issue. AIMS: To characterise trends in mortality and transfers at a remote hospital in reference to increasing capacity to provide palliative care. METHODS: Retrospective analysis of deaths in patients over 18 years of age, admitted between 2008 and 2018 at KH, Northern Territory. Outcome measures include number of deaths, aeromedical transfers to tertiary facility, palliative care episodes, demographics including Aboriginality, admission data and comorbidity. Statistical analysis included unpaired t-test, chi-square test and regression analysis. RESULTS: The number of deaths in KH increased from 23 (0.88% of inpatient admissions) in 2011 to 52 in 2018 (1.7%). During the same period, the proportion of all deaths classified as palliative increased from 51.4 to 66.0% (P = 0.001), with fewer deaths occurring in the emergency department (17.2-1.4% for the last 3 years, R = 0.75, P = 0.008). The number of aeromedical transfers of patients from KH to tertiary centres decreased from 769 (10.4% of all admissions) in 2011 to 434 (3.4%) in 2018 (P = 0.006). CONCLUSIONS: Increasing the capacity of a remote hospital to provide palliative care allowed more patients to die closer to home and decreased inappropriate aeromedical retrievals. An increased in-hospital mortality rate should not be misinterpreted as reflecting suboptimal care if palliative intent, patients' wishes and non-clinical risk factors have not been ascertained.

Opsonic Phagocytosis in Chronic Obstructive Pulmonary Disease Is Enhanced by Nrf2 Agonists.

RATIONALE: Previous studies have identified defects in bacterial phagocytosis by alveolar macrophages (AMs) in patients with chronic obstructive pulmonary disease (COPD), but the mechanisms and clinical consequences remain incompletely defined. OBJECTIVES: To examine the effect of COPD on AM phagocytic responses and identify the mechanisms, clinical consequences, and potential for therapeutic manipulation of these defects. METHODS: We isolated AMs and monocyte-derived macrophages (MDMs) from a cohort of patients with COPD and control subjects within the Medical Research Council COPDMAP consortium and measured phagocytosis of bacteria in relation to opsonic conditions and clinical features. MEASUREMENTS AND MAIN RESULTS: COPD AMs and MDMs have impaired phagocytosis of Streptococcus pneumoniae. COPD AMs have a selective defect in uptake of opsonized bacteria, despite the presence of antipneumococcal antibodies in BAL, not observed in MDMs or healthy donor AMs. AM defects in phagocytosis in COPD are significantly associated with exacerbation frequency, isolation of pathogenic bacteria, and health-related quality-of-life scores. Bacterial binding and initial intracellular killing of opsonized bacteria in COPD AMs was not reduced. COPD AMs have reduced transcriptional responses to opsonized bacteria, such as cellular stress responses that include transcriptional modules involving antioxidant defenses and Nrf2 (nuclear factor erythroid 2-related factor 2)-regulated genes. Agonists of the cytoprotective transcription factor Nrf2 (sulforaphane and compound 7) reverse defects in phagocytosis of S. pneumoniae and nontypeable Haemophilus influenzae by COPD AMs. CONCLUSIONS: Patients with COPD have clinically relevant defects in opsonic phagocytosis by AMs, associated with impaired transcriptional responses to cellular stress, which are reversed by therapeutic targeting with Nrf2 agonists.

Impaired Mitochondrial Microbicidal Responses in Chronic Obstructive Pulmonary Disease Macrophages.

RATIONALE: Chronic obstructive pulmonary disease (COPD) is characterized by impaired clearance of pulmonary bacteria. OBJECTIVES: The effect of COPD on alveolar macrophage (AM) microbicidal responses was investigated. METHODS: AMs were obtained from bronchoalveolar lavage from healthy donors or patients with COPD and challenged with opsonized serotype 14 Streptococcus pneumoniae. Cells were assessed for apoptosis, bactericidal activity, and mitochondrial reactive oxygen species (mROS) production. A transgenic mouse line in which the CD68 promoter ensures macrophage-specific expression of human induced myeloid leukemia cell differentiation protein Mcl-1 (CD68.hMcl-1) was used to model the molecular aspects of COPD. MEASUREMENTS AND MAIN RESULTS: COPD AMs had elevated levels of Mcl-1, an antiapoptotic B-cell lymphoma 2 family member, with selective reduction of delayed intracellular bacterial killing. CD68.hMcl-1 AMs phenocopied the microbicidal defect because transgenic mice demonstrated impaired clearance of pulmonary bacteria and increased neutrophilic inflammation. Murine bone marrow-derived macrophages and human monocyte-derived macrophages generated mROS in response to pneumococci, which colocalized with bacteria and phagolysosomes to enhance bacterial killing. The Mcl-1 transgene increased oxygen consumption rates and mROS expression in mock-infected bone marrow-derived macrophages but reduced caspase-dependent mROS production after pneumococcal challenge. COPD AMs also increased basal mROS expression, but they failed to increase production after pneumococcal challenge, in keeping with reduced intracellular bacterial killing. The defect in COPD AM intracellular killing was associated with a reduced ratio of mROS/superoxide dismutase 2. CONCLUSIONS: Up-regulation of Mcl-1 and chronic adaption to oxidative stress alter mitochondrial metabolism and microbicidal function, reducing the delayed phase of intracellular bacterial clearance in COPD.

Melioidosis in the remote Katherine region of northern Australia.

Melioidosis is endemic in the remote Katherine region of northern Australia. In a population with high rates of chronic disease, social inequities, and extreme remoteness, the impact of melioidosis is exacerbated by severe weather events and disproportionately affects First Nations Australians. All culture-confirmed melioidosis cases in the Katherine region of the Australian Top End between 1989-2021 were included in the study, and the clinical features and epidemiology were described. The diversity of Burkholderia pseudomallei strains in the region was investigated using genomic sequencing. From 1989-2021 there were 128 patients with melioidosis in the Katherine region. 96/128 (75%) patients were First Nations Australians, 72/128 (56%) were from a very remote region, 68/128 (53%) had diabetes, 57/128 (44%) had a history of hazardous alcohol consumption, and 11/128 (9%) died from melioidosis. There were 9 melioidosis cases attributable to the flooding of the Katherine River in January 1998; 7/9 flood-associated cases had cutaneous melioidosis, five of whom recalled an inoculating event injury sustained wading through flood waters or cleaning up after the flood. The 126 first-episode clinical B. pseudomallei isolates that underwent genomic sequencing belonged to 107 different sequence types and were highly diverse, reflecting the vast geographic area of the study region. In conclusion, melioidosis in the Katherine region disproportionately affects First Nations Australians with risk factors and is exacerbated by severe weather events. Diabetes management, public health intervention for hazardous alcohol consumption, provision of housing to address homelessness, and patient education on melioidosis prevention in First Nations languages should be prioritised.

Addressing Profound Disadvantages to Improve Indigenous Health and Reduce Hospitalisation: A Collaborative Community Program in Remote Northern Territory.

BACKGROUND: Aboriginal people in rural and remote areas of the Northern Territory of Australia have suffered longstanding issues of homelessness and profound health and social inequities. The town and region of Katherine are particularly impacted by such inequities and have the highest rates of homelessness in Australia, composed almost entirely of Aboriginal people who represent 51% of the total population of 24,000 people. The region is serviced by a 60-bed hospital, and a small cohort of frequent attenders (FAs) represent 11% of the Emergency Department (ED) case load. The vast majority of FAs are Aboriginal and have very high burdens of social inequity and homelessness. FAs are a challenge to efficient and effective use of resources for most hospitals around the world, and investment in programs to address underlying social and chronic health issues contributing to frequent attendance have been demonstrated to be effective. METHODS: These are the interim findings of a prospective cohort study using five sources of linked health and related data to evaluate a community-based case management pilot in a culturally competent framework to support frequent attenders to the Katherine Hospital ED. FAs were defined as people with six or more presentations in 12 preceding months. The intervention composed of a community-based case management program with a multi-agency service delivery addressing underlying vulnerabilities contributing to ED presentations. RESULTS: Among this predominantly Aboriginal cohort (91%), there were high rates of homelessness (64%), food insecurity (60%) and alcohol misuse (64%), limited access to transport, and complex comorbidities (average of 2.8 chronic conditions per client). Following intervention, there was a statistically significant reduction in ED presentations (IRR 0.77, 95% CI 0.69-0.85), increased engagement with primary health care (IRR 1.90, 95% CI 1.78-2.03), and ambulance utilisation (IRR 1.21, 95% CI 1.07-1.38). Reductions in hospital admissions (IRR 0.93, 95% CI 0.77-1.10) and aeromedical retrievals (IRR 0.67, 95% CI 0.35-1.20) were not statistically significant. CONCLUSIONS: This study demonstrates the short-term impacts of community-led case management extending beyond the hospital setting, to address causes of recurrent ED presentations among people with complex social and medical backgrounds. Improving engagement with primary care is a particularly important outcome given the national impetus to reduce preventable hospital admissions.

Chronic Obstructive Pulmonary Disease In Aboriginal Patients Of The Northern Territory Of Australia: A Landscape Perspective.

Background: The Aboriginal population of Australia has a higher burden of chronic health conditions than non-Aboriginal Australians. However, there is a paucity of data on clinical and demographic characteristics of chronic obstructive pulmonary disease (COPD) in this population. Method: In this retrospective study we evaluated the clinical, demographic and environmental influences in adult Aboriginal patients with COPD living in the regional and remote communities of the Northern Territory of Australia. Results: There were 380 patients (49%) with a diagnosis of COPD of the 767 patients referred to specialist respiratory outreach clinics. The mean age was 57 years (56% were female) and mean±SD BMI was 24.30±7.01 kg/m2. Smoking history was noted in 93% of the study cohort. The most common respiratory symptom was shortness of breath in 62%, and inhaled medications (salbutamol, tiotropium, salmeterol/fluticasone) were used by 79%, 44% and 58% of patients, respectively. Spirometry showed obstructive impairment (FEV1/FVC <0.7) in 79% (0.56±0.17), with mean FEV1 42% of predicted, and a bronchodilator response was present in 28.6%. Comorbid bronchiectasis was diagnosed in 49.8% along with COPD. The relationship between COPD and community demography showed a higher proportion of smokers and those with underlying bronchiectasis to have lower FEV1/FVC ratios. Communities with a higher proportion of asthma were younger and had higher smoking rates. Mortality increased with increasing number of exacerbations and hospital admissions. Conclusion: The Aboriginal population with COPD has a higher prevalence of smoking, moderate to severe airflow obstruction on spirometry and frequently co-diagnosed bronchiectasis with increased severity of ventilatory impairment.

Differential Effects of p38, MAPK, PI3K or Rho Kinase Inhibitors on Bacterial Phagocytosis and Efferocytosis by Macrophages in COPD.

Pulmonary inflammation and bacterial colonization are central to the pathogenesis of chronic obstructive pulmonary disease (COPD). Defects in macrophage phagocytosis of both bacteria and apoptotic cells contribute to the COPD phenotype. Small molecule inhibitors with anti-inflammatory activity against p38 mitogen activated protein kinases (MAPKs), phosphatidyl-inositol-3 kinase (PI3K) and Rho kinase (ROCK) are being investigated as novel therapeutics in COPD. Concerns exist, however, about off-target effects. We investigated the effect of p38 MAPK inhibitors (VX745 and SCIO469), specific inhibitors of PI3K α (NVS-P13K-2), δ (NVS-P13K-3) or γ (NVS-P13K-5) and a ROCK inhibitor PF4950834 on macrophage phagocytosis, early intracellular killing of bacteria and efferocytosis of apoptotic neutrophils. Alveolar macrophages (AM) obtained from broncho-alveolar lavage (BAL) or monocyte-derived macrophages (MDM) from COPD patients (GOLD stage II/III) enrolled from a well characterized clinical cohort (MRC COPD-MAP consortium) or from healthy ex-smoker controls were studied. Both COPD AM and MDM exhibited lower levels of bacterial phagocytosis (using Streptococcus pneumoniae and non-typeable Haemophilus influenzae) and efferocytosis than healthy controls. None of the inhibitors altered bacterial internalization or early intracellular bacterial killing in AM or MDM. Conversely PF4950834, but not other inhibitors, enhanced efferocytosis in COPD AM and MDM. These results suggest none of these inhibitors are likely to exacerbate phagocytosis-related defects in COPD, while confirming ROCK inhibitors can enhance efferocytosis in COPD.

Good acoustics central to recovery.

Good acoustic conditions in hospitals and other healthcare facilities are known not only to benefit patients by creating an environment that facilitates rest, sleeping, consultation and treatment, but also clinical and nursing staff. At the recent Healthcare Estates conference, Richard Budd of acoustic engineering and noise and vibration consultants Sound Research Laboratories, discussed the revised guidance on good acoustic design in a recently published Health Technical Memorandum, HTM 08-01-Acoustics.