Prevalence and risk factors associated within 48-hour unplanned paediatric intensive care unit readmissions: An integrative review.

BACKGROUND: Unplanned paediatric intensive care unit (PICU) readmission is associated with increased morbidity/mortality, hospital length of stay, and health service cost and is recognised as a key performance indicator of quality-of-care delivery. However, research evidence on unplanned PICU readmission risk factors is limited, and results were inconsistent across studies. AIM: The aim of this experiment was to collate and synthesise unplanned within-48-h PICU readmission prevalence and associated risk factors. METHODS: An integrative review was conducted, guided by a five-stage framework. Seven electronic databases were searched (2013-30th June 2023). Studies published in English with full-text accessibility and detailed methodologies were included. The quality of included studies was critically appraised using the Joanna Briggs Institute checklists. Prevalence and risk factors were extracted, synthesised, and presented narratively. RESULTS: Ten studies met eligibility criteria and reported a varied readmission rate from 0.008% to 6.49%. Fifteen types of significant risk factors were extracted. Twelve consistently cited risk factors were age, weight, complex chronic conditions, admission source, unplanned admission, PICU length of stay, positive pressure ventilation, discharge disposition, oxygen requirements, respiratory rate, heart rate, and Glasgow Coma Score at discharge. Of the 12, five predictors were classified as modifiable factors, including discharge disposition, oxygen requirement, abnormal respiratory rate, abnormal heart rate, and decreased Glasgow Coma Score at discharge. CONCLUSION: This review acknowledges the complexity of confounding factors impacting unplanned PICU readmission and the lack of standardisation examining potential risk factors. The five modifiable factors are suggestive of clinical instability and premature PICU discharge. Patients with modifiable risk factors should have their readiness for discharge re-evaluated. Scaffolding support to manage patients at risk of readmission includes senior bedside nursing allocation, use of PICU outreach services, and 1:2 nurse-to-patient ratios in the ward setting, which are warranted to ensure patient safety.

Malolactic fermentation in lingonberry juice and its use as a preservative.

Lingonberry is a common wild berry that is often sold as jams and beverages. It naturally contains high amounts of the weak acid preservative benzoic acid making it an interesting ingredient for shelf-life extension. Despite this, their use as a raw ingredient is limited by the inherently intense sour taste. This study aimed to improve the taste of lingonberry juice by subjecting it to malolactic fermentation in order to reduce the sourness, and to investigate the benzoic acid in lingonberries as a natural preservative in juice blends by determining the microbial stability. After initial screening of lactic acid bacteria, a Lactiplantibacillus plantarum strain was used as the starter for subsequent investigations. Upon raising the pH, all malic acid was completely converted to lactic acid after seven days. The fermented juice was mixed with blackcurrant juice in different proportions. Challenge tests of the blends showed Listeria monocytogenes could not grow in any juice samples, while Candida albicans only grew in the pure blackcurrant juice. Aspergillus brasiliensis growth was delayed in all samples containing benzoic acid in a concentration-dependent manner. The sourness and astringency were substantially reduced in the juice with added L. plantarum compared to the unfermented juice.

The 2023 report of the MJA-Lancet Countdown on health and climate change: sustainability needed in Australia's health care sector.

The MJA-Lancet Countdown on health and climate change in Australia was established in 2017 and produced its first national assessment in 2018 and annual updates in 2019, 2020, 2021 and 2022. It examines five broad domains: health hazards, exposures and impacts; adaptation, planning and resilience for health; mitigation actions and health co-benefits; economics and finance; and public and political engagement. In this, the sixth report of the MJA-Lancet Countdown, we track progress on an extensive suite of indicators across these five domains, accessing and presenting the latest data and further refining and developing our analyses. Our results highlight the health and economic costs of inaction on health and climate change. A series of major flood events across the four eastern states of Australia in 2022 was the main contributor to insured losses from climate-related catastrophes of $7.168 billion - the highest amount on record. The floods also directly caused 23 deaths and resulted in the displacement of tens of thousands of people. High red meat and processed meat consumption and insufficient consumption of fruit and vegetables accounted for about half of the 87 166 diet-related deaths in Australia in 2021. Correction of this imbalance would both save lives and reduce the heavy carbon footprint associated with meat production. We find signs of progress on health and climate change. Importantly, the Australian Government released Australia's first National Health and Climate Strategy, and the Government of Western Australia is preparing a Health Sector Adaptation Plan. We also find increasing action on, and engagement with, health and climate change at a community level, with the number of electric vehicle sales almost doubling in 2022 compared with 2021, and with a 65% increase in coverage of health and climate change in the media in 2022 compared with 2021. Overall, the urgency of substantial enhancements in Australia's mitigation and adaptation responses to the enormous health and climate change challenge cannot be overstated. Australia's energy system, and its health care sector, currently emit an unreasonable and unjust proportion of greenhouse gases into the atmosphere. As the Lancet Countdown enters its second and most critical phase in the leadup to 2030, the depth and breadth of our assessment of health and climate change will be augmented to increasingly examine Australia in its regional context, and to better measure and track key issues in Australia such as mental health and Aboriginal and Torres Strait Islander health and wellbeing.

Discovering how the amygdala shapes human behavior: From lesion studies to neuromodulation.

Case studies of patients with amygdala damage or those receiving direct amygdala stimulation have informed our understanding of the amygdala's role in emotion and cognition. These foundational studies illustrate how the human amygdala influences our present behavior and prioritizes memories of our past in service of future experiences. This broad influence makes the amygdala a novel target for clinical neuromodulation.

Does sports therapy affect momentary affective states? Feasibility of intensive longitudinal case studies in forensic psychiatry.

Physical exercise interventions improve quality of life in people with mental disorders and improve abstinence and cravings in substance use disorders patients in both the short term and long term. In people with mental illness, physical exercise interventions significantly reduce psychiatric symptoms of schizophrenia and symptoms of anxiety. For forensic psychiatry, there is little empirical evidence supporting mental health-enhancing effects of physical exercise interventions. Interventional studies in forensic psychiatry deal mainly with three problems: heterogeneity of the individuals, a small sample size, and a low compliance rate. Intensive longitudinal case studies could be a suitable approach to address these methodological challenges in forensic psychiatry. This study uses an intensive longitudinal design to determine whether forensic psychiatric patients are content to complete several data assessments per day over the course of several weeks. The feasibility of this approach is operationalized by the compliance rate. Additionally, single-case studies examine the effects of sports therapy (ST) on momentary affective states (energetic arousal, valence, and calmness). The results of these case studies reveal one aspect of feasibility and offer insights into the effects of forensic psychiatric ST on the affective states among patients with different conditions. The patients' momentary affective states were recorded before (PRE), after (POST) and 1 h after (FoUp1h) ST by questionnaires. Ten individuals (Mage = 31.7, SD = 11.94; 60% male) participated in the study. A total of 130 questionnaires were completed. To perform the single-case studies, data of three patients were considered. Repeated-measures ANOVA was performed for the individual affective states to test for main effects of ST. Due to the results, ST has no significant effect on none of the three affect dimensions. However, effect sizes varied between small to medium (energetic arousal: η2 = 0.01, η2 = 0.07, η2 = 0.06; valence: η2 = 0.07; calmness: η2 = 0.02) in the three patients. Intensive longitudinal case studies are a possible approach to address heterogeneity and the low sample size. The low compliance rate in this study reveals that the study design needs to be optimized for future studies.

Differential involvement of hippocampal subfields in the relationship between Alzheimer's pathology and memory interference in older adults.

Introduction: We tested whether Alzheimer's disease (AD) pathology predicts memory deficits in non-demented older adults through its effects on medial temporal lobe (MTL) subregional volume. Methods: Thirty-two, non-demented older adults with cerebrospinal fluid (CSF) (amyloid-beta [Aß]42/Aß40, phosphorylated tau [p-tau]181, total tau [t-tau]), positron emission tomography (PET; 18F-florbetapir), high-resolution structural magnetic resonance imaging (MRI), and neuropsychological assessment were analyzed. We examined relationships between biomarkers and a highly granular measure of memory consolidation, retroactive interference (RI). Results: Biomarkers of AD pathology were related to RI. Dentate gyrus (DG) and CA3 volume were uniquely associated with RI, whereas CA1 and BA35 volume were related to both RI and overall memory recall. AD pathology was associated with reduced BA35, CA1, and subiculum volume. DG volume and Aß were independently associated with RI, whereas CA1 volume mediated the relationship between AD pathology and RI. Discussion: Integrity of distinct hippocampal subfields demonstrate differential relationships with pathology and memory function, indicating specificity in vulnerability and contribution to different memory processes.

Posterior white matter hyperintensities are associated with reduced medial temporal lobe subregional integrity and long-term memory in older adults.

White matter hyperintensities are a marker of small vessel cerebrovascular disease that are strongly related to cognition in older adults. Similarly, medial temporal lobe atrophy is well-documented in aging and Alzheimer's disease and is associated with memory decline. Here, we assessed the relationship between lobar white matter hyperintensities, medial temporal lobe subregional volumes, and hippocampal memory in older adults. We collected MRI scans in a sample of 139 older adults without dementia (88 females, mean age (SD) = 76.95 (10.61)). Participants were administered the Rey Auditory Verbal Learning Test (RAVLT). Regression analyses tested for associations among medial temporal lobe subregional volumes, regional white matter hyperintensities and memory, while adjusting for age, sex, and education and correcting for multiple comparisons. Increased occipital white matter hyperintensities were related to worse RAVLT delayed recall performance, and to reduced CA1, dentate gyrus, perirhinal cortex (Brodmann area 36), and parahippocampal cortex volumes. These medial temporal lobe subregional volumes were related to delayed recall performance. The association of occipital white matter hyperintensities with delayed recall performance was fully mediated statistically only by perirhinal cortex volume. These results suggest that white matter hyperintensities may be associated with memory decline through their impact on medial temporal lobe atrophy. These findings provide new insights into the role of vascular pathologies in memory loss in older adults and suggest that future studies should further examine the neural mechanisms of these relationships in longitudinal samples.

Midlife Health in Britain and the US: A comparison of Two Nationally Representative Cohorts.

Background: Older adults in the United States (US) have worse health and wider socioeconomic inequalities in health compared to Britain. Less is known about how health in the two countries compares in midlife, a time of emerging health decline, including inequalities in health. Methods: We compare measures of smoking status, alcohol consumption, obesity, self-rated health, cholesterol, blood pressure, and glycated haemoglobin using population-weighted modified Poisson regression in the 1970 British Cohort Study (BCS70) in Britain (N= 9,665) and the National Longitudinal Study of Adolescent to Adult Health (Add Health) in the US (N=12,297), when cohort members were aged 34-46 and 33-43, respectively. We test whether associations vary by early- and mid-life socioeconomic position. Findings: US adults had higher levels of obesity, high blood pressure and high cholesterol. Prevalence of poor self-rated health, heavy drinking, and smoking was worse in Britain. We found smaller socioeconomic inequalities in midlife health in Britain compared to the US. For some outcomes (e.g., smoking), the most socioeconomically advantaged group in the US was healthier than the equivalent group in Britain. For other outcomes (hypertension and cholesterol), the most advantaged US group fared equal to or worse than the most disadvantaged groups in Britain. Interpretation: US adults have worse cardiometabolic health than British counterparts, even in early midlife. The smaller socioeconomic inequalities and better overall health in Britain may reflect differences in access to health care, welfare systems, or other environmental risk factors. Funding: ESRC, UKRI, MRC, NIH, European Research Council, Leverhulme Trust.

The 2022 report of the MJA-Lancet Countdown on health and climate change: Australia unprepared and paying the price.

The MJA-Lancet Countdown on health and climate change in Australia was established in 2017 and produced its first national assessment in 2018 and annual updates in 2019, 2020 and 2021. It examines five broad domains: climate change impacts, exposures and vulnerability; adaptation, planning and resilience for health; mitigation actions and health co-benefits; economics and finance; and public and political engagement. In this, the fifth year of the MJA-Lancet Countdown, we track progress on an extensive suite of indicators across these five domains, accessing and presenting the latest data and further refining and developing our analyses. Within just two years, Australia has experienced two unprecedented national catastrophes - the 2019-2020 summer heatwaves and bushfires and the 2021-2022 torrential rains and flooding. Such events are costing lives and displacing tens of thousands of people. Further, our analysis shows that there are clear signs that Australia's health emergency management capacity substantially decreased in 2021. We find some signs of progress with respect to health and climate change. The states continue to lead the way in health and climate change adaptation planning, with the Victorian plan being published in early 2022. At the national level, we note progress in health and climate change research funding by the National Health and Medical Research Council. We now also see an acceleration in the uptake of electric vehicles and continued uptake of and employment in renewable energy. However, we also find Australia's transition to renewables and zero carbon remains unacceptably slow, and the Australian Government's continuing failure to produce a national climate change and health adaptation plan places the health and lives of Australians at unnecessary risk today, which does not bode well for the future.

Glutathione-Hemin/Hematin Adduct Formation to Disintegrate Cytotoxic Oxidant Hemin/Hematin in Human K562 Cells and Red Blood Cells' Hemolysates: Impact of Glutathione on the Hemolytic Disorders and Homeostasis.

Hemin, an oxidized form of heme, acts as potent oxidant to regulate glutathione (GSH) content in pro-erythroid K562 nucleated cells, via activation of the KEAP1/NRF2 defensive signaling pathway. Moreover, GSH, as an essential metabolite, is involved in the regulation of cell-redox homeostasis and proposed to scavenge cytotoxic free heme, which is released from hemoglobin of damaged red blood cells (RBCs) during different hemolytic disorders. In the present study, we aimed to uncover the molecular mechanism by which GSH inhibits hemin-induced cytotoxicity (HIC) by affecting hemin's structural integrity in K562 cells and in RBC hemolysates. GSH, along with other thiols (cysteine, thioglycolic acid, and mercaptoethanol) altered the spectrum of hemin, while each of them co-added with hemin in cultures of K562 cells prevented HIC and growth arrest and markedly reduced the intracellular level of hemin. In addition, GSH endogenous levels served as a barrier to HIC in K562 cells, as shown by the depletion in GSH. LC-MS/MS analysis of the in vitro reaction between hemin and GSH revealed at least five different isomers of GSH-hemin adducts, as well as hydroxy derivatives as reaction products, which are characterized by unique mass spectra (MS). The latter allowed the detection of adducts in human RBC hemolysates. Based on these findings, we proposed a molecular mechanism via which GSH prevents HIC and structurally disintegrates heme. An analogous reaction was observed in RBC hemolysates via direct inter-reaction between hematin (ferric and hydroxide heme) released from hemoglobin and GSH. Overall, GSH-hematin adducts could be considered as novel entities of the human metabolome of RBCs in hemolytic disorders.

Suppression of heparan sulfation re-sensitizes YAP1-driven melanoma to MAPK pathway inhibitors.

Accumulating evidence identifies non-genetic mechanisms substantially contributing to drug resistance in cancer patients. Preclinical and clinical data implicate the transcriptional co-activators YAP1 and its paralog TAZ in resistance to multiple targeted therapies, highlighting the strong need for therapeutic strategies overcoming YAP1/TAZ-mediated resistance across tumor entities. Here, we show particularly high YAP1/TAZ activity in MITFlow/AXLhigh melanomas characterized by resistance to MAPK pathway inhibition and broad receptor tyrosine kinase activity. To uncover genetic dependencies of melanoma cells with high YAP1/TAZ activity, we used a genome-wide CRISPR/Cas9 functional screen and identified SLC35B2, the 3'-phosphoadenosine-5'-phosphosulfate transporter of the Golgi apparatus, as an essential gene for YAP1/TAZ-driven drug resistance. SLC35B2 expression correlates with tumor progression, and its loss decreases heparan sulfate expression, reduces receptor tyrosine kinase activity, and sensitizes resistant melanoma cells to BRAF inhibition in vitro and in vivo. Thus, targeting heparan sulfation via SLC35B2 represents a novel approach for breaking receptor tyrosine kinase-mediated resistance to MAPK pathway inhibitors.

The 2021 report of the MJA-Lancet Countdown on health and climate change: Australia increasingly out on a limb.

The MJA-Lancet Countdown on health and climate change in Australia was established in 2017, and produced its first national assessment in 2018, its first annual update in 2019, and its second annual update in 2020. It examines indicators across five broad domains: climate change impacts, exposures and vulnerability; adaptation, planning and resilience for health; mitigation actions and health co-benefits; economics and finance; and public and political engagement. Our special report in 2020 focused on the unprecedented and catastrophic 2019-20 Australian bushfire season, highlighting indicators that explore the relationships between health, climate change and bushfires. For 2021, we return to reporting on the full suite of indicators across each of the five domains and have added some new indicators. We find that Australians are increasingly exposed to and vulnerable to excess heat and that this is already limiting our way of life, increasing the risk of heat stress during outdoor sports, and decreasing work productivity across a range of sectors. Other weather extremes are also on the rise, resulting in escalating social, economic and health impacts. Climate change disproportionately threatens Indigenous Australians' wellbeing in multiple and complex ways. In response to these threats, we find positive action at the individual, local, state and territory levels, with growing uptake of rooftop solar and electric vehicles, and the beginnings of appropriate adaptation planning. However, this is severely undermined by national policies and actions that are contrary and increasingly place Australia out on a limb. Australia has responded well to the COVID-19 public health crisis (while still emerging from the bushfire crisis that preceded it) and it now needs to respond to and prepare for the health crises resulting from climate change.

Ultrasound and contrast enhanced CT imaging of a colon mesentery leiomyosarcoma.

Primary leiomyosarcoma of the colon mesentery is an extremely rare neoplasm, and only a small number of cases have been reported. We describe a case of leiomyosarcoma originating in the colonic mesentery, in a 68-year-old woman. Ultrasound showed a heterogeneous mass with varying vascularization in the left fossa. Central areas of the mass were hypoechoic, without detectable vascularization. Contrast enhanced computed tomography (CECT) of chest and abdomen showed a contrast enhanced tumour, with central non-enhanced areas. The tumour was radically resected and histopathology showed primary leiomyosarcoma. Two years after primary surgery, follow-up CECT revealed a local recurrence, which was re-resected. Subsequent follow-up CECT since have shown no sign of recurrence.

Secondary resistance to anti-EGFR therapy by transcriptional reprogramming in patient-derived colorectal cancer models.

BACKGROUND: The development of secondary resistance (SR) in metastatic colorectal cancer (mCRC) treated with anti-epidermal growth factor receptor (anti-EGFR) antibodies is not fully understood at the molecular level. Here we tested in vivo selection of anti-EGFR SR tumors in CRC patient-derived xenograft (PDX) models as a strategy for a molecular dissection of SR mechanisms. METHODS: We analyzed 21 KRAS, NRAS, BRAF, and PI3K wildtype CRC patient-derived xenograft (PDX) models for their anti-EGFR sensitivity. Furthermore, 31 anti-EGFR SR tumors were generated via chronic in vivo treatment with cetuximab. A multi-omics approach was employed to address molecular primary and secondary resistance mechanisms. Gene set enrichment analyses were used to uncover SR pathways. Targeted therapy of SR PDX models was applied to validate selected SR pathways. RESULTS: In vivo anti-EGFR SR could be established with high efficiency. Chronic anti-EGFR treatment of CRC PDX tumors induced parallel evolution of multiple resistant lesions with independent molecular SR mechanisms. Mutations in driver genes explained SR development in a subgroup of CRC PDX models, only. Transcriptional reprogramming inducing anti-EGFR SR was discovered as a common mechanism in CRC PDX models frequently leading to RAS signaling pathway activation. We identified cAMP and STAT3 signaling activation, as well as paracrine and autocrine signaling via growth factors as novel anti-EGFR secondary resistance mechanisms. Secondary resistant xenograft tumors could successfully be treated by addressing identified transcriptional changes by tailored targeted therapies. CONCLUSIONS: Our study demonstrates that SR PDX tumors provide a unique platform to study molecular SR mechanisms and allow testing of multiple treatments for efficient targeting of SR mechanisms, not possible in the patient. Importantly, it suggests that the development of anti-EGFR tolerant cells via transcriptional reprogramming as a cause of anti-EGFR SR in CRC is likely more prevalent than previously anticipated. It emphasizes the need for analyses of SR tumor tissues at a multi-omics level for a comprehensive molecular understanding of anti-EGFR SR in CRC.

Degradation of CCNK/CDK12 is a druggable vulnerability of colorectal cancer.

Novel treatment options for metastatic colorectal cancer (CRC) are urgently needed to improve patient outcome. Here, we screen a library of non-characterized small molecules against a heterogeneous collection of patient-derived CRC spheroids. By prioritizing compounds with inhibitory activity in a subset of-but not all-spheroid cultures, NCT02 is identified as a candidate with minimal risk of non-specific toxicity. Mechanistically, we show that NCT02 acts as molecular glue that induces ubiquitination of cyclin K (CCNK) and proteasomal degradation of CCNK and its complex partner CDK12. Knockout of CCNK or CDK12 decreases proliferation of CRC cells in vitro and tumor growth in vivo. Interestingly, sensitivity to pharmacological CCNK/CDK12 degradation is associated with TP53 deficiency and consensus molecular subtype 4 in vitro and in patient-derived xenografts. We thus demonstrate the efficacy of targeted CCNK/CDK12 degradation for a CRC subset, highlighting the potential of drug-induced proteolysis for difficult-to-treat types of cancer.

Functional States in Tumor-Initiating Cell Differentiation in Human Colorectal Cancer.

Intra-tumor heterogeneity of tumor-initiating cell (TIC) activity drives colorectal cancer (CRC) progression and therapy resistance. Here, we used single-cell RNA-sequencing of patient-derived CRC models to decipher distinct cell subpopulations based on their transcriptional profiles. Cell type-specific expression modules of stem-like, transit amplifying-like, and differentiated CRC cells resemble differentiation states of normal intestinal epithelial cells. Strikingly, identified subpopulations differ in proliferative activity and metabolic state. In summary, we here show at single-cell resolution that transcriptional heterogeneity identifies functional states during TIC differentiation. Furthermore, identified expression signatures are linked to patient prognosis. Targeting transcriptional states associated to cancer cell differentiation might unravel novel vulnerabilities in human CRC.

SIRT6-CBP-dependent nuclear Tau accumulation and its role in protein synthesis.

Several neurodegenerative diseases present Tau accumulation as the main pathological marker. Tau post-translational modifications such as phosphorylation and acetylation are increased in neurodegeneration. Here, we show that Tau hyper-acetylation at residue 174 increases its own nuclear presence and is the result of DNA damage signaling or the lack of SIRT6, both causative of neurodegeneration. Tau-K174ac is deacetylated in the nucleus by SIRT6. However, lack of SIRT6 or chronic DNA damage results in nuclear Tau-K174ac accumulation. Once there, it induces global changes in gene expression, affecting protein translation, synthesis, and energy production. Concomitantly, Alzheimer's disease (AD) case subjects show increased nucleolin and a decrease in SIRT6 levels. AD case subjects present increased levels of nuclear Tau, particularly Tau-K174ac. Our results suggest that increased Tau-K174ac in AD case subjects is the result of DNA damage signaling and SIRT6 depletion. We propose that Tau-K174ac toxicity is due to its increased stability, nuclear accumulation, and nucleolar dysfunction.

Inositol pyrophosphates promote the interaction of SPX domains with the coiled-coil motif of PHR transcription factors to regulate plant phosphate homeostasis.

Phosphorus is an essential nutrient taken up by organisms in the form of inorganic phosphate (Pi). Eukaryotes have evolved sophisticated Pi sensing and signaling cascades, enabling them to stably maintain cellular Pi concentrations. Pi homeostasis is regulated by inositol pyrophosphate signaling molecules (PP-InsPs), which are sensed by SPX domain-containing proteins. In plants, PP-InsP-bound SPX receptors inactivate Myb coiled-coil (MYB-CC) Pi starvation response transcription factors (PHRs) by an unknown mechanism. Here we report that a InsP8-SPX complex targets the plant-unique CC domain of PHRs. Crystal structures of the CC domain reveal an unusual four-stranded anti-parallel arrangement. Interface mutations in the CC domain yield monomeric PHR1, which is no longer able to bind DNA with high affinity. Mutation of conserved basic residues located at the surface of the CC domain disrupt interaction with the SPX receptor in vitro and in planta, resulting in constitutive Pi starvation responses. Together, our findings suggest that InsP8 regulates plant Pi homeostasis by controlling the oligomeric state and hence the promoter binding capability of PHRs via their SPX receptors.

Best Practice Recommendations for Optimizing Care in Structural Heart Programs: Planning Efficient and Resource Leveraging Systems (PEARLS).

The COVID19 pandemic brought unprecedented disruption to healthcare. Staggering morbidity, mortality, and economic losses prompted the review and refinement of care for structural heart disease (SHD). To mitigate negative impacts in the face of crisis or capacity constraints, this paper offers best practice recommendations for Planning Efficient and Resource Leveraging Systems (PEARLS) in structural heart programs. A systematic assessment is recommended for hospital capacity, Heart Team roles and functions, and patient and procedural risks associated with increased resource utilization. Strategies, tactics, and pathways are provided for the delivery of patient-centered, efficient and resource-leveraging care from referral to follow-up. Through the optimal use of capacity and resources, paired with dynamic triage, forecasting, and surveillance, Heart Teams may aspire to plan and implement an optimized system of care for SHD. Abbreviations: AS: aortic stenosis; ASD: atrioseptal defect; COVID19: Coronavirus disease 19; LAAO: left atrial appendage occlusion; MI: myocardial infarction; MR: mitral regurgitation; PFO: patent foramen ovale; PVL: paravalvular leak; SHD: structural heart disease; SAVR: surgical aortic valve replacement; SDM: shared decision-making; TAVR: transcatheter aortic valve replacement; TMVr: transcatheter mitral valve repair; TMVR: transcatheter mitral valve replacement; TEE: transesophageal echocardiography; TTE: transthoracic echocardiography.

The 2020 special report of the MJA-Lancet Countdown on health and climate change: lessons learnt from Australia's "Black Summer".

The MJA-Lancet Countdown on health and climate change was established in 2017, and produced its first Australian national assessment in 2018 and its first annual update in 2019. It examines indicators across five broad domains: climate change impacts, exposures and vulnerability; adaptation, planning and resilience for health; mitigation actions and health co-benefits; economics and finance; and public and political engagement. In the wake of the unprecedented and catastrophic 2019-20 Australian bushfire season, in this special report we present the 2020 update, with a focus on the relationship between health, climate change and bushfires, highlighting indicators that explore these linkages. In an environment of continuing increases in summer maximum temperatures and heatwave intensity, substantial increases in both fire risk and population exposure to bushfires are having an impact on Australia's health and economy. As a result of the "Black Summer" bushfires, the monthly airborne particulate matter less than 2.5 µm in diameter (PM2.5 ) concentrations in New South Wales and the Australian Capital Territory in December 2019 were the highest of any month in any state or territory over the period 2000-2019 at 26.0 µg/m3 and 71.6 µg/m3 respectively, and insured economic losses were $2.2 billion. We also found growing awareness of and engagement with the links between health and climate change, with a 50% increase in scientific publications and a doubling of newspaper articles on the topic in Australia in 2019 compared with 2018. However, despite clear and present need, Australia still lacks a nationwide adaptation plan for health. As Australia recovers from the compounded effects of the bushfires and the coronavirus disease 2019 (COVID-19) pandemic, the health profession has a pivotal role to play. It is uniquely suited to integrate the response to these short term threats with the longer term public health implications of climate change, and to argue for the economic recovery from COVID-19 to align with and strengthen Australia's commitments under the Paris Agreement.