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1.
J Pediatr Nurs ; 2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38762422

RESUMO

PURPOSE: Pediatric burn injuries are a global clinical issue causing significant morbidity. Early adjunctive negative pressure wound therapy improves re-epithelialization rates in children with burns, yet adoption in acute burn care is inconsistent. This investigation aimed to determine barriers to the implementation of adjunctive negative pressure wound therapy for the acute management of pediatric burns and co-design targeted implementation strategies. METHODS: A sequential mixed methods design was used explore barriers to adjunctive negative pressure wound therapy implementation in acute pediatric burn care. An online questionnaire was disseminated to healthcare professionals within four major Australian pediatric hospitals, each with a dedicated burns service. Barriers were coded according to the Consolidated Framework for Implementation Research (CFIR). Semi-structured interviews with senior clinicians tailored implementation strategies to local contexts. A stakeholder consensus meeting consolidated implementation strategies and local processes. RESULTS: Sixty-three healthcare professionals participated in the questionnaire, and semi-structured interviews involved nine senior burn clinicians. We identified eight implementation barriers across all five CFIR domains then co-designed targeted strategies to address identified barriers. Barriers included lack of available resources, limited access to knowledge and information, individual stage of change, patient needs and resources, limited knowledge and beliefs about the intervention, lack of external policies, intervention complexity, and poor implementation planning. CONCLUSION: Multiple contextual factors affect negative pressure wound therapy uptake in acute pediatric burn settings. Results will inform a multi-state stepped-wedge cluster randomized controlled trial. Additional resources, education, training, updated policies, and guidelines are required for successful implementation. It is anticipated that adjunctive negative pressure wound therapy, in conjunction with tailored implementation strategies, will enhance adoption and sustainability. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry: ACTRN12622000166774. Registered 1 February 2022.

2.
Clin Transl Immunology ; 13(3): e1496, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38463658

RESUMO

Objectives: The aim of this study was to characterise the dynamic immune profile of paediatric burn patients for up to 18 months post-burn. Methods: Flow cytometry was used to measure 25 cell markers, chemokines and cytokines which reflected both pro-inflammatory and anti-inflammatory immune profiles. Peripheral blood mononuclear cells from 6 paediatric burn patients who had returned for repeated burn and scar treatments for > 4 timepoints within 12 months post-burn were compared to four age-matched healthy controls. Results: While overall proportions of T cells, NK cells and macrophages remained relatively constant, over time percentages of these immune cells differentiated into effector and proinflammatory cell phenotypes including Th17 and activated γδ T cells. Circulating proportions of γδ T cells increased their expression of pro-inflammatory mediators throughout the burn recovery, with a 3-6 fold increase of IL-17 at 1-3 weeks, and NFκß 9-18 months post-burn. T-regulatory cell plasticity was also observed, and Treg phenotype proportions changed from systemically reduced skin-homing T-regs (CCR4+) and increased inflammatory (CCR6+) at 1-month post-burn, to double-positive cell types (CCR4+CCR6+) elevated in circulation for 18 months post-burn. Furthermore, Tregs were observed to proportionally express less IL-10 but increased TNF-α over 18 months. Conclusion: Overall, these results indicate the circulating percentages of immune cells do not increase or decrease over time post-burn, instead they become highly specialised, inflammatory and skin-homing. In this patient population, these changes persisted for at least 18 months post-burn, this 'immune distraction' may limit the ability of immune cells to prioritise other threats post-burn, such as respiratory infections.

3.
Burns ; 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38490838

RESUMO

Burn wound blister fluid is a valuable matrix for understanding the biological pathways associated with burn injury. In this study, 152 blister fluid samples collected from paediatric burn wounds at three different hospitals were analysed using mass spectrometry proteomic techniques. The protein abundance profile at different days after burn indicated more proteins were associated with cellular damage/repair in the first 24 h, whereas after this point more proteins were associated with antimicrobial defence. The inflammatory proteins persisted at a high level in the blister fluid for more than 7 days. This may indicate that removal of burn blisters prior to two days after burn is optimal to prevent excessive or prolonged inflammation in the wound environment. Additionally, many proteins associated with the neutrophil extracellular trap (NET) pathway were increased after burn, further implicating NETs in the post-burn inflammatory response. NET inhibitors may therefore be a potential treatment to reduce post-burn inflammation and coagulation pathology and enhance burn wound healing outcomes.

4.
bioRxiv ; 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38496445

RESUMO

Hydrolethalus Syndrome (HLS) is a lethal, autosomal recessive ciliopathy caused by the mutation of the conserved centriole protein HYLS1. However, how HYLS1 facilitates the centriole-based templating of cilia is poorly understood. Here, we show that mice harboring the HYLS1 disease mutation die shortly after birth and exhibit developmental defects that recapitulate several manifestations of the human disease. These phenotypes arise from tissue-specific defects in cilia assembly and function caused by a loss of centriole integrity. We show that HYLS1 is recruited to the centriole by CEP120 and functions to recruit centriole inner scaffold proteins that stabilize the centriolar microtubule wall. The HLS mutation disrupts the interaction of HYLS1 with CEP120 leading to HYLS1 displacement and degeneration of the centriole distal end. We propose that tissue-specific defects in centriole integrity caused by the HYLS1 mutation prevent ciliogenesis and drive HLS phenotypes.

5.
J Am Coll Surg ; 238(6): 1057-1066, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38345219

RESUMO

BACKGROUND: Hospital-acquired urinary tract infections (UTIs) have a detrimental effect on patients, families, and hospital resources. The Sydney Children's Hospital Network (SCHN) participates in the NSQIP-Pediatric (NSQIP-P) to monitor postoperative complications. NSQIP-P data revealed that the median UTI rate at SCHN was 1.75% in 2019, 3.5 times higher than the NSQIP-P target rate of 0.5%. Over three quarters of the NSQIP-P identified patients with UTI also had a urinary catheterization performed intraoperatively. A quality improvement project was conducted between mid-2018 and 2021 to minimize catheter-associated UTIs (CAUTIs) at SCHN. STUDY DESIGN: NSQIP-P samples include pediatric (younger than 18 years) surgical patients from an 8-day cycle operative log. NSQIP-P data are statistically analyzed by the American College of Surgeons and provide biannual internationally benchmarked reports. The project used clinical redesign methodology with a 6-phase process for quality improvement projects. RESULTS: The objectives of the project were to reduce urinary catheter duration of use, educate parents or carers, and improve catheter care and insertion technique by health staff. The duration of a urinary catheter in situ reduced from a median of 4.5 to 3 days from 2017 to 2021. The median NSQIP-P UTI rate at SCHN was reduced by 47.4% from 1.75% in 2019 to 0.9% in 2022. CONCLUSIONS: A multifactorial approach in quality improvement has been shown to be an effective strategy to reduce UTI rates at SCHN, and patient outcomes were improved within a 3-year timeframe. Although this project has reduced UTI rates at SCHN, there remain opportunities for further improvement.


Assuntos
Infecções Relacionadas a Cateter , Melhoria de Qualidade , Infecções Urinárias , Humanos , Infecções Urinárias/prevenção & controle , Infecções Urinárias/epidemiologia , Infecções Urinárias/etiologia , Criança , Infecções Relacionadas a Cateter/prevenção & controle , Infecções Relacionadas a Cateter/epidemiologia , Adolescente , Pré-Escolar , Feminino , Masculino , Cateterismo Urinário/efeitos adversos , Complicações Pós-Operatórias/prevenção & controle , Complicações Pós-Operatórias/epidemiologia , Lactente , Infecção Hospitalar/prevenção & controle , Infecção Hospitalar/epidemiologia , Hospitais Pediátricos/normas
6.
EMBO J ; 43(5): 666-694, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38279026

RESUMO

The efficacy of current antimitotic cancer drugs is limited by toxicity in highly proliferative healthy tissues. A cancer-specific dependency on the microtubule motor protein KIF18A therefore makes it an attractive therapeutic target. Not all cancers require KIF18A, however, and the determinants underlying this distinction remain unclear. Here, we show that KIF18A inhibition drives a modest and widespread increase in spindle assembly checkpoint (SAC) signaling from kinetochores which can result in lethal mitotic delays. Whether cells arrest in mitosis depends on the robustness of the metaphase-to-anaphase transition, and cells predisposed with weak basal anaphase-promoting complex/cyclosome (APC/C) activity and/or persistent SAC signaling through metaphase are uniquely sensitive to KIF18A inhibition. KIF18A-dependent cancer cells exhibit hallmarks of this SAC:APC/C imbalance, including a long metaphase-to-anaphase transition, and slow mitosis overall. Together, our data reveal vulnerabilities in the cell division apparatus of cancer cells that can be exploited for therapeutic benefit.


Assuntos
Ciclossomo-Complexo Promotor de Anáfase , Neoplasias , Humanos , Ciclossomo-Complexo Promotor de Anáfase/genética , Dineínas , Cinesinas/genética , Cinetocoros , Mitose , Neoplasias/genética
7.
J Burn Care Res ; 2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-38290701

RESUMO

Burns are a common mechanism of pediatric injury worldwide and are a notable cause of disability-adjusted life-years. Burns in children represent a unique challenge, due to the differences from adults regarding physical characteristics, physiology and psychology. This retrospective cohort study examined trends of pediatric burns in New South Wales (NSW), Australia from 2010-22. It specifically focused on the changes in burn etiology and patient characteristics, body area affected, total body surface area, first aid, location and management. It also compared a 'Pre-COVID-19' and 'Peri-COVID-19' era to analyze the impact of COVID-19 on the pattern of pediatric burns, as children are at higher risk of injury during times of social disruption. The study found that burns in children continue to be concentrated in the toddler and preschooler age group and the main mechanisms of injury remain as scald and contact burns. In recent years, there has been a rising trend of friction burns, alongside a fall in flame burns and severe burns. Management of pediatric burns has also evolved, with predominant use of ambulatory care and low rates of admission and operative intervention. Trends in burn injury continue to evolve with time and over the last decade in NSW, key changes in the pattern of pediatric burns have been observed, with evolving mechanisms of injury, reduced severity of burns and a shift towards ambulatory care.

8.
J Neurotrauma ; 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38115598

RESUMO

The objective of the Australian Traumatic Brain Injury (AUS-TBI) Initiative is to develop a data dictionary to inform data collection and facilitate prediction of outcomes of people who experience moderate-severe TBI in Australia. The aim of this systematic review was to summarize the evidence of the association between demographic, injury event, and social characteristics with outcomes, in people with moderate-severe TBI, to identify potentially predictive indicators. Standardized searches were implemented across bibliographic databases to March 31, 2022. English-language reports, excluding case series, which evaluated the association between demographic, injury event, and social characteristics, and any clinical outcome in at least 10 patients with moderate-severe TBI were included. Abstracts and full text records were independently screened by at least two reviewers in Covidence. A pre-defined algorithm was used to assign a judgement of predictive value to each observed association. The review findings were discussed with an expert panel to determine the feasibility of incorporation of routine measurement into standard care. The search strategy retrieved 16,685 records; 867 full-length records were screened, and 111 studies included. Twenty-two predictors of 32 different outcomes were identified; 7 were classified as high-level (age, sex, ethnicity, employment, insurance, education, and living situation at the time of injury). After discussion with an expert consensus group, 15 were recommended for inclusion in the data dictionary. This review identified numerous predictors capable of enabling early identification of those at risk for poor outcomes and improved personalization of care through inclusion in routine data collection.

10.
EMBO Rep ; 24(12): e57234, 2023 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-37888778

RESUMO

53BP1 acts at the crossroads between DNA repair and p53-mediated stress response. With its interactors p53 and USP28, it is part of the mitotic surveillance (or mitotic stopwatch) pathway (MSP), a sensor that monitors the duration of cell division, promoting p53-dependent cell cycle arrest when a critical time threshold is surpassed. Here, we show that Polo-like kinase 1 (PLK1) activity is essential for the time-dependent release of 53BP1 from kinetochores. PLK1 inhibition, which leads to 53BP1 persistence at kinetochores, prevents cytosolic 53BP1 association with p53 and results in a blunted MSP. Strikingly, the identification of CENP-F as the kinetochore docking partner of 53BP1 enabled us to show that measurement of mitotic timing by the MSP does not take place at kinetochores, as perturbing CENP-F-53BP1 binding had no measurable impact on the MSP. Taken together, we propose that PLK1 supports the MSP by generating a cytosolic pool of 53BP1 and that an unknown cytosolic mechanism enables the measurement of mitotic duration.


Assuntos
Proteínas de Ciclo Celular , Proteínas Serina-Treonina Quinases , Humanos , Proteínas de Ciclo Celular/metabolismo , Células HeLa , Cinetocoros/metabolismo , Mitose , Proteínas Serina-Treonina Quinases/metabolismo , Proteína Supressora de Tumor p53/genética , Ubiquitina Tiolesterase/genética
11.
J Cell Biol ; 222(12)2023 12 04.
Artigo em Inglês | MEDLINE | ID: mdl-37773039

RESUMO

Polo-like kinase 4 (PLK4) is a key regulator of centriole biogenesis, but how PLK4 selects a single site for procentriole assembly remains unclear. Using ultrastructure expansion microscopy, we show that PLK4 localizes to discrete sites along the wall of parent centrioles. While there is variation in the number of sites PLK4 occupies on the parent centriole, most PLK4 localize at a dominant site that directs procentriole assembly. Inhibition of PLK4 activity leads to stable binding of PLK4 to the centriole and increases occupancy to a maximum of nine sites. We show that self-phosphorylation of an unstructured linker promotes the release of active PLK4 from the centriole to drive the selection of a single site for procentriole assembly. Preventing linker phosphorylation blocks PLK4 turnover, leading to supernumerary sites of PLK4 localization and centriole amplification. Therefore, self-phosphorylation is a major driver of the spatial patterning of PLK4 at the centriole and plays a critical role in selecting a single centriole duplication site.


Assuntos
Proteínas de Ciclo Celular , Centríolos , Proteínas Serina-Treonina Quinases , Ciclo Celular/fisiologia , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Centríolos/genética , Centríolos/metabolismo , Fosforilação , Humanos , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo
12.
Metabolites ; 13(7)2023 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-37512482

RESUMO

The hormonal form of vitamin D3, 1,25(OH)2D3, reduces UV-induced DNA damage. UV exposure initiates pre-vitamin D3 production in the skin, and continued UV exposure photoisomerizes pre-vitamin D3 to produce "over-irradiation products" such as lumisterol3 (L3). Cytochrome P450 side-chain cleavage enzyme (CYP11A1) in skin catalyzes the conversion of L3 to produce three main derivatives: 24-hydroxy-L3 [24(OH)L3], 22-hydroxy-L3 [22(OH)L3], and 20,22-dihydroxy-L3 [20,22(OH)L3]. The current study investigated the photoprotective properties of the major over-irradiation metabolite, 24(OH)L3, in human primary keratinocytes and human skin explants. The results indicated that treatment immediately after UV with either 24(OH)L3 or 1,25(OH)2D3 reduced UV-induced cyclobutane pyrimidine dimers and oxidative DNA damage, with similar concentration response curves in keratinocytes, although in skin explants, 1,25(OH)2D3 was more potent. The reductions in DNA damage by both compounds were, at least in part, the result of increased DNA repair through increased energy availability via increased glycolysis, as well as increased DNA damage recognition proteins in the nucleotide excision repair pathway. Reductions in UV-induced DNA photolesions by either compound occurred in the presence of lower reactive oxygen species. The results indicated that under in vitro and ex vivo conditions, 24(OH)L3 provided photoprotection against UV damage similar to that of 1,25(OH)2D3.

13.
Arch Dis Child ; 108(10): 808-814, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37423641

RESUMO

OBJECTIVE: This study aimed to compare academic performance and high school completion of young people hospitalised for a burn compared with young people not hospitalised for an injury. DESIGN: A retrospective population-based matched case-comparison cohort study. PARTICIPANTS: Young people aged ≤18 years hospitalised for a burn during 2005-2018 in New South Wales, Australia, with age, sex and residential postcode-matched peers not hospitalised for any injury during 1 July 2001 and 31 December 2018. MAIN OUTCOME MEASURES: Performance below the national minimum standard (NMS) on the National Assessment Plan for Literacy and Numeracy assessments and not completing high school. RESULTS: Young females hospitalised for a burn had a 72% higher risk of poorer reading compared with their peers (adjusted relative risk (ARR) 1.72; 95% CI 1.33 to 2.23), while young males hospitalised with a burn showed no higher risk (ARR 1.14; 95% CI 0.91 to 1.43). Young males (ARR 1.05; 95% CI 0.81 to 1.35) and females (ARR 1.34; 95% CI 0.93 to 1.94) hospitalised with a burn had no higher risk of not reaching the NMS for numeracy compared with peers. Young people hospitalised with a burn had at least twice the risk of not completing year 10 (ARR 3.86; 95% CI 1.68 to 8.86), year 11 (ARR 2.45; 95% CI 1.89 to 3.18) and year 12 (ARR 2.09; 95% CI 1.63 to 2.67) compared with matched counterparts. CONCLUSIONS: Young females hospitalised with a burn displayed poorer academic performance for reading compared with matched peers, while males and females were more likely to leave school earlier. Identifying unmet learning support needs of young burn survivors should be investigated.


Assuntos
Queimaduras , Hospitalização , Masculino , Feminino , Humanos , Adolescente , Estudos Retrospectivos , Estudos de Coortes , Queimaduras/epidemiologia , Estudos de Casos e Controles
14.
BMC Health Serv Res ; 23(1): 604, 2023 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-37296401

RESUMO

BACKGROUND: Aboriginal and Torres Strait Islander peoples have a unique place in Australia as the original inhabitants of the land. Similar to other First Nations people globally, they experience a disproportionate burden of injury and chronic health conditions. Discharge planning ensures ongoing care to avoid complications and achieve better health outcomes. Analysing discharge interventions that have been implemented and evaluated globally for First Nations people with an injury or chronic conditions can inform the implementation of strategies to ensure optimal ongoing care for Aboriginal and Torres Strait Islander people. METHODS: A systematic review was conducted to analyse discharge interventions conducted globally among First Nations people who sustained an injury or suffered from a chronic condition. We included documents published in English between January 2010 and July 2022. We followed the reporting guidelines and criteria set in Preferred Reporting Items for Systematic Review (PRISMA). Two independent reviewers screened the articles and extracted data from eligible papers. A quality appraisal of the studies was conducted using the Mixed Methods Appraisal Tool and the CONSIDER statement. RESULTS: Four quantitative and one qualitative study out of 4504 records met inclusion criteria. Three studies used interventions involving trained health professionals coordinating follow-up appointments, linkage with community care services and patient training. One study used 48-hour post discharge telephone follow-up and the other text messages with prompts to attend check-ups. The studies that included health professional coordination of follow-up, linkage with community care and patient education resulted in decreased readmissions, emergency presentations, hospital length of stay and unattended appointments. CONCLUSION: Further research on the field is needed to inform the design and delivery of effective programs to ensure quality health aftercare for First Nations people. We observed that discharge interventions in line with the principal domains of First Nations models of care including First Nations health workforce, accessible health services, holistic care, and self-determination were associated with better health outcomes. REGISTRATION: This study was prospectively registered in PROSPERO (ID CRD42021254718).


Assuntos
Serviços de Saúde do Indígena , Alta do Paciente , Humanos , Assistência ao Convalescente , Povos Aborígenes Australianos e Ilhéus do Estreito de Torres , Austrália , Doença Crônica
15.
BMJ Open ; 13(5): e068530, 2023 05 16.
Artigo em Inglês | MEDLINE | ID: mdl-37192809

RESUMO

INTRODUCTION: Parents of children hospitalised in a burn unit experience psychological trauma and later post-traumatic stress. Aboriginal and Torres Strait Islander families whose child has been admitted to a burn unit encounter additional burdens through a culturally unsafe healthcare system. Psychosocial interventions can help reduce anxiety, distress and trauma among children and parents. There remains a lack of interventions or resources that reflect Aboriginal and Torres Strait Islander people's perspective of health. The objective of this study is to codevelop a culturally appropriate informative resource to assist Aboriginal and Torres Strait Islander parents whose child has been hospitalised in a burn unit. METHODS: In this participatory research study, the development of a culturally safe resource will build on Aboriginal and Torres Strait Islander families' experiences and voices, complemented by the knowledge and expertise of an Aboriginal Health Worker (AHW) and burn care experts. Data will be collected through recorded yarning sessions with families whose child has been admitted to a burn unit, the AHW and burn care experts. Audiotapes will be transcribed and data will be analysed thematically. Analysis of yarning sessions and resource development will follow a cyclical approach. ETHICS AND DISSEMINATION: This study has been approved by the Aboriginal Health and Medical Research Council (AH&MRC) (1690/20) and the Sydney Children's Hospitals Network ethics committee (2020/ETH02103). Findings will be reported to all participants and will be disseminated with the broader community, the funding body and health workers at the hospital. Dissemination with the academic community will be through peer-reviewed publications and presentations in relevant conferences.


Assuntos
Povos Aborígenes Australianos e Ilhéus do Estreito de Torres , Queimaduras , Serviços de Saúde do Indígena , Criança , Humanos , Queimaduras/psicologia , Queimaduras/terapia , Assistência à Saúde Culturalmente Competente , Pesquisa sobre Serviços de Saúde , Grupos Populacionais
16.
Int J Mol Sci ; 24(5)2023 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-36902353

RESUMO

The calcium-sensing receptor (CaSR) is an important regulator of epidermal function. We previously reported that knockdown of the CaSR or treatment with its negative allosteric modulator, NPS-2143, significantly reduced UV-induced DNA damage, a key factor in skin cancer development. We subsequently wanted to test whether topical NPS-2143 could also reduce UV-DNA damage, immune suppression, or skin tumour development in mice. In this study, topical application of NPS-2143 (228 or 2280 pmol/cm2) to Skh:hr1 female mice reduced UV-induced cyclobutane pyrimidine dimers (CPD) (p < 0.05) and oxidative DNA damage (8-OHdG) (p < 0.05) to a similar extent as the known photoprotective agent 1,25(OH)2 vitamin D3 (calcitriol, 1,25D). Topical NPS-2143 failed to rescue UV-induced immunosuppression in a contact hypersensitivity study. In a chronic UV photocarcinogenesis protocol, topical NPS-2143 reduced squamous cell carcinomas for only up to 24 weeks (p < 0.02) but had no other effect on skin tumour development. In human keratinocytes, 1,25D, which protected mice from UV-induced skin tumours, significantly reduced UV-upregulated p-CREB expression (p < 0.01), a potential early anti-tumour marker, while NPS-2143 had no effect. This result, together with the failure to reduce UV-induced immunosuppression, may explain why the reduction in UV-DNA damage in mice with NPS-2143 was not sufficient to inhibit skin tumour formation.


Assuntos
Receptores de Detecção de Cálcio , Neoplasias Cutâneas , Feminino , Animais , Camundongos , Humanos , Camundongos Pelados , Receptores de Detecção de Cálcio/metabolismo , Raios Ultravioleta , Dano ao DNA , Neoplasias Cutâneas/metabolismo , Dímeros de Pirimidina/metabolismo , Pele/metabolismo
17.
Aust N Z J Public Health ; 47(2): 100023, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36906999

RESUMO

OBJECTIVES: Hospitalisation rates for injury, including at playgrounds, have not changed in the past decade. There are nine Australian Standards specific to playgrounds. The impact (if any) of these standards on playground injury resulting in hospitalisation is unknown. METHODS: Retrospective data for patients under 18 years presenting to emergency departments and/or admitted between October 2015 and December 2019 due to an injury documented as occurring at a playground were retrieved by the Illawarra Shoalhaven Local Health District Planning, Information and Performance Department. Maintenance and Australian Standard (AS) compliance data for the 401 local playgrounds were requested from the four Local Governments in Illawarra Shoalhaven Local Health District. Descriptive statistics were used. RESULTS: A total of 548 children were treated in emergency departments and/or admitted following playground injury. There was an overall increase of 39.3% in playground injury across the study period, and expenditure rose from $43,478 in 2011 to $367,259 in 2019 (a 744.7% increase). CONCLUSIONS: Playground injury has not decreased in the Illawarra Shoalhaven. Data regarding maintenance and AS compliance are lacking. This is not unique to our region. IMPLICATIONS FOR PUBLIC HEALTH: Without a national approach to adequately resource and monitor playground injury, it is not possible to assess the impact of Australian Standards or any injury prevention program.


Assuntos
Jogos e Brinquedos , Ferimentos e Lesões , Criança , Humanos , Adolescente , Segurança , Estudos Retrospectivos , Austrália , Hospitalização , Ferimentos e Lesões/epidemiologia , Ferimentos e Lesões/prevenção & controle
18.
Mol Cancer Ther ; 22(4): 519-528, 2023 04 03.
Artigo em Inglês | MEDLINE | ID: mdl-36752776

RESUMO

Extra copies of centrosomes are frequently observed in cancer cells. To survive and proliferate, cancer cells have developed strategies to cluster extra-centrosomes to form bipolar mitotic spindles. The aim of this study was to investigate whether centrosome clustering (CC) inhibition (CCi) would preferentially radiosensitize non-small cell lung cancer (NSCLC). Griseofulvin (GF; FDA-approved treatment) inhibits CC, and combined with radiation treatment (RT), resulted in a significant increase in the number of NSCLC cells with multipolar spindles, and decreased cell viability and colony formation ability in vitro. In vivo, GF treatment was well tolerated by mice, and the combined therapy of GF and radiation treatment resulted in a significant tumor growth delay. Both GF and radiation treatment also induced the generation of micronuclei (MN) in vitro and in vivo and activated cyclic GMP-AMP synthase (cGAS) in NSCLC cells. A significant increase in downstream cGAS-STING pathway activation was seen after combination treatment in A549 radioresistant cells that was dependent on cGAS. In conclusion, GF increased radiation treatment efficacy in lung cancer preclinical models in vitro and in vivo. This effect may be associated with the generation of MN and the activation of cGAS. These data suggest that the combination therapy of CCi, radiation treatment, and immunotherapy could be a promising strategy to treat NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Animais , Camundongos , Griseofulvina/farmacologia , Griseofulvina/metabolismo , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Neoplasias Pulmonares/patologia , Centrossomo , Nucleotidiltransferases
19.
BMC Health Serv Res ; 22(1): 1428, 2022 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-36443783

RESUMO

BACKGROUND: Quality and safety in Australian healthcare is inequitably distributed, highlighted by gaps in the provision of quality care for Aboriginal and Torres Strait Islander children. Burns have potential for long-term adverse outcomes, and quality care, including culturally safe care, is critical to recovery. This study aimed to develop and apply an Aboriginal Patient Journey Mapping (APJM) tool to investigate the quality of healthcare systems for burn care with Aboriginal and Torres Strait Islander children. STUDY DESIGN: Interface research methodology, using biomedical and cultural evidence, informed the modification of an existing APJM tool. The tool was then applied to the journey of one family accessing a paediatric tertiary burn care site. Data were collected through yarning with the family, case note review and clinician interviews. Data were analysed using Emden's core story and thematic analysis methods. Reflexivity informed consideration of the implications of the APJM tool, including its effectiveness and efficiency in eliciting information about quality and cultural safety. RESULTS: Through application of a modified APJM tool, gaps in quality care for Aboriginal and Torres Strait Islander children and families were identified at the individual, service and system levels. Engagement in innovative methodology incorporating more than biomedical standards of care, uncovered critical information about the experiences of culturally safe care in complex patient journeys. CONCLUSION: Based on our application of the tool, APJM can identify and evaluate specific aspects of culturally safe care as experienced by Aboriginal and Torres Strait Islander peoples and be used for quality improvement.


Assuntos
Queimaduras , Assistência à Saúde Culturalmente Competente , Disparidades em Assistência à Saúde , Povos Indígenas , Criança , Humanos , Austrália , Instalações de Saúde , Qualidade da Assistência à Saúde , Grupos Raciais
20.
Artigo em Inglês | MEDLINE | ID: mdl-36141576

RESUMO

Severe injury and chronic conditions require long-term management by multidisciplinary teams. Appropriate discharge planning ensures ongoing care to mitigate the long-term impact of injuries and chronic conditions. However, First Nations peoples in Australia face ongoing barriers to aftercare. This systematic review will locate and analyse global evidence of discharge interventions that have been implemented to improve aftercare and enhance health outcomes among First Nations people with an injury or chronic condition. A systematic search will be conducted using five databases, Google, and Google scholar. Global studies published in English will be included. We will analyse aftercare interventions implemented and the health outcomes associated. Two independent reviewers will screen and select studies and then extract and analyse the data. Quality appraisal of the included studies will be conducted using the Mixed Methods Appraisal Tool and the CONSIDER statement. The proposed study will analyse global evidence on discharge interventions that have been implemented for First Nations people with an injury or chronic conditions and their associated health outcomes. Our findings will guide healthcare quality improvement to ensure Aboriginal and Torres Strait Islander peoples have ongoing access to culturally safe aftercare services.


Assuntos
Serviços de Saúde do Indígena , Havaiano Nativo ou Outro Ilhéu do Pacífico , Austrália , Doença Crônica , Atenção à Saúde , Humanos , Povos Indígenas , Revisões Sistemáticas como Assunto
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