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BACKGROUND: There is a paucity of high-quality evidence based on clinical endpoints for routine cleaning of shared medical equipment. We assessed the effect of enhanced cleaning and disinfection of shared medical equipment on health-care-associated infections (HAIs) in hospitalised patients. METHODS: We conducted a stepped-wedge, cluster randomised, controlled trial in ten wards of a single hospital located on the central coast of New South Wales, Australia. Hospitals were eligible for inclusion if they were classified as public acute group A according to the Australian Institute of Health and Welfare, were located in New South Wales, had an intensive care unit, had a minimum of ten wards, and provided care for patients aged 18 years or older. Each cluster consisted of two randomly allocated wards (by use of simple randomisation), with a new cluster beginning the intervention every 6 weeks. Wards were informed of their allocation 2 weeks before commencement of intervention exposure, and the researcher collecting primary outcome data and audit data was masked to treatment sequence allocation. In the control phase, there was no change to environmental cleaning practices. In the intervention phase, a multimodal cleaning bundle included an additional 3 h per weekday for the dedicated cleaning and disinfection of shared medical equipment by 21 dedicated cleaning staff, with ongoing education, audit, and feedback. The primary outcome was the number of confirmed cases of HAI, as assessed by a fortnightly point prevalence survey and measured in all patients admitted to the wards during the study period. The completed trial is registered with Australia New Zealand Clinical Trials Registry (ACTRN12622001143718). FINDINGS: The hospital was recruited on July 31, 2022, and the study was conducted between March 20 and Nov 24, 2023. We assessed 220 hospitals for eligibility, of which five were invited to participate, and the first hospital to formally respond was enrolled. 5002 patients were included in the study (2524 [50·5%] women and 2478 [49·5%] men). In unadjusted results, 433 confirmed HAI cases occurred in 2497 patients (17·3%, 95% CI 15·9 to 18·8) in the control phase and 301 confirmed HAI cases occurred in 2508 patients (12·0%, 10·7 to 13·3) in the intervention phase. In adjusted results, there was a relative reduction of -34·5% (-50·3 to -17·5) in HAIs following the intervention (odds ratio 0·62, 95% CI 0·45 to 0·80; p=0·0006), corresponding to an absolute reduction equal to -5·2% (-8·2 to -2·3). No adverse effects were reported. INTERPRETATION: Improving the cleaning and disinfection of shared medical equipment significantly reduced HAIs, underscoring the crucial role of cleaning in improving patient outcomes. Findings emphasise the need for dedicated approaches for cleaning shared equipment. FUNDING: National Health and Medical Research Council.
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The current fallback position for the elderly frail nearing the end of life (less than 12 months to live) is hospitalisation. There is a reluctance to use the term 'terminally ill' for this population, resulting in overtreatment, overdiagnosis and management that is not consistent with the wishes of people. This is the major contributor to the so-called hospital crisis, including decreased capacity of hospitals, reduced ability to conduct elective surgery, increased attendances at emergency departments and ambulance ramping. The authors recently conducted the largest randomised study, to their knowledge, attempting to inform specialist hospital medical teams about the terminally ill status of their admitted patients. This information did not influence their clinical decisions in any way. The authors discuss the reasons why this may have occurred, such as the current avoidance of discussing death and dying by society and the concentration of healthcare workers on actively managing the acute presenting problem and ignoring the underlying prognosis in the elderly frail. The authors discuss ways of improving the management of the elderly nearing the end of life, such as more detailed goals of care discussions using the concept of shared decision-making rather than simply completing Advanced Care Decision documents. Empowering people in this way could become the most important driver of people's health care.
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Assistência Terminal , Humanos , Assistência Terminal/psicologia , Idoso , Idoso Fragilizado , Hospitalização , Tomada de Decisão Compartilhada , Doente Terminal/psicologia , Idoso de 80 Anos ou maisRESUMO
BACKGROUND: Binary classification models are frequently used to predict clinical deterioration, however they ignore information on the timing of events. An alternative is to apply time-to-event models, augmenting clinical workflows by ranking patients by predicted risks. This study examines how and why time-to-event modelling of vital signs data can help prioritise deterioration assessments using lift curves, and develops a prediction model to stratify acute care inpatients by risk of clinical deterioration. METHODS: We developed and validated a Cox regression for time to in-hospital mortality. The model used time-varying covariates to estimate the risk of clinical deterioration. Adult inpatient medical records from 5 Australian hospitals between 1 January 2019 and 31 December 2020 were used for model development and validation. Model discrimination and calibration were assessed using internal-external cross validation. A discrete-time logistic regression model predicting death within 24 h with the same covariates was used as a comparator to the Cox regression model to estimate differences in predictive performance between the binary and time-to-event outcome modelling approaches. RESULTS: Our data contained 150,342 admissions and 1016 deaths. Model discrimination was higher for Cox regression than for discrete-time logistic regression, with cross-validated AUCs of 0.96 and 0.93, respectively, for mortality predictions within 24 h, declining to 0.93 and 0.88, respectively, for mortality predictions within 1 week. Calibration plots showed that calibration varied by hospital, but this can be mitigated by ranking patients by predicted risks. CONCLUSION: Time-varying covariate Cox models can be powerful tools for triaging patients, which may lead to more efficient and effective care in time-poor environments when the times between observations are highly variable.
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Deterioração Clínica , Humanos , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Mortalidade Hospitalar , Austrália , Idoso de 80 Anos ou mais , Fatores de Tempo , Medição de Risco/métodos , Medição de Risco/normas , Medição de Risco/estatística & dados numéricos , AdultoRESUMO
PURPOSE: We aimed to compare the incidence of stroke in low-and middle-income countries (LMICs) versus high-income countries (HICs) in critically ill patients with COVID-19 and its impact on in-hospital mortality. METHODS: International observational study conducted in 43 countries. Stroke and mortality incidence rates and rate ratios (IRR) were calculated per admitted days using Poisson regression. Inverse probability weighting (IPW) was used to address the HICs vs. LMICs imbalance for confounders. RESULTS: 23,738 patients [20,511(86.4 %) HICs vs. 3,227(13.6 %) LMICs] were included. The incidence stroke/1000 admitted-days was 35.7 (95 %CI = 28.4-44.9) LMICs and 17.6 (95 %CI = 15.8-19.7) HICs; ischemic 9.47 (95 %CI = 6.57-13.7) LMICs, 1.97 (95 %CI = 1.53, 2.55) HICs; hemorrhagic, 7.18 (95 %CI = 4.73-10.9) LMICs, and 2.52 (95 %CI = 2.00-3.16) HICs; unspecified stroke type 11.6 (95 %CI = 7.75-17.3) LMICs, 8.99 (95 %CI = 7.70-10.5) HICs. In regression with IPW, LMICs vs. HICs had IRR = 1.78 (95 %CI = 1.31-2.42, p < 0.001). Patients from LMICs were more likely to die than those from HICs [43.6% vs 29.2 %; Relative Risk (RR) = 2.59 (95 %CI = 2.29-2.93), p < 0.001)]. Patients with stroke were more likely to die than those without stroke [RR = 1.43 (95 %CI = 1.19-1.72), p < 0.001)]. CONCLUSIONS: Stroke incidence was low in HICs and LMICs although the stroke risk was higher in LMICs. Both LMIC status and stroke increased the risk of death. Improving early diagnosis of stroke and redistribution of healthcare resources should be a priority. TRIAL REGISTRATION: ACTRN12620000421932 registered on 30/03/2020.
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OBJECTIVES: To investigate if a prospective feedback loop that flags older patients at risk of death can reduce non-beneficial treatment at end of life. DESIGN: Prospective stepped-wedge cluster randomised trial with usual care and intervention phases. SETTING: Three large tertiary public hospitals in south-east Queensland, Australia. PARTICIPANTS: 14 clinical teams were recruited across the three hospitals. Teams were recruited based on a consistent history of admitting patients aged 75+ years, and needed a nominated lead specialist consultant. Under the care of these teams, there were 4,268 patients (median age 84 years) who were potentially near the end of life and flagged at risk of non-beneficial treatment. INTERVENTION: The intervention notified clinicians of patients under their care determined as at-risk of non-beneficial treatment. There were two notification flags: a real-time notification and an email sent to clinicians about the at-risk patients at the end of each screening day. The nudge intervention ran for 16-35 weeks across the three hospitals. MAIN OUTCOME MEASURES: The primary outcome was the proportion of patients with one or more intensive care unit (ICU) admissions. The secondary outcomes examined times from patients being flagged at-risk. RESULTS: There was no improvement in the primary outcome of reduced ICU admissions (mean probability difference [intervention minus usual care] = -0.01, 95% confidence interval -0.08 to 0.01). There were no differences for the times to death, discharge, or medical emergency call. There was a reduction in the probability of re-admission to hospital during the intervention phase (mean probability difference -0.08, 95% confidence interval -0.13 to -0.03). CONCLUSIONS: This nudge intervention was not sufficient to reduce the trial's non-beneficial treatment outcomes in older hospital patients. TRIAL REGISTRATION: Australia New Zealand Clinical Trial Registry, ACTRN12619000675123 (registered 6 May 2019).
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Assistência Terminal , Humanos , Masculino , Idoso de 80 Anos ou mais , Feminino , Idoso , Assistência Terminal/métodos , Estudos Prospectivos , Queensland , Unidades de Terapia Intensiva , Futilidade Médica , Retroalimentação , Admissão do Paciente , Fatores Etários , Medição de RiscoAssuntos
Staphylococcus aureus Resistente à Meticilina , Infecções Estafilocócicas , Enterococos Resistentes à Vancomicina , Humanos , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Enterococos Resistentes à Vancomicina/efeitos dos fármacos , Infecções Estafilocócicas/prevenção & controle , Infecções Estafilocócicas/microbiologia , Roupa de Proteção , Luvas Protetoras , Infecções por Bactérias Gram-Positivas/prevenção & controle , Infecções por Bactérias Gram-Positivas/microbiologia , Controle de Infecções/métodos , Infecção Hospitalar/prevenção & controle , Infecção Hospitalar/microbiologiaRESUMO
BACKGROUND: Breast cancer, particularly the estrogen receptor positive (ER+) subtype, remains a leading cause of cancer-related death among women. Endocrine therapy is the most effective treatment for ER+ breast cancer; however, the development of resistance presents a significant challenge. This study explored the role of the breast cancer antiestrogen resistance 4 (BCAR4) gene as a potential driver of resistance and a pivotal biomarker in breast cancer. PATIENTS AND METHODS: The researchers undertook a comprehensive analysis of 1743 patients spanning 6 independent cohorts. They examined the association of BCAR4 expression with patient outcomes across all breast cancer types and the PAM50 molecular subtypes. The relationship between elevated BCAR4 expression and resistance to endocrine therapy including AIs, the prevailing standard-of-care for endocrine therapy, was also investigated. RESULTS: This meta-analysis corroborated the link between BCAR4 expression and adverse outcomes as well as resistance to endocrine therapy in breast cancer. Notably, BCAR4 expression is clinically significant in luminal A and B subtypes. Additionally, an association between BCAR4 expression and resistance to AI treatment was discerned. CONCLUSION: This study expands on previous findings by demonstrating that BCAR4 expression is associated with resistance to newer therapies. The identification of patients with intrinsic resistance to hormone therapy is crucial to avoid ineffective treatment strategies. These findings contribute to our understanding of endocrine therapy resistance in breast cancer and could potentially guide the development of more effective treatment strategies.
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Antineoplásicos Hormonais , Biomarcadores Tumorais , Neoplasias da Mama , Resistencia a Medicamentos Antineoplásicos , Humanos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Feminino , Resistencia a Medicamentos Antineoplásicos/genética , Biomarcadores Tumorais/metabolismo , Biomarcadores Tumorais/genética , Antineoplásicos Hormonais/uso terapêutico , Antineoplásicos Hormonais/farmacologia , Receptores de Estrogênio/metabolismo , Prognóstico , Regulação Neoplásica da Expressão Gênica , RNA Longo não CodificanteRESUMO
OBJECTIVE: To investigate associations between transfusion of blood products close to the end of shelf-life and clinical outcomes in obstetric inpatients. METHODS: Mortality and morbidity were compared in patients transfused exclusively with red blood cells (RBC) stored for less than 21 days (fresh) versus RBC stored for 35 days or longer (old), and platelets (PLT) stored for 3 days or fewer (fresh) versus 4 days or longer (old) in Queensland, Australia from 2007 to 2013. Multivariable models were used to examine associations between these groups of blood products and clinical end points. RESULTS: There were 3371 patients who received RBC and 280 patients who received PLT of the eligible storage durations. Patients transfused with old RBC received fewer transfusions (2.7 ± 1.8 vs. 2.3 ± 1.0 units; P < 0.001). However, a higher rate of single-unit transfusions was also seen in those patients who exclusively received old RBC (252 [9.3%] vs. 92 [13.7%]; P = 0.003). Comparison of fresh vs. old blood products revealed no differences in the quantities of transfused RBC (9.5 ± 5.9 vs. 9.1 ± 5.2 units; P = 0.680) or PLT (1.5 ± 0.8 vs. 1.4 ± 1.1 units; P = 0.301) as well as the length of hospital stay for RBC (3 [2-5] vs. 3 [2-5] days; P = 0.124) or PLT (5 [4-8] vs. 6 [4-9] days; P = 0.120). CONCLUSION: Transfusing exclusively older RBC or PLT was not associated with increased morbidity or mortality.
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Transfusão de Eritrócitos , Eritrócitos , Humanos , Estudos Retrospectivos , Plaquetas , AustráliaRESUMO
BACKGROUND: Improving access to healthcare for ethnic minorities is a public health priority in many countries, yet little is known about how to incorporate information on race, ethnicity, and related social determinants of health into large international studies. Most studies of differences in treatments and outcomes of COVID-19 associated with race and ethnicity are from single cities or countries. METHODS: We present the breadth of race and ethnicity reported for patients in the COVID-19 Critical Care Consortium, an international observational cohort study from 380 sites across 32 countries. Patients from the United States, Australia, and South Africa were the focus of an analysis of treatments and in-hospital mortality stratified by race and ethnicity. Inclusion criteria were admission to intensive care for acute COVID-19 between January 14th, 2020, and February 15, 2022. Measurements included demographics, comorbidities, disease severity scores, treatments for organ failure, and in-hospital mortality. RESULTS: Seven thousand three hundred ninety-four adults met the inclusion criteria. There was a wide variety of race and ethnicity designations. In the US, American Indian or Alaska Natives frequently received dialysis and mechanical ventilation and had the highest mortality. In Australia, organ failure scores were highest for Aboriginal/First Nations persons. The South Africa cohort ethnicities were predominantly Black African (50%) and Coloured* (28%). All patients in the South Africa cohort required mechanical ventilation. Mortality was highest for South Africa (68%), lowest for Australia (15%), and 30% in the US. CONCLUSIONS: Disease severity was higher for Indigenous ethnicity groups in the US and Australia than for other ethnicities. Race and ethnicity groups with longstanding healthcare disparities were found to have high acuity from COVID-19 and high mortality. Because there is no global system of race and ethnicity classification, researchers designing case report forms for international studies should consider including related information, such as socioeconomic status or migration background. *Note: "Coloured" is an official, contemporary government census category of South Africa and is a term of self-identification of race and ethnicity of many citizens of South Africa.
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COVID-19 , Etnicidade , Disparidades em Assistência à Saúde , Grupos Raciais , Adulto , Humanos , COVID-19/terapia , Cuidados Críticos , Sistema de Registros , InternacionalidadeRESUMO
OBJECTIVE: Vital signs-based models are complicated by repeated measures per patient and frequently missing data. This paper investigated the impacts of common vital signs modeling assumptions during clinical deterioration prediction model development. STUDY DESIGN AND SETTING: Electronic medical record (EMR) data from five Australian hospitals (1 January 2019-31 December 2020) were used. Summary statistics for each observation's prior vital signs were created. Missing data patterns were investigated using boosted decision trees, then imputed with common methods. Two example models predicting in-hospital mortality were developed, as follows: logistic regression and eXtreme Gradient Boosting. Model discrimination and calibration were assessed using the C-statistic and nonparametric calibration plots. RESULTS: The data contained 5,620,641 observations from 342,149 admissions. Missing vitals were associated with observation frequency, vital sign variability, and patient consciousness. Summary statistics improved discrimination slightly for logistic regression and markedly for eXtreme Gradient Boosting. Imputation method led to notable differences in model discrimination and calibration. Model calibration was generally poor. CONCLUSION: Summary statistics and imputation methods can improve model discrimination and reduce bias during model development, but it is questionable whether these differences are clinically significant. Researchers should consider why data are missing during model development and how this may impact clinical utility.
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Hospitalização , Sinais Vitais , Humanos , Austrália , Modelos Logísticos , Estudos RetrospectivosRESUMO
OBJECTIVES: To determine the prevalence and outcomes associated with hemorrhage, disseminated intravascular coagulopathy, and thrombosis (HECTOR) complications in ICU patients with COVID-19. DESIGN: Prospective, observational study. SETTING: Two hundred twenty-nine ICUs across 32 countries. PATIENTS: Adult patients (≥ 16 yr) admitted to participating ICUs for severe COVID-19 from January 1, 2020, to December 31, 2021. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: HECTOR complications occurred in 1,732 of 11,969 study eligible patients (14%). Acute thrombosis occurred in 1,249 patients (10%), including 712 (57%) with pulmonary embolism, 413 (33%) with myocardial ischemia, 93 (7.4%) with deep vein thrombosis, and 49 (3.9%) with ischemic strokes. Hemorrhagic complications were reported in 579 patients (4.8%), including 276 (48%) with gastrointestinal hemorrhage, 83 (14%) with hemorrhagic stroke, 77 (13%) with pulmonary hemorrhage, and 68 (12%) with hemorrhage associated with extracorporeal membrane oxygenation (ECMO) cannula site. Disseminated intravascular coagulation occurred in 11 patients (0.09%). Univariate analysis showed that diabetes, cardiac and kidney diseases, and ECMO use were risk factors for HECTOR. Among survivors, ICU stay was longer (median days 19 vs 12; p < 0.001) for patients with versus without HECTOR, but the hazard of ICU mortality was similar (hazard ratio [HR] 1.01; 95% CI 0.92-1.12; p = 0.784) overall, although this hazard was identified when non-ECMO patients were considered (HR 1.13; 95% CI 1.02-1.25; p = 0.015). Hemorrhagic complications were associated with an increased hazard of ICU mortality compared to patients without HECTOR complications (HR 1.26; 95% CI 1.09-1.45; p = 0.002), whereas thrombosis complications were associated with reduced hazard (HR 0.88; 95% CI 0.79-0.99, p = 0.03). CONCLUSIONS: HECTOR events are frequent complications of severe COVID-19 in ICU patients. Patients receiving ECMO are at particular risk of hemorrhagic complications. Hemorrhagic, but not thrombotic complications, are associated with increased ICU mortality.
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COVID-19 , Trombose , Adulto , Humanos , COVID-19/complicações , COVID-19/epidemiologia , COVID-19/terapia , Estudos Prospectivos , Estado Terminal , Trombose/epidemiologia , Trombose/etiologia , Cuidados Críticos , Hemorragia/epidemiologia , Hemorragia/etiologia , Estudos RetrospectivosRESUMO
OBJECTIVE: Sustainable investment in computerized decision support systems (CDSS) requires robust evaluation of their economic impacts compared with current clinical workflows. We reviewed current approaches used to evaluate the costs and consequences of CDSS in hospital settings and presented recommendations to improve the generalizability of future evaluations. MATERIALS AND METHODS: A scoping review of peer-reviewed research articles published since 2010. Searches were completed in the PubMed, Ovid Medline, Embase, and Scopus databases (last searched February 14, 2023). All studies reported the costs and consequences of a CDSS-based intervention compared with current hospital workflows. Findings were summarized using narrative synthesis. Individual studies were further appraised against the Consolidated Health Economic Evaluation and Reporting (CHEERS) 2022 checklist. RESULTS: Twenty-nine studies published since 2010 were included. Studies evaluated CDSS for adverse event surveillance (5 studies), antimicrobial stewardship (4 studies), blood product management (8 studies), laboratory testing (7 studies), and medication safety (5 studies). All studies evaluated costs from a hospital perspective but varied based on the valuation of resources affected by CDSS implementation, and the measurement of consequences. We recommend future studies follow guidance from the CHEERS checklist; use study designs that adjust for confounders; consider both the costs of CDSS implementation and adherence; evaluate consequences that are directly or indirectly affected by CDSS-initiated behavior change; examine the impacts of uncertainty and differences in outcomes across patient subgroups. DISCUSSION AND CONCLUSION: Improving consistency in the conduct and reporting of evaluations will enable detailed comparisons between promising initiatives, and their subsequent uptake by decision-makers.
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Sistemas de Apoio a Decisões Clínicas , Humanos , Hospitais , Análise Custo-BenefícioRESUMO
OBJECTIVES: We aimed to examine the bias for statistical significance using published confidence intervals in sport and exercise medicine research. DESIGN: Observational study. METHODS: The abstracts of 48,390 articles, published in 18 sports and exercise medicine journals between 2002 and 2022, were searched using a validated text-mining algorithm that identified and extracted ratio confidence intervals (odds, hazard, and risk ratios). The algorithm identified 1744 abstracts that included ratio confidence intervals, from which 4484 intervals were extracted. After excluding ineligible intervals, the analysis used 3819 intervals, reported as 95â¯% confidence intervals, from 1599 articles. The cumulative distributions of lower and upper confidence limits were plotted to identify any abnormal patterns, particularly around a ratio of 1 (the null hypothesis). The distributions were compared to those from unbiased reference data, which was not subjected to p-hacking or publication bias. A bias for statistical significance was further investigated using a histogram plot of z-values calculated from the extracted 95â¯% confidence intervals. RESULTS: There was a marked change in the cumulative distribution of lower and upper bound intervals just over and just under a ratio of 1. The bias for statistical significance was also clear in a stark under-representation of z-values between -1.96 and +1.96, corresponding to p-values above 0.05. CONCLUSIONS: There was an excess of published research with statistically significant results just below the standard significance threshold of 0.05, which is indicative of publication bias. Transparent research practices, including the use of registered reports, are needed to reduce the bias in published research.
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Esportes , Humanos , Viés , Viés de Publicação , Exercício Físico , Razão de ChancesRESUMO
INTRODUCTION: Due to the increase in participation and risk of anterior cruciate ligament (ACL) injuries and concussion in women's Australian Football, an injury prevention programme (Prep-to-Play) was codesigned with consumers (eg, coaches, players) and stakeholders (eg, the Australian Football League). The impact of supported and unsupported interventions on the use of Prep-to-Play (primary aim) and injury rates (secondary aim) will be evaluated in women and girls playing community Australian Football. METHODS AND ANALYSIS: This stepped-wedge, cluster randomised controlled trial will include ≥140 teams from U16, U18 or senior women's competitions. All 10 geographically separated clusters (each containing ≥14 teams) will start in the control (unsupported) phase and be randomised to one of five dates (or 'wedges') during the 2021 or 2022 season to sequentially transition to the intervention (supported Prep-to-Play), until all teams receive the intervention. Prep-to-Play includes four elements: a neuromuscular training warm-up, contact-focussed football skills (eg, tackling), strength exercises and education (eg, technique cues). When transitioning to supported interventions, study physiotherapists will deliver a workshop to coaches and player leaders on how to use Prep-to-Play, attend team training at least two times and provide ongoing support. In the unsupported phase, team will continue usual routines and may freely access available Prep-to-Play resources online (eg, posters and videos about the four elements), but without additional face-to-face support. Outcomes will be evaluated throughout the 2021 and 2022 seasons (~14 weeks per season). PRIMARY OUTCOME: use of Prep-to-Play will be reported via a team designate (weekly) and an independent observer (five visits over the two seasons) and defined as the team completing 75% of the programme, two-thirds (67%) of the time. SECONDARY OUTCOMES: injuries will be reported by the team sports trainer and/or players. Injury definition: any injury occurring during a football match or training that results in: (1) being unable to return to the field of play for that match or (2) missing ≥ one match. Outcomes in the supported and unsupported phases will be compared using a generalised linear mixed model adjusting for clustering and time. Due to the type III hybrid implementation-effectiveness design, the study is powered to detect a improvement in use of Prep-to-Play and a reduction in ACL injuries. ETHICS AND DISSEMINATION: La Trobe University Ethics Committee (HREC 20488) approved. Coaches provided informed consent to receive the supported intervention and players provided consent to be contacted if they sustained a head or knee injury. Results will be disseminated through partner organisations, peer-reviewed publications and scientific conferences. TRIAL REGISTRATION NUMBER: NCT04856241.
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Lesões do Ligamento Cruzado Anterior , Traumatismos em Atletas , Traumatismos do Joelho , Esportes de Equipe , Feminino , Humanos , Traumatismos em Atletas/prevenção & controle , AustráliaRESUMO
Chromosomal rearrangements often result in active regulatory regions juxtaposed upstream of an oncogene to generate an expressed gene fusion. Repeated activation of a common downstream partner-with differing upstream regions across a patient cohort-suggests a conserved oncogenic role. Analysis of 9,638 patients across 32 solid tumor types revealed an annotated long noncoding RNA (lncRNA), Breast Cancer Anti-Estrogen Resistance 4 (BCAR4), was the most prevalent, uncharacterized, downstream gene fusion partner occurring in 11 cancers. Its oncogenic role was confirmed using multiple cell lines with endogenous BCAR4 gene fusions. Furthermore, overexpressing clinically prevalent BCAR4 gene fusions in untransformed cell lines was sufficient to induce an oncogenic phenotype. We show that the minimum common region to all gene fusions harbors an open reading frame that is necessary to drive proliferation. IMPLICATIONS: BCAR4 gene fusions represent an underappreciated class of gene fusions that may have biological and clinical implications across solid tumors.
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Neoplasias , RNA Longo não Codificante , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Fusão Gênica , Neoplasias/genética , Oncogenes , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismoRESUMO
BACKGROUND: Hospital patients experiencing clinical deterioration are at greater risk of adverse events. Monitoring patients through early warning systems is widespread, despite limited published evidence that they improve patient outcomes. Current limitations including infrequent or incorrect risk calculations may be mitigated by integration into electronic medical records. Our objective was to examine the impact on patient outcomes of systems for detecting and responding to real-time, automated alerts for clinical deterioration. METHODS: This review was conducted according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews checklist. We searched Medline, CINAHL and Embase for articles implementing real-time, automated deterioration alerts in hospitalised adults evaluating one or more patient outcomes including intensive care unit admission, length of stay, in-hospital cardiopulmonary arrest and in-hospital death. RESULTS: Of 639 studies identified, 18 were included in this review. Most studies did not report statistically significant associations between alert implementation and better patient outcomes. Four studies reported statistically significant improvements in two or more patient outcomes, and were the only studies to directly involve the patient's clinician. However, only one of these four studies was robust to existing trends in patient outcomes. Of the six studies using robust study designs, one reported a statistically significant improvement in patient outcomes; the rest did not detect differences. CONCLUSIONS: Most studies in this review did not detect improvements in patient outcomes following the implementation of real-time deterioration alerts. Future implementation studies should consider: directly involving the patient's physician or a dedicated surveillance nurse in structured response protocols for deteriorating patients; the workflow of alert recipients; and incorporating model features into the decision process to improve clinical utility.
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Deterioração Clínica , Adulto , Registros Eletrônicos de Saúde , Mortalidade Hospitalar , Hospitalização , Humanos , Unidades de Terapia IntensivaRESUMO
Late-stage relapse (LSR) in patients with breast cancer (BC) occurs more than five years and up to 10 years after initial treatment and has less than 30% 5-year relative survival rate. Long non-coding RNAs (lncRNAs) play important roles in BC yet have not been studied in LSR BC. Here, we identify 1127 lncRNAs differentially expressed in LSR BC via transcriptome sequencing and analysis of 72 early-stage and 24 LSR BC patient tumors. Decreasing expression of the most up-regulated lncRNA, LINC00355, in BC and MCF7 long-term estrogen deprived cell lines decreases cellular invasion and proliferation. Subsequent mechanistic studies show that LINC00355 binds to MENIN and changes occupancy at the CDKN1B promoter to decrease p27Kip. In summary, this is a key study discovering lncRNAs in LSR BC and LINC00355 association with epigenetic regulation and proliferation in BC.
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Appropriate descriptions of statistical methods are essential for evaluating research quality and reproducibility. Despite continued efforts to improve reporting in publications, inadequate descriptions of statistical methods persist. At times, reading statistical methods sections can conjure feelings of dèjá vu, with content resembling cut-and-pasted or "boilerplate text" from already published work. Instances of boilerplate text suggest a mechanistic approach to statistical analysis, where the same default methods are being used and described using standardized text. To investigate the extent of this practice, we analyzed text extracted from published statistical methods sections from PLOS ONE and the Australian and New Zealand Clinical Trials Registry (ANZCTR). Topic modeling was applied to analyze data from 111,731 papers published in PLOS ONE and 9,523 studies registered with the ANZCTR. PLOS ONE topics emphasized definitions of statistical significance, software and descriptive statistics. One in three PLOS ONE papers contained at least 1 sentence that was a direct copy from another paper. 12,675 papers (11%) closely matched to the sentence "a p-value < 0.05 was considered statistically significant". Common topics across ANZCTR studies differentiated between study designs and analysis methods, with matching text found in approximately 3% of sections. Our findings quantify a serious problem affecting the reporting of statistical methods and shed light on perceptions about the communication of statistics as part of the scientific process. Results further emphasize the importance of rigorous statistical review to ensure that adequate descriptions of methods are prioritized over relatively minor details such as p-values and software when reporting research outcomes.