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1.
BMC Med Res Methodol ; 24(1): 109, 2024 May 04.
Article in English | MEDLINE | ID: mdl-38704520

ABSTRACT

BACKGROUND: During the COVID-19 pandemic, many intensive care units (ICUs) halted research to focus on COVID-19-specific studies. OBJECTIVE: To describe the conduct of an international randomized trial of stress ulcer prophylaxis (Re-Evaluating the Inhibition of Stress Erosions in the ICU [REVISE]) during the pandemic, addressing enrolment patterns, center engagement, informed consent processes, data collection, a COVID-specific substudy, patient transfers, and data monitoring. METHODS: REVISE is a randomized trial among mechanically ventilated patients, comparing pantoprazole 40 mg IV to placebo on the primary efficacy outcome of clinically important upper gastrointestinal bleeding and the primary safety outcome of 90-day mortality. We documented protocol implementation status from March 11th 2020-August 30th 2022. RESULTS: The Steering Committee did not change the scientific protocol. From the first enrolment on July 9th 2019 to March 10th 2020 (8 months preceding the pandemic), 267 patients were enrolled in 18 centers. From March 11th 2020-August 30th 2022 (30 months thereafter), 41 new centers joined; 59 were participating by August 30th 2022 which enrolled 2961 patients. During a total of 1235 enrolment-months in the pandemic phase, enrolment paused for 106 (8.6%) months in aggregate (median 3 months, interquartile range 2;6). Protocol implementation involved a shift from the a priori consent model pre-pandemic (188, 58.8%) to the consent to continue model (1615, 54.1%, p < 0.01). In one new center, an opt-out model was approved. The informed consent rate increased slightly (80.7% to 85.0%, p = 0.05). Telephone consent encounters increased (16.6% to 68.2%, p < 0.001). Surge capacity necessitated intra-institutional transfers; receiving centers continued protocol implementation whenever possible. We developed a nested COVID-19 substudy. The Methods Centers continued central statistical monitoring of trial metrics. Site monitoring was initially remote, then in-person when restrictions lifted. CONCLUSION: Protocol implementation adaptations during the pandemic included a shift in the consent model, a sustained high consent rate, and launch of a COVID-19 substudy. Recruitment increased as new centers joined, patient transfers were optimized, and monitoring methods were adapted.


Subject(s)
COVID-19 , Humans , COVID-19/prevention & control , COVID-19/epidemiology , Pantoprazole/therapeutic use , SARS-CoV-2 , Intensive Care Units/statistics & numerical data , Pandemics/prevention & control , Female , Respiration, Artificial/statistics & numerical data , Male , Clinical Protocols , Middle Aged , Gastrointestinal Hemorrhage/prevention & control , Anti-Ulcer Agents/therapeutic use , Anti-Ulcer Agents/administration & dosage
2.
Trials ; 24(1): 796, 2023 Dec 06.
Article in English | MEDLINE | ID: mdl-38057875

ABSTRACT

BACKGROUND: The REVISE (Re-Evaluating the Inhibition of Stress Erosions in the ICU) trial will evaluate the impact of the proton pump inhibitor pantoprazole compared to placebo in invasively ventilated critically ill patients. OBJECTIVE: To outline the statistical analysis plan for the REVISE trial. METHODS: REVISE is a randomized clinical trial ongoing in intensive care units (ICUs) internationally. Patients ≥ 18 years old, receiving invasive mechanical ventilation, and expected to remain ventilated beyond the calendar day after randomization are allocated to either 40 mg pantoprazole intravenously or placebo while mechanically ventilated. RESULTS: The primary efficacy outcome is clinically important upper GI bleeding; the primary safety outcome is 90-day mortality. Secondary outcomes are ventilator-associated pneumonia, Clostridioides difficile infection, new renal replacement therapy, ICU and hospital mortality, and patient-important GI bleeding. Tertiary outcomes are total red blood cells transfused, peak serum creatinine concentration, and duration of mechanical ventilation, ICU, and hospital length of stay. Following an interim analysis of results from 2400 patients (50% of 4800 target sample size), the data monitoring committee recommended continuing enrolment. CONCLUSIONS: This statistical analysis plan outlines the statistical analyses of all outcomes, sensitivity analyses, and subgroup analyses. REVISE will inform clinical practice and guidelines worldwide. TRIAL REGISTRATION: www. CLINICALTRIALS: gov NCT03374800. November 21, 2017.


Subject(s)
Intensive Care Units , Pneumonia, Ventilator-Associated , Adolescent , Humans , Critical Illness , Gastrointestinal Hemorrhage/therapy , Gastrointestinal Hemorrhage/drug therapy , Pantoprazole/adverse effects , Pneumonia, Ventilator-Associated/drug therapy , Proton Pump Inhibitors/adverse effects , Respiration, Artificial , Adult
3.
BMC Health Serv Res ; 23(1): 1319, 2023 Nov 29.
Article in English | MEDLINE | ID: mdl-38031109

ABSTRACT

OBJECTIVE: To report trends in Australian hospitalisations coded for sepsis and their associated costs. DESIGN: Retrospective analysis of Australian national hospitalisation data from 2002 to 2021. METHODS: Sepsis-coded hospitalisations were identified using the Global Burden of Disease study sepsis-specific ICD-10 codes modified for Australia. Costs were calculated using Australian-Refined Diagnosis Related Group codes and National Hospital Cost Data Collection. RESULTS: Sepsis-coded hospitalisations increased from 36,628 in 2002-03 to 131,826 in 2020-21, an annual rate of 7.8%. Principal admission diagnosis codes contributed 13,843 (37.8%) in 2002-03 and 44,186 (33.5%) in 2020-21; secondary diagnosis codes contributed 22,785 (62.2%) in 2002-03 and 87,640 (66.5%) in 2020-21. Unspecified sepsis was the most common sepsis code, increasing from 15,178 hospitalisations in 2002-03 to 68,910 in 2020-21. The population-based incidence of sepsis-coded hospitalisations increased from 18.6 to 10,000 population (2002-03) to 51.3 per 10,000 (2021-21); representing an increase from 55.1 to 10,000 hospitalisations in 2002-03 to 111.4 in 2020-21. Sepsis-coded hospitalisations occurred more commonly in the elderly; those aged 65 years or above accounting for 20,573 (55.6%) sepsis-coded hospitalisations in 2002-03 and 86,135 (65.3%) in 2020-21. The cost of sepsis-coded hospitalisations increased at an annual rate of 20.6%, from AUD199M (€127 M) in financial year 2012 to AUD711M (€455 M) in 2019. CONCLUSION: Hospitalisations coded for sepsis and associated costs increased significantly from 2002 to 2021 and from 2012 to 2019, respectively.


Subject(s)
Hospitalization , Sepsis , Aged , Humans , Australia/epidemiology , Retrospective Studies , Sepsis/epidemiology , Sepsis/therapy , Hospital Costs
4.
Indian J Radiol Imaging ; 33(3): 373-381, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37362368

ABSTRACT

Background The inguinal region is an area of complex anatomy that could contain diverse uncommon contents in routine clinical practice. Although inguinal hernia repair is one of the commonest surgeries done routinely, thorough preoperative imaging has a significant impact on the outcome of the surgery, by revealing the presence of unusual contents in the inguinal region. Aim The aim of this article is to review the differential diagnosis of the uncommon inguinal pathologies, which can simulate an inguinal hernia, to determine, and to simplify the treatment approach. Conclusions A profound understanding of the imaging characteristics of uncommon inguinal pathologies is crucial for both the radiologists (to prevent misdiagnosis) and the treating physicians (to avoid surgical complications) and ensure optimal management.

5.
Sci Rep ; 12(1): 10113, 2022 06 16.
Article in English | MEDLINE | ID: mdl-35710798

ABSTRACT

We examined systems-level costs before and after the implementation of an emergency department paediatric sepsis screening, recognition and treatment pathway. Aggregated hospital admissions for all children aged < 18y with a diagnosis code of sepsis upon admission in Queensland, Australia were compared for 16 participating and 32 non-participating hospitals before and after pathway implementation. Monte Carlo simulation was used to generate uncertainty intervals. Policy impacts were estimated using difference-in-difference analysis comparing observed and expected results. We compared 1055 patient episodes before (77.6% in-pathway) and 1504 after (80.5% in-pathway) implementation. Reductions were likely for non-intensive length of stay (- 20.8 h [- 36.1, - 8.0]) but not intensive care (-9.4 h [- 24.4, 5.0]). Non-pathway utilisation was likely unchanged for interhospital transfers (+ 3.2% [- 5.0%, 11.4%]), non-intensive (- 4.5 h [- 19.0, 9.8]) and intensive (+ 7.7 h, [- 20.9, 37.7]) care length of stay. After difference-in-difference adjustment, estimated savings were 596 [277, 942] non-intensive and 172 [148, 222] intensive care days. The program was cost-saving in 63.4% of simulations, with a mean value of $97,019 [- $857,273, $1,654,925] over 24 months. A paediatric sepsis pathway in Queensland emergency departments was associated with potential reductions in hospital utilisation and costs.


Subject(s)
Emergency Service, Hospital , Sepsis , Australia , Child , Hospitalization , Humans , Length of Stay , Queensland/epidemiology , Sepsis/diagnosis , Sepsis/epidemiology , Sepsis/therapy
6.
Crit Care Explor ; 3(11): e0573, 2021 Nov.
Article in English | MEDLINE | ID: mdl-34765981

ABSTRACT

OBJECTIVES: To evaluate the implementation of a pediatric sepsis pathway in the emergency department as part of a statewide quality improvement initiative in Queensland, Australia. DESIGN: Multicenter observational prospective cohort study. SETTING: Twelve emergency departments in Queensland, Australia. PATIENTS: Children less than 18 years evaluated for sepsis in the emergency department. Patients with signs of shock, nonshocked patients with signs of organ dysfunction, and patients without organ dysfunction were assessed. INTERVENTIONS: Introduction of a pediatric sepsis pathway. MEASUREMENTS AND MAIN RESULTS: Process measures included compliance with and timeliness of the sepsis bundle, and bundle components. Process and outcome measures of children admitted to the ICU with sepsis were compared with a baseline cohort. Five-hundred twenty-three children were treated for sepsis including 291 with suspected sepsis without organ dysfunction, 86 with sepsis-associated organ dysfunction, and 146 with septic shock. Twenty-four (5%) were admitted to ICU, and three (1%) died. The median time from sepsis recognition to bundle commencement for children with septic shock was 56 minutes (interquartile range, 36-99 min) and 47 minutes (interquartile range, 34-76 min) for children with sepsis-associated organ dysfunction without shock; 30% (n = 44) and 40% (n = 34), respectively, received the bundle within the target timeframe. In comparison with the baseline ICU cohort, bundle compliance improved from 27% (n = 45) to 58% (n = 14) within 60 minutes of recognition and from 47% (n = 78/167) to 75% (n = 18) within 180 minutes of recognition (p < 0.05). CONCLUSIONS: Our findings on the introduction of protocolized care in a large and diverse state demonstrate ongoing variability in sepsis bundle compliance. Although bundle compliance improved compared with a baseline cohort, continued efforts are required to ensure guideline targets and sustainability are achieved.

7.
Med Sci Monit ; 27: e929512, 2021 Apr 18.
Article in English | MEDLINE | ID: mdl-33866323

ABSTRACT

BACKGROUND Sepsis is a serious clinical problem that results from the systemic response of the body to infection. Left ventricular (LV) diastolic dysfunction is increasingly appreciated as a contributor to morbidity and mortality in sepsis. Animal models may offer a method of studying diastolic dysfunction while controlling for many potential clinical confounders, such as sepsis duration, premorbid condition, and therapeutic interventions. This study sought to evaluate an endotoxemia (LPS) rodent model of sepsis, with regard to echocardiographic evidence, including tissue Doppler, of LV diastolic dysfunction and histopathology findings. MATERIAL AND METHODS Fourteen male Sprague-Dawley rats were randomly allocated (1: 1) to LPS or saline (control). Mean arterial blood pressure (MAP) was measured through cannulation of the carotid artery. After a 30-min stabilization, baseline assessment with echocardiography and blood collection was performed. Rats were administered 0.9% saline or LPS (10 mg/mL). Follow-up echocardiography and blood collection were performed after 2 h. Hearts were removed post-mortem and pathology studied using histology and immunohistochemistry. RESULTS LPS was associated with hypotension (MAP 81.86±31.67 mmHg; 124.29±20.16; p=0.02) and LV impaired relaxation (myocardial early diastolic velocity [e'] 0.06±0.02 m/s; 0.09±0.02; P=0.008). Histopathology and immunohistochemistry demonstrated evidence of interstitial myocarditis (hydropic changes and inflammation). CONCLUSIONS LPS was associated with both diastolic dysfunction (impaired relaxation) and interstitial myocarditis. These features may offer a link between the structural and functional changes that have previously been described separately in clinical sepsis. This may facilitate further studies focused upon the mechanism and potential benefit treatment of sepsis-associated cardiac dysfunction.


Subject(s)
Heart Ventricles/metabolism , Myocarditis/metabolism , Myocardium/metabolism , Sepsis/metabolism , Ventricular Dysfunction, Left/metabolism , Animals , Diastole , Disease Models, Animal , Echocardiography, Doppler , Heart Ventricles/pathology , Humans , Immunohistochemistry , Male , Myocarditis/pathology , Rats , Rats, Sprague-Dawley , Sepsis/pathology , Ventricular Dysfunction, Left/pathology
8.
Nurse Educ Today ; 97: 104703, 2021 Feb.
Article in English | MEDLINE | ID: mdl-33360011

ABSTRACT

BACKGROUND: Sepsis is a leading cause of death and disability in adults and children. Evidence suggests that early recognition and management can significantly improve patient outcomes, therefore education of healthcare workers around sepsis is critical. Little is known about the preparation of final year nursing students regarding recognition and response to sepsis. OBJECTIVES: To explore Australian final year nursing student's exposure to and knowledge of sepsis, and their awareness of the importance of early recognition, escalation and management of patients with sepsis. METHODS: An online 17-question survey was developed, validated and then used to evaluate final year nursing students' awareness and knowledge about sepsis. DESIGN: Multi-site, cross-sectional, study. SETTINGS: Data were prospectively collected from final year nursing students from five university (graduate entry and undergraduate) programmes from four Universities in Queensland, Australia. RESULTS: Response rate of 22% (237/1075 eligible students responded). Final year nursing students possessed limited knowledge about sepsis (mean scores = 3.8/9; SD = 1.6), and very limited knowledge of paediatric sepsis (median 1[interquartile range 0-1]). Many participants (54%; 128/237) had heard of sepsis prior to commencing their nursing studies, however only 22% (53/237) reported formal dedicated educational units on sepsis. Sepsis education was delivered primarily through didactic lectures (32%; 77/237) and often as part of courses encompassing acute care (38%; 91/237). Only 6% (14/237) of participants recalled exposure to education dedicated to paediatric sepsis. CONCLUSIONS: The knowledge of final year nursing students in relation to recognising, escalating and managing sepsis was limited. There is an urgent need to design education which adequately and safely prepares nurses for the challenges they face when caring for patients with sepsis, particularly paediatric sepsis. Accrediting bodies should consider mandating inclusion of sepsis education as part of all nursing programmes.


Subject(s)
Education, Nursing, Baccalaureate , Sepsis , Students, Nursing , Adult , Australia , Child , Cross-Sectional Studies , Humans , Queensland , Surveys and Questionnaires , Universities
9.
Sensors (Basel) ; 20(21)2020 Oct 22.
Article in English | MEDLINE | ID: mdl-33105863

ABSTRACT

In this paper, we propose an environment perception framework for autonomous driving using state representation learning (SRL). Unlike existing Q-learning based methods for efficient environment perception and object detection, our proposed method takes the learning loss into account under deterministic as well as stochastic policy gradient. Through a combination of variational autoencoder (VAE), deep deterministic policy gradient (DDPG), and soft actor-critic (SAC), we focus on uninterrupted and reasonably safe autonomous driving without steering off the track for a considerable driving distance. Our proposed technique exhibits learning in autonomous vehicles under complex interactions with the environment, without being explicitly trained on driving datasets. To ensure the effectiveness of the scheme over a sustained period of time, we employ a reward-penalty based system where a negative reward is associated with an unfavourable action and a positive reward is awarded for favourable actions. The results obtained through simulations on DonKey simulator show the effectiveness of our proposed method by examining the variations in policy loss, value loss, reward function, and cumulative reward for 'VAE+DDPG' and 'VAE+SAC' over the learning process.

11.
Crit Care Resusc ; 22(2): 158-165, 2020 Jun.
Article in English | MEDLINE | ID: mdl-32389108

ABSTRACT

OBJECTIVE: Hyperammonaemia contributes to complications in acute liver failure (ALF) and may be treated with continuous renal replacement therapy (CRRT), but current practice is poorly understood. DESIGN: We retrospectively analysed data for baseline characteristics, ammonia concentration, CRRT use, and outcomes in a cohort of Australian and New Zealand patients with ALF. SETTING: All liver transplant ICUs across Australia and New Zealand. PARTICIPANTS: Sixty-two patients with ALF. MAIN OUTCOME MEASURES: Impact of CRRT on hyperammonaemia and patient outcomes. RESULTS: We studied 62 patients with ALF. The median initial (first 24 h) peak ammonia was 132 µmol/L (interquartile range [IQR], 91-172), median creatinine was 165 µmol/L (IQR, 92-263) and median urea was 6.9 mmol/L (IQR, 3.1-12.0). Most patients (43/62, 69%) received CRRT within a median of 6 hours (IQR, 2-12) of ICU admission. At CRRT commencement, three-quarters of such patients did not have Stage 3 acute kidney injury (AKI): ten patients (23%) had no KDIGO creatinine criteria for AKI, 12 (28%) only had Stage 1, and ten patients (23%) had Stage 2 AKI. Compared with non-CRRT patients, those treated with CRRT had higher ammonia concentrations (median, 141 µmol/L [IQR, 102-198] v 91 µmol/L [IQR, 54-115]; P = 0.02), but a nadir Day 1 pH of only 7.25 (standard deviation, 0.16). Prevention of extreme hyperammonaemia (> 140 µmol/L) after Day 1 was achieved in 36 of CRRT-treated patients (84%) and was associated with transplant-free survival (55% v 13%; P = 0.05). CONCLUSION: In Australian and New Zealand patients with ALF, CRRT is typically started early, before Stage 3 AKI or severe acidaemia, and in the presence hyperammonaemia. In these more severely ill patients, CRRT use was associated with prevention of extreme hyperammonaemia, which in turn, was associated with increased transplant-free survival.


Subject(s)
Acute Kidney Injury/therapy , Ammonia/blood , Continuous Renal Replacement Therapy/methods , Hyperammonemia/prevention & control , Liver Failure, Acute/surgery , Australia , Humans , Hyperammonemia/blood , Liver Failure, Acute/blood , Liver Transplantation , New Zealand , Retrospective Studies , Treatment Outcome
12.
J Gastroenterol Hepatol ; 35(5): 846-854, 2020 May.
Article in English | MEDLINE | ID: mdl-31689724

ABSTRACT

BACKGROUND AND AIM: To study the management of coagulation and hematological derangements among severe acute liver failure (ALF) patients in Australia and New Zealand liver transplant intensive care units (ICUs). METHODS: Analysis of key baseline characteristics, etiology, coagulation and hematological tests, use of blood products, thrombotic complications, and clinical outcomes during the first ICU week. RESULTS: We studied 62 ALF patients. The first day median peak international normalized ratio was 5.5 (inter-quartile range [IQR] 3.8-8.7), median longest activated partial thromboplastin time was 62 s (IQR 44-87), and median lowest fibrinogen was 1.1 (IQR 0.8-1.6) g/L. Fibrinogen was only measured in 85% of patients, which was less than other tests (P < 0.0001). Median initial lowest platelet count was 83 (IQR 41-122) × 109 /L. Overall, 58% of patients received fresh frozen plasma, 40% cryoprecipitate, 35% platelets, and 15% prothrombin complex concentrate. Patients with bleeding complications (19%) had more severe overall hypofibrinogenemia and thrombocytopenia. Thrombotic complications were less common (10% of patients), were not associated with consistent patterns of abnormal hemostasis, and were not immediately preceded by clotting factor administration and half occurred only after liver transplantation surgery. CONCLUSION: In ALF patients admitted to dedicated Australia and New Zealand ICUs, fibrinogen was measured less frequently than other coagulation parameters but, together with platelets, appeared more relevant to bleeding risk. Blood products and procoagulant factors were administered to most patients at variable levels of hemostatic derangement, and bleeding complications were more common than thrombotic complications. This epidemiologic information and practice variability provide baseline data for the design and powering of interventional studies.


Subject(s)
Blood Coagulation Disorders/etiology , Blood Coagulation Factors/administration & dosage , Hematologic Agents/administration & dosage , Hemorrhage/etiology , Liver Failure, Acute/etiology , Thrombosis/etiology , Adult , Australia/epidemiology , Blood Coagulation Disorders/blood , Blood Coagulation Disorders/epidemiology , Blood Coagulation Tests , Female , Hemorrhage/blood , Hemorrhage/epidemiology , Hemostasis , Humans , Liver Failure, Acute/blood , Liver Failure, Acute/epidemiology , Male , Middle Aged , New Zealand/epidemiology , Thrombosis/blood , Thrombosis/epidemiology , Young Adult
13.
Crit Care ; 22(1): 211, 2018 09 10.
Article in English | MEDLINE | ID: mdl-30196796

ABSTRACT

BACKGROUND: Despite increasing female enrolment into medical schools, persistent gender gaps exist in the physician workforce. There are limited published data on female representation in the critical care medicine workforce. METHODS: To obtain a global perspective, societies (n = 84; 79,834 members (40,363 physicians, 39,471 non-physicians)) registered with the World Federation of Societies of Intensive and Critical Care Medicine were surveyed. Longitudinal data on female trainee and specialist positions between 2006-2017 were obtained from Australia and New Zealand. Data regarding leadership and academic faculty representation were also collected from national training bodies and other organisations of critical care medicine. RESULTS: Of the 84 societies, 23 had a registered membership of greater than 500 members. Responses were received from 27 societies (n = 55,996), mainly high-income countries, covering 70.1% of the membership. Amongst the physician workforce, the gender distribution was available from six (22%) participating societies-mean proportion of females 37 ± 11% (range 26-50%). Longitudinal data from Australia and New Zealand between 2006 and 2017 demonstrate rising proportions of female trainees and specialists. Female trainee and specialist numbers increased from 26 to 37% and from 13 to 22% respectively. Globally, female representation in leadership positions was presidencies of critical care organisations (0-41%), representation on critical care medicine boards and councils (8-50%) and faculty representation at symposia (7-34%). Significant gaps in knowledge exist: data from low and middle-income countries, the age distribution and the time taken to enter and complete training. CONCLUSIONS: Despite limited information globally, available data suggest that females are under-represented in training programmes, specialist positions, academic faculty and leadership roles in intensive care. There are significant gaps in data on female participation in the critical care workforce. Further data from intensive care organisations worldwide are required to understand the demographics, challenges and barriers to their professional progress.


Subject(s)
Health Workforce/statistics & numerical data , Intensive Care Units/statistics & numerical data , Physicians, Women/statistics & numerical data , Adult , Australia , Faculty, Medical/statistics & numerical data , Female , Humans , Intensive Care Units/organization & administration , Internationality , Leadership , Longitudinal Studies , New Zealand , Students, Medical/statistics & numerical data , Surveys and Questionnaires
14.
BMJ Open ; 7(6): e016847, 2017 06 30.
Article in English | MEDLINE | ID: mdl-28667229

ABSTRACT

INTRODUCTION: Sepsis is associated with a dysregulated host response to infection and impaired endogenous corticosteroid metabolism. As such, therapeutic use of exogenous corticosteroids is a promising adjunctive intervention. Despite a large number of trials examining this research question, uncertainty persists regarding the effect of corticosteroids on survival in sepsis. Several large randomised controlled trials have been published recently prompting a re-evaluation of the available literature. METHODS AND ANALYSIS: A rigorous and reproducible search and screening process from a Cochrane review on the same topic was comprehensive to October 2014. We will search MEDLINE, EMBASE, LILACS, the Cochrane trial registry and clinicaltrials.gov for eligible randomised controlled trials investigating the use of corticosteroids in patients with sepsis from September 2014. Outcomes have been chosen by a semi-independent guideline panel, created in the context of a parallel BMJ Rapid Recommendation on the topic. This panel includes clinicians, content experts, methodologists and patient representatives, who will help identify patient-important outcomes that are critical for deciding whether to use or not use corticosteroids in sepsis. Two reviewers will independently screen and identify eligible studies; a third reviewer will resolve any disagreements. We will use RevMan to pool effect estimates from included studies for each outcome using a random-effect model. We will present the results as relative risk with 95% CI for dichotomous outcomes and as mean difference or standardised mean difference for continuous outcomes with 95% CI. We will assess the certainty of evidence at the outcome level using the Grading of Recommendations, Assessment, Development and Evaluation approach. We will conduct a priori subgroup analyses, which have been chosen by the parallel BMJ Rapid Recommendation panel. ETHICS AND DISSEMINATION: The aim of this systematic review is to summarise the updated evidence on the efficacy and safety of corticosteroids in patients with sepsis. TRIAL REGISTRATION NUMBER: CRD42017058537.


Subject(s)
Adrenal Cortex Hormones/therapeutic use , Sepsis/drug therapy , Humans , Length of Stay/statistics & numerical data , Organ Dysfunction Scores , Quality of Life , Randomized Controlled Trials as Topic , Research Design , Sepsis/mortality , Systematic Reviews as Topic , Treatment Outcome
16.
Intensive Care Med ; 43(4): 496-508, 2017 Apr.
Article in English | MEDLINE | ID: mdl-28130686

ABSTRACT

Because of its high incidence and clinical complexity, sepsis is a major challenge to clinicians and researchers and a global burden to healthcare systems and society. Despite recent progress, short- and long-term morbidity, mortality and costs remain high in both developed and developing countries. Thus, further improvements in supportive interventions and organisation of care are likely to have a substantial impact upon global health. In this narrative review, invited experts describe the challenges and progress to be made in sepsis research and care in the near future. We focus on supportive care (pulmonary, endocrine, renal, and nutritional support, mediator modulation and precision medicine), organisational themes (guidelines, outcome measures and stakeholder involvement) and clinical research as key areas to improving the care and outcomes of patients with sepsis.


Subject(s)
Biomedical Research/organization & administration , Cost of Illness , Outcome and Process Assessment, Health Care , Sepsis/therapy , Global Burden of Disease , Guidelines as Topic , Health Services Administration , Humans , Incidence , Precision Medicine , Sepsis/mortality
17.
Blood Adv ; 1(16): 1274-1286, 2017 Jul 11.
Article in English | MEDLINE | ID: mdl-29296769

ABSTRACT

Improved understanding of the molecular mechanisms underlying dysregulated inflammatory responses in severe infection and septic shock is urgently needed to improve patient management and identify new therapeutic opportunities. The WNT signaling pathway has been implicated as a novel constituent of the immune response to infection, but its contribution to the host response in septic shock is unknown. Although individual WNT proteins have been ascribed pro- or anti-inflammatory functions, their concerted contributions to inflammation in vivo remain to be clearly defined. Here we report differential expression of multiple WNT ligands in whole blood of patients with septic shock and reveal significant correlations with inflammatory cytokines. Systemic challenge of mice with lipopolysaccharide (LPS) similarly elicited differential expression of multiple WNT ligands with correlations between WNT and cytokine expression that partially overlap with the findings in human blood. Molecular regulators of WNT expression during microbial encounter in vivo are largely unexplored. Analyses in gene-deficient mice revealed differential contributions of Toll-like receptor signaling adaptors, a positive role for tumor necrosis factor, but a negative regulatory role for interleukin (IL)-12/23p40 in the LPS-induced expression of Wnt5b, Wnt10a, Wnt10b, and Wnt11. Pharmacologic targeting of bottlenecks of the WNT network, WNT acylation and ß-catenin activity, diminished IL-6, tumor necrosis factor, and IL-12/23p40 in serum of LPS-challenged mice and cultured splenocytes, whereas IL-10 production remained largely unaffected. Taken together, our data support the conclusion that the concerted action of WNT proteins during severe infection and septic shock promotes inflammation, and that this is, at least in part, mediated by WNT/ß-catenin signaling.

18.
Heart Lung Circ ; 26(4): e22-e25, 2017 Apr.
Article in English | MEDLINE | ID: mdl-27743856

ABSTRACT

Intracardiac leiomyomatosis is a rare complication that occurs when a uterine leiomyoma (fibroid) undergoes vascular invasion and propagates within the inferior vena cava to reach the right atrium. This article describes a case of intracardiac leiomyomatosis in a middle-aged woman, exploring the presentation, diagnosis and surgical management of this condition. In this case the presenting complaints were syncope and atrial fibrillation, illustrating the importance of performing a transthoracic echocardiogram in patients presenting with their first episode of atrial fibrillation. Clinicians should consider intracardiac leiomyomatosis when evaluating women with right heart masses, especially those with a history of uterine leiomyomas.


Subject(s)
Atrial Fibrillation , Echocardiography , Heart Neoplasms , Leiomyomatosis , Syncope , Uterine Neoplasms , Atrial Fibrillation/etiology , Atrial Fibrillation/physiopathology , Atrial Fibrillation/surgery , Female , Heart Neoplasms/physiopathology , Heart Neoplasms/secondary , Heart Neoplasms/surgery , Humans , Leiomyomatosis/physiopathology , Leiomyomatosis/surgery , Middle Aged , Syncope/etiology , Syncope/physiopathology , Syncope/surgery , Uterine Neoplasms/physiopathology , Uterine Neoplasms/surgery
20.
Crit Care Resusc ; 18(4): 230-234, 2016 Dec.
Article in English | MEDLINE | ID: mdl-27903203

ABSTRACT

BACKGROUND: Anecdotal reports about bullying behaviour in intensive care emerged during College of Intensive Care Medicine (CICM) hospital accreditation visits. Bullying, discrimination and sexual harassment (BDSH) in the medical profession, particularly in surgery, were widely reported in the media recently. This prompted the College to formally survey its Fellows and trainees to identify the prevalence of these behaviours in the intensive care workplace. METHODS: An online survey of all trainees (n = 951) and Fellows (n = 970) of the CICM. RESULTS: The survey response rate was 51% (Fellows, 60%; trainees, 41%). The overall prevalences of bullying, discrimination and sexual harassment were 32%, 12% and 3%, respectively. The proportions of Fellows and trainees who reported being bullied and discriminated against were similar across all age groups. Women reported a greater prevalence of sexual harassment (odds ratio [OR], 2.97 [95% CI, 1.35-6.51]; P = 0.006) and discrimination (OR, 2.10 [95% CI, 1.39-3.17]; P = 0.0004) than men. Respondents who obtained their primary medical qualification in Asia or Africa appeared to have been at increased risk of discrimination (OR, 1.88 [95% CI, 1.15-3.05]; P = 0.03). Respondents who obtained their degree in Australia, New Zealand or Hong Kong may have been at increased risk of being bullied. In all three domains of unprofessional behaviour, the perpetrators were predominantly consultants (70% overall), and the highest proportion of these was ICU consultants. CONCLUSIONS: The occurrence of BDSH appears to be common in the intensive care environment in Australia and New Zealand.


Subject(s)
Bullying/statistics & numerical data , Fellowships and Scholarships , Sexual Harassment/statistics & numerical data , Social Discrimination/statistics & numerical data , Students, Medical , Adult , Aged , Australia , Critical Care , Female , Humans , Male , Middle Aged , New Zealand , Prevalence , Schools, Medical , Surveys and Questionnaires
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