The Alfred Hospital, also known as The Alfred or Alfred Hospital, is a leading tertiary teaching hospital in Melbourne, Victoria. It is the second oldest hospital in Victoria, and the oldest Melbourne hospital still operating on its original site. The Alfred is one of two major adult trauma centres in Victoria, and houses the largest intensive care unit in Australia. In 2021 it was ranked as one of the world's best hospitals. It is located at the corner of Commercial and Punt Roads, Prahran, opposite Fawkner Park.The Alfred Hospital is managed by Alfred Health along with Caulfield Hospital and Sandringham Hospital.
Introduction Ocrelizumab (OCR), a CD20+ B-cell depleting monoclonal antibody, is a highly effective therapy for Multiple Sclerosis (MS). However, safety concerns may lead to treatment discontinuation, raising questions about the clinical consequences of such decisions.Materials and Methods This propensity score-matched study utilized data from the MSBase registry to compare outcomes between patients discontinuing OCR due to safety concerns ("Switchers") and those continuing treatment ("Continuers"). Matching was performed using inverse probability of treatment weighting (IPTW) to balance treatment duration and baseline characteristics. Primary outcomes included annualized relapse rate (ARR), time to first relapse, 24-48 weeks confirmed disability worsening (CDW), and progression independent of relapse activity (PIRA).Results From an initial cohort of 310 Switchers and 1,315 Continuers, 66 patients who experienced at least one safety event and switched from OCR were matched with 66 Continuers. PS-IPTW analyses revealed higher ARR in Switchers (0.08, 95% CI: 0.05-0.14) versus Continuers (0.038, 95% CI: 0.02-0.07; p=0.040). Time to first relapse showed no significant difference (HR=2.23, 95% CI: 0.68-7.28; p=0.183). Trends toward increased CDW24 weeks risk (PS-IPTW HR=2.11, 95% CI: 0.93-4.75; p=0.073), while no significant difference was found at 48 weeks (HR=1.81, 95% CI: 0.83-3.30; p=0.201). PIRA risk showed a trend toward an increase in Switchers (HR=2.45, 95% CI: 0.95-6.29; p=0.063).Discussion In this propensity-score-matched analysis, OCR discontinuation due to safety concerns was associated with increased relapse activity and trends toward greater disability progression. These findings highlight the importance of maintaining therapeutic intensity and systematic monitoring during treatment transitions to mitigate safety risksConclusion Further research is needed to develop strategies for effectively managing adverse events to optimize patient outcomes.
QuestionIn patients at increased risk of pulmonary complications undergoing cardiac surgery, does prophylactic high-flow nasal oxygen therapy (HFNOT) initiated at the time of extubation have important clinical benefits vs the use of standard oxygen therapy (SOT)?FindingsIn this randomized clinical trial that included 1280 adults, HFNOT did not improve clinical outcomes compared with SOT.MeaningThese findings do not support the routine implementation of prophylactic HFNOT for noninvasive respiratory support following cardiac surgery. This randomized clinical trial investigates the use of high-flow nasal oxygen therapy in patients at high risk of pulmonary complications following nonemergent cardiac surgery and assesses the clinical benefits of this technique compared with standard oxygen therapy. ImportanceHigh-flow nasal oxygen therapy (HFNOT) is used for noninvasive respiratory support following cardiac surgery despite uncertainty about its clinical effectiveness or associated costs.ObjectiveTo determine whether prophylactic HFNOT in patients at increased risk of respiratory complications following cardiac surgery has clinical benefits compared with standard oxygen therapy (SOT).Design, Setting, and ParticipantsThis adaptive, parallel group, randomized clinical trial collected and analyzed data from 17 cardiac surgery centers in 3 countries between October 7, 2020, and June 19, 2024. Eligible participants included adults undergoing nonemergent cardiac surgery with any of the following risk factors for pulmonary complications: chronic obstructive pulmonary disease, asthma, lower respiratory tract infection in the last 4 weeks, a body mass index of 35 or greater, or currently or recently smoking for longer than 10 pack-years. Outcome assessors were blinded. A preplanned sample size re-estimation was conducted after 300 participants completed the 90-day follow-up.InterventionParticipants were randomized at a 1:1 ratio with concealed allocation to HFNOT or SOT administered for at least 16 hours immediately after postoperative extubation.Main Outcomes and MeasuresThe primary effectiveness outcome was days alive and at home (DAH) without increased support compared with baseline in the first 90 days (DAH90). Any day of increased support, including at home, would provide a value of 0 for that day. Secondary outcomes included DAH90 without considering the additional support component.ResultsA total of 1280 patients were recruited (mean [SD] age, 62.9 [10.5] years; 892 [69.7%] men; 640 in each group), of whom 1224 (95.6%) had complete DAH90 data. The primary outcome of median DAH90 was 0 (IQR, 0-79) for the HFNOT group and 0 (IQR, 0-87) for the SOT group (median difference, 0 [95% CI, 0-0]; P = .75). Secondary clinical outcomes, including DAH90 without considering whether additional support was required, were similar between groups.Conclusions and RelevanceIn this randomized clinical trial of HFNOT in patients at increased risk of postoperative pulmonary complications after nonemergent cardiac surgery, HFNOT did not improve DAH90 without increased support. These findings do not support the implementation of routine prophylactic HFNOT after cardiac surgery.Trial Registrationisrctn.org Identifier: ISRCTN14092678
Patients with traumatic shock represent a high-risk subgroup within major trauma populations, yet the operative burden and resuscitation resource utilisation associated with urgent surgical and endovascular intervention in trauma systems managing predominantly blunt injury remain incompletely described. To describe the epidemiology, resuscitation resource utilisation, and operative burden of patients presenting with traumatic shock who require urgent surgical or endovascular intervention. We conducted a retrospective observational study at an Australian level 1 trauma centre using prospectively maintained trauma registries. Adult major trauma patients (≥ 16 years, Injury Severity Score ≥ 13) meeting institutional shocked trauma activation criteria between December 2022 and December 2024 were included. Resource utilisation, blood product transfusion, operative and endovascular interventions, procedural timing, and critical care outcomes were described. Comparisons were performed between shocked patients requiring urgent surgical or endovascular intervention and those managed without urgent procedures. Of 3667 major trauma patients, 324 (8.8
BACKGROUND:Penetrating traumatic brain injury (pTBI) affects civilian and military populations resulting in significant morbidity, mortality, and health care costs. No up-to-date and evidence-based guidelines exist to assist modern medical and surgical management of these complex injuries. METHODS:A preliminary literature search informed a need for updated guidelines. Methodologists experienced in TBI guidelines supported 2 co-chairs, a diverse steering committee and three expert working groups. Over half of our panelists were active service military or military veterans and they addressed twenty-six Key Questions (KQs). We searched Ovid MEDLINE®, EMBASE, and Cochrane CENTRAL from inception to August 31, 2022, reference lists, and clinical trial registries. Penetrating, perforating and tangential penetrating brain injuries were included. Predefined criteria were used to identify studies; pre-specified methods were used to assess study quality and strength of evidence for key outcomes. Effects were analyzed qualitatively and quantitatively where appropriate. RESULTS:125 studies provided evidence and another 80 studies provided contextual data for these guidelines. In general there was a paucity of literature and most of the identified evidence was judged to be high risk of bias due to study design. We did not identify any studies meeting inclusion criteria for 12 KQs. The highest quality evidence, rated moderate in strength, was identified for four KQs that covered: cerebral angiography vs computed tomography angiography, the relationship between bihemispheric injury in adult pTBI and mortality, the ability of the Surviving Penetrating Injury to the Brain (SPIN) score to predict mortality, and the relationship between infection and cerebrospinal fluid fistula. Evidence for most KQs came from case series. CONCLUSIONS:The development of up-to-date evidence and consensus based clinical care guidelines and algorithms for pTBI provide guidance to care providers in the prehospital and emergency medicine, surgical and intensive care settings. Few moderately strong conclusions on the benefit of specific management strategies for penetrating brain injury could be made. Detailed reporting of patient outcomes in future studies could advance the field by providing greater evidence for specific treatments by patient population, mechanism of injury, severity of injury, and specific interventions employed.
The Antarctic Circumpolar Current (ACC) plays a central role in regulating the global ocean circulation, climate and Antarctic Ice Sheet dynamics. Yet the spatiotemporal variability of the ACC during the Pleistocene remains poorly constrained. Here we reconstruct ACC flow-speed variation using a meridional transect of sediment cores from the Indian sector of the Southern Ocean. Our results reveal zonally asymmetric changes in ACC strength across the Southern Ocean on orbital timescales over the past one million years; the ACC intensified in the South Indian Ocean but weakened in the South Pacific during glacial and low-obliquity periods, with the opposite pattern during interglacial and high-obliquity periods. These anti-phased changes probably reflect an integrated response to bathymetric constraints, shifts in the Southern Hemisphere westerlies, sea-ice extent, buoyancy forcing and current confluence. Such zonally asymmetric and anti-phased ACC dynamics persisted during warmer-than-present intervals of the Pleistocene, offering a potential analogue for future anthropogenic warming-albeit under fundamentally different boundary conditions.
