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In a study of fluid resuscitation, patients received 6% hydroxyethyl starch (HES; 130/0.4) or saline until ICU discharge or death or for 90 days. There was no significant difference in 90-day mortality, although more patients in the HES group received renal-replacement therapy. The administration of intravenous fluids to increase intravascular volume is a frequent intervention in the intensive care unit (ICU), but the choice of resuscitation fluid remains controversial. 1 , 2 Globally, 0.9% sodium chloride (saline) is the most commonly used fluid, although colloids are administered as often as crystalloids, and hydroxyethyl starch (HES) is the most frequently used colloid. 3 Several studies have questioned the safety of HES in critically ill patients, with particular concern that its use increases the risk of acute kidney injury. 4 , 5 Most concern has focused on the use of concentrated HES solutions (10%) with a molecular weight of . . .

In 2007, the Saline versus Albumin Fluid Evaluation-Translation of Research Into Practice Study (SAFE-TRIPS) reported that 0.9% sodium chloride (saline) and hydroxyethyl starch (HES) were the most commonly used resuscitation fluids in intensive care unit (ICU) patients. Evidence has emerged since 2007 that these fluids are associated with adverse patient-centred outcomes. Based on the published evidence since 2007, we sought to determine the current type of fluid resuscitation used in clinical practice and the predictors of fluid choice and determine whether these have changed between 2007 and 2014. In 2014, an international, cross-sectional study was conducted (Fluid-TRIPS) to document current patterns of intravenous resuscitation fluid use and determine factors associated with fluid choice. We examined univariate and multivariate associations between patients and prescriber characteristics, geographical region and fluid type. Additionally, we report secular trends of resuscitation fluid use in a cohort of ICUs that participated in both the 2007 and 2014 studies. Regression analysis were conducted to determine changes in the administration of crystalloid or colloid between 2007 and 2014. In 2014, a total of 426 ICUs in 27 countries participated. Over the 24 hour study day, 1456/6707 (21.7%) patients received resuscitation fluid during 2716 resuscitation episodes. Crystalloids were administered to 1227/1456 (84.3%) patients during 2208/2716 (81.3%) episodes and colloids to 394/1456 (27.1%) patients during 581/2716 (21.4%) episodes. In multivariate analyses, practice significantly varied between geographical regions. Additionally, patients with a traumatic brain injury were less likely to receive colloid when compared to patients with no trauma (adjusted OR 0.24; 95% CI 0.1 to 0.62; p = 0.003). Patients in the ICU for one or more days where more likely to receive colloid compared to patients in the ICU on their admission date (adjusted OR 1.75; 95% CI 1.27 to 2.41; p = <0.001). For secular trends in fluid resuscitation, 84 ICUs in 17 countries contributed data. In 2007, 527/1663 (31.7%) patients received fluid resuscitation during 1167 episodes compared to 491/1763 (27.9%) patients during 960 episodes in 2014. The use of crystalloids increased from 498/1167 (42.7%) in 2007 to 694/960 (72.3%) in 2014 (odds ratio (OR) 3.75, 95% confidence interval (CI) 2.95 to 4.77; p = <0.001), primarily due to a significant increase in the use of buffered salt solutions. The use of colloids decreased from 724/1167 (62.0%) in 2007 to 297/960 (30.9%) in 2014 (OR 0.29, 95% CI 0.19 to 0.43; p = <0.001), primarily due to a decrease in the use of HES, but an overall increase in the use of albumin. Clinical practices of intravenous fluid resuscitation have changed between 2007 and 2014. Geographical location remains a strong predictor of the type of fluid administered for fluid resuscitation. Overall, there is a preferential use of crystalloids, specifically buffered salt solutions, over colloids. There is now an imperative to conduct a trial determining the safety and efficacy of these fluids on patient-centred outcomes. Clinicaltrials.gov: Fluid-Translation of research into practice study (Fluid-TRIPS) NCT02002013.

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.

IntroductionWith the announcement of the health technology assessment (HTA) review in Australia, a HTA Summit was organized by ISPOR Australia in November 2022. The aim of the Summit was to provide a forum for industry, academia, and patients to share ideas and find common ground with respect to HTA policy, processes, and methods. Topics were determined by a Steering Committee and included: managing uncertainty; patient engagement; second order effects; genetics, genomics and precision medicines; conditional listing; and real-world evidence. Presentations on each topic were conducted by industry and non-industry experts. Breakout sessions led by facilitators were also held for each topic with members of the audience.MethodsDiscussions were recorded during the event and a thematic analysis was performed.ResultsThe following themes were identified from the event.• There was a strong sentiment that participants enjoyed the opportunity to discuss ideas and work toward solutions.• There was a consistent theme that many of the issues arising in HTA were due to a lack of communication between sponsors, evaluators, patients, and decision makers.• It was noted that HTA encompasses several technical terms that have different meanings among various stakeholders.• There was a clear consensus that patients should be involved in HTA earlier and throughout the process.• HTA reform can help drive better access to real-world evidence.• To improve the efficiency of the process, uncertainty could be reframed as risk management, which incorporates the effect of uncertainty in the funding decision.• HTA includes policies, processes, and methods and is used as a tool by decision makers to make informed funding decisions. It was noted on several occasions during the Summit that funding decisions have a political element that should be separated from the HTA process.ConclusionsIt is possible to achieve better collaboration between industry, academic, and patient groups with respect to HTA reform. To promote more collaborative work a consistent conflict of interest definition would be helpful.

Strategies to prevent pyrexia in patients with acute neurological injury may reduce secondary neuronal damage. The aim of this study was to determine the safety and efficacy of the routine administration of 6 grams/day of intravenous paracetamol in reducing body temperature following severe traumatic brain injury, compared to placebo. A multicentre, randomised, blind, placebo-controlled clinical trial in adult patients with traumatic brain injury (TBI). Patients were randomised to receive an intravenous infusion of either 1g of paracetamol or 0.9% sodium chloride (saline) every 4 hours for 72 hours. The primary outcome was the mean difference in core temperature during the study intervention period. Forty-one patients were included in this study: 21 were allocated to paracetamol and 20 to saline. The median (interquartile range) number of doses of study drug was 18 (17-18) in the paracetamol group and 18 (16-18) in the saline group (P = 0.85). From randomisation until 4 hours after the last dose of study treatment, there were 2798 temperature measurements (median 73 [67-76] per patient). The mean ± standard deviation temperature was 37.4±0.5°C in the paracetamol group and 37.7±0.4°C in the saline group (absolute difference -0.3°C; 95% confidence interval -0.6 to 0.0; P = 0.09). There were no significant differences in the use of physical cooling, or episodes of hypotension or hepatic abnormalities, between the two groups. The routine administration of 6g/day of intravenous paracetamol did not significantly reduce core body temperature in patients with TBI. Australian New Zealand Clinical Trials Registry ACTRN12609000444280.

Background Dietary sodium reduction is recommended to reduce the burden of cardiovascular disease. In Vietnam food products including salt, fish sauce and bot canh contribute to ~ 70% of dietary sodium intake. Reduced sodium versions of these products can be produced by replacing some of the sodium chloride with potassium chloride. We aimed to assess the cost-effectiveness of three alternative approaches to introducing reduced sodium products onto the market with a view to lowering population sodium intake in Vietnam. Methods The three salt substitution strategies included voluntary, subsidised and regulatory approaches targeting salt, fish sauce and bot canh products. Costs were modelled using the WHO-CHOICE methodology. A Markov cohort model was developed to evaluate the cost-effectiveness of each strategy versus no intervention from the government perspective. The model linked each intervention strategy to assumed changes in levels of sodium intake and then to systolic blood pressure. Changes in SBP were linked to a probability of ischaemic heart disease or stroke. The model followed people over their lifetime to assess average costs and quality adjusted life years (QALYs) gained for each strategy. Results The voluntary salt substitution strategy was assumed to require no investment by government. Following ramp up (years 6+), the average annual costs for the subsidised and regulatory strategies were 21,808,968,902 ₫ (US$ 977,354) and 12,949,953,247 ₫ (US$ 580,410) respectively. Relative to no intervention, all three salt substitution strategies were found to be cost-effective. Cost savings were driven by reductions in strokes (32,595; 768,384; 2,366,480) and ischaemic heart disease (IHD) events (22,830; 537,157; 1,648,590) for the voluntary, subsidised & regulatory strategies, respectively. The voluntary strategy was least cost-effective (− 3445 ₫ US$ -0.15; 0.009 QALYs gained) followed by the subsidised strategy (− 43,189 ₫ US$ -1.86; 0.022 QALYs gained) and the regulatory strategy delivered the highest cost savings and health gains (− 243,530 ₫ US$ -10.49; 0.074 QALYs gained). Conclusion This research shows that all three modelled salt substitution strategies would be good value for money relative to no intervention in Vietnam. The subsidised alternative would require the highest level of government investment; however the implementation costs will be exceeded by healthcare savings assuming a reasonable time horizon is considered.

Introduction This analysis evaluated the cost-effectiveness of newborn screening (NBS) for spinal muscular atrophy (SMA) from the perspective of Australian state hospital payers. Methods A cost–utility analysis consisting of a decision tree and Markov cohort designed to calculate the difference in costs and health outcomes between two scenarios: (1) disease-modifying treatment (DMT) for SMA after diagnosis through NBS, and (2) DMT for SMA after diagnosis as symptoms appear. A population of 295,906 newborns was modeled, based on the total number of live births in Australia in 2023. Inputs included screening parameters, epidemiology inputs, SMA natural history data and DMT parameters (nusinersen and onasemnogene abeparvovec), costs, and health-related quality of life parameters. Assumed participation in NBS was 100%. A one-way sensitivity analysis and probabilistic sensitivity analysis were conducted to examine the impact of parameter uncertainty. Results There were 30 patients identified with SMA, of whom 25 patients would be eligible for presymptomatic treatment. NBS for SMA was dominant compared with no NBS for SMA. On a population level, NBS demonstrated a lifetime gain of 267 quality-adjusted life years (QALY) and incremental costs of −AUD$3,983,263 (i.e., cost savings). Every dollar invested in NBS would save hospitals $3.69. Deterministic and probabilistic sensitivity analyses demonstrated the robustness of the base-case results. Conclusion NBS for SMA was dominant compared with no NBS for SMA in Australia from a state and territory payer perspective. Universal implementation of NBS for SMA would support access equity, as well as early diagnosis and treatment in infants with SMA, potentially leading to improved outcomes.

Background In order to assist health service planning, understanding factors that influence higher trauma treatment costs is essential. The majority of trauma costing research reports the cost of trauma from the perspective of the receiving hospital. There has been no comprehensive synthesis and little assessment of the drivers of cost variation, such as country, trauma, subgroups and methods. The aim of this review is to provide a synthesis of research reporting the trauma treatment costs and factors associated with higher treatment costs in high income countries. Methods A systematic search for articles relating to the cost of acute trauma care was performed and included studies reporting injury severity scores (ISS), per patient cost/charge estimates; and costing methods. Cost and charge values were indexed to 2011 cost equivalents and converted to US dollars using purchasing power parities. Results A total of twenty-seven studies were reviewed. Eighty-one percent of these studies were conducted in high income countries including USA, Australia, Europe and UK. Studies either reported a cost (74.1%) or charge estimate (25.9%) for the acute treatment of trauma. Across studies, the median per patient cost of acute trauma treatment was $22,448 (IQR: $11,819-$33,701). However, there was variability in costing methods used with 18% of studies providing comprehensive cost methods. Sixty-three percent of studies reported cost or charge items incorporated in their cost analysis and 52% reported items excluded in their analysis. In all publications reviewed, predictors of cost included Injury Severity Score (ISS), surgical intervention, hospital and intensive care, length of stay, polytrauma and age. Conclusion The acute treatment cost of trauma is higher than other disease groups. Research has been largely conducted in high income countries and variability exists in reporting costing methods as well as the actual costs. Patient populations studied and the cost methods employed are the primary drivers for the treatment costs. Targeted research into the costs of trauma care is required to facilitate informed health service planning.