Continuous vs Intermittent ß-Lactam Antibiotic Infusions in Critically Ill Patients With Sepsis: The BLING III Randomized Clinical Trial.

Importance: Whether ß-lactam antibiotics administered by continuous compared with intermittent infusion reduces the risk of death in patients with sepsis is uncertain. Objective: To evaluate whether continuous vs intermittent infusion of a ß-lactam antibiotic (piperacillin-tazobactam or meropenem) results in decreased all-cause mortality at 90 days in critically ill patients with sepsis. Design, Setting, and Participants: An international, open-label, randomized clinical trial conducted in 104 intensive care units (ICUs) in Australia, Belgium, France, Malaysia, New Zealand, Sweden, and the United Kingdom. Recruitment occurred from March 26, 2018, to January 11, 2023, with follow-up completed on April 12, 2023. Participants were critically ill adults (≥18 years) treated with piperacillin-tazobactam or meropenem for sepsis. Intervention: Eligible patients were randomized to receive an equivalent 24-hour dose of a ß-lactam antibiotic by either continuous (n = 3498) or intermittent (n = 3533) infusion for a clinician-determined duration of treatment or until ICU discharge, whichever occurred first. Main Outcomes and Measures: The primary outcome was all-cause mortality within 90 days after randomization. Secondary outcomes were clinical cure up to 14 days after randomization; new acquisition, colonization, or infection with a multiresistant organism or Clostridioides difficile infection up to 14 days after randomization; ICU mortality; and in-hospital mortality. Results: Among 7202 randomized participants, 7031 (mean [SD] age, 59 [16] years; 2423 women [35%]) met consent requirements for inclusion in the primary analysis (97.6%). Within 90 days, 864 of 3474 patients (24.9%) assigned to receive continuous infusion had died compared with 939 of 3507 (26.8%) assigned intermittent infusion (absolute difference, -1.9% [95% CI, -4.9% to 1.1%]; odds ratio, 0.91 [95% CI, 0.81 to 1.01]; P = .08). Clinical cure was higher in the continuous vs intermittent infusion group (1930/3467 [55.7%] and 1744/3491 [50.0%], respectively; absolute difference, 5.7% [95% CI, 2.4% to 9.1%]). Other secondary outcomes were not statistically different. Conclusions and Relevance: The observed difference in 90-day mortality between continuous vs intermittent infusions of ß-lactam antibiotics did not meet statistical significance in the primary analysis. However, the confidence interval around the effect estimate includes the possibility of both no important effect and a clinically important benefit in the use of continuous infusions in this group of patients. Trial Registration: ClinicalTrials.gov Identifier: NCT03213990.

Levodopa-based device-aided therapies for the treatment of advanced Parkinson's disease: a social return on investment analysis.

Introduction: Parkinson's disease (PD) is an incurable, progressive, neurodegenerative disorder. As PD advances and symptoms progress, patients become increasingly dependent on family and carers. Traditional cost-effectiveness analyses (CEA) only consider patient and payer-related outcomes, failing to acknowledge impacts on families, carers, and broader society. This novel Social Return on Investment (SROI) analysis aimed to evaluate the broader impact created by improving access to levodopa (LD) device-aided therapies (DATs) for people living with advanced PD (aPD) in Australia. Methods: A forecast SROI analysis over a three-year time horizon was conducted. People living with aPD and their families were recruited for qualitative interviews or a quantitative survey. Secondary research and clinical trial data was used to supplement the primary research. Outcomes were valued and assessed in a SROI value map in Microsoft Excel™. Financial proxies were assigned to each final outcome based on willingness-to-pay, economic valuation, and replacement value. Treatment cost inputs were sourced from Pharmaceutical Benefits Schedule (PBS) and Medicare Benefits Scheme (MBS) published prices. Results: Twenty-four interviews were conducted, and 55 survey responses were received. For every $1 invested in access to LD-based DATs in Australia, an estimated $1.79 of social value is created. Over 3 years, it was estimated $277.16 million will be invested and $406.77 million of social return will be created. This value is shared between people living with aPD (27%), their partners (22%), children (36%), and the Australian Government (15%). Most of the value created is social and emotional in nature, including reduced worry, increased connection to family and friends, and increased hope for the future. Discussion: Investment in LD-based DATs is expected to generate a positive social return. Over 50% of the value is created for the partners and children of people living with aPD. This value would not be captured in traditional CEA. The SROI methodology highlights the importance of investing in aPD treatment, capturing the social value created by improved access to LD-based DATs.

Costs of Australian intensive care: A systematic review.

Objective: Intensive care unit (ICU) cost estimates are critical to achieving healthcare system efficiency and sustainability. We aimed to review the published literature describing ICU costs in Australia. Design: A systematic review was conducted to identify studies that estimated the cost of ICU care in Australia. Studies conducted in specific patient cohorts or on specific treatments were excluded. Data sources: Relevant studies were sourced from a previously published review (1970-2016), a systematic search of MEDLINE and EMBASE (2016-5 May 2023), and reference checking. Review methods: A tool was developed to assess study quality and risk of bias (maximum score 57/57). Total and component costs were tabulated and indexed to 2022 Australian Dollars. Costing methodologies and study quality assessments were summarised. Results: Six costing studies met the inclusion criteria. Study quality scores were low (15/41 to 35/47). Most studies were conducted only in tertiary metropolitan public ICUs; sample sizes ranged from 100 to 10,204 patients. One study used data collected within the past 10 years. Mean daily ICU costs ranged from $966 to $5381 and mean total ICU admission costs $4888 to $14,606. Three studies used a top-down costing approach, deriving cost estimates from budget reports. The other three studies used both bottom-up and top-down costing approaches. Bottom-up approaches collected individual patient resource use. Conclusions: Available ICU cost estimates are largely outdated and lack granular data. Future research is needed to estimate ICU costs that better reflect current practice and patient complexity and to determine the best methods for generating these estimates.

How environmental impact is considered in economic evaluations of critical care: a scoping review.

PURPOSE: Health care is a major contributor to climate change, and critical care is one of the sector's highest carbon emitters. Health economic evaluations form an important component of critical care and may be useful in identifying economically efficient and environmentally sustainable strategies. The purpose of this scoping review was to synthesise available literature on whether and how environmental impact is considered in health economic evaluations of critical care. METHODS: A robust scoping review methodology was used to identify studies reporting on environmental impact in health economic evaluations of critical care. We searched six academic databases to locate health economic evaluations, costing studies and life cycle assessments of critical care from 1993 to present. RESULTS: Four studies met the review's inclusion criteria. Of the 278 health economic evaluations of critical care identified, none incorporated environmental impact into their assessments. Most included studies (n = 3/4) were life cycle assessments, and the remaining study was a prospective observational study. Life cycle assessments used a combination of process-based data collection and modelling to incorporate environmental impact into their economic assessments. CONCLUSIONS: Health economic evaluations of critical care have not yet incorporated environmental impact into their assessments, and few life cycle assessments exist that are specific to critical care therapies and treatments. Guidelines and standardisation regarding environmental data collection and reporting in health care are needed to support further research in the field. In the meantime, those planning health economic evaluations should include a process-based life cycle assessment to establish key environmental impacts specific to critical care.

Cost-Effectiveness of Extracorporeal Photopheresis in Patients With Chronic Graft-vs-Host Disease.

Background: The mainstay first-line therapy for chronic graft-vs-host disease (cGVHD) is corticosteroids; however, for steroid-refractory patients, there is a distinct lack of cost-effective or efficacious treatment. The aim of this study was to assess the cost-effectiveness of extracorporeal photopheresis (ECP) compared with standard-of-care therapies for the treatment of cGVHD in Australia. The study formed part of an application to the Australian Government to reimburse ECP for these patients. Methods: A cost-utility analysis was conducted comparing ECP to standard of care, which modeled the response to treatment and disease progression of cGVHD patients in Australia. Mycophenolate, tacrolimus, and cyclosporin comprised second-line standard of care based on a survey of Australian clinicians. Health states in the model included treatment response, disease progression, and death. Transition probabilities were obtained from Australian-specific registry data and randomized controlled evidence. Quality-of-life values were applied based on treatment response. The analysis considered costs of second-line treatment and disease management including immunosuppressants, hospitalizations and subsequent therapy. Disease-specific mortality was calculated for treatment response and progression. Results: Over a 10-year time horizon, ECP resulted in an average cost reduction of $23 999 and an incremental improvement of 1.10 quality-adjusted life-years per patient compared with standard of care. The sensitivity analysis demonstrated robustness over a range of plausible scenarios. Conclusion: This analysis demonstrates that ECP improves quality of life, minimizes the harms associated with immunosuppressant therapy, and is a highly cost-effective option for steroid-refractory cGVHD patients in Australia. Based in part on this analysis, ECP was listed on the Medicare Benefits Schedule for public reimbursement.

Strategies for the implementation of the living guidelines for cochlear implantation in adults.

Introduction: Clinical guidelines for cochlear implants (CI) exist in several countries, however, they lack consistency and often do not encompass the full user journey. This study aims to explore the barriers and facilitators for implementing global Living Guidelines for cochlear implantation in adults with severe, profound or moderate sloping to profound sensorineural hearing loss (SPSNHL) as well as identify guideline implementation (GI) tools that may support uptake. Methods: A convenience sample of Task Force members were recruited for semi-structured interviews. Interview transcripts were thematically analysed to group country-specific barriers, facilitators and GI tools into three levels: health care provider (HCP), consumer and structural. Once identified, barriers and facilitators were classified into four themes related to awareness, economic, guideline or other. Results: Interviews were conducted with 38 Task Force members, representing 20 countries. Lack of CI and hearing loss awareness was a major barrier at the HCP (85% of countries), consumer (80%) and structural (20%) levels. Economic and guideline barriers followed at the HCP (35%; 25%), consumer (45%; 0%) and structural (55%; 30%) levels, respectively. Facilitators focused on raising awareness of hearing loss and CIs as well as guideline related initiates at the HCP (80%; 70%), consumer (70%; 10%) and structural (25%; 70%) levels. GI tools including education, economic evaluations, quick reference resources and social media can help improve awareness and uptake. Conclusion: Awareness is the primary barrier to implementing Living Guidelines globally for adults with SPSNHL. Endorsement from key professional bodies and using the best available evidence can enhance uptake.