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SUMMARY Objectives: To describe the methodology to estimate the total cost of administration of a single unit of red blood cells (RBC) in adults with beta thalassaemia major in an Australian specialist haemoglobinopathy centre. Background: Beta thalassaemia major is a genetic disorder of haemoglobin associated with multiple end‐organ complications and typically requiring lifelong RBC transfusion therapy. New therapeutic agents are becoming available based on advances in understanding of the disorder and its consequences. Assessment of the true total cost of transfusion, incorporating both product and activity costs, is required in order to evaluate the benefits and costs of these new therapies. Methods: We describe the bottom‐up, time‐driven, activity‐based costing methodology used to develop process maps to provide a step‐by‐step outline of the entire transfusion pathway. Detailed flowcharts for each process are described. Direct observations and timing of the process maps document all activities, resources, staff, equipment and consumables in detail. The analysis will include costs associated with performing these processes, including resources and consumables. Sensitivity analyses will be performed to determine the impact of different staffing levels, timings and probabilities associated with performing different tasks. Results: Thirty‐one process maps have been developed, with over 600 individual activities requiring multiple timings. These will be used for future detailed cost analyses. Conclusions: Detailed process maps using bottom‐up, time‐driven, activity‐based costing for determining the cost of RBC transfusion in thalassaemia major have been developed. These could be adapted for wider use to understand and compare the costs and complexities of transfusion in other settings. [ABSTRACT FROM AUTHOR]

Objectives.  To explore the extent to which structural stigma (sociocultural and institutional constraining factors) is associated with sexual orientation disparities in long-term health conditions. Methods.  We measured structural stigma using the regional percentage of votes against same-sex marriage from Australia's 2017 Marriage Equality Survey and mapped this to the 2021 Census survey of 10 093 399 and 136 988 individuals in different-sex and same-sex relationships, respectively. Controlling for individual and area-level confounders, we used logistic regression analyses to examine the association between quartiles of structural stigma and sexual orientation disparities in long-term health conditions (e.g., any, mental health, asthma, cardiovascular). Results.  In the lowest stigma quartile, individuals in same-sex relationships had 56% higher odds of reporting any long-term health condition (odds ratio [OR] = 1.56; 95% confidence interval [CI] = 1.53, 1.59) and this increased to 63% in the highest stigma quartile (OR = 1.63; 95% CI = 1.58, 1.68). Effects were particularly pronounced for cardiovascular, respiratory, and mental health conditions as well as for men, younger populations, and those living in socioeconomically deprived regions. Conclusions.  Living in stigmatizing environments may have deleterious health effects for sexual minorities in Australia. Policy action and enhanced protections for sexual minorities are urgently required. ( Am J Public Health . 2024;114(10):1110-1122. https://doi.org/10.2105/AJPH.2024.307759).

Background: Community attitudes influence health outcomes especially for racially diverse and minority groups exposed to the detrimental effects of racism and discrimination. Using the results from Australia's national referendum to establish an Aboriginal and Torres Strait Islander Voice to Parliament ('the Voice') as a proxy for attitudes to Indigenous Australians, this study examined health outcomes for Indigenous and non-Indigenous Australians according to levels of opposition to the Voice., Methods: The regional share of votes against the Voice was linked to 2021 data from the Household, Income and Labour Dynamics in Australia survey, a large, national probability sample (n∽17,000) of Australian adults. Adjusting for regional-level confounders, we used logistic regression analyses to predict health outcomes, healthcare use, and risk-taking behaviours among Indigenous and non-Indigenous Australians for different levels (quartiles) of opposition to the Voice., Findings: Greater opposition to the Voice was associated with widening Indigenous disparities in health, healthcare use, and health behaviours. Indigenous Australians living in regions with the highest opposition to the Voice (top quartile: ≥ 72% community voting 'No') were more likely to report fair/poor health [OR 2.28 (95% CI 1.45-3.58)] and poor mental health [OR 2.24 (95% CI 1.48-3.39)], were less likely to have visited any healthcare provider [OR 0.52 (95% CI 0.36-0.75)], and were more likely to smoke [OR 4.21 (95% CI 2.78-6.38)] or engage in risky drinking [OR 2.66 (95% CI 1.60-4.43)] relative to non-Indigenous Australians., Interpretation: Indigenous Australians living in communities with greater opposition to the Voice experience poorer health relative to non-Indigenous Australians. Disparities in health may be partially due to poorer healthcare access and increased risk-taking behaviours, which may be associated with racism. These findings align with discrimination-related stress processes and potentially reduced availability of culturally inclusive healthcare. Health and social policy should consider how broader societal level conditions shape Indigenous health disparities in Australia., Funding: This work is supported by the Australian Research Council (project ID FT200100630), the University of Melbourne Faculty Research Grant, and the National Health and Medical Research Council of Australia Investigator Grant (project ID 1201937)., Competing Interests: There are no relevant interests to declare., (© 2024 The Author(s).)

Objective: The aim of this study was to test the effectiveness of a tailored quitline tobacco treatment ('Quitlink') among people receiving support for mental health conditions., Methods: We employed a prospective, cluster-randomised, open, blinded endpoint design to compare a control condition to our 'Quitlink' intervention. Both conditions received a brief intervention delivered by a peer researcher. Control participants received no further intervention. Quitlink participants were referred to a tailored 8-week quitline intervention delivered by dedicated Quitline counsellors plus combination nicotine replacement therapy. The primary outcome was self-reported 6 months continuous abstinence from end of treatment (8 months from baseline). Secondary outcomes included additional smoking outcomes, mental health symptoms, substance use and quality of life. A within-trial economic evaluation was conducted., Results: In total, 110 participants were recruited over 26 months and 91 had confirmed outcomes at 8 months post baseline. There was a difference in self-reported prolonged abstinence at 8-month follow-up between Quitlink (16%, n = 6) and control (2%, n = 1) conditions, which was not statistically significant (OR = 8.33 [0.52, 132.09] p = 0.131 available case). There was a significant difference in favour of the Quitlink condition on 7-day point prevalence at 2 months (OR = 8.06 [1.27, 51.00] p = 0.027 available case). Quitlink costs AU$9231 per additional quit achieved., Conclusion: The Quitlink intervention did not result in significantly higher rates of prolonged abstinence at 8 months post baseline. However, engagement rates and satisfaction with the 'Quitlink' intervention were high. While underpowered, the Quitlink intervention shows promise. A powered trial to determine its effectiveness for improving long-term cessation is warranted., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Adjuvant breast radiotherapy as a standard component of breast-conserving treatment for early cancer can overtreat many women. Breast MRI is the most sensitive modality to assess local tumour burden. The aim of this study was to determine whether a combination of MRI and pathology findings can identify women with truly localised breast cancer who can safely avoid radiotherapy., Methods: PROSPECT is a prospective, multicentre, two-arm, non-randomised trial of radiotherapy omission in patients selected using preoperative MRI and postoperative tumour pathology. It is being conducted at four academic hospitals in Australia. Women aged 50 years or older with cT1N0 non-triple-negative breast cancer were eligible. Those with apparently unifocal cancer had breast-conserving surgery (BCS) and, if pT1N0 or N1mi, had radiotherapy omitted (group 1). Standard treatment including excision of MRI-detected additional cancers was offered to the others (group 2). All were recommended systemic therapy. The primary outcome was ipsilateral invasive recurrence rate (IIRR) at 5 years in group 1. Primary analysis occurred after the 100th group 1 patient reached 5 years follow-up. Quality-adjusted life-years (QALYs) and cost-effectiveness of the PROSPECT pathway were analysed. This study is registered with the Australian New Zealand Clinical Trials Registry (ACTRN12610000810011)., Findings: Between May 17, 2011, and May 6, 2019, 443 patients with breast cancer underwent MRI. Median age was 63·0 years. MRI detected 61 malignant occult lesions separate from the index cancer in 48 patients (11%). Of 201 group 1 patients who had BCS without radiotherapy, the IIRR at 5 years was 1·0% (upper 95% CI 5·4%). In group 1, one local recurrence occurred at 4·5 years and a second at 7·5 years. In group 2, nine patients had mastectomy (2% of total cohort), and the 5-year IIRR was 1·7% (upper 95% CI 6·1%). The only distant metastasis in the entire cohort was genetically distinct from the index cancer. The PROSPECT pathway increased QALYs by 0·019 (95% CI 0·008-0·029) and saved AU$1980 (95% CI 1396-2528) or £953 (672-1216) per patient., Interpretation: PROSPECT suggests that women with unifocal breast cancer on MRI and favourable pathology can safely omit radiotherapy., Funding: Breast Cancer Trials, National Breast Cancer Foundation, Cancer Council Victoria, the Royal Melbourne Hospital Foundation, and the Breast Cancer Research Foundation., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objective: Employment can improve mental health among people with disability (PWD), however, little is known about how different levels of workforce participation influence mental healthcare use. The aim of this study was to estimate the extent to which different levels of working hours are associated with changes in mental healthcare use among PWD., Methods: Data on working hours and healthcare use among working age PWD who were receiving government benefits (N=260 825) was obtained from Australian Census-linked administrative records between 2011 and 2019. Individual fixed effects panel models were used to estimate the impact of increased working hours on mental healthcare (services and prescriptions). Heterogeneity analyses by job security and key sociodemographic characteristics were conducted., Results: Compared to not working, we found that working 1-14, 15-29, and ≥30 hours per week was respectively associated with a 3.3%, 18.0%, and 9.9% reduction in the use of mental healthcare prescriptions as well as a 6.8%, 18.4%, and 22.3% reduction in the use of mental healthcare services by PWD. The effects were larger for PWD in more secure work and those living in rural and disadvantaged areas., Conclusions: Working more hours was associated with reduced mental healthcare use among PWD. Policy interventions should consider the broader benefits of enabling part-time and secure work placements for PWD, particularly for those living in rural and disadvantaged regions.

Introduction: This study estimates the extent to which individuals' smoking cessation and relapse patterns are associated with the smoking behavior of their household members., Aims and Methods: Longitudinal data on household members' smoking behavior was sourced from a representative sample of 12 723 Australians who ever reported smoking between 2001 and 2019. Controlling for a rich set of confounders, multivariate regression analyses were used to predict the likelihood of smoking cessation and relapse given other household members' smoking status and their relationship type. The models were then used to forecast smoking prevalence over 10 years across different household types., Results: Individuals living with a smoking spouse were less likely to quit (OR 0.77 [95% CI 0.72;0.83]) and more likely to relapse (OR 1.47 [95% CI 1.28;1.69]) compared to those living with nonsmoking spouses. Subsequently, the proportion of smokers living with other smoking household members increased by 15% between 2011 and 2019. A 10-year forecast using the smoking cessation and relapse models predicts that, on average, smokers living with nonsmokers will reduce by 43%, while those living alone or with a smoking partner will only reduce by 26% and 28% respectively., Conclusions: Over time, those who are still smoking are more likely to live with other smokers. Therefore, the current cohort of smokers is increasingly less likely to quit and more likely to relapse. Smoking projection models that fail to account for this dynamic risk may overstate the downstream health benefits and health cost savings. Interventions that encourage smoking cessation at the household level, particularly for spouses, may assist individuals to quit and abstain from smoking., Implications: The current and future paradigm shift in the smoking environment suggests that smoking cessation and relapse prevention policies should consider household structure. Policies designed to affect smoking at the household level are likely to be particularly effective. When estimating the long-term benefits of current smoking policies intrahousehold smoking behavior needs to be considered., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Globally, Indigenous populations experience poorer health but use less primary healthcare than their non-Indigenous counterparts. In 2010, the Australian government introduced a targeted reform aimed at reducing these disparities. The reform reduced, or abolished prescription medicine co-payments and provided financial incentives for GPs to better manage chronic disease care for Indigenous peoples. Exploiting the framework of a natural experiment, we investigate how the reform affected these health disparities in primary and specialist healthcare utilization using longitudinal administrative data from 75,826 Australians, including 1896 Indigenous peoples, with cardiovascular disease. The differences-in-differences estimates indicate that the reform increased primary healthcare use among Indigenous peoples, including 12.9% more prescription medicines, 6.6% more GP services, and 34.0% more chronic disease services, but also reduced specialist attendances by 11.8%. Increases in primary care were larger for those who received the largest co-payment relief and lived in metropolitan regions, whereas the reduction in specialist attendances was concentrated among lower income Indigenous patients. Affirmative action can reduce inequalities in Indigenous use of primary healthcare, albeit careful design is required to ensure that benefits are equitable and do not lead to substitution away from valuable, or necessary, care., (© 2023 The Authors. Health Economics published by John Wiley & Sons Ltd.)

Introduction: Free-of-charge (FoC) medicine schemes are increasingly available and allow access to investigational treatments outside clinical trials or in advance of licensing or NHS commissioning., Methods: We retrospectively reviewed FoC medicine schemes evaluated between 2013 and 2019 by a single NHS trust and a regional drug and therapeutics committee (DTC). The details of each locally reviewed FoC scheme, and any nationally available Medicines and Healthcare products Regulatory Agency Early Access to Medicines Scheme (MHRA EAMS) in the same period, were recorded and categorised., Results: Most FoC schemes (95%) allowed access to medicines intended to address an unmet clinical need. Over 7 years, 90% were company-FoC schemes and 10% were MHRA EAMS that were locally reviewed. Phase 3 clinical trial data were available for 44% of FoC schemes, 37% had phase 2 data and 19% were supported only by phase 1 data, retrospective observational studies or preclinical data. Utilisation of company-FoC schemes increased on average by 50% per year, while MHRA EAMS schemes showed little growth., Conclusion: Company-FoC medicine schemes are increasingly common. This may indicate a preference for pharmaceutical companies to independently co-ordinate schemes. Motivations for company-FoC schemes remain unclear and many provide access to treatments that are yet to be evaluated in appropriately conducted clinical trials, and whose efficacy and risk of harm remain uncertain. There is no standardisation of this practice and there is no regulatory oversight. Moreover, no standardised data collection framework is in place that could demonstrate the utility of such programmes in addressing unmet clinical need or to allow generation of further evidence., (© 2021 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

Background: Discrimination and stigmatization at the institutional and sociocultural level (conceptualized as "structural stigma") has been associated with adverse health outcomes among sexual and gender minorities. However, few studies explore whether structural stigma is associated with sexual health outcomes. Addressing this gap, here, we explore this relationship among Australian gay, bisexual, and other men who have sex with men (GBM)-a population disproportionately affected by HIV., Setting and Methods: Using responses from the 2017 Australian Marriage Law Postal Survey, we operationalized structural stigma related to sexual minority status as the regional percentage of votes against legalizing same-sex marriage. These responses were then linked to national HIV behavioral surveillance data from Australian GBM (43,811 responses between 2015 and 2019). Controlling for a rich set of individual and regional level confounders, regression analyses were used to estimate the extent to which structural stigma was associated with testing for, and diagnoses of, HIV and sexually transmitted infections (STIs), and awareness and use of HIV prevention and treatment interventions (pre-exposure and postexposure prophylaxis, combination therapy, and HIV-related clinical care)., Results: Australian GBM living in regions with higher levels of structural stigma were less likely to undergo HIV/STI testing, receive HIV/STI diagnoses, and be taking, or aware of, biomedical prevention strategies. Among GBM living with HIV, structural stigma was associated with a reduced likelihood of being on combination therapy and fewer HIV-related clinical visits., Conclusions: Altogether, these results suggest that structural stigma may undermine HIV prevention strategies as well as adequate management of HIV infection among GBM., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Hypertension  (HTN) affects approximately 25% of the UK population and is a leading cause of mortality. Associated annual health care costs run into billions. National treatment guidance includes initial lifestyle advice, followed by anti-hypertensive medication if blood pressure (BP) remains high. However, adoption and adherence to recommended exercise guidelines, dietary advice and anti-hypertensive medication is poor. Four short bouts of isometric exercise (IE) performed 3 days per week (d/wk) at home elicits clinically significant reductions in BP in those with normal to high-normal BP. This study will determine the feasibility of delivering personalised IE to patients with stage 1 hypertension for whom lifestyle changes would be recommended before medication within NHS primary care., Methods: This is a randomised controlled feasibility study. Participants were 18+ years, with stage 1 hypertension, not on anti-hypertensive medication and without significant medical contraindications. Trial arms will be standard lifestyle advice (control) or isometric wall squat exercise and standard lifestyle advice. Primary outcomes include the feasibility of healthcare professionals to deliver isometric exercise prescriptions in a primary care NHS setting and estimation of the variance of change in systolic BP. Secondary outcomes include accuracy of protocol delivery, execution of and adherence to protocol, recruitment rate, attrition, perception of intervention viability, cost, participant experience and accuracy of home BP. The study will last 18 months. Sample size of 100 participants (50 per arm) allows for 20% attrition and 6.5% incomplete data, based upon 74 (37 each arm) participants (two-sided 95% confidence interval, width of 1.33 and standard deviation of 4) completing 4 weeks. Ethical approval IRAS ID is 274676., Discussion: Before the efficacy of this novel intervention to treat stage 1 hypertension can be investigated in any large randomised controlled trial, it is necessary to ascertain if it can be delivered and carried out in a NHS primary care setting. Findings could support IE viability as a prophylactic/alternative treatment option., Trial Registration: ISRCTN13472393 , registered 18 August 2020., (© 2021. The Author(s).)

Background :Although evaluations of breast cancer screening programs frequently estimate quality-adjusted life-year (QALY) losses by stage, other breast cancer characteristics influence treatment and vary by mode of detection - i.e. whether the cancer is detected through screening (screen-detected), between screening rounds (interval-detected) or outside screening (community-detected). Here, we estimate the association between early-stage invasive breast cancer (ESIBC) characteristics and treatment-related QALY losses. Methods :Using clinicopathological and treatment information from 675 women managed for ESIBC, we estimated the average five-year treatment-related QALY loss by detection group. We then used regression analysis to estimate the extent to which known cancer characteristics and the detection mode, are associated with treatment and treatment-related QALY losses. Results :Community-detected cancers had the largest QALY loss (0.76 QALYs [95% CI 0.73;0.80]), followed by interval-detected cancers (0.75 QALYs [95% CI 0.68;0.82]) and screen-detected cancers (0.69 QALYs [95%CI 0.67;0.71]). Adverse prognostic factors more common in community-detected and interval-detected breast cancers (large tumours, lymph node involvement, high grade) were largely associated with QALY losses from mastectomies and chemotherapy. Receptor-positive subtypes, more common in screen-detected cancers, were associated with QALY losses related to endocrine therapy. Conclusions :The associations between ESIBC characteristics and treatment-related QALY losses should be considered when evaluating breast cancer screening and treatment strategies.

This study explores the extent to which structural stigma (which encompasses sociocultural and institutional constraining factors) is associated with sexual orientation disparities in healthcare service and prescription medicine use. Using the responses to the 2017 Australian Marriage Law Postal Survey, we use the regional percentage of votes against legalising same-sex marriage as a measure of structural stigma. We then map these results to Census-linked-administrative data, including 83,519 individuals in same-sex relationships - one of the largest administrative datasets to date where individuals in same-sex relationships are identified. Controlling for regional and individual-level confounders, we find that structural stigma is associated with increased use of nervous system medications (which largely comprise antidepressants) but reduced GP visits for both females and males in same-sex relationships. More regional stigma is also associated with reduced use of pathology services and anti-infective prescriptions for males in same-sex relationships. Altogether, our results suggest that individuals in same-sex relationships living in stigmatised regions are in poorer health but are less likely to access primary healthcare., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objective: To determine the government and out-of-pocket community costs (out-of-hospital medical services and prescription medicines) associated with screen-detected and community-detected cancers (i.e. cancers detected outside of Australia's organised screening program [BreastScreen])., Methods: We analyse administrative data on government-subsidised medical services and prescription medicines for 568 Victorian women diagnosed with breast cancer or ductal carcinoma in situ (DCIS). Using multivariable regression analysis, we estimate the government and out-of-pocket community costs incurred in the three years after diagnosis for screen-detected cancers and community-detected cancers. Additionally, we estimate the government costs associated with diagnosis within and outside of BreastScreen., Results: Average government costs for breast cancer diagnosis were similar within and outside of BreastScreen [$808 (lower limit 676; upper limit 940) vs $837 (95%CI 671; 1,003) respectively]; however, women with community-detected cancers incurred an additional $254 (95%CI 175; 332) out-of-pocket. Controlling for differences in known cancer characteristics, compared to screen-detected cancers, community-detected breast cancers were associated with an additional $2,622 (95%CI 644; 4,776) in government expenditure in the three years following diagnosis. Adverse cancer characteristics that were more prevalent in community-detected cancers (high grade, lymph node involvement, HER2 positive receptor status) were associated with increased government and out-of-pocket costs., Conclusions: Community-detected breast cancers were associated with increased government and out-of-pocket costs. Implications for public health: These costs should be considered when evaluating current and alternative breast cancer screening strategies., (© 2020 The Authors.)

Aims To assess the transfer of patients treated with originator biological therapies to biosimilar products in a large UK tertiary referral hospital reflecting practice within the National Health Service (NHS) using prospectively collected data by a hospital-based registry administered by the Biologics Steering Group (BSG)., Methods: We analysed data collected prospectively in a hospital-based registry in a large NHS tertiary referral hospital in the UK. The registry was administered by the hospital's BSG, which considered requests for patients to remain on or revert to originator products. The registry contained prospectively collected data on patients switching therapy from an originator to a biosimilar. The data included clinical circumstances or rationale for each request, whether it was granted, and the results of clinical reviews at 3-6 months., Results: In a 12-month period, we identified 1299 patients who could switch to the respective biosimilar and, of these, 1196 (92%) did so. Of the 260 patients taking infliximab, 250 (96%) switched to infliximab biosimilar; of the 390 patients taking etanercept 50 mg, 298 (76%) switched to etanercept 50 mg biosimilar; and of the 649 patients taking rituximab, 648 (99%) switched to rituximab biosimilar. The BSG received 39 applications: 12 (out of 39) applications were to remain on the originator and 27 (out of 39) were to switch back to the originator. Of the applications to remain on the originator 10 (out of 12) were approved. At 3-6 month review, 2 of these approvals reported continued efficacy, 3 switched to the biosimilar, 3 switched to an alternative therapy and 2 stopped treatment. Two (out of 10) applications were not approved, both applicants reported efficacy with the biosimilar at follow up. Of the 27 applications to switch back to the originator, 16 (out of 27) applications were approved. At 3-6 months, 9 (out of 16) applicants reported regain of efficacy, 6 (out of 16) reported cessation of reported adverse effects and 1 (out of 16) switched to alternative therapy. Eight (out of 27) applications were not approved, and, at point of follow up, 50% reported efficacy with the biosimilar and 50% had switched to an alternative therapy. Three (out of 27) applications were withdrawn by the clinical team as efficacy was achieved with the biosimilar., Conclusion: We have set up a system within a busy NHS clinical practice to successfully switch patients to biosimilars, and established a mechanism to guide decisions on continuing with or reverting back to the originator. Such a system could be of use more broadly within the NHS and other health care systems., (© 2019 The British Pharmacological Society.)

Background: To accurately quantify the costs of care for patients with transfusion-dependent thalassemia (TDT), and to evaluate cost-effectiveness of new treatments, data are required on costs of regular red blood cell (RBC) transfusions. However, no previous studies have evaluated the costs of RBC transfusion specifically in chronically transfused patients., Methods and Materials: We performed a time-driven activity-based costing (TDABC) study using a health care provider perspective. This was performed over a 1-month period, capturing every step of the transfusion pathway for patients with TDT at a designated provider of specialist thalassemia services in Australia. Detailed process maps were developed to outline treatments and processes directly related to transfusion. For each process map, detailed data collection, including timing of activities, was performed multiple times to account for variation in practice. Costs associated with RBC transfusion were broken down into fixed, process, and RBC procurement costs., Results: The total per-unit cost was US$695.59 (95% confidence interval, US$694.45-US$696.73). Approximately 40% of cost was for procurement of the RBC unit, with process costs accounting for 55%. The single largest contributor to process costs was attributed to iron chelation medication (approximately 80%). In sensitivity analyses, seniority of staff, time to perform processes, and probabilities of different processes occurring did not substantially influence the RBC transfusion cost; however the number of RBC units per transfusion episode did impact the overall cost per RBC unit., Conclusions: We found significant costs associated with RBC transfusion for TDT, with the product cost contributing less than one-half of the total cost., (© 2019 AABB.)

Herein we report synthesis of complex heparan sulfate oligosaccharide precursors by automated glycan assembly using disaccharide donor building blocks. Rapid access to a hexasaccharide was achieved through iterative solid phase glycosylations on a photolabile resin using Glyconeer™, an automated oligosaccharide synthesiser, followed by photochemical cleavage and glycan purification using simple flash column chromatography.

Carbon monoxide releasing molecules (CORMs) have been suggested as a new synthetic class of antimicrobials to treat bacterial infections. Here we utilized a novel EBOR-CORM-1 ([NEt 4 ][MnBr 2 (CO) 4 ]) capable of water-triggered CO-release, and tested its efficacy against a collection of clinical Pseudomonas aeruginosa strains that differ in infection-related virulence traits. We found that while EBOR-CORM-1 was effective in clearing planktonic and biofilm cells of P. aeruginosa strain PAO1 in a concentration dependent manner, this effect was less clear and varied considerably between different P. aeruginosa cystic fibrosis (CF) lung isolates. While a reduction in cell growth was observed after 8 h of CORM application, either no effect or even a slight increase in cell densities and the amount of biofilm was observed after 24 h. This variation could be partly explained by differences in bacterial virulence traits: while CF isolates showed attenuated in vivo virulence and growth compared to strain PAO1, they formed much more biofilm, which could have potentially protected them from the CORM. Even though no clear therapeutic benefits against a subset of isolates was observed in an in vivo wax moth acute infection model, EBOR-CORM-1 was more efficient at reducing the growth of CF isolate co-culture populations harboring intraspecific variation, in comparison with efficacy against more uniform single isolate culture populations. Together these results suggest that CORMs could be effective at controlling genetically diverse P. aeruginosa populations typical for natural chronic CF infections and that the potential benefits of some antibiotics might not be observed if tested only against clonal bacterial populations.