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Multiple sclerosis (MS) is a chronic neurological disease that causes substantial health economic impacts, however, the cost of informal care for MS is often excluded from health economic analysis. As a result there is a paucity of information for decision-making. This review aims to summarise, synthesise and where appropriate meta-analyse the global evidence regarding the health economics of informal care for people with MS. The findings will provide consolidated evidence that policymakers and other stakeholders can use to inform decisions, including the development of health economics models. This review was conducted with a pre-determined study protocol (PROSPERO- CRD42023396457). Biomedical and economic databases were searched. Costs were converted to 2022 United States dollars (USD). Mean cost was calculated and pooled with a random-effects model. Subgroup analysis and meta-regression was conducted for stratified variables such as country income level and Expanded Disability Status Scale (EDSS). Of 6,306 identified studies, 61 were retained for narrative synthesis and 50 for meta-analysis. Studies were conducted in 25 countries. Cost information was collected from the person with MS, not the caregiver. 83.6% of studies used the opportunity cost method. Average monthly caregiving time was 60.1 h. Informal care costs accounted for 15% of total societal cost of MS. Pooled mean annual cost of informal care per person was USD $6,308 (95% CI $5,022-7,594). Informal care costs were USD $6,797 and $1,478 in high- and middle-income countries. Costs for mild, moderate, and severe disability of the person with MS were $1,123, $6,643, and $15,855, respectively. Informal care cost contributes considerably to MS-related costs. Despite study heterogeneity, cost of informal care increases with MS-related disability severity, time attributed to care and country income level. These results can be used to inform health economic models for reimbursement decisions for MS. Future studies regarding the health economic burden of informal care should gather the data from the informal carers themselves., Competing Interests: Declaration of competing interest All authors declare that they have no conflict of interest., (Copyright © 2024. Published by Elsevier Ltd.)

Background: Bariatric surgery is the most effective long-term therapy for severe obesity; however, empirical investigation of its economic impacts has been based on limited samples, short-term costs, and a narrow range of cost categories. This study aimed to evaluate the economic impacts of bariatric surgery in a large cohort of Australians aged ≥ 45 years., Methods: N = 1157 operated (surgery) and 1157 non-operated participants were selected from the 45 and Up Study. Data sources included the baseline and follow-up surveys along with linked state and national administrative health datasets. Linear mixed-effects regression predicted the cost trajectory 8 years pre- and post-bariatric surgery, and the difference-in-differences approach evaluated its economic impact. Sensitivity analyses included an approximation of indirect costs and subgroup analysis by surgery type., Results: The matched cohort composed 77% female, had an average age of 58.1 ± 5.8 years. Direct healthcare costs increased over time in both groups. Costs for the operated group peaked ($15,884) during the surgery year and became up to 23.8% lower than those for the non-operated group from the second year post-surgery when including indirect costs. Surgery's economic benefits increased over longer horizons, with a maximum annual cost-saving of $3196 per person in the eighth post-surgery year. However, even after accounting for indirect costs, cumulative cost-savings were not achieved. Subgroup analysis revealed sleeve gastrectomy as the least costly surgical option., Conclusion: Higher short-term costs in the surgery year primarily drove inter-group cost differences. The economic value of bariatric surgery lies in the long-term benefits, particularly when considering indirect costs., Competing Interests: Declarations. Ethical Approval: The Study was approved by the University of NSW Human Research Ethics Committee, and approval for the current study was granted by the NSW Population and Health Service Research Ethics Committee (Approval Number: ETH01569). Informed Consent: Informed consent was obtained from all individual participants included in the study. Conflict of Interest: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: This study leveraged data from 11 independent international diabetes models to evaluate the impact of unrelated future medical costs on the outcomes of health economic evaluations in diabetes mellitus., Methods: Eleven models simulated the progression of diabetes and occurrence of its complications in hypothetical cohorts of individuals with type 1 (T1D) or type 2 (T2D) diabetes over the remaining lifetime of the patients to evaluate the cost effectiveness of three hypothetical glucose improvement interventions versus a hypothetical control intervention. All models used the same set of costs associated with diabetes complications and interventions, using a United Kingdom healthcare system perspective. Standard utility/disutility values associated with diabetes-related complications were used. Unrelated future medical costs were assumed equal for all interventions and control arms. The statistical significance of changes on the total lifetime costs, incremental costs and incremental cost-effectiveness ratios (ICERs) before and after adding the unrelated future medical costs were analysed using t-test and summarized in incremental cost-effectiveness diagrams by type of diabetes., Results: The inclusion of unrelated costs increased mean total lifetime costs substantially. However, there were no significant differences between the mean incremental costs and ICERs before and after adding unrelated future medical costs. Unrelated future medical cost inclusion did not alter the original conclusions of the diabetes modelling evaluations., Conclusions: For diabetes, with many costly noncommunicable diseases already explicitly modelled as complications, and with many interventions having predominantly an effect on the improvement of quality of life, unrelated future medical costs have a small impact on the outcomes of health economic evaluations., (© 2024. The Author(s).)

Aims: To estimate the direct costs during the prenatal, delivery and postpartum periods in mothers with diabetes in pregnancy, compared to those without., Methods: This study used a population-based dataset from 2004 to 2017, including 57,090 people with diabetes and 114,179 people without diabetes in Tasmania, Australia. Based on diagnostic codes, delivery episodes with gestational diabetes mellitus (GDM) were identified and matched with delivery episodes without diabetes in pregnancy. A group of delivery episodes with pre-existing diabetes was identified for comparison. Hospitalisation, emergency department and pathology costs of these groups were calculated and adjusted to 2020-2021 Australian dollars., Results: There were 2774 delivery episodes with GDM, 2774 delivery episodes without diabetes and 237 delivery episodes with pre-existing diabetes identified. Across the 24-month period, the pre-existing diabetes group required the highest costs, totalling $23,536/person. This was followed by the GDM ($13,210/person), and the no diabetes group ($11,167/person). The incremental costs of GDM over the no diabetes group were $890 (95% CI 635; 1160) in the year preceding delivery; $812 (616; 1031) within the delivery period and $341 (110; 582) in the year following delivery (p < 0.05). Within the year preceding delivery, the incremental costs in the prenatal period were $803 (579; 1058) (p < 0.05). Within the year following delivery, the incremental costs in the postpartum period were $137 (55; 238) (p < 0.05)., Conclusions: Our results emphasised the importance of proper management of diabetes in pregnancy in the prenatal and postpartum periods and highlighted the significance of screening and preventative strategies for diabetes in pregnancy., (© 2024 The Author(s). Diabetic Medicine published by John Wiley & Sons Ltd on behalf of Diabetes UK.)

Objectives: The Mount Hood Diabetes Challenge Network aimed to examine the impact of model structural uncertainty on the estimated cost-effectiveness of interventions for type 2 diabetes., Methods: Ten independent modeling groups completed a blinded simulation exercise to estimate the cost-effectiveness of 3 interventions in 2 type 2 diabetes populations. Modeling groups were provided with a common baseline population, cost and utility values associated with different model health states, and instructions regarding time horizon and discounting. We collated the results to identify variation in predictions of net monetary benefit (NMB) and the drivers of those differences., Results: Overall, modeling groups agreed which interventions had a positive NMB (ie, were cost-effective), Although estimates of NMB varied substantially-by up to £23 696 for 1 intervention. Variation was mainly driven through differences in risk equations for complications of diabetes and their implementation between models. The number of modeled health states was also a significant predictor of NMB., Conclusions: This exercise demonstrates that structural uncertainty between different health economic models affects cost-effectiveness estimates. Although it is reassuring that a decision maker would likely reach similar conclusions on which interventions were cost-effective using most models, the range in numerical estimates generated across different models would nevertheless be important for price-setting negotiations with intervention developers. Minimizing the impact of structural uncertainty on healthcare decision making therefore remains an important priority. Model registries, which record and compare the impact of structural assumptions, offer one potential avenue to improve confidence in the robustness of health economic modeling., Competing Interests: Author Disclosures Author disclosure forms can be accessed below in the Supplemental Material section., (Copyright © 2024. Published by Elsevier Inc.)

Objectives: Subjective wellbeing has been defined as an individual's personal appraisal of their quality of life. Subjective wellbeing is associated with positive health behaviours and improved coping abilities. This study aimed to investigate the subjective wellbeing of people living with multiple sclerosis (MS), using the novel Personal Wellbeing Index, and make comparisons with the general population., Methods: Cross-sectional data was obtained from the Australian Multiple Sclerosis Longitudinal Study and the How Is Your Life Australian general population study in August-October 2020. Subjective wellbeing was measured as life satisfaction using the Personal Wellbeing Index. This instrument measures life satisfaction globally and in seven life domains, allowing the importance of domain-specific life satisfaction to be explored. Descriptive and multivariable regression analyses were conducted., Results: One thousand six hundred eighty-three MS and 1,021 general population participants entered the study (mean age 52.4 and 58.6; female 79.9% and 52.4%, respectively). For people living with MS the most important life domains were standard of living and achieving in life. The domain of personal health was more influential for people living with MS (p < 0.01) than the general population. The life domains most susceptible to MS-related disability were personal health, achieving in life, and community connectedness (p < 0.01 for these domains)., Conclusion: Personal health and achieving in life are key domains through which the subjective wellbeing of people living with MS is modified. This study recommends the development of interventions to support healthy perceptions of illness and continued employment as paramount in improving the subjective wellbeing of people living with MS., (© 2024. The Author(s).)

Background: Greater public transport use has been linked to higher physical activity levels. However, neither the amount of physical activity associated with each daily public transport trip performed, nor the potential total physical activity gain associated with an increase in trips/day, has been determined. Using objective measures, we aimed to quantify the association between public transport use, physical activity and sedentary time., Methods: A longitudinal study of Australian adults living in Hobart, Tasmania, who were infrequent bus users (≥ 18 years; used bus ≤ 2 times/week). The number of bus trips performed each day was determined from objective smartcard data provided by the public transportation (bus) provider across a 36-week study timeframe. Accelerometer measured steps/day (primary outcome), moderate-to-vigorous physical activity (min/day), and sedentary time (min/day) were assessed across four separate one-week periods., Results: Among 73 participants across 1483 day-level observations, on days that public transport was used, participants achieved significantly more steps (β = 2147.48; 95%CI = 1465.94, 2829.03), moderate to vigorous physical activity (β = 22.79; 95% CI = 14.33, 31.26), and sedentary time (β = 37.00; 95% CI = 19.80, 54.21) compared to days where no public transport trips were made. The largest increase in steps per day associated with a one-trip increase was observed when the number of trips performed each day increased from zero to one (β = 1761.63; 95%CI = 821.38, 2701.87). The increase in the number of steps per day was smaller and non-significant when the number of trips performed increased from one to two (β = 596.93; 95%CI=-585.16, 1779.01), and two to three or more (β = 632.39; 95%CI=-1331.45, 2596.24) trips per day. Significant increases in sedentary time were observed when the number of trips performed increased from zero to one (β = 39.38; 95%CI = 14.38, 64.39) and one to two (β = 48.76; 95%CI = 25.39, 72.12); but not when bus trips increased from two to three or more (β=-27.81; 95%CI=-76.00, 20.37)., Conclusions: Greater public transport use was associated with higher physical activity and sedentary behaviour. Bus use may yield cumulative increases in steps that amount to 15-30% of the daily recommended physical activity target. A policy and public health focus on intersectoral action to promote public transport may yield meaningful increases in physical activity and subsequent health benefits., (© 2024. The Author(s).)

Background: Multiple sclerosis (MS) is a chronic autoimmune/neurodegenerative disease associated with progressing disability affecting mostly women. We aim to estimate transition probabilities describing MS-related disability progression from no disability to severe disability. Transition probabilities are a vital input for health economics models. In MS, this is particularly relevant for pharmaceutical agency reimbursement decisions for disease-modifying therapies (DMTs)., Methods: Data were obtained from Australian participants of the MSBase registry. We used a four-state continuous-time Markov model to describe how people with MS transition between disability milestones defined by the Expanded Disability Status Scale (scale 0-10): no disability (EDSS of 0.0), mild (EDSS of 1.0-3.5), moderate (EDSS of 4.0-6.0), and severe (EDSS of 6.5-9.5). Model covariates included sex, DMT usage, MS-phenotype, and disease duration, and analysis of covariate groups were also conducted. All data were recorded by the treating neurologist., Results: A total of N = 6369 participants (mean age 42.5 years, 75.00% female) with 38,837 person-years of follow-up and 54,570 clinical reviews were identified for the study. Annual transition probabilities included: remaining in the no, mild, moderate, and severe states (54.24%, 82.02%, 69.86%, 77.83% respectively) and transitioning from no to mild (42.31%), mild to moderate (11.38%), and moderate to severe (9.41%). Secondary-progressive MS was associated with a 150.9% increase in the hazard of disability progression versus relapsing-remitting MS., Conclusions: People with MS have an approximately 45% probability of transitioning from the no disability state after one year, with people with progressive MS transitioning from this health state at a much higher rate. These transition probabilities will be applied in a publicly available health economics simulation model for Australia and similar populations, intended to support reimbursement of a plethora of existing and upcoming interventions including medications to reduce progression of MS., (© 2024. The Author(s).)

Background: Multiple sclerosis (MS) prevalence is increasing globally., Objectives: To determine whether increased prevalence is continuing within Australia using our validated prescription-based ascertainment method., Methods: We used methods employed in our 2010 and 2017 prevalence estimates. Disease-modifying therapy (DMT) prescriptions were extracted from Australia's Pharmaceutical Benefits Scheme data for January-December 2021. DMT penetrance was calculated using data from the Australian MS Longitudinal Study. We divided the total number of monthly prescriptions by 12 or 2 (except alemtuzumab), adjusted for DMT penetrance and Australian population estimates. Prevalences in Australian states/territories were age-standardised. 2021 prevalence estimates were compared with 2010 and 2017 prevalence estimates using Poisson regression., Results: Number of people with MS in Australia in 2021 was 33,335; an increase of 7728 from 2017 (30.2%) and 12,092 from 2010 (56.6%) and increasing at a faster rate than population change (+10.1%, +14.1%). Age-standardised prevalence was 136.1/100,000 (increased from 103.7/100,000 in 2017). The previously demonstrated positive latitudinal gradient in 2010 and 2017 persisted in 2021, with Tasmania (southernmost state) having the highest prevalence (age-standardised: 203.5/100,000) while northernmost states had the lowest., Conclusions: In line with global trends, MS prevalence is escalating in Australia, particularly in higher-latitude states. MS prevention is crucial to halt this disturbing trend., 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: High unemployment rate of people with multiple sclerosis (PwMS) is associated with substantial economic costs. Whilst the impact of MS symptoms and other disease-related factors on employment outcomes of PwMS has been assessed, limited evidence exists on the impacts of workplace factors., Objective: To investigate the most common individual and group workplace factors associated with unemployment or a perceived risk of unemployment in PwMS, and to identify patient subgroups that are more susceptible to changes in employment status due to such factors., Methods: Data from the Australian MS Longitudinal Study (AMSLS) on employment status and workplace factors were used. Fifteen workplace factors were classified under four groups: organisational, commuting, moving around at work, and equipment usage factors. Participants answered 'Yes' to each factor if it related to their unemployment and/or perceived risk of becoming unemployed and a group factor was considered "Yes" if at least one individual factor within it was answered as "Yes". The proportions of "Yes" responses were calculated for both individual and group factors. Total number of individual factors was calculated and descriptive analyses and ordered logistic regression were used to summarize the total number of factors affecting each participant, and their association with participants' occupations, sex, disability severity and disease duration., Results: Common workplace factors influencing employment were organisational (39.8 % perceived risk, 44.0 % lost employment), commuting (28.9 % perceived risk) and equipment usage difficulty (30.9 % lost employment). Common individual factors included inflexible working conditions, lack of suitable work, commuting difficulties, architectural barriers, and requirement to stand for long periods to use equipment. Professionals, blue-collar workers, and those with moderate/severe disability were more likely to report a higher number of workplace factors risking their employment., Conclusions: Workplace factors undermine PwMS employment, with variations among subgroups based on occupation and disability severity. Understanding these barriers is crucial for supporting PwMS in the workforce., Competing Interests: Declaration of competing interest The author(s) declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article., (Copyright © 2024. Published by Elsevier B.V.)

Purpose: People living with multiple sclerosis (PwMS) in metropolitan Victoria, Australia, experienced a 112-day, COVID-19-related lockdown in mid-2020. Contemporaneously, Australian PwMS elsewhere experienced minimal restrictions, resulting in a natural experiment. This study investigated the relationships between lockdowns, COVID-19-related adversity, and health-related quality of life (HRQoL). It also generated health state utilities (HSU) representative of changes in HRQoL., Methods: Data were extracted from Australian MS Longitudinal Study surveys, which included the Assessment of Quality of Life-Eight Dimensions (AQoL-8D) instrument and a COVID-19 questionnaire. This COVID-19 questionnaire required participants to rank their COVID-19-related adversity across seven health dimensions. Ordered probits were used to identify variables contributing to adversity. Linear and logit regressions were applied to determine the impact of adversity on HRQoL, defined using AQoL-8D HSUs. Qualitative data were examined thematically., Results: N = 1666 PwMS (average age 58.5; 79.8% female; consistent with the clinical presentation of MS) entered the study, with n = 367 (22.0%) exposed to the 112-day lockdown. Lockdown exposure and disability severity were strongly associated with higher adversity rankings (p < 0.01). Higher adversity rankings were associated with lower HSUs. Participants reporting major adversity, across measured health dimensions, had a mean HSU 0.161 (p < 0.01) lower than participants reporting no adversity and were more likely (OR: 2.716, p < 0.01) to report a clinically significant HSU reduction. Themes in qualitative data supported quantitative findings., Conclusions: We found that COVID-19-related adversity reduced the HRQoL of PwMS. Our HSU estimates can be used in health economic models to evaluate lockdown cost-effectiveness for people with complex and chronic (mainly neurological) diseases., (© 2024. The Author(s).)

Background: Interstitial lung diseases (ILD) are a heterogenous group of over 200 disorders affecting the pulmonary interstitium. Although there have been advances in knowledge on ILDs in Australia, the characterisation of the health and economic burden of disease remained largely undetermined until recently., Objective: The main objective of this review is to provide a synopsis of health and economic burden of ILDs in Australia, based on recently completed research., Discussion: Recent research has demonstrated that idiopathic pulmonary fibrosis (IPF) is the most frequent ILD in Australia. Incidence and prevalence of IPF have demonstrated an increasing trend over the past decades. Mortality has also increased over the past decades, but has shown a slight decreasing trend recently, since the introduction of antifibrotic medication. Health-related quality of life is poor in patients with IPF, and care is estimated to cost approximately AU$299 million per year in Australia. Early diagnosis and referral to tertiary care is crucial for favourable outcomes, and general practitioners are considerably important to this as the first interface to identify patients at risk and detect early symptoms of ILDs.

Background: Increasing evidence suggests the potential of Epstein-Barr virus (EBV) vaccination in preventing multiple sclerosis (MS). We aimed to explore the cost-effectiveness of a hypothetical EBV vaccination to prevent MS in an Australian setting., Methods: A five-state Markov model was developed to simulate the incidence and subsequent progression of MS in a general Australian population. The model inputs were derived from published Australian sources. Hypothetical vaccination costs, efficacy and strategies were derived from literature. Total lifetime costs, quality-adjusted life years (QALYs) and incremental cost-effectiveness ratios (ICERs) were estimated for two hypothetical prevention strategies versus no prevention from the societal and health system payer perspectives. Costs and QALYs were discounted at 5% annually. One-way, two-way and probabilistic sensitivity analyses were performed., Results: From societal perspective, EBV vaccination targeted at aged 0 and aged 12 both dominated no prevention (ie, cost saving and increasing QALYs). However, vaccinating at age 12 was more cost-effective (total lifetime costs reduced by $A452/person, QALYs gained=0.007, ICER=-$A64 571/QALY gained) than vaccinating at age 0 (total lifetime costs reduced by $A40/person, QALYs gained=0.003, ICER=-$A13 333/QALY gained). The probabilities of being cost-effective under $A50 000/QALY gained threshold for vaccinating at ages 0 and 12 were 66% and 90%, respectively. From health system payer perspective, the EBV vaccination was cost-effective at age 12 only. Sensitivity analyses demonstrated the cost-effectiveness of EBV vaccination to prevent MS under a wide range of plausible scenarios., Conclusions: MS prevention using future EBV vaccinations, particularly targeted at adolescence population, is highly likely to be cost-effective., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: To visualise the geographic variations of diabetes burden and identify areas where targeted interventions are needed., Methods: Using diagnostic criteria supported by hospital codes, 51,324 people with diabetes were identified from a population-based dataset during 2004-2017 in Tasmania, Australia. An interactive map visualising geographic distribution of diabetes prevalence, mortality rates, and healthcare costs in people with diabetes was generated. The cluster and outlier analysis was performed based on statistical area level 2 (SA2) to identify areas with high (hot spot) and low (cold spot) diabetes burden., Results: There were geographic variations in diabetes burden across Tasmania, with highest age-adjusted prevalence (6.1%), excess cost ($2627), and annual costs per person ($5982) in the West and Northwest. Among 98 SA2 areas, 16 hot spots and 25 cold spots for annual costs, and 10 hot spots and 10 cold spots for diabetes prevalence were identified (p<0.05). 15/16 (94%) and 6/10 (60%) hot spots identified were in the West and Northwest., Conclusions: We have developed a method to graphically display important diabetes outcomes for different geographical areas., Implications for Public Health: The method presented in our study could be applied to any other diseases, regions, and countries where appropriate data are available to identify areas where interventions are needed to improve diabetes outcomes., Competing Interests: Conflicts of interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: MJ is a member of the Australia and New Zealand Dialysis and Transplant Registry (ANZDATA)., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Hip and knee replacement surgery is a well-established means of improving quality of life, but is associated with a significant risk of bleeding. One-third of people are estimated to be anaemic before hip or knee replacement surgery; coupled with the blood lost during surgery, up to 90% of individuals are anaemic postoperatively. As a result, people undergoing orthopaedic surgery receive 3.9% of all packed red blood cell transfusions in the UK. Bleeding and the need for allogeneic blood transfusions has been shown to increase the risk of surgical site infection and mortality, and is associated with an increased duration of hospital stay and costs associated with surgery. Reducing blood loss during surgery may reduce the risk of allogeneic blood transfusion, reduce costs and improve outcomes following surgery. Several pharmacological interventions are available and currently employed as part of routine clinical care., Objectives: To determine the relative efficacy of pharmacological interventions for preventing blood loss in elective primary or revision hip or knee replacement, and to identify optimal administration of interventions regarding timing, dose and route, using network meta-analysis (NMA) methodology., Search Methods: We searched the following databases for randomised controlled trials (RCTs) and systematic reviews, from inception to 18 October 2022: CENTRAL (the Cochrane Library), MEDLINE (Ovid), Embase (Ovid), CINAHL (EBSCOhost), Transfusion Evidence Library (Evidentia), ClinicalTrials.gov and WHO International Clinical Trials Registry Platform (ICTRP)., Selection Criteria: We included RCTs of people undergoing elective hip or knee surgery only. We excluded non-elective or emergency procedures, and studies published since 2010 that had not been prospectively registered (Cochrane Injuries policy). There were no restrictions on gender, ethnicity or age (adults only). We excluded studies that used standard of care as the comparator. Eligible interventions included: antifibrinolytics (tranexamic acid (TXA), aprotinin, epsilon-aminocaproic acid (EACA)), desmopressin, factor VIIa and XIII, fibrinogen, fibrin sealants and non-fibrin sealants., Data Collection and Analysis: We performed the review according to standard Cochrane methodology. Two authors independently assessed trial eligibility and risk of bias, and extracted data. We assessed the certainty of the evidence using CINeMA. We presented direct (pairwise) results using RevMan Web and performed the NMA using BUGSnet. We were interested in the following primary outcomes: need for allogenic blood transfusion (up to 30 days) and all-cause mortality (deaths occurring up to 30 days after the operation), and the following secondary outcomes: mean number of transfusion episodes per person (up to 30 days), re-operation due to bleeding (within seven days), length of hospital stay and adverse events related to the intervention received., Main Results: We included a total of 102 studies. Twelve studies did not report the number of included participants; the other 90 studies included 8418 participants. Trials included more women (64%) than men (36%). In the NMA for allogeneic blood transfusion, we included 47 studies (4398 participants). Most studies examined TXA (58 arms, 56%). We found that TXA, given intra-articularly and orally at a total dose of greater than 3 g pre-incision, intraoperatively and postoperatively, ranked the highest, with an anticipated absolute effect of 147 fewer blood transfusions per 1000 people (150 fewer to 104 fewer) (53% chance of ranking 1st) within the NMA (risk ratio (RR) 0.02, 95% credible interval (CrI) 0 to 0.31; moderate-certainty evidence). This was followed by TXA given orally at a total dose of 3 g pre-incision and postoperatively (RR 0.06, 95% CrI 0.00 to 1.34; low-certainty evidence) and TXA given intravenously and orally at a total dose of greater than 3 g intraoperatively and postoperatively (RR 0.10, 95% CrI 0.02 to 0.55; low-certainty evidence). Aprotinin (RR 0.59, 95% CrI 0.36 to 0.96; low-certainty evidence), topical fibrin (RR 0.86, CrI 0.25 to 2.93; very low-certainty evidence) and EACA (RR 0.60, 95% CrI 0.29 to 1.27; very low-certainty evidence) were not shown to be as effective compared with TXA at reducing the risk of blood transfusion. We were unable to perform an NMA for our primary outcome all-cause mortality within 30 days of surgery due to the large number of studies with zero events, or because the outcome was not reported. In the NMA for deep vein thrombosis (DVT), we included 19 studies (2395 participants). Most studies examined TXA (27 arms, 64%). No studies assessed desmopressin, EACA or topical fibrin. We found that TXA given intravenously and orally at a total dose of greater than 3 g intraoperatively and postoperatively ranked the highest, with an anticipated absolute effect of 67 fewer DVTs per 1000 people (67 fewer to 34 more) (26% chance of ranking first) within the NMA (RR 0.16, 95% CrI 0.02 to 1.43; low-certainty evidence). This was followed by TXA given intravenously and intra-articularly at a total dose of 2 g pre-incision and intraoperatively (RR 0.21, 95% CrI 0.00 to 9.12; low-certainty evidence) and TXA given intravenously and intra-articularly, total dose greater than 3 g pre-incision, intraoperatively and postoperatively (RR 0.13, 95% CrI 0.01 to 3.11; low-certainty evidence). Aprotinin was not shown to be as effective compared with TXA (RR 0.67, 95% CrI 0.28 to 1.62; very low-certainty evidence). We were unable to perform an NMA for our secondary outcomes pulmonary embolism, myocardial infarction and CVA (stroke) within 30 days, mean number of transfusion episodes per person (up to 30 days), re-operation due to bleeding (within seven days), or length of hospital stay, due to the large number of studies with zero events, or because the outcome was not reported by enough studies to build a network. There are 30 ongoing trials planning to recruit 3776 participants, the majority examining TXA (26 trials)., Authors' Conclusions: We found that of all the interventions studied, TXA is probably the most effective intervention for preventing bleeding in people undergoing hip or knee replacement surgery. Aprotinin and EACA may not be as effective as TXA at preventing the need for allogeneic blood transfusion. We were not able to draw strong conclusions on the optimal dose, route and timing of administration of TXA. We found that TXA given at higher doses tended to rank higher in the treatment hierarchy, and we also found that it may be more beneficial to use a mixed route of administration (oral and intra-articular, oral and intravenous, or intravenous and intra-articular). Oral administration may be as effective as intravenous administration of TXA. We found little to no evidence of harm associated with higher doses of tranexamic acid in the risk of DVT. However, we are not able to definitively draw these conclusions based on the trials included within this review., (Copyright © 2024 The Authors. Cochrane Database of Systematic Reviews published by John Wiley & Sons, Ltd. on behalf of The Cochrane Collaboration.)

Purpose: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic condition with a constellation of symptoms presenting as severe and profound fatigue of ≥ 6 months not relieved by rest. ME/CFS affects health-related quality of life (HRQoL), which can be measured using multi-attribute health state utility (HSU) instruments. The aims of this study were to quantify HSUs for people living with ME/CFS, and to identify an instrument that is preferentially sensitive for ME/CFS., Methods: Cross-sectional national survey of people with ME/CFS using the AQoL-8D and EQ-5D-5L. Additional questions from the AQoL-8D were used as 'bolt-ons' to the EQ-5D-5L (i.e., EQ-5D-5L-Psychosocial). Disability and fatigue severity were assessed using the De Paul Symptom Questionnaire-Short Form (DSQ-SF). HSUs were generated using Australian tariffs. Mean HSUs were stratified for sociodemographic and clinical factors. Bland-Altman plots were used to compare the three HSU instruments., Results: For the 198 participants, mean HSUs (95% confidence intervals) were EQ-5D-5L: 0.46 (0.42-0.50); AQoL-8D: 0.43 (0.41-0.45); EQ-5D-5L-Psychosocial: 0.44 (0.42-0.46). HSUs were substantially lower than population norms: EQ-5D-5L: 0.89; AQoL-8D: 0.77. As disability and fatigue severity increased, HSUs decreased in all three instruments. Bland-Altman plots revealed interchangeability between the AQoL-8D and EQ-5D-5LPsychosocial. Floor and ceiling effects of 13.5% and 2.5% respectively were observed for the EQ-5D-5L instrument only., Conclusions: ME/CFS has a profound impact on HRQoL. The AQoL-8D and EQ-5D-5L-Psychosocial can be used interchangeably: the latter represents a reduced participant burden., (© 2023. The Author(s).)

Background: The MS disease-modifying therapies (DMTs) prescribing landscape in Australia have changed over time., Objectives: This study evaluated the utilisation and cost trends of MS-related DMTs in Australia over 10 years and investigated differences between States/Territories., Methods: The prescription and costs of 16 DMTs were extracted from the Pharmaceutical Benefits Scheme for 2013-2022. Descriptive approaches analysed the total number of people prescribed DMTs and total DMT costs per 10,000 population, proportions of prescriptions/costs by DMT groups and the number of people prescribed each individual DMT and costs of each DMT over the 10-year period. All estimates were for Australia and each State/Territory individually., Results: The number of people prescribed DMT and costs per 10,000 population had substantial growth between 2013 and 2022: 125%/164% for Australia, and 94%-251%/129%-373% for individual States/Territories. Higher efficacy group accounted for 54% of total people prescribed DMTs in 2013 and 75% in 2022. Fingolimod was the most popular DMT until 2020, then was dominated by ocrelizumab. The trends of individual DMT prescriptions and costs differed between states particularly in Western Australia (WA), Tasmania and Northern Territory (NT)., Conclusion: DMT prescriptions and costs continuously increased over the last decade, particularly for higher efficacy DMTs, and their trends differed between States/Territories., 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.

No one doubts the significant variation in the practice of transfusion medicine. Common examples are the variability in transfusion thresholds and the use of tranexamic acid for surgery with likely high blood loss despite evidence-based standards. There is a long history of applying different strategies to address this variation, including education, clinical guidelines, audit and feedback, but the effectiveness and cost-effectiveness of these initiatives remains unclear. Advances in computerised decision support systems and the application of novel electronic capabilities offer alternative approaches to improving transfusion practice. In England, the National Institute for Health and Care Research funded a Blood and Transplant Research Unit (BTRU) programme focussing on 'A data-enabled programme of research to improve transfusion practices'. The overarching aim of the BTRU is to accelerate the development of data-driven methods to optimise the use of blood and transfusion alternatives, and to integrate them within routine practice to improve patient outcomes. One particular area of focus is implementation science to address variation in practice., (© 2023 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)