Values, challenges, and responses associated with high-priced potential cures: perspectives of diverse stakeholders in South Korea.

BACKGROUND: The emergence of high-priced potential cures has sparked significant health policy discussions in South Korea, where the healthcare system is funded through a single-payer National Health Insurance model. We conducted focus group interviews (FGIs) and accompanying surveys with diverse stakeholders to comprehensively understand related issues and find better solutions to the challenges brought by these technologies. METHODS: From October to November 2022, 11 FGIs were conducted with stakeholders from various sectors, including government payers, policy and clinical experts, civic and patient organisations, and the pharmaceutical industry, involving a total of 25 participants. These qualitative discussions were supplemented by online surveys to effectively capture and synthesise stakeholder perspectives. RESULTS: Affordability was identified as a critical concern by 84% of stakeholders, followed by clinical uncertainty (76%) and limited value for money (72%). Stakeholders expressed a preference for both financial-based controls and outcome-based pricing strategies to mitigate these challenges. Despite the support for outcome-based refunds, payers raised concerns about the feasibility of instalment payment models, whether linked to outcomes or not, due to the specific challenges of the Korean reimbursement system and the potential risk of 'cumulative liabilities' from ongoing payments for previously administered treatments. In addition, the FGIs highlighted the need for clear budgetary limits for drugs with high uncertainties, with mixed opinions on the creation of special silo funds (64.0% agreement). Less than half (48%) endorsed the use of external reference pricing, currently applied to such essential drugs in South Korea. A significant majority (84%), predominantly non-pharma stakeholders, advocated for addressing cost-effectiveness uncertainty through re-assessment once long-term clinical data become available. CONCLUSIONS: This study uncovers a broad agreement among stakeholders on the need for more effective value assessment methodologies for high-priced potential cures, stressing the importance of more robust and comprehensive re-assessment supported by long-term data collection, rather than primarily relying on external reference pricing. Each type of stakeholders exhibited a cautious approach to their specific uncertainties, suggesting that new funding strategies should accommodate these uncertainties with predefined guidelines and agreements prior to the initiation of managed entry agreements.

Modulation of the pre-metastatic bone niche: molecular changes mediated by bone-homing prostate cancer extracellular vesicles.

Prostate cancer (PCa) is a leading male malignancy worldwide, often progressing to bone metastasis, with limited curative options. Extracellular vesicles (EVs) have emerged as key players in cancer communication and metastasis, promoting the formation of supportive microenvironments in distant sites. Our previous studies have highlighted the role of PCa EVs in modulating osteoblasts and facilitating tumor progression. However, the early pre-metastatic changes induced by PCa EVs within the bone microenvironment remain poorly understood. To investigate the early effects of repeated exposure to PCa EVs in vivo, mimicking EVs being shed from the primary tumor, PCa EVs isolated from cell line PC3MLuc2a were fluorescently labelled and repeatedly administered via tail vein injection to adult CD1 NuNu male mice for a period of 4 weeks. In vivo imagining, histological analysis and gene expression profiling were performed to assess the impact of PCa EVs on the bone microenvironment. We demonstrate for the first time that PCa EVs home to both bone and lymph nodes following repeated exposures. Furthermore, the accumulation of EVs within the bone leads to distinct molecular changes indicative of disrupted bone homeostasis (e.g., changes to signaling pathways such as Paxillin p = 0.0163, Estrogen Receptor p = 0.0271, RHOA p = 0.0287, Ribonucleotide reductase p = 0.0307 and ERK/MAPK p = 0.0299). Changes in key regulators of these pathways were confirmed in vitro on human osteoblasts. In addition, our data compares the known gene signature of osteocytes and demonstrates a high proportion of overlap (52.2%), suggesting a potential role for this cell type in response to PCa EV exposure. No changes in bone histology or immunohistochemistry were detected, indicating that PCa EV mediated changes were induced at the molecular level. This study provides novel insights into the alterations induced by PCa EVs on the bone microenvironment. The observed molecular changes indicate changes in key pathways and suggest a role for osteocytes in these EV mediated early changes to bone. Further research to understand these early events may aid in the development of targeted interventions to disrupt the metastatic cascade in PCa.

Health poverty among people with type 2 diabetes mellitus (T2DM) in Malaysia.

In the context of the escalating burden of diabetes in low and middle-income countries (LMICs), there is a pressing concern about the widening disparities in care and outcomes across socioeconomic groups. This paper estimates health poverty measures among individuals with type 2 diabetes mellitus (T2DM) in Malaysia. Using data from the National Diabetes Registry between 2009 and 2018, the study linked 932,855 people with T2DM aged 40-75 to death records. Cox proportional hazards models were used to estimate the 5-year survival probabilities for each patient, stratified by age and sex, while controlling for comorbidities and area-based indicators of socio-economic status (SES), such as district-level asset-based indices and night-time luminosity. Measures of health poverty, based on the Foster-Greer-Thorbecke (FGT) measures, were employed to capture excessive risk of premature mortality. Two poverty line thresholds were used, namely a 5% and 10% reduction in survival probability compared to age and sex-adjusted survival probability of the general population. Counterfactual simulations estimated the extent to which comorbidities contribute to health poverty. 43.5% of the sample experienced health poverty using the 5% threshold, and 8.9% were health poor using the 10% threshold. Comorbidities contribute 2.9% for males and 5.4% for females, at the 5% threshold. At the 10% threshold, they contribute 7.4% for males and 3.4% for females. If all patients lived in areas of highest night-light intensity, poverty would fall by 5.8% for males and 4.6% for females at the 5% threshold, and 4.1% for males and 0.8% for females at the 10% threshold. In Malaysia, there is a high incidence of health poverty among people with diabetes, and it is strongly associated with comorbidities and area-based measures of SES. Expanding the application of health poverty measurement, through a combination of clinical registries and open spatial data, can facilitate simulations for health poverty alleviation.

Economic effects for citizens and the government of a country-level tobacco endgame strategy: a modelling study.

BACKGROUND: Aotearoa-New Zealand (A/NZ) was the first country to pass a comprehensive commercial tobacco endgame strategy into law. Key components include the denicotinisation of smoked tobacco products and a major reduction in tobacco retail outlets. Understanding the potential long-term economic impacts of such measures is important for government planning. DESIGN: A tobacco policy simulation model that evaluated the health impacts of the A/NZ Smokefree Action Plan was extended to evaluate the economic effects from both government and citizen perspectives. Estimates were presented in 2021 US$, discounted at 3% per annum. RESULTS: The modelled endgame policy package generates considerable growth in income for the A/NZ population with a total cumulative gain of US$31 billion by 2050. From a government perspective, increased superannuation payments and reduced tobacco excise tax revenue result in a negative net financial position and a cumulative shortfall of US$11.5 billion by 2050. In a sensitivity analysis considering future labour force changes, the government's cumulative net position remained negative by 2050, but only by US$1.9 billion. CONCLUSIONS: A policy such as the A/NZ Smokefree Action Plan is likely to produce substantial economic benefits for citizens, and modest impacts on government finances related to reduced tobacco tax and increases in aged pensions due to increased life expectancy. Such costs can be anticipated and planned for and might be largely offset by future increases in the size of the labour force and the proportion of people 65+ years old working in the formal economy.

Financial incentives for COVID-19 vaccines in a rural low-resource setting: a cluster-randomized trial.

We implemented a clustered randomized controlled trial with 6,963 residents in six rural Ghana districts to estimate the causal impact of financial incentives on coronavirus disease 2019 (COVID-19) vaccination uptake. Villages randomly received one of four video treatment arms: a placebo, a standard health message, a high cash incentive (60 Ghana cedis) and a low cash incentive (20 Ghana cedis). For the first co-primary outcome-COVID-19 vaccination intentions-non-vaccinated participants assigned to the cash incentive treatments had an average rate of 81% (1,733 of 2,168) compared to 71% (1,895 of 2,669) for those in the placebo treatment arm. For the other co-primary outcome of self-reported vaccinations 2 months after the initial intervention, the average rate for participants in the cash treatment was 3.5% higher than for participants in the placebo treatment (95% confidence interval (CI): 0.001, 6.9; P = 0.045): 40% (602 of 1,486) versus 36.3% (672 of 1,850). We also verified vaccination status of participants: in the cash treatment arm, 36.6% (355 of 1,058) of verified participants had at least one dose of the COVID-19 vaccine compared to 30.3% (439 of 1,544) for those in the placebo-a difference of 6.3% (95% CI: 2.4, 10.2; P = 0.001). For the intention and the vaccination outcomes, the low cash incentive (20 Ghana cedis) had a larger positive effect on COVID-19 vaccine uptake than the high cash incentive (60 Ghana cedis). Trial identifier: AEARCTR-0008775 .

Trends in all-cause mortality among adults with diagnosed type 2 diabetes in West Malaysia: 2010 - 2019.

AIMS: We determined 10-year all-cause mortality trends in diagnosed type 2 diabetes (T2D) population in West Malaysia, a middle-income country in the Western-Pacific region. METHODS: One million T2D people aged 40-79 registered in the National Diabetes Registry (2009-2018) were linked to death records (censored on 31 December 2019). Standardized absolute mortality rates and standardized mortality ratios (SMRs) were estimated relative to the Malaysian general population, and standardized to the 2019 registry population with respect to sex, age group, and disease duration. RESULTS: Overall all-cause standardized mortality rates were unchanged in both sexes. Rates increased in males aged 40-49 (annual average percent change [AAPC]: 2.46 % [95 % CI 0.42 %, 4.55 %]) and 50-59 (AAPC: 1.91 % [95 % CI 0.73 %, 3.10 %]), and females aged 40-49 (AAPC: 3.39 % [95 % CI 1.32 %, 5.50 %]). In both sexes, rates increased among those with 1) > 15 years disease duration, 2) prior cardiovascular disease, and 3) Bumiputera (Malay/native) ethnicity. The overall SMR was 1.83 (95 % CI 1.80, 1.86) for males and 1.85 (95 % CI 1.82, 1.89) for females, being higher in younger age groups and showed an increasing trend in those with either > 15 years disease duration or prior cardiovascular disease. CONCLUSIONS: Mortality trends worsened in certain T2D population in Malaysia.

Prevalence, predictors and reasons for COVID-19 vaccine hesitancy: Results of a global online survey.

Vaccine hesitancy has the potential to cripple efforts to end the COVID-19 pandemic. Policy makers need to be informed about the scale, nature and drivers of this problem, both domestically and globally, so that effective interventions can be designed. To this end, we conducted a statistical analysis of data from the CANDOUR survey (n = 15,536), which was carried out in 13 countries representing approximately half of the global population. Both pooled and country-level ordered regression models were estimated to identify predictors of vaccine hesitancy and reasons for not getting vaccinated. We found high levels of hesitancy, particularly in high-income countries. Factors driving moderate hesitancy differed from those driving extreme hesitancy. A lack of trust in health care providers was consistently the underlying driver of more extreme hesitancy. Predictors of moderate hesitancy varied across countries, though being younger and female was typically associated with greater hesitancy. While political ideology played a role in vaccine hesitancy in some countries, this effect was often moderated by income level, particularly in the US. Overall, the results suggest that different interventions such as mass-media campaigns and monetary incentives may be needed to target the moderately versus extremely hesitant. The lack of trust in health care professionals that drives extreme hesitancy may reflect deep societal mistrust in science and institutions and be challenging to overcome.

Chain-extension in hyperbranched polymers alters tissue distribution and cytotoxicity profiles in orthotopic models of triple negative breast cancers.

The therapeutic efficacy of nanomedicines is highly dependent on their access to target sites in the body, and this in turn is markedly affected by their size, shape and transport properties in tissue. Although there have been many studies in this area, the ability to design nanomaterials with optimal physicochemical properties for in vivo efficacy remains a significant challenge. In particular, it is often difficult to quantify the detailed effects of cancer drug delivery systems in vivo as tumour volume reduction, a commonly reported marker of efficacy, does not always correlate with cytotoxicity in tumour tissue. Here, we studied the behaviour in vivo of two specific poly(2-hydroxypropyl methacrylamide) (pHPMA) pro-drugs, with hyperbranched and chain-extended branched architectures, redox-responsive backbone components, and pH-sensitive linkers to the anti-cancer drug doxorubicin. Evaluation of the biodistribution of these polymers following systemic injection indicated differences in the circulation time and organ distribution of the two polymers, despite their very similar hydrodynamic radii (∼10 and 15 nm) and architectures. In addition, both polymers showed improved tumour accumulation in orthotopic triple-negative breast cancers in mice, and decreased accumulation in healthy tissue, as compared to free doxorubicin, even though neither polymer-doxorubicin pro-drug decreased overall tumour volume as much as the free drug under the dosing regimens selected. However, the results of histopathological examinations by haematoxylin and eosin, and TUNEL staining indicated a higher population of apoptotic cells in the tumours for both polymer pro-drug treatments, and in turn a lower population of apoptotic cells in the heart, liver and spleen, as compared to free doxorubicin treatment. These data suggest that the penetration of these polymer pro-drugs was enhanced in tumour tissue relative to free doxorubicin, and that the combination of size, architecture, bioresponsive backbone and drug linker degradation yielded greater efficacy for the polymers as measured by biomarkers than that of tumour volume. We suggest therefore that the effects of nanomedicines may be different at various length scales relative to small molecule free drugs, and that penetration into tumour tissue for some nanomedicines may not be as problematic as prior reports have suggested. Furthermore, the data indicate that dual-responsive crosslinked polymer-prodrugs in this study may be effective nanomedicines for breast cancer chemotherapy, and that endpoints beyond tumour volume reduction can be valuable in selecting candidates for pre-clinical trials.

The COVID-19 pandemic and health-related quality of life across 13 high- and low-middle-income countries: A cross-sectional analysis.

BACKGROUND: Most research on the Coronavirus Disease 2019 (COVID-19) health burden has focused on confirmed cases and deaths, rather than consequences for the general population's health-related quality of life (HRQoL). It is also important to consider HRQoL to better understand the potential multifaceted implications of the COVID-19 pandemic in various international contexts. This study aimed to assess the association between the COVID-19 pandemic and changes in HRQoL in 13 diverse countries. METHODS AND FINDINGS: Adults (18+ years) were surveyed online (24 November to 17 December 2020) in 13 countries spanning 6 continents. Our cross-sectional study used descriptive and regression-based analyses (age adjusted and stratified by gender) to assess the association between the pandemic and changes in the general population's HRQoL, measured by the EQ-5D-5L instrument and its domains (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression), and how overall health deterioration was associated with individual-level (socioeconomic, clinical, and experiences of COVID-19) and national-level (pandemic severity, government responsiveness, and effectiveness) factors. We also produced country-level quality-adjusted life years (QALYs) associated to COVID-19 pandemic-related morbidity. We found that overall health deteriorated, on average across countries, for more than one-third of the 15,480 participants, mostly in the anxiety/depression health domain, especially for younger people (<35 years old) and females/other gender. This translated overall into a 0.066 mean "loss" (95% CI: -0.075, -0.057; p-value < 0.001) in the EQ-5D-5L index, representing a reduction of 8% in overall HRQoL. QALYs lost associated with morbidity were 5 to 11 times greater than QALYs lost based on COVID-19 premature mortality. A limitation of the study is that participants were asked to complete the prepandemic health questionnaire retrospectively, meaning responses may be subject to recall bias. CONCLUSIONS: In this study, we observed that the COVID-19 pandemic was associated with a reduction in perceived HRQoL globally, especially with respect to the anxiety/depression health domain and among younger people. The COVID-19 health burden would therefore be substantially underestimated if based only on mortality. HRQoL measures are important to fully capture morbidity from the pandemic in the general population.

Site-specific factors associated with clinical trial recruitment efficiency in general practice settings: a comparative descriptive analysis.

BACKGROUND: Recruitment of participants is crucial to the success of randomised control trials (RCTs) but can be challenging and expensive. Current research on trial efficiency is often focused at the patient-level with an emphasis on effective recruitment strategies. Less is known about selection of study sites to optimise recruitment. We examine site-level factors that are associated with patient recruitment and cost efficiency using data from an RCT conducted across 25 general practices (GP) in Victoria, Australia. METHODS: Data on number of participants screened, excluded, eligible, recruited, and randomised from each study site were extracted from a clinical trial. Details regarding site characteristics, recruitment practices, and staff time commitment were collected using a three-part survey. The key outcomes assessed were recruitment efficiency (ratio of screened to randomised), average time, and cost for each participant recruited and randomised. To identify practice-level factors associated with efficient recruitment and lower cost, outcomes were dichotomised (25th percentile vs others) and each practice-level factor assessed against the outcomes to determine its association. RESULTS: Across 25 GP study sites, 1968 participants were screened of which 299 (15.2%) were recruited and randomised. The mean recruitment efficiency was 7.2, varying from 1.4 to 19.8 across sites. The strongest factor associated with efficiency was assigning clinical staff to identify potential participants (57.14% vs. 22.2%). The more efficient sites were smaller practices and were more likely to be rural locations and in areas of lower socioeconomic status. The average time used for recruitment was 3.7 h (SD2.4) per patient randomised. The mean cost per patient randomised was $277 (SD161), and this varied from $74 to $797 across sites. The sites identified with the 25% lowest recruitment cost (n = 7) were more experienced in research participation and had high levels of nurse and/or administrative support. CONCLUSION: Despite the small sample size, this study quantified the time and cost used to recruit patients and provides helpful indications of site-level characteristics that can help improve feasibility and efficiency of conducting RCT in GP settings. Characteristics indicative of high levels of support for research and rural practices, which often tends to be overlooked, were observed to be more efficient in recruiting.

Clinically Translatable Transcrocetin Delivery Platform for Correction of Tumor Hypoxia and Enhancement of Radiation Therapy Effects.

Improving the tumor reoxygenation to sensitize the tumor to radiation therapy is a cornerstone in radiation oncology. Here, the pre-clinical development of a clinically transferable liposomal formulation encapsulating trans sodium crocetinate (NP TSC) is reported to improve oxygen diffusion through the tumor environment. Early pharmacokinetic analysis of the clinical trial of this molecule performed on 37 patients orient to define the optimal fixed dosage to use in a triple-negative breast cancer model to validate the therapeutic combination of radiation therapy and NP TSC. Notably, it is reported that this formulation is non-toxic in both humans and mice at the defined fixed concentration, provides a normalization of the tumor vasculature within 72 h window after systemic injection, leads to a transient increase (50% improvement) in the tumor oxygenation, and significantly improves the efficacy of both mono-fractionated and fractionated radiation therapy treatment. Together, these findings support the introduction of a first-in-class therapeutic construct capable of tumor-specific reoxygenation without associated toxicities.

Analysis of Rates of Completion, Delays, and Participant Recruitment in Randomized Clinical Trials in Surgery.

Importance: Discontinuation and nonpublication are established sources of avoidable waste among surgical trials, but rates of delayed completion and recruiting shortfalls remain unclear. Objectives: To examine the rate of delayed completion, incomplete enrollment, and discontinuation among randomized clinical trials in surgical populations and the duration of delays and extent of recruiting shortfalls among these trials. Design, Setting, and Participants: This cross-sectional study examined randomized clinical trials in surgical populations registered on ClinicalTrials.gov between January 1, 2010, and December 31, 2014. Analysis was conducted between October 27, 2021, and June 30, 2022. Main Outcomes and Measures: The main outcomes were the percentages of trials completed on time or with full enrollment. Delays and recruiting shortfalls were identified by comparing projected enrollment and study timeframes prespecified at the time of registration with the actual study duration and enrollment reported on completion or discontinuation. Absolute and relative differences between planned and actual trial conduct were presented for discontinued trials and those completed with delays or recruiting shortfalls. Results: In total, 2542 randomized clinical trials in surgical populations were included in the study sample, of which 370 (14.6%; 95% CI, 13.2%-15.9%) were completed both on time and with full enrollment. Approximately 1 in 5 trials (20.4%; 95% CI, 18.9%-22.0%) were completed within their planned timeframe, and 1166 trials (45.9%; 95% CI, 43.9%-47.8%) met their prespecified enrollment target. The median delay among completed trials was 12.2 months (IQR, 5.1-24.3 months) or 66.7% (IQR, 30.1%-135.8%) longer than planned. Among completed trials that did not meet their prespecified enrollment target, the median recruiting shortfall was equivalent to 31.0% (IQR, 12.7%-55.5%) of the planned study sample. A total of 546 trials (21.5%; 95% CI, 19.9%-23.1%) were discontinued. The median time to discontinuation was 26.4 months (IQR, 15.2-45.7 months), and the median recruiting shortfall among discontinued trials was equivalent to 92.7% (IQR, 65.0%-100.0%) of the trial's prespecified enrollment target. Conclusions and Relevance: This cross-sectional study found that delayed completion, recruiting shortfalls, and untimely discontinuation were common among surgical trials. These findings highlight the importance of ensuring that investigators and funders do not overestimate the feasibility of planned trials.

An Economic Model for Estimating Trial Costs with an Application to Placebo Surgery Trials.

BACKGROUND AND OBJECTIVE: Waste in clinical trials remains rife. We developed an economic model to predict the cost of trials based on input costs, duration, power, number of sites, recruitment eligibility and consenting rates. METHODS: We parameterised the model for three proxy placebo-controlled surgical trials using data from a systematic review, a bespoke cost survey, and from the literature. We used the model to compare target and actual trial performance for (i) a trial that was completed on time but with more sites, (ii) a trial that completed after a time extension, and (iii) an incomplete trial. RESULTS: Successful trials more accurately anticipated the true recruitment rate that they achieved and those that overestimated this were most likely to fail. The costs of overestimating recruitment rates were dramatic: all proxy trials had significantly higher costs than planned, with additional funding of at least AUD$600,000 (50% above budget) required for trials that completed after adding more sites or more time, and over AUD$2 million (260% above budget) for incomplete trials. CONCLUSIONS: This model shows the trade-offs between time and cost, or both, when recruitment is lower than anticipated. Greater consideration is needed to improve trial planning, reviewing, and funding of these trials to avoid costly overruns and incomplete trials.

Holistic Wellness Coaching for Older Adults: Preliminary Evidence for a Novel Wellness Intervention in Senior Living Communities.

Although resident wellness is increasingly a priority in senior living communities, there are few programs that promote holistic wellness in later life. A total of 79 residents (ages 71 to 97; M = 84.27, SD = 6.46) from eight senior living communities completed a pilot study of a novel, staff-led wellness coaching program consisting of resident-driven goals and individual and group coaching sessions. Participants completed surveys at three time points (pre-program, post-program, and 1-month follow-up). Repeated measures ANOVAs revealed positive changes in resident health satisfaction, physical quality of life (QOL), psychological QOL, loneliness, relatedness, competence, and sense of purpose. Some of these results (i.e., psychological QOL, loneliness) persisted at follow-up. Residents reported high satisfaction with the program. These findings have implications for the application of holistic wellness frameworks in later life, as well as the development and implementation of wellness coaching programs with older adults.

Understanding the impact of lockdowns on short-term excess mortality in Australia.

During 2020 and 2021, Australia implemented relatively stringent government restrictions yet had few COVID-19 deaths. This provides an opportunity to understand the effects of lockdowns and quarantining restrictions on short-term mortality and to help provide evidence in understanding how such public health policies can impact on health. Our analysis is based on preliminary mortality data collected by the Australian Bureau of Statistics. Rates were estimated by disease and over time and compared with mortality statistics in the period 2015-2019. Comparing deaths in 2020-2021 with 2015-2019 show the annual mortality rate (per 100 000 people) fell by 5.9% from 528.4 in 2015-2019 to 497.0 in 2020-2021. Declines in mortality are across many disease categories including respiratory diseases (down 9.4 deaths per 100 000), cancer (down 7.5 deaths per 100 000) and heart disease (down 8.4 deaths per 100 000). During 2020 and 2021, Australian age-standardised mortality rates fell by 6%. This drop was similar for men and women, and was driven by a reduction in both communicable and non-communicable causes of death. Such evidence can help inform public health policies designed to both control COVID-19 and other infectious diseases.

A systematic review: Cost-effectiveness of continuous glucose monitoring compared to self-monitoring of blood glucose in type 1 diabetes.

Continuous glucose monitoring (CGM) is rapidly becoming a vital tool in the management of type 1 diabetes. Its use has been shown to improve glycaemic management and reduce the risk of hypoglycaemic events. The cost of CGM remains a barrier to its widespread application. We aimed to identify and synthesize evidence about the cost-effectiveness of utilizing CGM in patients with type 1 diabetes. Studies were identified from MEDLINE, Embase and Cochrane Library from January 2010 to February 2022. Those that assessed the cost-effectiveness of CGM compared to self-monitored blood glucose (SMBG) in patients with type 1 diabetes and reported lifetime incremental cost-effectiveness ratio (ICER) were included. Studies on critically ill or pregnant patients were excluded. Nineteen studies were identified. Most studies compared continuous subcutaneous insulin infusion and SMBG to a sensor-augmented pump (SAP). The estimated ICER range was [$18,734-$99,941] and the quality-adjusted life year (QALY) gain range was [0.76-2.99]. Use in patients with suboptimal management or greater hypoglycaemic risk revealed more homogenous results and lower ICERs. Limited studies assessed CGM in the context of multiple daily injections (MDI) (n = 4), MDI and SMBG versus SAP (n = 2) and three studies included hybrid closed-loop systems. Most studies (n = 17) concluded that CGM is a cost-effective tool. This systematic review suggests that CGM appears to be a cost-effective tool for individuals with type 1 diabetes. Cost-effectiveness is driven by reducing short- and long-term complications. Use in patients with suboptimal management or at risk of severe hypoglycaemia is most cost-effective.

Malaysian public preferences and decision making for COVID-19 vaccination: A discrete choice experiment.

Background: Low vaccine uptake has the potential to seriously undermine COVID-19 vaccination programs, as very high coverage levels are likely to be needed for virus suppression to return life to normal. We aimed to determine the influence of vaccine attributes (including access costs) on COVID-19 vaccination preferences among the Malaysian public to improve national uptake. Methods: An online Discrete Choice Experiment (DCE) was conducted on a representative sample of 2028 Malaysians. Respondents were asked to make vaccination decisions in a series of hypothetical scenarios. A nested, mixed logit model was used to estimate the preferences for vaccination over vaccine refusal and for how those preferences varied between different sub-populations. The attributes were the risk of developing severe side effects of the vaccine, vaccine effectiveness, vaccine content, vaccination schedule, and distance from home to vaccination centre. Findings: Reported public uptake of COVID-19 vaccination was primarily influenced by the risk of developing severe side effects (b = -1·747, 95% CI = -2·269, -1·225), vaccine effectiveness (b = 3·061, 95% CI = 2·628, 3·494) and its Halal status (b = 3·722, 95% CI = 3·152, 4·292). Other factors such as appointment timing and travel distance to the vaccination centre also had an effect on vaccine uptake. There was substantial heterogeneity in preferences between different populations, particularly for age groups, ethnicity, regions, and underlying health conditions. Interpretation: Perceived effectiveness and side effects are likely to affect COVID-19 vaccine uptake in Malaysia. Halal content is critical to Malays' vaccination choices. Reducing the physical distance to vaccination centres, particularly in rural areas where uptake is lower, is likely to improve uptake. Funding: Ministry of Health Research Grant from the Malaysian government [NIH/800-3/2/1 Jld.7(46), grant reference no: 57377 and warrant no: 91000776].

Effect of rapid weight loss incorporating hot salt water immersion on changes in body mass, blood markers, and indices of performance in male mixed martial arts athletes.

PURPOSE: To investigate the effects of rapid weight loss (RWL), incorporating comparison of hot water immersion (HWI) in fresh or salt water, on changes in body mass, blood markers, and indices of performance in mixed martial arts athletes. METHODS: In a crossover design comparing fresh water (FWB) to salt water (SWB; 5.0%wt/vol Epsom salt) bathing, 13 males performed 20 min of HWI (~ 40.3 °C) followed by 40 min wrapped in a heated blanket, twice in sequence (2 h total). Before bathing, ~ 26 to ~ 28 h of fluid and dietary restriction was undertaken, and ~ 24 to ~ 26 h of a high carbohydrate diet and rehydration was undertaken as recovery. RESULTS: During the entire RWL process, participants lost ~ 5.3% body mass. Body mass lost during the 2 h hot bath protocol was 2.17 ± 0.81 kg (~ 2.7% body mass) and 2.24 ± 0.64 kg (~ 2.8% body mass) for FWB and SWB, respectively (P = 0.647 between trials). Blood urea nitrogen, creatinine, sodium, chloride, hemoglobin, and hematocrit were increased (all P < 0.05), and plasma volume was decreased (~ 14%; P < 0.01), but did not differ between FWB and SWB, and were similar to baseline values after recovery. No indices of performance (e.g., countermovement jump, isometric strength, and functional threshold power) were impacted when RWL was followed by the recovery process. CONCLUSION: Under the conditions of this hot bath protocol, fluid loss was not augmented by the addition of ~ 5.0%wt/vol of Epsom salt during HWI, and RWL of ~ 5.3% body mass followed by > 24 h of recovery did not impact indices of performance.