Exploring the cost-effectiveness of EBV vaccination to prevent multiple sclerosis in an Australian setting.

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.

The disease-modifying therapy utilisation and cost trend for multiple sclerosis in Australia between 2013 and 2022.

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.

The economic burden of myalgic encephalomyelitis/chronic fatigue syndrome in Australia.

Objective This study aimed to estimate costs of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) to patients, government and Australian society. Methods Australian ME/CFS patients and their carers were recruited using convenience sampling. Patients completed an online retrospective cost diary, providing ME/CFS-related direct medical, non-medical and indirect costs. Informal care costs were collected directly from carers. Data from the Pharmaceutical Benefits Scheme and Medicare Benefits Schedule were linked to participant survey data. Annual per patient and total societal costs were estimated, broken down by category and presented in 2021 AUD. Factors associated with higher costs were investigated using generalised linear models. Results One hundred and seventy five patients (mean age 49 years s.d. 14, 79.4% female) completed the cost diary. Estimated total annual societal costs of ME/CFS in Australia ranged between $1.38 and $10.09 billion, with average annual total costs of $63 400/patient. Three-quarters of these costs were due to indirect costs ($46 731). Disability severity was the key factor associated with higher costs, particularly for indirect costs (being 2.27-fold higher for severe disability than no/mild disability). Conclusions ME/CFS poses a significant economic burden in Australia, owing mainly to high indirect and informal care costs.

Estimating the disutility of relapse in relapsing-remitting and secondary progressive multiple sclerosis using the EQ-5D-5L, AQoL-8D, EQ-5D-5L-psychosocial, and SF-6D: implications for health economic evaluation models.

BACKGROUND AND AIMS: Relapses are an important clinical feature of multiple sclerosis (MS) that result in temporary negative changes in quality of life (QoL), measured by health state utilities (HSUs) (disutilities). We aimed to quantify disutilities of relapse in relapsing remitting MS (RRMS), secondary progressive MS (SPMS), and relapse onset MS [ROMS (including both RRMS and SPMS)] and examine these values by disability severity using four multi-attribute utility instruments (MAUIs). METHODS: We estimated (crude and adjusted and stratified by disability severity) disutilities (representing the mean difference in HSUs of 'relapse' and 'no relapse' groups as well as 'unsure' and 'no relapse' groups) in RRMS (n = 1056), SPMS (n = 239), and ROMS (n = 1295) cohorts from the Australian MS Longitudinal Study's 2020 QoL survey, using the EQ-5D-5L, AQoL-8D, EQ-5D-5L-Psychosocial, and SF-6D MAUIs. RESULTS: Adjusted mean overall disutilities of relapse in RMSS/SPMS/ROMS were - 0.101/- 0.149/- 0.129 (EQ-5D-5L), - 0.092/- 0.167/- 0.113 (AQoL-8D), - 0.080/- 0.139/- 0.097 (EQ-5D-5L-Psychosocial), and - 0.116/- 0.161/- 0.130 (SF-6D), approximately 1.5 times higher in SPMS than in RRMS, in all MAUI. All estimates were statistically significant and/or clinically meaningful. Adjusted disutilities of RRMS and ROMS demonstrated a U-shaped relationship between relapse disutilities and disability severity. Relapse disutilities were higher in 'severe' disability than 'mild' and 'moderate' in the SPMS cohort. CONCLUSION: MS-related relapses are associated with substantial utility decrements. As the type and severity of MS influence disutility of relapse, the use of disability severity and MS-type-specific disutility inputs is recommended in future health economic evaluations of MS. Our study supports relapse management and prevention as major mechanisms to improve QoL in people with MS.

Can human activities enhance the trade-off intensity of ecosystem services in arid inland river basins? Taking the Taolai River asin as an example.

Driven by economic and social factors, more and more human beings intervene in nature to promote rapid economic and social development at the expense of ecosystem services (ES), which inevitably leads to the occurrence and even aggravation of ES trade-offs. Especially in the arid inland river basin is more serious. Therefore, this paper takes the Taolai River Basin as an example and uses the InVEST model to evaluate the spatial distribution of four typical ES, including carbon sequestration, oxygen release, windbreak and sand fixation, and water production, under the potential-actual states of the watershed. And use the Pearson correlation coefficient and the root mean square error (RMSE) to analyze the trade-off relationship between services from qualitative and quantitative aspects, respectively. Finally, the spatial matching types of trade-offs in the potential-actual states are discussed using Bivariate Local Indicators of Spatial Association, and the degree and scope of the impact of human activities on trade-offs are analyzed. The results show that the spatial distribution of the four ES has obvious heterogeneity in the potential-actual states, and the service volume of most services in the potential state is much higher than in the actual state. Secondly, there is a significant trade-offs relationship between Water production and Carbon sequestration and Oxygen release services under the potential state, while the actual state under the impact of human activities shows a significant synergistic relationship, which shows that human activities will not only increase the probability of trade-off will also increase the probability of synergy between ES. Finally, through the analysis of the meaning and causes of "high and low space dislocation" and "low and high space dislocation", it is shown that human activities will not only increase but also weaken the trade-off intensity of ES. The results of this study can provide a certain scientific basis for regional ecological environment planning and promote regional people to share ecological well-being.

Seasonal variation and ecological risk assessment of Pharmaceuticals and Personal Care Products (PPCPs) in a typical semi-enclosed bay - The Bohai Bay in northern China.

The Bohai Bay as a typical semi-enclosed bay in northern China with poor water exchange capacity and significant coastal urbanization, is greatly influenced by land-based inputs and human activities. As a class of pseudo-persistent organic pollutants, the spatial and temporal distribution of Pharmaceuticals and Personal Care Products (PPCPs) is particularly important to the ecological environment, and it will be imperfect to assess the ecological risk of PPCPs for the lack of systematic investigation of their distribution in different season. 14 typical PPCPs were selected to analyze the spatial and temporal distribution in the Bohai Bay by combining online solid-phase extraction (SPE) and HPLC-MS/MS techniques in this study, and their ecological risks to aquatic organisms were assessed by risk quotients (RQs) and concentration addition (CA) model. It was found that PPCPs widely presented in the Bohai Bay with significant differences of spatial and seasonal distribution. The concentrations of ∑PPCPs were higher in autumn than in summer. The distribution of individual pollutants also showed significant seasonal differences. The high values were mainly distributed in estuaries and near-shore outfalls. Mariculture activities in the northern part of the Bohai Bay made a greater contribution to the input of PPCPs. Caffeine, florfenicol, enrofloxacin and norfloxacin were the main pollutants in the Bohai Bay, with detection frequencies exceeding 80 %. The ecological risk of PPCPs to algae was significantly higher than that to invertebrates and fish. CA model indicated that the potential mixture risk of total PPCPs was not negligible, with 34 % and 88 % of stations having mixture risk in summer and autumn, respectively. The temporary stagnation of productive life caused by Covid-19 weakened the input of PPCPs to the Bohai Bay, reducing the cumulative effects of the pollutants. This study was the first full-coverage investigation of PPCPs in the Bohai Bay for different seasons, providing an important basis for the ecological risk assessment and pollution prevention of PPCPs in the bay.

The relative contribution of co-morbidities to health-related quality of life of people with idiopathic pulmonary fibrosis using the Assessment of Quality of Life-8-Dimension multi-attribute utility instrument.

PURPOSE: Little is known about the impact of co-morbidities on health-related quality of life (HRQoL) for people with idiopathic pulmonary fibrosis (IPF). We aimed to investigate the relative contribution of co-morbidities to HRQoL of people with IPF. METHODS: N = 157 participants were recruited from the Australian IPF Registry (AIPFR). Health state utilities (HSUs), and the super-dimensions of physical and psychosocial scores were measured using the Assessment of Quality of Life-8-Dimensions (AQoL-8D). The impact of co-morbidities on HRQoL was investigated using linear regression and general dominance analyses. RESULTS: A higher number of co-morbidities was associated with lower HSUs (p trend = 0.002). Co-morbidities explained 9.1% of the variance of HSUs, 16.0% of physical super-dimensional scores, and 4.2% of psychosocial super-dimensional scores. Arthritis was associated with a significant reduction on HSUs (ß = - 0.09, 95% confidence interval [CI] - 0.16 to - 0.02), largely driven by reduced scores on the physical super-dimension (ß = - 0.13, 95% CI - 0.20 to - 0.06). Heart diseases were associated with a significant reduction on HSUs (ß = - 0.09, 95% CI - 0.16 to - 0.02), driven by reduced scores on physical (ß = - 0.09, 95% CI - 0.16 to - 0.02) and psychosocial (ß = -0.10, 95% CI - 0.17 to - 0.02) super-dimensions. CONCLUSIONS: Co-morbidities significantly impact HRQoL of people with IPF, with markedly negative impacts on their HSUs and physical health. A more holistic approach to the care of people with IPF is important as better management of these co-morbidities could lead to improved HRQoL in people with IPF.

Ecosystem service trade-offs and spatial non-stationary responses to influencing factors in the Loess hilly-gully region: Lanzhou City, China.

The identification of trade-offs and synergies relationships among ecosystem services is one of the important contents of evaluating the regional ecological environment, and is of great significance to regional ecological governance and sustainable development. In this study, Lanzhou was selected as the research area. Four key ecosystem services, such as habitat quality, soil retention, food production, and ecological leisure were evaluated by using the InVEST model and related formulas. The difference comparison method was used to measure trade-offs and synergies relationships among ecosystem services. Then the spatial non-stationarity response of the trade-offs to influencing factors was explored through GWLR model. Finally, the trade-offs intensity among the ecosystem services of each township was calculated by using the PPF and the trade-offs intensity index, and township development strategies to enhance synergies had been formulated. The results showed: (1) The high-value areas of habitat quality, soil retention, and ecological leisure were all distributed in the areas with high vegetation coverage such as nature reserves, national forest parks, and forest farms, while the high-value areas of food production services were distributed in the Qinwangchuan Basin, Zhuanglang River and Wanchuan Basin and other areas with abundant water resources. (2) The spatial distribution pattern of trade-offs and synergies relatiionships among ecosystem services had heterogeneity. Among them, the habitat quality-food production, soil rentention-food production and habitat quality-ecological leisure services were mainly trade-offs in the whole study area, and the remaining services were mainly synergistic. (3) The relationships between ecosystem services trade-offs and influencing factors, including ≥0 °C accumulated temperature, DEM and construction land area proportion, were robust, and the response of trade-offs to ≥0 °C accumulated temperature and DEM was highly similar. (4) Based on the principle of superposition analysis method, the whole study area was divided into four types of areas: I (4 types of services coexistence), II (3 types of services coexistence), III (2 types of services coexistence) and IV (to develop at most one service). This study can provide certain scientific guidance for the optimization and governance of regional ecosystems and the synergic development of townships.

[Assessment of soil fertility in Artemisia argyi planting areas in Qichun county based on minimum data set].

This study aims to explore the soil fertility in the main Artemisia argyi planting areas in Qichun county.To be specific, the soil physical and chemical properties in the main planting areas of A.argyi in Qichun county were analyzed.On this basis, 12 indexes were selected for principal component analysis(PCA) which was then combined with the norm value of each index and the correlation coefficients between the indexes to establish the minimum data set(MDS).The radar map was plotted to directly demonstrate the level of each index and the comprehensive level of the sampling sites.The comprehensive index model was used to calculate the soil fertility quality index(SFQI) of the total data set(TDS) and MDS(SFQI-TDS and SFQI-MDS, respectively), and linear regression of the two was performed.The results showed that the indexes that made up the MDS for soil fertility evaluation were pH, available potas-sium, available iron, available zinc, available manganese, available copper, and available magnesium.The radar map suggested the greatest difference in soil organic matter and smallest difference in available nitrogen among the 14 sampling sites.Moreover, the overall content of available phosphorus and available iron was high, while that of available nitrogen was the lowest.The SFQI-MDS which was yielded based on the weight of each index in MDS calculated with the norm value was more sensitive and the SFQI had stronger correlation with TDS-SFQI, which can better represent TDS-SFQI.SFQI-MDS was in the range of 0.298-0.784, with the average of 0.565 and variation coefficient of 18.38%.Caohe Town had the highest average SFQI-MDS.Clustering of SFQI-MDS value suggested that the soil fertility can be classified into 4 levels: level Ⅰ(SFQI ≥ 0.677) indicated excellent soil fertility, which accounted for 11.24%(mainly in Qingshi town, Balihu, and Zhangbang town); level Ⅱ(0.571≤SFQI≤0.680) meant good fertility, which made up 43.82%(mainly in Caohe town, Hengche town, and Pengsi town); level Ⅲ(0.466≤SFQI≤0.557) indicated average fertility, which took up 32.58%(mainly in Chidong town and Zhulin town); level Ⅳ(SFQI≤0.421) suggested poor fertility, which accounted for 12.36%(mainly in Guanyao town).It is recommended that nitrogen, potassium, magnesium, and calcium fertilizers should be increased and organic ferti-lizer should be applied for the cultivation of A.argyi in Qichun county to improve soil fertility and soil physical and chemical properties.

Survival outcome assessment for triple-negative breast cancer: a nomogram analysis based on integrated clinicopathological, sonographic, and mammographic characteristics.

OBJECTIVE: This study aimed to incorporate clinicopathological, sonographic, and mammographic characteristics to construct and validate a nomogram model for predicting disease-free survival (DFS) in patients with triple-negative breast cancer (TNBC). METHODS: Patients diagnosed with TNBC at our institution between 2011 and 2015 were retrospectively evaluated. A nomogram model was generated based on clinicopathological, sonographic, and mammographic variables that were associated with 1-, 3-, and 5-year DFS determined by multivariate logistic regression analysis in the training set. The nomogram model was validated according to the concordance index (C-index) and calibration curves in the validation set. RESULTS: A total of 636 TNBC patients were enrolled and divided into training cohort (n = 446) and validation cohort (n = 190). Clinical factors including tumor size > 2 cm, axillary dissection, presence of LVI, and sonographic features such as angular/spiculated margins, posterior acoustic shadows, and presence of suspicious lymph nodes on preoperative US showed a tendency towards worse DFS. The multivariate analysis showed that no adjuvant chemotherapy (HR = 6.7, 95% CI: 2.6, 17.5, p < 0.0005), higher axillary tumor burden (HR = 2.7, 95% CI: 1.0, 7.1, p = 0.045), and ≥ 3 malignant features on ultrasound (HR = 2.4, CI: 1.1, 5.0, p = 0.021) were identified as independent prognostic factors associated with poorer DFS outcomes. In the nomogram, the C-index was 0.693 for the training cohort and 0.694 for the validation cohort. The calibration plots also exhibited excellent consistency between the nomogram-predicted and actual survival probabilities in both the training and validation cohorts. CONCLUSIONS: Clinical variables and sonographic features were correlated with the prognosis of TNBCs. The nomogram model based on three variables including no adjuvant chemotherapy, higher axillary tumor load, and more malignant sonographic features showed good predictive performance for poor survival outcomes of TNBC. KEY POINTS: • The absence of adjuvant chemotherapy, heavy axillary tumor load, and malignant-like sonographic features can predict DFS in patients with TNBC. • Mammographic features of TNBC could not predict the survival outcomes of patients with TNBC. • The nomogram integrating clinicopathological and sonographic characteristics is a reliable predictive model for the prognostic outcome of TNBC.

A gender-specific assessment of tobacco use risk factors: evidence from the latest Pakistan demographic and health survey.

BACKGROUND: The high prevalence of tobacco use in Pakistan poses a substantial health and economic burden to Pakistani individuals, families, and society. However, a comprehensive assessment of the key risk factors of tobacco use in Pakistan is very limited in the literature. A better understanding of the key risk factors of tobacco use is needed to identify and implement effective tobacco control measures. OBJECTIVES: To investigate the key socioeconomic, demographic, and psychosocial determinants of tobacco smoking in a recent large nationally representative sample of Pakistani adults. METHODS: N = 18,737 participants (15,057 females and 3680 males) from the 2017-18 Pakistan Demographic Health Survey, aged 15-49 years, with data on smoking use and related factors were included. Characteristics of male and female participants were compared using T-tests (for continuous variables) and χ2-tests (for categorical variables). Multivariable logistic regression models were used to identify gender-specific risk factors of tobacco use. The Receiver Operating Characteristic Curve test was used to evaluate the predictive power of models. RESULTS: We found that the probability of smoking for both males and females is significantly associated with factors such as their age, province/region of usual residence, education level, wealth, and marital status. For instance, the odds of smoking increased with age (from 1.00 [for ages 15-19 years] to 3.01 and 5.78 respectively for females and males aged 45-49 years) and decreased with increasing education (from 1.00 [for no education] to 0.47 and 0.50 for females and males with higher education) and wealth (from 1.00 [poorest] to 0.43 and 0.47 for richest females and males). Whilst the odd ratio of smoking for rural males (0.67) was significantly lower than that of urban males (1.00), the odds did not differ significantly between rural and urban females. Finally, factors such as occupation type, media influence, and domestic violence were associated with the probability of smoking for Pakistani females only. CONCLUSIONS: This study identified gender-specific factors contributing to the risk of tobacco usage in Pakistani adults, suggesting that policy interventions to curb tobacco consumption in Pakistan should be tailored to specific population sub-groups based on their sociodemographic and psychosocial features.

Spatiotemporal distribution, ecological risk assessment and source analysis of legacy and emerging Per- and Polyfluoroalkyl Substances in the Bohai Bay, China.

The Bohai Sea is one of the most polluted hotspots by per- and Polyfluoroalkyl substances (PFASs) in the world and studies on the vertical distribution of PFASs at different water layers and phase partitioning between water and suspended particulate matter (SPM) were still limited. 23 legacy and emerging PFASs were investigated in seawater and SPM throughout the Bay in this study. The average concentrations of ∑PFASs in seawater were 48.21 ng/L and 52.71 ng/L during the periods of wet and normal water, respectively. In general, the concentrations of ∑PFASs in surface water were higher than that in deep water. Legacy PFASs in seawater were dominated by PFOA and short-chain PFASs, while the emerging alternative HFPO-DA was detected in the whole water layer of the Bohai Bay with an average concentration of 1.09 ng/L. The spatial distribution showed that ∑PFASs were higher nearshore than inside the bay and higher in the south than that in the north of the bay. The average concentration of ∑PFASs in SPM was 9.02 ng/g. Long-chain PFASs and the emerging alternative 6:2 Cl-PFESA accounted for the major contaminants. The partition coefficients log Kd and φspm-w showed a linear positive correlation with carbon chain length. Preliminary risk assessments revealed that the ecological risk of common PFASs in the Bohai Bay was low, while PFOA was at moderate risk. The principal component analysis demonstrated that the production process of traditional fluorochemical factories, fire-fighting and emerging electroplating industries were the main sources of PFASs. This was the first comprehensive survey of emerging PFASs in different water depths and in SPM of the Bohai Bay during different seasons, which provided important scientific data for studying the ecological risks and pollution prevention of PFASs.

Assessment of soil quality for guided fertilization in 7 barley agro-ecological areas of China.

Soil quality is the basis for the development of sustainable agriculture and may be used for evaluating the sustainability of soil management practices. Soil quality status and integrated soil quality index (SQI) in sampled 97 farmlands distributed in 7 barley agro-ecological areas of China were analyzed by using 13 soil chemical parameters. The results showed six principal components totally explained 72% variability for the 13 parameters and identified 9 parameters (includes pH, NH4+-N, NO3--N, available P, available K, exchangeable Mg, DTPA-Fe, DTPA-Cu and Cl-) with high factor loading values as the minimum data set (MDS) for assessing soil quality. Average soil quality of all farmlands is moderate (SQI = 0.62). The SQI of barley farmlands in 7 agro-ecological areas showed the following order: Inner Mongolia Plateau (0.75 ± 0.02) > Yunnan-Kweichow Plateau (0.72 ± 0.06) > Qinghai-Tibet Plateau (0.63 ± 0.08) > Yangtze Plain (0.62 ± 0.10) > Huanghuai Region (0.58 ± 0.09) > Northeast China Plain (0.56 ± 0.07) > Xinjiang Province (0.54 ± 0.07). Total 29 out of 97 farmlands in 7 areas have low SQI level (< 0.55). Hence, these farmlands require urgent attention for soil quality improvement through modification of the soil parameters in the MDS.

Systematic Review and Meta-Analysis of Health State Utility Values for Osteoarthritis-Related Conditions.

OBJECTIVE: Health state utility values (HSUVs) are a key input in health economic modeling, but HSUVs of people with osteoarthritis (OA)-related conditions have not been systematically reviewed and meta-analyzed. Our objective was to systematically review and meta-analyze the HSUVs for people with OA. METHODS: Searches within health economic/biomedical databases were performed to identify eligible studies reporting OA-related HSUVs. Data on study design, participant characteristics, affected OA joint sites, treatment type, HSUV elicitation method, considered health states, and the reported HSUVs were extracted. HSUVs for people with knee, hip, and mixed OA in pre- and posttreatment populations were meta-analyzed using random effects models. RESULTS: A total of 151 studies were included in the systematic review, and 88 in meta-analyses. Of 151 studies, 56% were conducted in Europe, 75% were in people with knee and/or hip OA, and 79% were based on the EuroQoL 5-dimension instrument. The pooled mean baseline HSUVs for knee OA core interventions, medication, injection, and primary surgery treatments were 0.64 (95% confidence interval [95% CI] 0.61-0.66), 0.56 (95% CI 0.45-0.68), 0.58 (95% CI 0.50-0.66), and 0.52 (95% CI 0.49-0.55), respectively. These were 0.71 (95% CI 0.59-0.84) for hip OA core interventions and 0.52 (95% CI 0.49-0.56) for hip OA primary surgery. For all knee OA treatments and hip OA primary surgery, pooled HSUVs were significantly higher in the post- than the pretreatment populations. CONCLUSION: This study provides a comprehensive summary of OA-related HSUVs and generates an HSUV database for people with different affected OA joint sites undergoing different treatments to guide HSUV choices in future health economic modeling of OA interventions.

Ablation of Sam68 in adult mice increases thermogenesis and energy expenditure.

Genetic deletion of Src associated in mitosis of 68kDa (Sam68), a pleiotropic adaptor protein prevents high-fat diet-induced weight gain and insulin resistance. To clarify the role of Sam68 in energy metabolism in the adult stage, we generated an inducible Sam68 knockout mice. Knockout of Sam68 was induced at the age of 7-10 weeks, and then we examined the metabolic profiles of the mice. Sam68 knockout mice gained less body weight over time and at 34 or 36 weeks old, had smaller fat mass without changes in food intake and absorption efficiency. Deletion of Sam68 in mice elevated thermogenesis, increased energy expenditure, and attenuated core-temperature drop during acute cold exposure. Furthermore, we examined younger Sam68 knockout mice at 11 weeks old before their body weights deviate, and confirmed increased energy expenditure and thermogenic gene program. Thus, Sam68 is essential for the control of adipose thermogenesis and energy homeostasis in the adult.

Does health-related quality of life differ between people with relapse onset and progressive onset Multiple Sclerosis?

BACKGROUND: Multiple Sclerosis (MS) can be categorised as relapse onset MS (ROMS) and progressive onset MS (PROMS). We aimed to examine if health-related quality of life (in terms of health state utilities [HSUs] and dimensional scores) differed by onset type, in which health dimensions the differences were most pronounced, and whether these differences remained when stratified by disability severity. METHODS: We estimated HSUs and the unique composite 'super-dimension' and 'individual dimension' scores (crude, age, sex, disease duration and disease modifying therapies use adjusted; and stratified by onset type and disability severity) for a sample of 1577 participants in the Australian MS Longitudinal Study, using the Assessment of Quality of Life (AQoL)-8D. RESULTS: Adjusted mean overall HSU of PROMS was 0.55, 0.07 lower than ROMS. Adjusted mean physical and psychosocial super-dimension scores for PROMS were 0.51 and 0.28, 0.07 and 0.06 lower than for ROMS, respectively. For the individual health dimensions, the largest difference was seen in independent living (-0.12), followed by relationships (-0.07), and self-worth (-0.07). Whilst HSUs and dimensional scores were negatively associated with increasing disability severity in both onset types, estimates by disability severity did not differ between the two cohorts. CONCLUSIONS: Our study provides a comprehensive assessment of the effects of MS onset type on the overall and disability-severity specific HRQoL scores using a detailed preferentially sensitive AQoL-8D instrument. While overall HRQoL was substantially lower in PROMS than in ROMS, the mean HRQoL values for each disability level did not differ by onset type, indicating that future health economic models can use the same HSU inputs for both onset types.

Systematic Review of the Evolution of Health-Economic Evaluation Models of Osteoarthritis.

OBJECTIVE: To comprehensively synthesize the evolution of health-economic evaluation models (HEEMs) of all osteoarthritis (OA) interventions, including preventions, core treatments, adjunct nonpharmacologic interventions, pharmacologic interventions, and surgical treatments. METHODS: The literature was searched within health-economic/biomedical databases. Data extracted included OA type, population characteristics, model setting/type/events, study perspective, and comparators; the reporting quality of the studies was also assessed. The review protocol was registered at the International Prospective Register of Systematic Reviews (CRD42018092937). RESULTS: Eighty-eight studies were included. Pharmacologic and surgical interventions were the focus in 51% and 44% of studies, respectively. Twenty-four studies adopted a societal perspective (with increasing popularity after 2013), but most (63%) did not include indirect costs. Quality-adjusted life years was the most popular outcome measure since 2008. Markov models were used by 62% of studies, with increasing popularity since 2008. Until 2010, most studies used short-to-medium time horizons; subsequently, a lifetime horizon became popular. A total of 86% of studies reported discount rates (predominantly between 3% and 5%). Studies published after 2002 had a better coverage of OA-related adverse events (AEs). Reporting quality significantly improved after 2001. CONCLUSION: OA HEEMs have evolved and improved substantially over time, with the focus shifting from short-to-medium-term pharmacologic decision-tree models to surgical-focused lifetime Markov models. Indirect costs of OA are frequently not considered, despite using a societal perspective. There was a lack of reporting sensitivity of model outcome to input parameters, including discount rate, OA definition, and population parameters. While the coverage of OA-related AEs has improved over time, it is still not comprehensive.

The increasing economic burden of multiple sclerosis by disability severity in Australia in 2017: Results from updated and detailed data on types of costs.

BACKGROUND: Economic costs of Multiple Sclerosis (MS) in Australia were last estimated in 2010 and are likely to have changed over time, especially given this new era of increased access to higher efficacy disease modifying therapies (DMTs) with a strong focus on earlier MS diagnosis and treatment. OBJECTIVES: To provide a comprehensive contemporary analysis of the updated direct and indirect costs of MS in Australia from a societal perspective and to examine how the cost landscape has changed overtime. METHODS: Costs were estimated from the 2016 Economic Impact Survey (EIS) of the Australian MS longitudinal Study (AMSLS) and were stratified by various (indirect and direct) cost categories/sub-categories and disability severity. Disability was assessed with the patient determined disease steps (PDDS) and mapped against the gold-standard Expanded Disability Status Scale (EDSS), and classified as no disability (EDSS level: 0), mild (EDSS 1-3.5), moderate (EDSS 4-6) and severe (EDSS 6.5-9.5). A generalized linear model (GLM) predicted covariate adjusted costs for each disability severity. All costs are presented in 2017 Australian dollars. RESULTS: 488 (15.5% of the 3,163) AMSLS participants completed the survey. Annual costs per person with MS increased 17% from 2010 to $68,382 in 2017, driven largely by increased direct costs (from $16,306 in 2010 to $30,346 in 2017) (particularly those related to DMTs, hospitalizations, consultations, and medical tests), but offset by decreased costs of lost wages (from $29,030 in 2010 to $21,858 in 2017) as a result of recent positive shifts in the employment landscape for Australians with MS. Costs increased with increasing disability severity: $30,561 (95% confidence intervals [CI]: $25,672-$35,451), $55,815 (95%CI: $47,503-$64,126), $76,915 (95%CI: $68,866-$84,964), and $114,813 (95%CI: $102,252-$127,374) for no, mild, moderate and severe disability, respectively. The differences in costs between the four disability groups remained statistically significant even after adjustment for age, sex, DMT usage status, disease course and areas of remoteness. CONCLUSIONS: MS has an increasing economic burden in Australia. The study provides current economic data on MS in Australia that are important for policy development, priority setting and management of public health.

Measuring and decomposing the effort regarding the equity of inpatient benefits based on the adjustment of the new cooperative medical scheme in western rural China.

BACKGROUND: The ultimate objective of rural health reform and development is to establish a mature healthcare service system that adapts to the socialist market economy and the developmental level of the Chinese economy and meets the health demands of the people. Reform of the payment system is one of the key elements. This article explores the effect of the system and the causes of benefit inequity, provides an objective evaluation of policy implementation and offers data support for policy adjustment. METHODS: A two-stage stratified random sampling data collection method comprising a survey in 2009 (the sample size was 3832 families) and a follow-up survey in 2015 (the sample size was 3992 families) was used. Qualitative data are presented as rates or ratios and the χ2 test was used for descriptive statistics. Quantitative data were analysed using a t test. A generalized linear model (GLM) with gamma distribution of the log connection function was adopted to analyse the factors of the compensation benefit inequity. The degree of the compensation benefit inequity contribution was analysed using the concentration index (CI) decomposition method and the Oaxaca decomposition method. RESULTS: Reimbursement refers to the reimbursement expense received by inpatients from the New Cooperative Medical System (NCMS). In the GLM, there were some positive factors for reimbursement in the NCMS, including economic level, level of health facility and deductibles. The CI decomposition analysis results show that the main factors that increased the compensation benefit inequity were economic levels and deductibles over the past 2 y. However, inpatient days (2009) and the actual reimbursement ratio (2015) decreased the inequity. The Oaxaca decomposition analysis results suggest that changes in compensation benefit inequity between 2009 and 2015 were more attributable to changes in economic status and variables related to policy compensation than to demographic variables. Conclusions: This study showed that inequity decreased from 2009 to 2015, which could be the result of adjustment of the compensation policy. However, we should remain vigilant lest the gap between the rich and the poor leads to an increase in inequity.

Viral dynamics of an HIV stochastic model with cell-to-cell infection, CTL immune response and distributed delays.

Recent studies have demonstrated that both virus-to-cell infection and cell-to-cell transmission play an important role in the process of HIV infection. In this paper, stochastic perturbation is introduced into HIV model with virus-to-cell infection, cell-to-cell transmission, CTL immune response and three distributed delays. The stochastic integro-delay differential equations is transformed into a degenerate stochastic differential equations. Through rigorous analysis of the model, we obtain the solution is unique, positive and global. By constructing appropriate Lyapunov functions, the existence of the stationary Markov process is derived when the critical condition is bigger than one. Furthermore, the extinction of the virus for sufficiently big noise intensity is established. Numerically, we investigate that the small noise intensity of fluctuations could help to sustain the number of virions and CTL immune response within a certain range, while the big noise intensity may be beneficial to the extinction of the virus. We also examine that the influence of random fluctuations on model dynamics may be more significant than that of the delay.