Huang L†, Devlin N, Chen G & Dalziel K. Social Science & Medicine, 2024, 348: 116802. DOI: 10.1016/j.socscimed.2024.116802.

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To date, health state utilities are predominantly derived using stated preference methods based on decision utility. This study contribute to the literature by showing that using experienced utility methods to generate preference weights for health states is possible, and we discuss some important methodological challenges for future studies such as the impracticability of anchoring to ‘dead’ when utilizing experienced utility.

Chen G, Olsen JA† & Lamu AN. Social Science & Medicine, 2024, 343: 116581. DOI: 10.1016/j.socscimed.2024.116581.

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This study facilitates a better understanding of education-health behaviours nexus from a life course perspective. Results support the hypothesis that own health behaviour is affected by the educational attainments of our ‘nearest and dearest’ (i.e. spouse, mother, and father), net of own education. In particular, partners' education attainments are relatively more important for avoiding unhealthy behaviour than choosing healthy behaviour; on the contrary, parents' education is more important for healthy behaviour.

Woode ME & Chen G†. Value in Health, DOI: https://doi.org/10.1016/j.jval.2024.02.010.

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This study adopts a partial least squares structural equation modelling (PLS-SEM) approach to investigate the relative importance and performance of 14 key life domains of early adolescents across age cohorts and 10 countries at different levels of economic development. 

Mpundu-Kaambwa C†, Bulamu NB, Lines L, Chen G, Whitehurst DGT, Dalziel K, Devlin K & Ratcliffe J, on behalf of the QUality Of life in Kids: Key evidence to strengthen decisions in Australia (QUOKKA) project team. PharmacoEconomics, DOI: 10.1007/s40273-024-01357-z.

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A total of 22 paediatric pictorial PROMs, comprising 28 unique versions, were identified. Likert scales with pictorial anchors, particularly happy–sad faces, were commonly used for response options. Various graphic methods, such as happy–sad faces, cartoons, and thermometers, were adapted to specific content domains. There is some evidence that pictorial PROMs facilitate self-report in this population and improve measurement properties compared to text-only PROMs. 

O’Loughlin R†, Jones R, Chen G, Mulhern B, Hiscock H, Devlin N & Dalziel K, in collaboration with the QUality Of life in Kids: Key evidence to strengthen decisions in Australia (QUOKKA) project team. PharmacoEconomics, DOI: 10.1007/s40273-024-01354-2.

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Our results indicate that the CHU9D, PedsQL, EQ-5D-Y-3L and EQ-5D-Y-5L perform equally well in children and adolescents with ADHD or anxiety and/or depression, regarding acceptability/feasibility, known-group and convergent validity. However, relative strengths of the CHU9D and PedsQL were observed regarding their lack of ceiling effects, greater test–retest reliability, and consistently good performance across all psychometric properties. The CHU9D and EQ-5D-Y-3L were the most responsive to improvements in health status.

Khanna D†, Khadka J, Mpundu-Kaambwa C, Chen G, Dalziel K, Devlin N & Ratcliffe J, in collobration with the QUality Of life in Kids: Key evidence to strengthen decisions in Australia (QUOKKA) project team. PharmacoEconomics, DOI: 10.1007/s40273-024-01356-0.

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There are two ways to complete a proxy report—from the proxy’s own perspective (proxy-proxy, Proxy 1) or answer as the child would (proxy-child, Proxy 2). Proxy-child perspective showed a stronger agreement at the dimension level for the psychosocial dimension compared with the traditional proxy-proxy perspective. While no statistically significant difference was observed for the preference-weighted HRQoL across the two proxy perspectives, the child- and parent-reported EQ-VAS scores differed significantly when the proxy-child perspective was adopted, indicating that perspective may influence this aspect of HRQoL measurement.

Xiong X†, Carvalho N, Huang L, Chen G, Jones R, Devlin N, Mulhern B & Dalziel K. PharmacoEconomics, DOI: 10.1007/s40273-024-01355-1.

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The CHU9D was found to be valid and reliable to measure health-related quality-of-life in children aged 2–4 years, although with relatively low test–retest reliability in some dimensions. Further development and validation work is warranted.

Jones R†, O’Loughlin R, Xiong X, Bahrampour M, Devlin N, Hiscock H, Chen G, Mulhern B & Dalziel K, on behalf of the QUality Of life in Kids: Key evidence to strengthen decisions in Australia (QUOKKA) project team. PharmacoEconomics, DOI: 10.1007/s40273-023-01330-2. 

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In the total sample, the EQ-5D-Y-5L and CHU9D descriptive systems demonstrated evidence of good performance (i.e., meeting prespecified criteria) across all psychometric attributes tested. Considering results for ceiling effects, test–retest reliability, and responsiveness varied by child age and report type, future instrument users should consider the decision-making context, target population, and study design when deciding which instrument will be most appropriate.

Peasgood T, Howell M†, Raghunandan R, Salisbury A, Sellars M, Chen G, Coast J, Craig JC, Devlin NJ, Howard K, Lancsar E, Petrou S, Ratcliffe J, Viney R, Wong G, Norman R & Donaldson C, on behalf of the Quality of Life in Kids: Key evidence to strengthen decisions in Australia (QUOKKA), Tools for Outcomes Research to measure, value Child Health (TORCH) project teams. PharmacoEconomics, 2024, 42 (2): 199-217. DOI: 10.1007/s40273-023-01327-x. 

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The balance of evidence suggests the general public favours prioritising children over adults, but this view was not found across all studies. There are research gaps in understanding the public’s views on the value of health gains to very young children and the motivation behind the public’s views on the value of child relative to adult health gains.

Ren Y, Liu Y† & Chen G. Children and Youth Services Review, 2024, 158: 107488. DOI: 10.1016/j.childyouth.2024.107488.

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Using two waves of nationally representative data, this study examined the evolving time-use patterns of Chinese junior high school students and their associations with self-reported health, depressive symptoms, and cognitive abilities. Four stable time-use clusters were identified from the latent class analysis. 

Xie S, Wu J† & Chen G†. European Journal of Health Economics, 2024, 25 (1): 7-19. DOI: 10.1007/s10198-023-01566-x.

Both EQ-5D-5L and SF-6Dv2 showed comparable discriminative validity. Systematic differences in utilities were found, and on average, the EQ-5D-5L generates higher values than the SF-6Dv2. Good test-retest reliability was found for both EQ-5D-5L (ICC=0.86) and SF-Dv2 (ICC=0.83). Mapping algorithms between the EQ-5D-5L and SF-6Dv2 are reported to enable transformations between these two measures in China.

Ma BH†, Chen G, Badji S & Petrie D. Quality of Life Research, 2024, 33 (2): 411-422. DOI: 10.1007/s11136-023-03532-9.

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The developed mapping algorithm enables cost-utility analyses of interventions for people with disability where the WHODAS 2.0 has been collected.

Orji NC†, Cox IA, Jason LA, Chen G, Zhao T, Rogerson MJ, Kelly RM, Wills K, Hensher M, Palmer AJ, de Graaff B & Campbell JA. Quality of Life Research, 2024, 33 (1): 45-57. DOI: 10.1007/s11136-023-03498-8.

ME/CFS has a profound impact on HRQoL. The AQoL-8D and EQ-5D-5L-Psychosocial can be used interchangeably.

Bulamu NB†, Chen G, McGrane E, Cock C, Young GP & Symonds EL. Cancer Causes & Control, 2024, 35 (2): 347-357. DOI: 10.1007/s10552-023-01789-6.

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HRQoL does not change one year following a diagnosis of the bowel at colonoscopy and it does not differentiate between different colonoscopy diagnoses including cancer. However, patients undergoing colonoscopy because of symptoms have poorer HRQoL compared to those undergoing surveillance colonoscopy for cancer. Participants reporting full health with EQ-5D-5L still had problems on the QLU-C10D, with fatigue and sleep at baseline and with role function and fatigue at follow-up. 

Lamu AN, Chen G & Olsen JA†. Social Science & Medicine, 2023, 323: 115832. DOI: 10.1016/j.socscimed.2023.115832.

This study has provided empirical evidence that spousal education contributes to explaining the amplified health gradient in an egalitarian country like Norway.

Kularatna S†, Chen G, Norman R, Mukuria C, Rowen D, Senanayake S, Hettiarachchi R, Mulhern B, Fozzard K, Parsonage W & McPhail SM. Quality of Life Research, 2023, 32 (4): 1151-1163. DOI: 10.1007/s11136-022-03325-6. 

The MacNew-7D Australian utility value set ranged from −0.4456 to 1 for health states defined by the classification system.

Mihalopoulos C†, Chen G, Scott JG, Bucholc JB, Allen C, Coghill D, Jenkins P, Norman R, Ratcliffe J, Richardson J, Stathis S & Viney R. Value in Health, 2023, 26 (5): 733-741. DOI: 10.1016/j.jval.2022.12.007.

Multi-attribute utility instruments (MAUIs), such as the EQ-5D-Y, CHU9D, HUI-2&3 & the AQoL-6D, were found to have good concurrent and construct validity when compared to self-report outcome measures but poor validity when compared to clinician or parent/guardian reported measures in children/adolescents with mental disorders.

Chen G & Olsen JA†. Quality of Life Research, 2023, 32 (2): 495-505. DOI: 10.1007/s11136-022-03243-7.

This study empirically explored the performance of a coherent set of four psycho-social bolt-ons for EQ-5D: Vitality; Sleep; Personal relationships; & Social isolation. It also investigated the relative importance of nine dimensions for explaining variations in health vs subjective wellbeing.

Chen G†, Bulamu NB, McGrane E & Richardson J. Cancers, 2023, 15 (4): 1351. DOI: 10.3390/cancers15041351.

This study investigated the extent to which patients’ SWB and generic and cancer‐specific health utility instruments are sensitive to the functional and symptom subscales employed by the QLQ‐C30 cancer‐specific instrument. The QLU‐C10D was the most sensitive instrument to most patient problems; the 15D was the most successful generic health utility instrument. This study also shows that to improve the overall life satisfaction of cancer patients, life domains, such as achievement in life, relationships, the standard of living, and future security, all play an important role in addition to health.

Hettiarachchi RM†, Kularatna S, Byrnes J, Mulhern B, Chen G & Scuffham PA. Medical Decision Making, 2023, 43(7-8): 901-913. DOI: 10.1007/s11136-023-03498-8.

This study developed an Australian-specific value set for the DCUI using DCE and VAS. The DCUI consists of five domains: pain/discomfort, difficulty eating food/drinking, worried, ability to participate in activities, and appearance (PMID: 34859442). 

Chen G, Woode ME, Sia K-L, Ellis N, Citroen C & Harris A†. Disability and Rehabilitation, 2023, 45 (3): 534-541. DOI: 10.1080/09638288.2022.2029958.

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Life Back on Track (LBoT) is a novel & valid self-reported single-item global measure of the trajectory of wellbeing after a transport accident..

Campbell JA†, Ahmad H, Chen G, van der Mei I, Taylor BV, Claflin S, Henson GJ, Simpson-Yap S, Laslett LL, Hawkes K, Hurst C, Waugh H & Palmer AJ. Quality of Life Research, 2023, 32 (2): 553-568. DOI: 10.1007/s11136-022-03214-y.

The empirical results demonstrate that the EQ-5D-5L-Psychosocial & AQoL-8D utilities are interchangeable. Additionally, when the respondent burden is taken into account and given the interchangeability of the two instruments, the EQ-5D-5L-Psychosocial is preferential to the AQoL-8D in people with multiple sclerosis. 

Shi Z, Nie H, Geng L, Wang X, Chen G & Li S†. Quality of Life Research, 2023, 32 (5): 1469-1480. DOI: 10.1007/s11136-022-03330-9. 

Patients diagnosed with primary infertility had significantly lower HRQoL and SWB than those with secondary infertility. There exists a poor agreement between EQ-5D-5L and AQoL-8D and the difference in the psychosocial components may explain the difference.

Shi Z, Mao Z, Xue S, Chen G & Li S†. BMC Psychology, 2023, 11: 346. DOI: 10.1186/s40359-023-01375-0. 

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This study explored the HRQoL of scoliosis patients and their caregivers, and identified the factors influencing caregiver burden. Overall, the caregiver burden of adolescent patients was higher than that of adult patients. 

Dou L, Xu Y, Chen G & Li S†. Health and Quality of Life Outcomes, 2023, 21: 66. DOI: 10.1186/s12955-023-02150-w.

This study compared the psychometric properties (concurrent validity, known-group validity, sensitivity, & agreement) of 4 approaches to elicit health state utility among myopia patients, including TTO, SG, AQoL-7D, and the Visual Function Questionnaire–Utility Index (VFQ-UI). Moderate to high correlations have been observed between disease-specific measures and the AQoL-7D and the VFQ-UI, while weak correlations were observed with TTO and SG. Among 4 approaches, significant differences among known groups were found in the severity of myopia and duration of myopia for VFQ-UI. Overall, the VFQ-UI had the best performance based on the psychometric analysis.

Olsen JA†, Chen G & Lamu AN. BMC Public Health, 2023, 23: 1981. DOI: 10.1186/s12889-023-16943-7.

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Indicators of socioeconomic position and health behaviours are widely used predictors of health variations. In the institutional context of a rich egalitarian country, variations in health and wellbeing are to a larger extent explained by health behaviours than educational attainment. 

Ibarra-Sanchez AS†, Chen G & Wisløff T. Frontiers in Public Health, 2023, 11: 1190087. DOI: 10.3389/fpubh.2023.1190087.

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This study explored changes in relative educational inequality in multiple variables related to health behavior (smoking, physical activity, alcohol intake, and body mass index), separately and collectively (healthy lifestyle), among middle-aged adults living in Northern Norway. Persistent and increasing relative disparities in health behavior between the highest and lower education levels were found.

Ibarra-Sanchez AS†, Abelsen B, Chen G & Wisløff T. PLoS ONE, 2023, 18 (12): e0295302. DOI: 10.1371/journal.pone.0295302.

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This study presents findings from a longitudinal multiple correspondence analysis on patterns of BMI & multiple health behaviors (smoking, physical activity and alcohol consumption) over time. The findings suggest that most in the study population remained in the same categories of body mass index and the three health behaviors at the follow-up, with a clear educational gradient in healthy patterns. 

Chen G† & Olsen JA. Quality of Life Research, 2022, 31 (8): 2281-2293. DOI: 10.1007/s11136-021-03043-5.

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From both revealed and stated preference data there was robust evidence that health, relationships, and standard of living represent the three most important life domains for older adults in Australia. This study also identified diminishing marginal utilities across the levels of each life domain.

Xie S, Wu J† & Chen G†. Quality of Life Research, 2022, 31 (9): 2791-2803. DOI: 10.1007/s11136-022-03159-2.

This is the first study to compare the test-retest reliability of TTO and DCETTO approaches. Results indicate that individual responses to both approaches are relatively stable over time (with a mean interval of 16 days).

Kwon J, Freijser L, Huynh E, Howell M, Chen G, Khan K, Daher S, Roberts N, Harrison C, Smith S, Devlin N, Howard K, Lancsar E, Bailey C, Craig J, Dalziel K, Hayes A, Mulhern B, Wong G, Ratcliffe J & Petrou S†. PharmacoEconomics, 2022, 40 (4): 379–431. DOI: 10.1007/s40273-021-01128-0.

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This systematic review identified 110 versions of generic, multidimensional patient-reported outcome measures (PROMs) for children (aged ≤18 years) spanning childhood age groups and conceptual bases of functional, disability and health status, quality of life and health-related quality of life. A supplementary systematic review identified 21 preference-based value sets for 10 PROMs designed to be accompanied by preference-based value sets.

Bailey C†, Howell M, Raghunandan R, Salisbury A, Chen G, Coast J, Craig JC, Devlin NJ, Huynh E, Lancsar E, Mulhern BJ, Norman R, Petrou S, Ratcliffe J, Street DJ, Howard K & Viney R, on behalf of the Quality Of Life in Kids: Key evidence to strengthen decisions in Australia (QUOKKA), Tools for Outcomes Research to Measure, Value Child Health (TORCH) Project Teams. PharmacoEconomics, 2022, 40 (7): 663-698. DOI: 10.1007/s40273-022-01149-3.

Studies included in this review used a range of preference elicitation methods such as standard gamble, time-trade off, discrete choice modelling, best-worst scaling and visual analogue scales, with and without modification, for different sources of values (who was asked, children or adults or both) and perspectives (point of view that participants were asked to consider). Differences in reporting limited the conclusions that can be formed about which methods are most suitable for eliciting preferences for children’s health and the influence of differing perspectives and values.

Mpundu-Kaambwa C†, Bulamu N, Lines L, Chen G, Dalziel K, Devlin N & Ratcliffe J, on behalf of the Quality Of Life in Kids: Key Evidence for Decision Makers in Australia (QUOKKA) Project Team. Value in Health, 2022, 25 (10): 1791-1804. DOI: 10.1016/j.jval.2022.04.1723.

The review has identified and summarized published guidance and recommendations for child self- and proxy assessment of existing child-specific instruments of HRQoL that are accompanied by utilities. The findings suggest a lack of guidance and an urgent need to fill evidence gaps to inform the generation of guidance. 

Kularatna S†, Rowen D, Mukuria C, McPhail S, Chen G, Mulhern B, Whitty JA, Byrnes J, Scuffham P, Atherton J, Höfer S & Parsonage W. Quality of Life Research, 2022, 31 (1): 257-268. DOI: 10.1007/s11136-021-02884-4.

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This study created a brief heart disease-specific classification system, consisting of 7 dimensions (frustrated, wornout, shortness of breath, chest pain, self-confidence, excluded, physical restriction) with 4 severity levels in each.

Hettiarachchi RM†, Kularatna S, Byrnes J, Chen G, Mulhern B & Scuffham PA. Journal of Public Health Dentistry, 2022, 82 (3): 253-261. DOI: 10.1111/jphd.12490.

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The DCUI consists of five dimensions/items (pain/discomfort, difficulty in eating food/drinking, worried, ability to participate in activities, and appearance) and each item adopts a four-level response scale.

Chen G†, DunnGalvin A & Campbell DE. Clinical & Experimental Allergy, 2022, 52 (1): 162-166. DOI: 10.1111/cea.13973.

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We surveyed parents of children and adolescents with food allergy before and during the pandemic. Parent/carer report of a negative impact was associated with worse quality of life and life satisfaction. Across 14 life domains, statistically significant differences were found for children and adolescents between those with negative and neutral/positive impacts from COVID-19 in 7 domains. The most notable were family life, future security, friendship, and personal relationships.

Lins de Holanda Coelho G†, DunnGalvin A, Greenhawt M, Hourihane JO’B, Fleischer DM, Chen G, Shaker M, Campbell DE, Green TD & Bégin P. Allergy, 2022, 77 (9): 2770-2777. DOI: 10.1111/all.15323.

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This paper present a novel re-analysis of the FAQLQ-PF items using item response theory. The longitudinal performance of individual items and subscales was corroborated, and items with the highest discrimination were identified, showing that the tool is suitable for longitudinal measurements in food allergy treatment trials.

Lindberg MH†, Chen G, Olsen JA & Abelsen B. BMC Public Health, 2022, 22: 969. DOI: 10.1186/s12889-022-13366-8. 

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This study adopts a regression-based method for developing a composite socioeconomic position (SEP) score with empirically derived education and income weights along a [1-10] SEP scale.

Si Y, Li S†, Xu Y & Chen G. Quality of Life Research, 2022, 31 (5): 1561-1572. DOI: 10.1007/s11136-021-03047-1.

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This study compared the psychometric properties of 5 preference-based measures, including the 15D, AQoL-7D, EQ-5D-5L, ICECAP-A, & ICECAP-O.

Shi Z, Li S† & Chen G. Psychology Research and Behavior Management, 2022, 15: 1247-1258. DOI: 10.2147/PRBM.S357913.

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TIPI-C primarily stands out as a feasible instrument for brief measurements of the Extraversion, Emotional Stability, and Conscientiousness domains. However, the internal consistency coefficients of Agreeableness and Openness were low and the structural validity was not supported.

Yang Z, Li S†, Wang X & Chen G. Journal of Dermatological Treatment, 2022, 33 (2): 1029-1036. DOI: 10.1080/09546634.2020.1800571.

Dou L, Mao Z, Fu Q, Chen G & Li S†. Patient Preference and Adherence, 2022, 16: 781-795. DOI: 10.2147/PPA.S347681.

Si L, Tu L, Xie Y, Chen G, Hiligsmann M, Yang M, Zhang Y, Zhang X, Jiang Y, Wei Q, Gu J† & Palmer AJ. Social Indicators Research, 2022, 160 (2-3), 809–824. DOI: 10.1007/s11205-020-02414-8.

Shi Z, Mao Z, Nie H, Geng L, Chen G & Li S†. Health and Quality of Life Outcomes, 2022, 20: 54. DOI: 10.1186/s12955-022-01957-3. 

Vatandoust S†, Watthow D, Sposato L, Michael MZ, Leung J, Gormly K, Chen G, Symonds EL, Tie J, Papanicolas LE, Woods S, Gebski V, Mead K, Kuruni A & Karapetis CS. BMC Cancer, 2022, 22: 222.. DOI: 10.1186/s12885-022-09304-x.

Chen G†, Ratcliffe J, Milte R, Khadka J & Kaambwa B. Social Science & Medicine, 2021, 289: 114440. DOI: 10.1016/j.socscimed.2021.114440.

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Person-centred care is a key dimension of quality of care across health and social care sectors. A preference-based Quality of Care Experience (QCE) in aged care measure was developed in this study. A novel first-stage discrete choice experiment (DCE) and a second-stage quality rating task were designed to empirically estimate the relative importance of six key aged care quality criteria from more than 10,000 Australian general population sample. 

Osman AMY, Wu J†, He X & Chen G†. Social Science & Medicine, 2021, 279: 114018. DOI: 10.1016/j.socscimed.2021.114018.

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This study proposed using an anchored best-worst scaling technique to develop preference weights directly for a preference-based health-related quality of life instrument.

Wu J†, Xie S, He X, Chen G, Bai G, Feng D, Hu M, Jiang J, Wang X, Wu H, Wu Q & Brazier JE. PharmacoEconomics, 2021, 39 (5): 521-535. DOI: 10.1007/s40273-020-00997-1.

De Albornoz SC & Chen G†. Journal of Psychosomatic Research, 2021, 142, 110356. DOI: 10.1016/j.jpsychores.2021.110356.

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This study revealed significant heterogeneity on the relative importance of key life domains satisfaction on overall life satisfaction in asthma patients.

Lindberg MH†, Chen G, Olsen JA & Abelsen B. SSM – Population Health, 2021, 15: 100864. DOI: 10.1016/j.ssmph.2021.100864.

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This study provides new insights into respondents’ implicit weighting of objective and childhood factors in predicting subjective socioeconomic position (SEP). We have estimated the contribution of each of the commonly used objective SEP indicators (education, occupation & income) in explaining subjective SEP. In addition, we have added childhood SEP as an important determinant of subjective SEP; while controlling for the objective SEP variables, we found that the influence of childhood SEP persisted into adulthood.

Wall D†, Meah N, York K, [...], Chen G, [...] & Sinclair R. JAMA Dermatology, 2021, 157 (4): 439-448. DOI: 10.1001/jamadermatol.2020.5839.

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This study seeks to reach international consensus regarding the core domains and data items required to build a network of patient registries to monitor real-world demographics and outcomes of alopecia areata.

Crocker M†, Hutchinson C, Mpundu-Kaambwa C, Walker R, Chen G & Ratcliffe J. Health and Quality of Life Outcomes, 2021, 19: 264. DOI: 10.1186/s12955-021-01901-x.

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Respondents were asked to rank the importance of 12 quality of life dimensions extracted from the content of established preference‑based quality of life measures (EQ‑5D, AQoL-4D and ASCOT). People with a disability placed relatively higher importance on broader quality of life dimensions (e.g. Control, Independence, Self-care) relative to health status focused dimensions (e.g. Vision, Hearing, Physical mobility). This distinction was less differentiable for those ‘without a disability’.

Chen G†, DunnGalvin A, Greenhawt M, Shafer M & Campbell DE. Pediatric Allergy and Immunology, 2021, 32 (8): 1773-1780. DOI: 10.1111/pai.13604.

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Food Allergy Quality of Life Questionnaire-Parental Form (FAQLQ-PF) is one of the most widely used food allergy specific instruments for assessing the psychosocial impacts of the disease. This study developed mapping algorithms that can predict AQoL-6D or CHU9D health utility scores from FAQLQ-PF. Outputs from this study can facilitate health economic evaluation for food allergy related interventions.

Wolf RT†, Ratcliffe J, Chen G & Jeppesen P. Quality of Life Research, 2021, 30 (6): 1747-1756. DOI: 10.1007/s11136-021-02774-9.

Bulamu NB, Vissapragada R, Chen G, Ratcliffe J, Mudge LA, Smithers MB, Isenring EA, Smith L, Jamieson GG & Watson DI†, on behalf of The Australian Immunonutrition Study Group. Health and Quality of Life Outcomes, 2021, 19: 233. DOI: 10.1186/s12955-021-01867-w.

Lai VWY†, Chen G & Sinclair R. Journal of Dermatological Treatment, 2021, 32 (2): 250-257. DOI: 10.1080/09546634.2019.1654068.

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The mean health utility for patients with alopecia areata was 0.748.

Mpundu-Kaambwa C†, Chen G, Dalziel K, Devlin N & Ratcliffe J, on behalf of the Quality Of Life in Kids: Key evidence to strengthen decisions in Australia (QUOKKA) project team. BMJ Open, 2021, 11: e052049. DOI: 10.1136/bmjopen-2021-052049.

Chen G & Olsen JA†. Quality of Life Research, 2020, 29 (11): 3119-3129. DOI: 10.1007/s11136-020-02576-5.

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This study provided empirical support for complementing the current EQ-5D descriptive system with a coherent set of four bolt-on dimensions that will fill its psycho-social gap: vitality, sleep, social relationships, and community connectedness. Such an extended health state classification system would, in particular, be relevant for programme evaluations within the expanding fields of mental health and community care. An interim scoring algorithm developed based on a mapping analysis is also reported.

Xia R, Zeng H, Liu Q, Liu S, Zhang Z, Liu Y, Guo G, Song G, Zhu Y, Wu X, Song B, Liao X, Chen Y, Wei W, Chen G†, Chen W† & Zhuang G†. European Journal of Cancer Care, 2020, 29 (6): e13283. DOI: 10.1111/ecc.13283.

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Compared to healthy controls, the mean utility scores of gastric cancer patients were significantly lower, with mean decrements of 0.077, 0.254, 0.249, 0.353 and 0.591 for high-grade intraepithelial neoplasia/CIS, stage I, stage II, stage III and stage IV cancer, using the Chinese-specific EQ-5D-3L 2014 tariff; with mean decrements of 0.039, 0.121, 0.123, 0.182 and 0.309 for the corresponding clinical stages using the Chinese-specific EQ-5D-3L 2018 tariff. In addition, among these clinical stages, the magnitudes of decrement on the EQ-5D-3L index values were not significantly different between stages I to II regardless of which tariff was used.

Gao L†, Luo W, Tonmukayakul U, Moodie M & Chen G. European Journal of Health Economics, 2021, 22 (2): 341-350. DOI: 10.1007/s10198-020-01259-9.

Hettiarachchi R†, Kularatna S, Byrnes J, Mulhern B, Chen G & Scuffham PA. BMJ Open, 2020, 10: e038626. DOI: 10.1136/bmjopen-2020-038626.

Xie S, Wu J†, He X, Chen G & Brazier JE. Value in Health, 2020, 23 (10): 1391-1399. DOI: 10.1016/j.jval.2020.06.010.

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Two DCE approaches (with/without life duration) are feasible for eliciting health state utility values; however, they are not considered to be easier to understand/answer than TTO. There are systematic differences in the health state utility values generated by 3 approaches. The issue of non-monotonicity from 2 DCE approaches remains a concern.

Wu J†, Xie S, He X, Chen G & Brazier JE. Quality of Life Research, 2020, 29 (5): 1385-1391. DOI: 10.1007/s11136-020-02419-3.

Sweeney R†, Chen G, Gold L, Mensah F & Wake M. Quality of Life Research, 2020, 29 (3): 639-652. DOI: 10.1007/s11136-019-02357-9. [Correction]

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This study externally validates the two published mapping algorithms: (a) Self-report 15-item Short-Form PedsQL onto CHU9D & (b) Proxy-report 23-item PedsQL onto CHU9D. Next, a set of new mapping algorithms were developed for use when the Self-report version of the 23-item PedsQL instrument has been employed.

Kularatna S, Senanayake S†, Chen G & Parsonage W. Health and Quality of Life Outcomes, 2020, 18: 115. DOI: 10.1186/s12955-020-01368-2.

Liu T, Li S†, Wang M, Sun Q & Chen G. Patient, 2020, 13 (5): 537-555. DOI: 10.1007/s40271-020-00422-x.

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Mapping algorithms reported from EORTC QLQ-C30 and/or QLQ-BR23 onto EQ-5D-5L or SF-6Dv1.

Tonmukayakul U†, Imms C, Mihalopoulos C, Reddihough D, Carter R, Mulhern B & Chen G. Developmental Medicine & Child Neurology, 2020, 62 (7): 854-860. DOI: 10.1111/dmcn.14488.

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​Mapping algorithms reported from CP Quality of Life Questionnaire for Children (CPQoL-Child) onto the Child Health Utility 9D (CHU9D). The Manual Ability Classification System (MACS) and the Neurological Hand Deformity Classification (NHDC) explained the impact of the upper limb impairment on HRQoL better than the other classifications.

Chen G, Xu F†, Huynh E, Wang Z, Li C, Stevens K & Ratcliffe J. Quality of Life Research, 2019, 28 (1): 163-176. DOI: 10.1007/s11136-018-2032-z.

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This study used the best-worst scaling (BWS) method and time trade-off (TTO) method to derive Chinese-specific tariff for the CHU9D instrument. The value set reported in this study can be used to estimate quality-adjusted life years (QALYs) for economic evaluation in China.

Ishaque S†, Karnon J, Chen G, Nair R & Salter AB. Quality of Life Research, 2019, 28 (3): 567-592. DOI: 10.1007/s11136-018-2016-z.

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While combined evidence supports the use of PROMs in clinical practice, standards of reporting remain inadequate with many published RCTs failing to pre-specify primary outcomes and/or adequately powering their comparisons for clinically meaningful differences.

Gao L†, Moodie M & Chen G. Quality of Life Research, 2019, 28 (4): 1017-1028. DOI: 10.1007/s11136-018-2094-y.

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Assessing SWB provides complementary information on understanding heart patients’ subjective outcome over the use of quality of life instruments alone. The life domains that were significantly important to patients with heart disease were standard of living, followed by achieving in life, personal relationships, personal health, and future security. Compared to the healthy public, personal health and future security were significantly more important life domains among patients with heart disease.

Bell L†, Ullah S, Leslie E, Magarey A, Olds T, Ratcliffe J, Chen G, Miller M, Jones M & Cobiac L. BMC Public Health, 2019, 19: 1338. DOI: 10.1186/s12889-019-7710-4.

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​This study demonstrates the complexity of evaluating complex, multi-component, community-based interventions under real-world conditions.

Mpundu-Kaambwa C†, Chen G, Huynh E, Russo R & Ratcliffe J. PharmacoEconomics, 2019, 37 (9); 1139-1153. DOI: 10.1007/s40273-019-00808-2.

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The published mapping algorithms have acceptable predictive accuracy. The findings of this study indicate that the choice of the most appropriate mapping algorithm to apply may vary according to the population under consideration.

Li S, Wang M, Liu L & Chen G†. European Journal of Cancer Care, 2019, 28 (2): e12965. DOI: 10.1111/ecc.12965.

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This study empirically investigated both indirect approaches (including EQ-5D-5L & SF-6D), as well as a direct approach (the TTO) for eliciting utilities in breast cancer patients. Results suggested that the EQ-5D-5L is currently the optimal approach (followed by the SF-6D) to elicit health state utilities from breast cancer patients in mainland China.

Bulamu NB, Chen G†, Ratcliffe J, Schloithe A, Bright T & Watson DI. World Journal of Surgery, 2019, 43 (6): 1554-1562. DOI: 10.1007/s00268-019-04936-w.

Petersen KD†, Ratcliffe J, Chen G, Serles D, Frøsig CS & Olesen AV. Health and Quality of Life Outcomes, 2019, 17: 187. DOI: 10.1186/s12955-019-1256-0.

Lai VWY†, Chen G, Gin D & Sinclair R. Australasian Journal of Dermatology, 2019, 60 (1): e1-e13. DOI: 10.1111/ajd.12913.

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Alopecia areata is associated with a marked burden on utility; however, so far no study evaluated the impact of pharmacotherapy on QoL using complete quantitative QoL instruments.

Chen G†, Ratcliffe J, Kaambwa B, McCaffrey N & Richardson J. Social Indicators Research, 2018, 140 (1): 175-190. DOI: 10.1007/s11205-017-1788-9.

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Conceptually, the ICECAP differs from HRQoL as the focus is upon the ability or capacity to achieve as distinct from the current experience of the attributes. Empirical results suggest that ICECAP-A should be included in evaluation studies along with a HRQoL instrument is more persuasive when the instrument is the EQ-5D. The case for its inclusion with other HRQoL instruments (e.g. AQoL-8D) requires further research and evaluation.

Engel L†, Chen G, Richardson J & Mihalopoulos C. Quality of Life Research, 2018, 27 (11): 2873-2884. DOI: 10.1007/s11136-018-1936-y.

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This study identified important dimensions of HRQoL and wellbeing (PWI, SWLS, IHS, and ICECAP-A) that are most affected by depression and examined the extent to which these are captured by MAUIs (15D, AQoL-8D, EQ-5D-5L, HUI-3, and SF-6D).

Milte R†, Ratcliffe J, Chen G & Crotty M. Value in Health, 2018, 21 (7): 843-849. DOI: 10.1016/j.jval.2017.11.004.

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The Consumer Choice Index – Six Dimension (CCI-6D) instrument was designed to fill this gap in measuring and valuing the quality of nursing home care from the perspective of consumers. This study elicited preference weights for the CCI-6D in Australia.

Mpundu-Kaambwa C†, Chen G, Huynh E, Russo R & Ratcliffe J. Quality of Life Research, 2018, 27 (7): 1781-1799. DOI: 10.1007/s11136-018-1837-0.

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​This review examined the psychometric properties and suitability for use within the context of cerebral palsy research in children and adolescents of generic preference-based health-related quality of life (HRQoL) instruments. Four preference-based HRQoL instruments were identified from eight studies: HUI-2, HUI-3, AQoL-4D, & EQ-5D-3L.

Liu L, Li S†, Zhao Y, Zhang J & Chen G. Quality of Life Research, 2018, 27 (5): 1323-1333. DOI: 10.1007/s11136-018-1819-2.

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There is a poor agreement between direct (TTO & SG) and indirect (EQ-5D-5L) methods on measuring health state utility. Exploratory factor analysis further suggests a complementary relationship between the EQ-5D-5L and WHO-5 wellbeing index.

Liu Q, Zeng H, Xia R, Chen G, Liu S, Zhang Z, Liu Y, Guo G, Song G, Zhu Y, Wu X, Song B, Liao X, Chen Y, Wei W, Chen W† & Zhuang G†. Cancer Medicine, 2018, 7 (11): 5803-5811. DOI: 10.1002/cam4.1817.

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Compared to the healthy controls, the mean EQ-5D-3L index values of the esophageal cancer patients were significantly lower, with decrements of 0.158 (severe dysplasia/CIS), 0.289 (Stage I), 0.303 (Stage II), 0.296 (Stage III) and 0.505 (Stage IV), respectively. In addition, among these clinical stages, the magnitudes of decrement on the EQ-5D-3L index values were not significantly different among stages I to III.

Zhou Z, Zhou Z†, Gao J†, Lai S & Chen G. PLoS ONE, 2018, 13 (9): e0204118. DOI: 10.1371/journal.pone.0204118.

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HRQoL of the single elderly either living alone or living with adult children were lower than the elderly living with a spouse in urban areas. In rural areas only the single elderly living with adult children were more disadvantaged. Additionally, living-alone elderly had worse psychological health and the single elderly living with adult children had worse physical health.

Su Min, Zhou Z†, Si Y, Wei X, Xu Y, Fan X & Chen G. Health and Quality of Life Outcomes, 2018, 16: 41. DOI: 10.1186/s12955-018-0868-0.

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This study compared the equity of health-related quality of life (HRQoL) of residents under any two of three basic health insurance schemes in China. Findings demonstrated the pro-rich health inequity was much higher for the rural scheme than that for the urban ones.

Yang P, Chen G†, Wang P, Zhang K, Deng F, Yang H & Zhuang G†. Quality of Life Research, 2018, 27 (7): 1921-1931. DOI: 10.1007/s11136-018-1864-x.

Lamu AN, Chen G†, Gamst-Klaussen T & Olsen JA. Quality of Life Research, 2018, 27 (7): 1801-1814. DOI: 10.1007/s11136-018-1840-5.

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Mapping algorithms reported from Diabetes-39 onto EQ-5D-5L. The fractional regression model, which is appropriate for handling bounded outcomes, outperformed other candidate methods in this mapping study.

Chen G, Garcia-Gordillo MA†, Collado-Mateo D, del Pozo-Cruz B, Adsuar JC, Cordero-Ferrera JM, Abellán-Perpiñán JM & Sánchez-Martínez FI. Patient, 2018, 11 (6): 665-675. DOI: 10.1007/s40271-018-0317-5.

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Mapping algorithms reported from Parkinson’s Disease Questionnaire-8 (PDQ-8) onto EQ-5D-3L, EQ-5D-5L, and 15D.

Gamst-Klaussen T†, Lamu AN, Chen G & Olsen JA. BJPsych Open, 2018, 4 (4): 160-166. DOI: 10.1192/bjo.2018.21.

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Mapping algorithms reported from Depression Anxiety Stress Scales (DASS-21) and Kessler Psychological Distress Scale (K-10) onto EQ-5D-5L.

Chen Q, Li S†, Wang M, Liu L & Chen G. BioMed Research International, 2018, 1452635. DOI: 10.1155/2018/1452635.

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This study explored which dimensions of HRQOL played important roles in breast cancer patients’ overall quality of life, and explored the latent factor structure and the potential complementary relationship between these two EORTC questionnaires (QLQ-C30 & QLQ-BR23) in breast cancer patients.

Petersen KD, Chen G†, Mpundu-Kaambwa C, Stevens K, Brazier J & Ratcliffe J. Patient, 2018, 11 (1): 29-37. DOI: 10.1007/s40271-017-0265-5.

Zhou Z, Fang Y, Zhou Z, Li D, Wang D, Li Y, Lu L, Gao J & Chen G†. Social Indicators Research, 2017, 132 (1): 241-256. DOI: 10.1007/s11205-015-1221-1.

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​The study investigates both income-related health inequality and horizontal equity in urban and rural China (2008 & 2013). Results suggested that there was a pro-rich inequality of HRQoL in both urban and rural China. Comparing the CIs of HRQoL between 2008 and 2013, an increasing trend could be observed, especially in the urban sample. Results from the decomposition exercises suggest that economic and education status were two key factors of the pro-rich inequity.

Mpundu-Kaambwa C†, Chen G, Russo R, Stevens K, Petersen KD & Ratcliffe J. PharmacoEconomics, 2017, 35 (4): 453-467. DOI: 10.1007/s40273-016-0476-y.

Kaambwa B†, Chen G, Ratcliffe J, Iezzi A, Maxwell A & Richardson J. PharmacoEconomics, 2017, 35 (1): 111-124. DOI: 10.1007/s40273-016-0446-4.

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Mapping algorithms reported from Sydney Asthma Quality of Life Questionnaire (AQLQ-S) onto 15D, AQoL-8D, EQ-5D-5L, HUI3, or SF-6D.

Zhao Y, Li S-P†, Liu L, Zhang J-L & Chen G. Medicine, 2017, 96 (34): e7840. DOI: 10.1097/MD.0000000000007840.

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The evidence from this study supports the choice of the country-specific tariff to be used in clinical research.

Collado-Mateo D, Chen G, Garcia-Gordillo MA†, Iezzi A, Adsuar JC, Olivares PR & Gusi N. F. Health and Quality of Life Outcomes, 2017, 15: 114. DOI: 10.1186/s12955-017-0690-0.

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Mapping algorithms reported from Revised Fibromyalgia Impact Questionnaire (FIQR) onto 15D, AQoL-8D, EQ-5D-5L, or SF-6D.

Liu L, Li S†, Wang M & Chen G. Patient Preference and Adherence, 2017, 11: 1049-1056. DOI: 10.2147/PPA.S138028.

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Although 4 country-specific EQ-5D-5L tariffs have shown an overall high level of correlation and agreement, none of them could be regarded as interchangeable. The higher correlation and agreement between Chinese and UK tariffs may be due to the similar functions that were used in the tariff development.

Kularatna S†, Chen G, Byrnes J & Scuffham PA. Value in Health Regional Issues, 2017, 12 C: 20-23. DOI: 10.1016/j.vhri.2017.01.001.

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This study produced the Sri Lankan EQ-5D-5L interim value set from EQ-5D-3L value set using a mapping approach.

Mpundu-Kaambwa C†, Chen G, Huynh E, Russo R & Ratcliffe J. BMJ Open, 2017, 7: e015924. DOI: 10.1136/bmjopen-2017-015924.

Ratcliffe J†, Huynh E, Chen G, Stevens K, Swait J, Brazier J, Sawyer M, Roberts R & Flynn T. Social Science and Medicine, 2016, 157: 48-59. DOI: 10.1016/j.socscimed.2016.03.042.

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This paper reports upon a study to apply profile case best worst scaling (BWS) and time trade-off (TTO) methods to derive a new adolescent-specific scoring algorithm for the Child Health Utility 9D (CHU9D), a generic preference-based instrument that has been specifically designed for the estimation of quality-adjusted life years for the economic evaluation of health care treatment and preventive programs targeted at young people. 

Chen G†, Khan MA, Iezzi A, Ratcliffe J & Richardson J. Medical Decision Making, 2016, 36 (2): 160-175. DOI: 10.1177/0272989X15578127.

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Different multiattribute utility (MAU) instruments predict significantly different utilities, which makes the comparison of results from different evaluation studies problematical. This article presents mapping functions (“crosswalks”) from 6 MAU instruments (15D, AQoL-8D, EQ-5D-5L, HUI 3, QWB, SF-6D) to each of the other 5 instruments in the study: a total of 30 mapping functions.

Gamst-Klaussen T†, Chen G, Lamu AN & Olsen JA. Quality of Life Research, 2016, 25 (7): 1667-1678. DOI: 10.1007/s11136-015-1212-3.

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This paper inquires into the degree of nonlinearity across the 4 health state utility instruments (EQ-5D-5L, SF-6D, HUI-3, and 15D) & proposes exchange rates that differ depending on the severity levels of the utility scale. Accounting for nonlinearities will increase the validity of the comparison for decision makers when faced with a choice between interventions whose calculations of QALY gains have been based on different HSU-instruments.

Richardson J†, Khan MA, Iezzi A, Chen G & Maxwell A. Medical Decision Making, 2016, 36 (2): 147-159. DOI: 10.1177/0272989X15613522.

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The present article has 2 objectives: 1) to compare the results of 3 measures of the sensitivity of 6 multiattribute utility (MAU) instruments and the results of 6 tests of construct validity in 7 disease areas, and 2) to rank the MAU instruments by each of the test results in each disease area and by an overall composite index constructed from the tests. The apparent sensitivity of instruments varied significantly with the measurement method and by disease area. Validation test results varied with the comparator instruments. Notwithstanding this variability, 15D, AQoL-8D, & SF-6D generally achieved better test results than QWB & EQ-5D-5L.

Chen G, Finger R, Holloway EE, Iezzi A & Richardson J†. Optometry and Vision Science, 2016, 93 (12): 1495-1501. DOI: 10.1097/OPX.0000000000000966.

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Mapping algorithms reported from Vision Related Quality of Life (VisQoL) onto AQoL-7D. 

Xu Y, Yang J, Gao J†, Zhou Z, Zhang T, Ren J, Li Y, Qian Y, Lai S & Chen G†. BMC Public Health, 2016, 16: 1214. DOI: 10.1186/s12889-016-3876-1.

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Results from 2nd wave of the China Health and Retirement Longitudinal Study (CHARLS) indicate a pro-rich inequality in depressive symptoms amongst elderly Chinese with the overall concentration index of depressive symptoms was -0.0645 among the elderly.

Zhang X, Chen G, Xu F, Zhou K & Zhuang G†. International Journal of Environmental Research and Public Health, 2016, 13, 1192. DOI: 10.3390/ijerph13121192.

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Long or irregular working schedules were the most important factors that were negatively associated with HRQOL of railway workers in China.

Chen G & Ratcliffe J†. PharmacoEconomics, 2015, 33 (10): 1013-1028. DOI: 10.1007/s40273-015-0286-7.

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T​his paper critically reviews the development and application of nine multiattribute utility (MAU) instruments (QWB, HUI2, HUI3, 16D, 17D, AQoL-6D, CHU9D, EQ-5D-Y, AHUM) that have been used in paediatric populations internationally. Areas for further research relating to the development and application of generic MAU instruments in paediatric populations are highlighted.

Richardson J†, Chen G, Khan MA & Iezzi A. Medical Decision Making, 2015, 35 (3): 292-304. DOI: 10.1177/0272989X14567354.

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This article explores a hypothesis that a failure of an multiattribute utility (MAU) instrument to account for variation in subjective wellbeing (SWB) is primarily a result of the failure of its descriptive system to include the elements of health that determine SWB and that cannot therefore be included in assessment of the health state utility. Results suggest that, to a large extent, utility can account for variation in SWB.

Chen G†, Flynn T, Stevens K, Brazier J, Huynh E, Sawyer M, Roberts R & Ratcliffe J. Value in Health, 2015, 18 (4): 432-438. DOI: 10.1016/j.jval.2015.02.014.

Ratcliffe J†, Chen G, Stevens K, Bradley S, Couzner L, Brazier J, Sawyer M, Roberts R, Huynh E & Flynn T. Applied Health Economics and Health Policy, 2015, 13 (5): 485-492. DOI: 10.1007/s40258-015-0184-3.

Xu Y, Zhou Z, Li Y, Yang J, Guo X, Gao J†, Yan J & Chen G. Health and Quality of Life Outcomes, 2015, 13: 153. DOI: 10.1186/s12955-015-0347-9.

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There were statistically significant nonlinear relationships between BMI and HRQOL, with optimal HRQOL achieved at a BMI of near 23 kg/m2 for men and 24 kg/m2 for women. Before BMI reached optimal HRQOL, the EQ-5D utility scores were increasing faster among men than the women, whilst after the BMI value reached the optimal utility scores, women showed a faster decline in utility scores than men. 

Chen G, McKie J, Khan MA & Richardson JR†. European Journal of Cardiovascular Nursing, 2015, 14 (5): 405-415. DOI: 10.1177/1474515114536096.

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Mapping algorithms reported from MacNew Heart Disease Quality of Life Questionnaire onto 15D, AQoL-8D, EQ-5D-5L, HUI3, QWB, or SF-6D. 

Chen G, Iezzi A†, McKie J, Khan M & Richardson J. Diabetes Research and Clinical Practice, 2015, 109 (2): 326-333. DOI: 10.1016/j.diabres.2015.05.011.

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Mapping algorithms reported from Diabetes-39 onto 15D, AQoL-8D, EQ-5D-5L, HUI3, QWB, or SF-6D. 

Chen G, Ratcliffe J†, Olds T, Magarey A, Jones M & Leslie E. Pediatrics, 2014, 133 (4): e868-e874. DOI: 10.1542/peds.2013-0622.

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Irrespective of BMI, young people engaging in more physical activities or less sedentary behavior, and having healthier sleep patterns or eating behavior exhibited higher utilities. Associations between utilities and sleep patterns or eating behavior were stronger than the associations with BMI.

Mihalopoulos C†, Chen G, Iezzi A, Khan MA & Richardson J. British Journal of Psychiatry, 2014, 205 (5): 390-397. DOI: 10.1192/bjp.bp.113.136036.

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This paper firstly investigated the sensitivity of 5 commonly used health utility instruments in depression. Next, mapping algorithms were developed from Depression Anxiety Stress Scales (DASS-21) and/or Kessler Psychological Distress Scale (K10) onto 15D, AQoL-8D, EQ-5D-5L, HUI3 or SF-6D. 

Chen G†, Stevens K, Rowen D & Ratcliffe J. Health and Quality of Life Outcomes, 2014, 12: 134. DOI: 10.1186/s12955-014-0134-z.

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NOTE: Both KS_I3 ("Have you felf sad") & KS_I4 ("Have you felt lonely") were firstly reverse coded, before including into the analyses. In this case, the response level of "never" should be coded as "5" and "always" should be coded as "1". 

Chen G, Tan JT†, Ng K, Iezzi A & Richardson J. Health and Quality of Life Outcomes, 2014, 12: 133. DOI: 10.1186/s12955-014-0133-0.

Li S†, Wang G, Xu Y, Gray A & Chen G. Optometry and Vision Science, 2014, 91 (7): 723-729. DOI: 10.1097/OPX.0000000000000299.

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This study elicited utility values of adult myopic patients in mainland China using both TTO and SG methods. Although they produced similar mean utility values, a poor agreement on individuals utility values were found from these two methods.

Xu F§†, Chen G§, Stevens K, Zhou H, Qi S, Wang Z, Hong X, Chen X, Yang H, Wang C & Ratcliffe J. PLoS ONE, 2014, 9 (2): e89222. DOI: 10.1371/journal.pone.0089222.