The Ceiling Effects of EQ-5D-3L and 5L in General Population Health Surveys: A Systematic Review and Meta-analysis.

OBJECTIVES: This review aims to examine the ceiling effects of EQ-5D-3L (3L) and EQ-5D-5L (5L) in general adult populations and identify the factors influencing these effects. METHODS: We searched 8 databases for observational studies published in English from inception to 24 July 2023. Ceiling effects were calculated by dividing the number of participants reporting full health at dimension or profile level by the total sample size. Subgroup analysis and meta-regression using the metafor package in R software were performed. RESULTS: We identified 94 studies from 70 articles, including 4 543 647 adults across 37 countries. The global pooled proportion of individuals reporting full health ("11111") was 56% (95% CI 51%-62%) for 3L and 49% (95% CI 44%-54%) for 5L. The self-care dimension showed the highest ceiling effects (3L: 97%; 5L: 94%), whereas pain/discomfort had the lowest (3L: 69%; 5L: 60%). The ceiling effects in East/South-East Asia were higher than in Europe by 25% (95% CI 18%-32%) in 3L and 9% (95% CI -2%-20%) in 5L. Adjusting for mean age and proportion of males, significant regional differences persisted in the overall profile level of 3L, in all 3L dimensions (except for self-care), and 5L dimensions (except for pain/discomfort and anxiety/depression). CONCLUSIONS: This review highlights significant ceiling effects in the EQ-5D, especially in Asian populations. The 5L version exhibited fewer ceiling effects than the 3L, indicating its superiority for general population surveys. Further research is crucial to understand the disparities in self-reported health outcomes between Asians and other populations.

QALYs and rare diseases: exploring the responsiveness of SF-6D, EQ-5D-5L and AQoL-8D following genomic testing for childhood and adult-onset rare genetic conditions in Australia.

BACKGROUND: Genomic testing transforms the diagnosis and management of rare conditions. However, uncertainty exists on how to best measure genomic outcomes for informing healthcare priorities. Using the HTA-preferred method should be the starting point to improve the evidence-base. This study explores the responsiveness of SF-6D, EQ-5D-5L and AQoL-8D following genomic testing across childhood and adult-onset genetic conditions. METHOD: Self-reported patient-reported outcomes (PRO) were obtained from: primary caregivers of children with suspected neurodevelopmental disorders (NDs) or genetic kidney diseases (GKDs) (carers' own PRO), adults with suspected GKDs using SF-12v2; adults with suspected complex neurological disorders (CNDs) using EQ-5D-5L; and adults with dilated cardiomyopathy (DCM) using AQol-8D. Responsiveness was assessed using the standardised response mean effect-size based on diagnostic (having a confirmed genomic diagnosis), personal (usefulness of genomic information to individuals or families), and clinical (clinical usefulness of genomic information) utility anchors. RESULTS: In total, 254 people completed PRO measures before genomic testing and after receiving results. For diagnostic utility, a nearly moderate positive effect size was identified by the AQoL-8D in adult DCM patients. Declines in physical health domains masked any improvements in mental or psychosocial domains in parents of children affected by NDs and adult CNDs and DCM patients with confirmed diagnosis. However, the magnitude of the changes was small and we did not find statistically significant evidence of these changes. No other responsiveness evidence related to diagnostic, clinical, and personal utility of genomic testing was identified. CONCLUSION: Generic PRO measures may lack responsiveness to the diagnostic, clinical and personal outcomes of genomics, but further research is needed to establish their measurement properties and relevant evaluative space in the context of rare conditions. Expected declines in the physical health of people experiencing rare conditions may further challenge the conventional application of quality of life assessments.

Using Age-Specific Values for Pediatric HRQoL in Cost-Effectiveness Analysis: Is There a Problem to Be Solved? If So, How?

Value sets for the EQ-5D-Y-3L published to date appear to have distinctive characteristics compared with value sets for corresponding adult instruments: in many cases, the value for the worst health state is higher and there are fewer values < 0. The aim of this paper is to consider how and why values for child and adult health differ; and what the implications of that are for the use of EQ-5D-Y-3L values in economic evaluations to inform healthcare resource allocation decisions. We posit four potential explanations for the differences in values: (a) The wording of severity labels may mean the worst problems on the EQ-5D-Y-3L are descriptively less severe than those on the EQ-5D-5L; (b) Adults may genuinely consider that children are less badly affected than adults by descriptively similar health issues. That is, for any given health problem, adult respondents in valuation studies consider children's overall health-related quality of life (HRQoL) on average to be higher than that for adults; (c) Values are being sought by eliciting adults' stated preferences for HRQoL in another person, rather than in themselves (regardless of whether the 'other person' concerned is a child); and (d) The need to elicit preferences for child HRQoL that are anchored at dead = 0 invokes special considerations regarding children's survival. Existing evidence does not rule out the possibility that (c) and (d) exert an upward bias in values. We consider the implications of that for the interpretation and use of values for pediatric HRQoL. Alternative methods for valuing children's HRQoL in a manner that is not 'age specific' are possible and may help to avoid issues of non-comparability. Use of these methods would place the onus on health technology assessment bodies to reflect any special considerations regarding child quality-adjusted life-year gains.

Health-related quality of life of children with Williams syndrome and caregivers in China.

Introduction: Williams syndrome (WS) is a rare genetic disorder that impacts multiple systems and may cause developmental delays. These medical and developmental issues impose a heavy burden on affected children and their families. However, there was no study on children's health-related quality of life (HRQoL) with WS and only two studies about family quality of life globally. Therefore, the primary purpose of this study was to assess the HRQoL of children with WS and their caregivers in China, and the secondary purpose was to identify the potential determinants of children's and caregivers' HRQoL. Methods: In total, 101 children and caregivers were included. We applied the proxy-reported PedsQL 4.0 Generic Core Module (PedsQL GCM) and PedsQL 3.0 Family Impact Module (FIM) to measure the HRQoL of children and caregivers. Additionally, we collected information on a comprehensive set of social demographic and clinical characteristics. Differences in HRQoL scores across subgroups were assessed by two-independent-samples t-tests, one-way ANOVA, and post hoc tests. We also calculated effect sizes to indicate clinical relevance. Multivariate linear regression models were applied to assess the potential determinants of HRQoL. Results: We found that the HRQoL of children with WS and their caregivers was dramatically worse than the norm average scores of the healthy controls of children published in previous studies. Paternal educational level, household income, and the perceived financial burden significantly influenced the HRQoL of both children and families (p-values < 0.05). Multivariate linear regression analysis showed that the perceived financial burden was independently associated with family quality of life (p-values < 0.05)., and the presence of sleeping problem was independently associated with children's HRQoL (p-value = 0.01). Conclusion: We call for attention from policymakers and other stakeholders on the health status and well-being of children with WS and their families. Supports are needed to relieve psychosocial distress and financial burden.

Understanding the measurement relationship between EQ-5D-5L, PROMIS-29 and PROPr.

PURPOSE: Many generic patient-reported instruments are available for the measurement of health outcomes, including EQ-5D-5L, and the Patient-Reported Outcome Measurement Information System (PROMIS). Assessing their measurement characteristics informs users about the consistency between, and limits of, evidence produced. The aim was to assess the measurement relationship between the EQ-5D-5L descriptive system and value sets, the PROMIS-29 and PROPr (PROMIS value set). METHODS: Data were extracted from a cross-sectional survey administering measures of quality of life online in Australia. Descriptive analysis, agreement and construct validity assessment methods were used to compare instruments at the item, domain and value set level. RESULTS: In total, 794 Australians completed the survey. Convergent validity analysis found that similar dimensions across instruments were highly correlated (> 0.50), but the PROMIS-29 assesses additional health concepts not explicitly covered by EQ-5D (sleep and fatigue). Known-group assessment found that EQ-5D-5L and PROPr were able to detect those with and without a condition (ES range 0.78-0.83) but PROPr could more precisely detect differing levels of self-reported health. Both instruments were sensitive to differences in levels of pain. DISCUSSION: There is some consistency in what the EQ-5D-5L, PROMIS-29 and PROPr measure. Differences between value set characteristics can be linked to differences what is measured and the valuation approaches used. This has implications for the use of each in assessing health outcomes, and the results can inform decisions about which instrument should be used in which context.

The association between obesity, health service use, and work productivity in Australia: a cross-sectional quantile regression analysis.

The burden of disease attributable to obesity is rapidly increasing and becoming a public health challenge globally. Using a nationally representative sample in Australia, this study aims to examine the association of obesity with healthcare service use and work productivity across outcome distributions. We used Household, Income and Labour Dynamics Australia (HILDA) Wave 17 (2017-2018), including 11,211 participants aged between 20 and 65 years. Two-part models using multivariable logistic regressions and quantile regressions were employed to understand variations in the association between obesity levels and the outcomes. The prevalence of overweight and obesity was 35.0% and 27.6%, respectively. After adjusting for socio-demographic factors, low socioeconomic status was associated with a higher probability of overweight and obesity (Obese III: OR = 3.79; 95% CI 2.53-5.68) while high education group was associated with a lower likelihood of being high level of obesity (Obese III OR = 0.42, 95% CI 0.29-0.59). Higher levels of obesity were associated with higher probability of health service use (GP visit Obese, III: OR = 1.42 95% CI 1.04-1.93,) and work productivity loss (number of paid sick leave days, Obese III: OR = 2.40 95% CI 1.94-2.96), compared with normal weight. The impacts of obesity on health service use and work productivity were larger for those with higher percentiles compared to lower percentiles. Overweight and obesity are associated with greater healthcare utilisation, and loss in work productivity in Australia. Australia's healthcare system should prioritise interventions to prevent overweight and obesity to reduce the cost on individuals and improve labour market outcomes.

Re-examining the reversal hypothesis: A nationwide population-based study of the association between socioeconomic status, and NCDs and risk factors in China.

Background: According to the reversal hypothesis, as a country's economic and social development progresses, the burden of NCDs and risk factors shifts from rich to poor. The aim of this research is to examine the reversal hypothesis in the Chinese setting. Methods: Using data from the China Health and Retirement Longitudinal Study (CHARLS) in 2015, we explored whether the reversal hypothesis applies at the subnational level. Participants aged 45 years and older in 2015 were included. We examined five risk factors (smoking, heavy drinking, physical inactivity, overweight, and obesity) and three objectively measured NCDs (diabetes, hypertension, dyslipidemia). Binary logistic regressions were performed to examine outcomes across people of differing SES in provincial level, in urban and rural areas, and across generations. Results: Nationally, SES is positively associated with heavy drinking, obesity, diabetes and dyslipidemia, whereas it is negatively associated with physical inactivity. The association between SES and smoking and hypertension was not statistically significant. Except in the cases of diabetes and dyslipidemia, we found that risk factors of all kinds were more concentrated among richer people in rural than in urban areas. Across provinces with increasing GDP per capita, a downward trend in risk factors among those with high SES compared to those with low SES could be interpreted, while the opposite trend could be interpreted with respect to the metabolic syndrome conditions. Obesity and overweight exhibited slight downward trends (in line with those for risk factors) and upward trends (in line with those for metabolic syndrome conditions), respectively. Conclusion: We conclude that China is at a relatively early stage of 'reversal', visible with respect to risk factors. If these patterns persist over time, the trend will likely feed through to metabolic disorders which will increasingly become diseases of the poor.

The impact of depression and physical multimorbidity on health-related quality of life in China: a national longitudinal quantile regression study.

The co-occurrence of mental and physical chronic conditions is a growing concern and a largely unaddressed challenge in low-and-middle-income countries. This study aimed to investigate the independent and multiplicative effects of depression and physical chronic conditions on health-related quality of life (HRQoL) in China, and how it varies by age and gender. We used two waves of the China Health and Retirement Longitudinal Study (2011, 2015), including 9227 participants aged ≥ 45 years, 12 physical chronic conditions and depressive symptoms. We used mixed-effects linear regression to assess the effects of depression and physical multimorbidity on HRQoL, which was measured using a proxy measure of Physical Component Scores (PCS) and Mental Component Scores (MCS) of the matched SF-36 measure. We found that each increased number of physical chronic conditions, and the presence of depression were independently associated with lower proxy PCS and MCS scores. There were multiplicative effects of depression and physical chronic conditions on PCS (- 0.83 points, 95% CI - 1.06, - 0.60) and MCS scores (- 0.50 points, 95% CI - 0.73, - 0.27). The results showed that HRQoL decreased markedly with multimorbidity and was exacerbated by the presence of co-existing physical and mental chronic conditions.

The relationship between physical and mental health multimorbidity and children's health-related quality of life.

PURPOSE: To examine the relationships between physical health problems, and borderline or clinical levels of mental health symptoms and children's health-related quality of life (HRQoL). METHODS: Data were from the Longitudinal Study of Australian Children (2004-2018). Parents reported on their child's HRQoL (PedsQL), physical health problems and mental health symptoms (Strengths and Difficulties Questionnaire, SDQ). A pooled cross-sectional analysis using linear regressions examined the relationships between physical health and clinical/borderline mental health symptoms, individually and when multi-morbid, and children's HRQoL, and whether these relationships vary by a range of child, family and social factors. RESULTS: The sample comprised 47,567 observations of children aged 4-17 years. Borderline and clinical levels of mental health symptoms were associated with significantly lower HRQoL, equal to more than two-times (10.5 points) and more than three-times (16.8 points) the clinically meaningful difference, respectively. This was a larger difference than that associated with physical health problems (4.4 points). We found a significant interaction effect between physical health problems and clinical mental health symptoms which was associated with even poorer HRQoL after accounting for the individual relationships of both problems. Mental health problems were associated with poorer HRQoL for older versus younger children; and the interaction effect was significant for boys but not girls. CONCLUSION: Findings highlight the importance of identifying and addressing mental health symptoms in children of all ages, even if these problems do not meet formal clinical criteria. Particular attention should be paid to the mental health and HRQoL of children with physical-mental multimorbidity, who are at risk of disproportionately poorer HRQoL.

A Comparison of PROPr and EQ-5D-5L Value Sets.

OBJECTIVES: The EQ-5D-5L and its value sets are widely used internationally. However, in the US and elsewhere, there is growing use of PROMIS, which has a value set (PROPr) based on the stated preferences of the US population. This paper aims to compare the characteristics of EQ-5D-5L and PROPr value sets and to highlight potential implications for users. METHODS: US, Australian and English value sets were used for EQ-5D-5L. PROPr utilities were calculated based on PROMIS-29 + 2. We examined, in each case, (i) the characteristics (e.g. range of values, number of unique values) and distribution of all possible 'theoretical' utilities; (ii) dimension/domain importance ranking by the utility of corner states (i.e. health states with the worst level in one domain and the best in all others); (iii) comparisons of utilities for health states hypothesised to be comparable in terms of severity across EQ-5D-5L descriptive systems and PROMIS-29 + 2 domain scores; (iv) the changes in values of adjacent states (i.e. a one-level change in one dimension for EQ-5D-5L and a four-point change in raw scores for PROMIS-29 + 2, with the other dimensions held constant) for dimensions hypothesised to overlap conceptually or be correlated between the two instruments. RESULTS: EQ-5D-5L and PROPr utilities differ systematically. First, the US EQ-5D-5L utilities range from - 0.573 to 1, whereas PROPr values for PROMIS-29 + 2 range from - 0.022 to 0.954. Second, in the US (and English) EQ-5D-5L value sets, pain is the most important dimension whereas in PROPr pain is one of the least important (apart from sleep disturbance). Third, classified based on severity across EQ-5D-5L descriptive systems and PROMIS-29 + 2 domain scores, PROPr has substantially lower values than EQ-5D-5L values for comparable 'mild' health states, but higher values for more 'severe' health states. Last, when one dimension is considered across its best to worst levels and all other dimensions are held constant at their best or moderate level, in EQ-5D-5L value sets, the greatest changes in utility occur between levels 3 and 4 (moderate and severe) problems; in PROPr that occurred between the most severe states and their descriptively adjacent health states. CONCLUSION: There are very considerable differences between US EQ-5D-5L and PROPr utilities, despite both in principle representing utility on the same scale anchored at 0 and 1 and both representing the preferences of the US general public. It is important for decision makers and clinical triallists to be aware of these differences. Further work is needed to assess the impact of these differences in value sets using population and patient data, and in longitudinal settings.

Evidence on the relationship between PROMIS-29 and EQ-5D: a literature review.

PURPOSE: EQ-5D and PROMIS-29 are both concise, generic measures of patient-reported outcomes accompanied by preference weights that allow the estimation of quality-adjusted life years (QALYs). Both instruments are candidates for use in economic evaluation. However, they have different features in terms of the domains selected to measure respondents' self-perceived health and the characteristics of (and methods used to obtain) the preference weights. It is important to understand the relationship between the instruments and the implications of choosing either for the evidence used in decision-making. This literature review aimed to synthesise existing evidence on the relationship between PROMIS-29 (and measures based on it, such as PROMIS-29+2) and EQ-5D (both EQ-5D-3L and EQ-5D-5L). METHODS: A literature review was conducted in PubMed and Web of Science to identify studies investigating the relationship between PROMIS-29 and EQ-5D-based instruments. RESULTS: The literature search identified 95 unique studies, of which nine studies met the inclusion criteria, i.e. compared both instruments. Six studies examined the relationship between PROMIS-29 and EQ-5D-5L. Three main types of relationship have been examined in the nine studies: (a) comparing PROMIS-29 and EQ-5D as descriptive systems; (b) mapping PROMIS-29 domains to EQ-5D utilities; and (c) comparing and transforming PROMIS-29 utilities to EQ-5D utilities. CONCLUSION: This review has highlighted the lack of evidence regarding the relationship between PROMIS-29 and EQ-5D. The impact of choosing either instrument on the evidence used in cost-effectiveness analysis is currently unclear. Further research is needed to understand the relationship between the two instruments.

Multimorbidity and out-of-pocket expenditure on medicine in Europe: Longitudinal analysis of 13 European countries between 2013 and 2015.

Background: Many European Health Systems are implementing or increasing levels of cost-sharing for medicine in response to the growing constrains on public spending on health despite their negative impact on population health due to delay in seeking care. Objective: This study aims to examine the relationships between multimorbidity (two or more coexisting chronic diseases, CDs), complex multimorbidity (three or more CDs impacting at least three different body systems), and out-of-pocket expenditure (OOPE) for medicine across European nations. Methods: This study utilized data on participants aged 50 years and above from two recent waves of the Survey of Health, Aging, and Retirement in Europe conducted in 2013 (n = 55,806) and 2015 (n = 51,237). Pooled cross-sectional and longitudinal study designs were used, as well as a two-part model, to analyse the association between multimorbidity and OOPE for medicine. Results: The prevalence of multimorbidity was 50.4% in 2013 and 48.2% in 2015. Nearly half of those with multimorbidity had complex multimorbidity. Each additional CD was associated with a 34% greater likelihood of incurring any OOPE for medicine (Odds ratio = 1.34, 95% CI = 1.31-1.36). The average incremental OOPE for medicine was 26.4 euros for each additional CD (95% CI = 25.1-27·7), and 32.1 euros for each additional body system affected (95% CI 30.6-33.7). In stratified analyses for country-specific quartiles of household income the average incremental OOPE for medicine was not significantly different across groups. Conclusion: Between 2013 and 2015 in 13 European Health Systems increased prevalence of CDs was associated with greater likelihood of having OOPE on medication and an increase in the average amount spent when one occurred. Monitoring this indicator is important considering the negative association with treatment adherence and subsequent effects on health.

Effect of multimorbidity on utilisation and out-of-pocket expenditure in Indonesia: quantile regression analysis.

BACKGROUND: Multimorbidity (the presence of two or more non-communicable diseases) is a major growing challenge for many low-income and middle-income countries (LMICs). Yet, its effects on health care costs and financial burden for patients have not been adequately studied. This study investigates the effect of multimorbidity across the different percentiles of healthcare utilisation and out-of-pocket expenditure (OOPE). METHODS: We conducted a secondary data analysis of the 2014/2015 Indonesian Family Life Survey (IFLS-5), which included 13,798 respondents aged ≥40 years. Poisson regression was used to assess the association between sociodemographic characteristics and the total number of non-communicable diseases (NCDs), while multivariate logistic regression and quantile regression analysis was used to estimate the associations between multimorbidity, health service use and OOPE. RESULTS: Overall, 20.8% of total participants had two or more NCDs in 2014/2015. The number of NCDs was associated with higher healthcare utilisation (coefficient 0.11, 95% CI 0.07-0.14 for outpatient care and coefficient 0.09 (95% CI 0.02-0.16 for inpatient care) and higher four-weekly OOPE (coefficient 27.0, 95% CI 11.4-42.7). The quantile regression results indicated that the marginal effect of having three or more NCDs on the absolute amount of four-weekly OOPE was smaller for the lower percentiles (at the 25th percentile, coefficient 1.0, 95% CI 0.5-1.5) but more pronounced for the higher percentile of out-of-pocket spending distribution (at the 90th percentile, coefficient 31.0, 95% CI 15.9-46.2). CONCLUSION: Multimorbidity is positively correlated with health service utilisation and OOPE and has a significant effect, especially among those in the upper tail of the utilisation/costs distribution. Health financing strategies are urgently required to meet the needs of patients with multimorbidity, particularly for vulnerable groups that have a higher level of health care utilisation.

Medical costs and out-of-pocket expenditures associated with multimorbidity in China: quantile regression analysis.

OBJECTIVE: Multimorbidity is a growing challenge in low-income and middle-income countries. This study investigates the effects of multimorbidity on annual medical costs and the out-of-pocket expenditures (OOPEs) along the cost distribution. METHODS: Data from the nationally representative China Health and Retirement Longitudinal Study (CHARLS 2015), including 10 592 participants aged ≥45 years and 15 physical and mental chronic diseases, were used for this nationally representative cross-sectional study. Quantile multivariable regressions were employed to understand variations in the association of chronic disease multimorbidity with medical cost and OOPE. RESULTS: Overall, 69.5% of middle-aged and elderly Chinese had multimorbidity in 2015. Increased number of chronic diseases was significantly associated with greater health expenditures across every cost quantile groups. The effect of chronic diseases on total medical cost was found to be larger among the upper tail than those in the lower tail of the cost distributions (coefficients 12, 95% CI 6 to 17 for 10th percentile; coefficients 296, 95% CI 71 to 522 for 90th percentile). Annual OOPE also increased with chronic diseases from the 10th percentile to the 90th percentile. Multimorbidity had larger effects on OOPE and was more pronounced at the upper tail of the health expenditure distribution (regression coefficients of 8 and 84 at the 10th percentile and 75th percentile, respectively). CONCLUSION: Multimorbidity is associated with escalating healthcare costs in China. Further research is required to understand the impact of multimorbidity across different population groups.

The association between mental-physical multimorbidity and disability, work productivity, and social participation in China: a panel data analysis.

BACKGROUND: The co-occurrence of mental and physical chronic conditions (mental-physical multimorbidity) is a growing and largely unaddressed challenge for health systems and wider economies in low-and middle-income countries. This study investigated the independent and combined (additive or synergistic) effects of mental and physical chronic conditions on disability, work productivity, and social participation in China. METHODS: Panel data study design utilised two waves of the China Health and Retirement Longitudinal Study (2011, 2015), including 5616 participants aged ≥45 years, 12 physical chronic conditions and depression. We used a panel data approach of random-effects regression models to assess the relationships between mental-physical multimorbidity and outcomes. RESULTS: After adjusting for socio-economic and demographic factors, an increased number of physical chronic conditions was independently associated with a higher likelihood of disability (Adjusted odds ratio (AOR) = 1.39; 95% CI: 1.33, 1.45), early retirement (AOR = 1.37 [1.26, 1.49]) and increased sick leave days (1.25 days [1.16, 1.35]). Depression was independently associated with disability (AOR = 3.78 [3.30, 4.34]), increased sick leave days (2.18 days [1.72, 2.77]) and a lower likelihood of social participation (AOR = 0.57 [0.47, 0.70]), but not with early retirement (AOR = 1.24 [0.97, 1.58]). There were small and statistically insignificant interactions between physical chronic conditions and mental health on disability, work productivity and social participation, suggesting an additive effect of mental-physical multimorbidity on productivity loss. CONCLUSION: Mental-physical multimorbidity poses substantial negative health and economic effects on individuals, health systems, and societies. More research that addresses the challenges of mental-physical multimorbidity is needed to inform the development of interventions that can be applied to the workplace and the wider community in China.

Impact of non-communicable disease multimorbidity on health service use, catastrophic health expenditure and productivity loss in Indonesia: a population-based panel data analysis study.

OBJECTIVES: To examine non-communicable diseases (NCDs) multimorbidity level and its relation to households' socioeconomic characteristics, health service use, catastrophic health expenditures and productivity loss. DESIGN: This study used panel data of the Indonesian Family Life Survey conducted in 2007 (Wave 4) and 2014 (Wave 5). SETTING: The original sampling frame was based on 13 out of 27 provinces in 1993, representing 83% of the Indonesian population. PARTICIPANTS: We included respondents aged 50 years and above in 2007, excluding those who did not participate in both Waves 4 and 5. The total number of participants in this study are 3678 respondents. PRIMARY OUTCOME MEASURES: We examined three main outcomes; health service use (outpatient and inpatient care), financial burden (catastrophic health expenditure) and productivity loss (labour participation, days primary activity missed, days confined in bed). We applied multilevel mixed-effects regression models to assess the associations between NCD multimorbidity and outcome variables, RESULTS: Women were more likely to have NCD multimorbidity than men and the prevalence of NCD multimorbidity increased with higher socioeconomic status. NCD multimorbidity was associated with a higher number of outpatient visits (compared with those without NCD, incidence rate ratio (IRR) 4.25, 95% CI 3.33 to 5.42 for individuals with >3 NCDs) and inpatient visits (IRR 3.68, 95% CI 2.21 to 6.12 for individuals with >3 NCDs). NCD multimorbidity was also associated with a greater likelihood of experiencing catastrophic health expenditure (for >3 NCDs, adjusted OR (aOR) 1.69, 95% CI 1.02 to 2.81) and lower participation in the labour force (aOR 0.23, 95% CI 0.16 to 0.33) compared with no NCD. CONCLUSIONS: NCD multimorbidity is associated with substantial direct and indirect costs to individuals, households and the wider society. Our study highlights the importance of preparing health systems for addressing the burden of multimorbidity in low-income and middle-income countries.

The clinical utility of exome sequencing and extended bioinformatic analyses in adolescents and adults with a broad range of neurological phenotypes: an Australian perspective.

Currently there is no secured ongoing funding in Australia for next generation sequencing (NGS) such as exome sequencing (ES) for adult neurological disorders. Studies have focused on paediatric populations in research or highly specialised settings, utilised standard NGS pipelines focusing only on small insertions, deletions and single nucleotide variants, and not explored impacts on management in detail. This prospective multi-site study performed ES and an extended bioinformatics repeat expansion analysis pipeline, on patients with broad phenotypes (ataxia, dementia, dystonia, spastic paraparesis, motor neuron disease, Parkinson's disease and complex/not-otherwise-specified), with symptom onset between 2 and 60 years. Genomic data analysis was phenotype-driven, using virtual gene panels, reported according to American College of Medical Genetics and Genomics guidelines. One-hundred-and-sixty patients (51% female) were included, median age 52 years (range 14-79) and median 9 years of symptoms. 34/160 (21%) patients received a genetic diagnosis. Highest diagnostic rates were in spastic paraparesis (10/25, 40%), complex/not-otherwise-specified (10/38, 26%) and ataxia (7/28, 25%) groups. Findings were considered 'possible/uncertain' in 21/160 patients. Repeat expansion detection identified an unexpected diagnosis of Huntington disease in an ataxic patient with negative ES. Impacts on management, such as more precise and tailored care, were seen in most diagnosed patients (23/34, 68%). ES and a novel bioinformatics analysis pipepline had a substantial diagnostic yield (21%) and management impacts for most diagnosed patients, in heterogeneous, complex, mainly adult-onset neurological disorders in real-world settings in Australia, providing evidence for NGS and complementary multiple, new technologies as valuable diagnostic tools.

The long-run effects of noncommunicable disease shocks.

The health shocks literature typically does not take into account the temporal patterns of loss since the time of the shock. This limits understanding of the long-run impact of health shocks and the capacity of individuals to cope over time. This study estimates the dynamic effects of a noncommunicable disease shock on the economic well-being of working-age individuals in China up to 6 years after onset. We find that after a period of temporal loss, individuals and their families can insure consumption against the average noncommunicable disease shock over the long-run. We observe significant heterogeneity according to the persistence of the disease, value of household wealth, and health insurance status. Individuals with consistent onset, with below median wealth, and without health insurance are least equipped to smooth consumption over the long-term.