A riboside hydrolase that salvages both nucleobases and nicotinamide in the auxotrophic parasite Trichomonas vaginalis.

Pathogenic parasites of the Trichomonas genus are causative agents of sexually transmitted diseases affecting millions of individuals worldwide and whose outcome may include stillbirths and enhanced cancer risks and susceptibility to HIV infection. Trichomonas vaginalis relies on imported purine and pyrimidine nucleosides and nucleobases for survival, since it lacks the enzymatic activities necessary for de novo biosynthesis. Here we show that T. vaginalis additionally lacks homologues of the bacterial or mammalian enzymes required for the synthesis of the nicotinamide ring, a crucial component in the redox cofactors NAD+ and NADP. Moreover, we show that a yet fully uncharacterized T. vaginalis protein homologous to bacterial and protozoan nucleoside hydrolases is active as a pyrimidine nucleosidase but shows the highest specificity toward the NAD+ metabolite nicotinamide riboside. Crystal structures of the trichomonal riboside hydrolase in different states reveals novel intermediates along the nucleoside hydrolase-catalyzed hydrolytic reaction, including an unexpected asymmetry in the homotetrameric assembly. The active site structure explains the broad specificity toward different ribosides and offers precise insights for the engineering of specific inhibitors that may simultaneously target different essential pathways in the parasite.

Is anchoring at 'dead' a theoretical requirement for health state valuation?

Values that accompany generic health measures are typically anchored at 1 = full health and 0 = dead. Some health states may then be considered 'worse than dead' (WTD) and assigned negative values, which causes fundamental measurement problems. In this paper, we challenge the assumption that anchoring values at 'dead = 0' is necessary for quality-adjusted life year (QALY) estimation. We summarise the role of 'dead' in health state valuation and consider three critical questions: (i) whether the measurement properties of health state values require 'dead'; (ii) whether 'dead' needs to be valued relative to health states; and (iii) whether values for states WTD are meaningful or useful. We conclude that anchoring 0 at dead is not a requirement of health status measurement or cost-effectiveness analysis. This results from reframing QALYs as the relevant unit of measurement and reframing values as being derived from QALYs rather than the reverse.

Cost-effectiveness of outpatient versus inpatient non-invasive ventilation setup in obesity hypoventilation syndrome: the OPIP trial.

BACKGROUND: Current guidelines recommend that patients with obesity hypoventilation syndrome (OHS) are electively admitted for inpatient initiation of home non-invasive ventilation (NIV). We hypothesised that outpatient NIV setup would be more cost-effective. METHODS: Patients with stable OHS referred to six participating European centres for home NIV setup were recruited to an open-labelled clinical trial. Patients were randomised via web-based system using stratification to inpatient setup, with standard fixed level NIV and titrated during an attended overnight respiratory study or outpatient setup using an autotitrating NIV device and a set protocol, including home oximetry. The primary outcome was cost-effectiveness at 3 months with daytime carbon dioxide (PaCO2) as a non-inferiority safety outcome; non-inferiority margin 0.5 kPa. Data were analysed on an intention-to-treat basis. Health-related quality of life (HRQL) was measured using EQ-5D-5L (5 level EQ-5D tool) and costs were converted using purchasing power parities to £(GBP). RESULTS: Between May 2015 and March 2018, 82 patients were randomised. Age 59±14 years, body mass index 47±10 kg/m2 and PaCO2 6.8±0.6 kPa. Safety analysis demonstrated no difference in ∆PaCO2 (difference -0.27 kPa, 95% CI -0.70 to 0.17 kPa). Efficacy analysis showed similar total per-patient costs (inpatient £2962±£580, outpatient £3169±£525; difference £188.20, 95% CI -£61.61 to £438.01) and similar improvement in HRQL (EQ-5D-5L difference -0.006, 95% CI -0.05 to 0.04). There were no differences in secondary outcomes. DISCUSSION: There was no difference in medium-term cost-effectiveness, with similar clinical effectiveness, between outpatient and inpatient NIV setup. The home NIV setup strategy can be led by local resource demand and patient and clinician preference. TRIAL REGISTRATION NUMBERS: NCT02342899 and ISRCTN51420481.

Experience-based health state valuation using the EQ VAS: a register-based study of the EQ-5D-3L among nine patient groups in Sweden.

BACKGROUND: The EQ VAS component of the EQ-5D questionnaire has been used to assess patients' valuation of their own health besides its use for self-reporting of overall health status. The objective of the present study was to identify patients' valuation of EQ-5D-3L health states using the EQ VAS in different patient groups over time and in comparison to the general population. METHODS: Data were obtained from patients from nine National Quality Registers (n = 172,070 patients) at baseline and at 1-year follow-up and compared with data from the general population (n = 41,761 participants). The correlation between EQ VAS scores and EQ-5D-3L index based on the Swedish experience-based VAS value set was assessed. Ordinary least squares (OLS) regression models were used to determine the association between EQ-5D-3L dimensions and EQ VAS valuation. RESULTS: EQ VAS scores showed consistency with severity of health states both at baseline and at 1-year follow-up in the nine selected EQ-5D-3L health states. The regression models showed mostly consistent decrements by severity levels in each dimension at both time points and similar to the general population. The dimension mainly associated with inconsistency was the self-care severity level three. Problems in the anxiety/depression dimension had the largest impact on overall health status in most of the patient groups and the general population. CONCLUSION: The study has demonstrated the important role EQ VAS can play in revealing patients' valuation of their health and showed the variation in valuation of EQ-5D-3L dimensions and levels of severity across different patient groups.

Estimating health system opportunity costs: the role of non-linearities and inefficiency.

BACKGROUND: Empirical estimates of health system opportunity costs have been suggested as a basis for the cost-effectiveness threshold to use in Health Technology Assessment. Econometric methods have been used to estimate these in several countries based on data on spending and mortality. This study examines empirical evidence on four issues: non-linearity of the relationship between spending and mortality; the inclusion of outcomes other than mortality; variation in the efficiency with which expenditures generate health outcomes; and the relationship among efficiency, mortality rates and outcome elasticities. METHODS: Quantile Regression is used to examine non-linearities in the relationship between mortality and health expenditures along the mortality distribution. Data Envelopment Analysis extends the approach, using multiple measures of health outcomes to measure efficiency. These are applied to health expenditure data from 151 geographical units (Primary Care Trusts) of the National Health Service in England, across eight different clinical areas (Programme Budget Categories), for 3 fiscal years from 2010/11 to 2012/13. RESULTS: The results suggest differences in efficiency levels across geographical units and clinical areas as to how health resources generate outcomes, which indicates the capacity to adjust to a decrease in health expenditure without affecting health outcomes. Moreover, efficient units have lower absolute levels of mortality elasticity to health expenditure than inefficient ones. CONCLUSIONS: The policy of adopting thresholds based on estimates of a single system-wide cost-effectiveness threshold assumes a relationship between expenditure and health outcomes that generates an opportunity cost estimate which applies to the whole system. Our evidence of variations in that relationship and therefore in opportunity costs suggests that adopting a single threshold may exacerbate the efficiency and equity concerns that such thresholds are designed to counter. In most health care systems, many decisions about provision are not made centrally. Our analytical approach to understanding variability in opportunity cost can help policy makers target efficiency improvements and set realistic targets for local and clinical area health improvements from increased expenditure.

Definitive chemoradiotherapy for cervical cancer: A 11-year population-based study.

PURPOSE: To assess the recurrence pattern and survival in women treated with definitive chemoradiotherapy for cervical cancer. METHODS: A retrospective cohort study of women FIGO (2012) stage IB2 to IVA from the Grampian region of Scotland between February 2000 and March 2011. These women were followed up until April 2018. RESULTS: A total of 121 eligible women allocated with mean age at treatment 50.59 years (SD = 13.98, range 22-82). Tumours staged: IB2: n = 24 (19.8%), II: n = 45 (37.2%), III: n = 43 (35.5%) and IVA: n = 7 (5.8%). Two (1.7%) women had no available data. Fifty-five (45.5%) women had recurrence after treatment, and 51 (42.15%) women died from the disease. The sites of recurrence were as follows: central pelvic only (n = 4, 7.27%), pelvic and distant (n = 39, 70.91%) and distant only (n = 12, 21.82%) with median time from end of treatment to first recurrence 44 months (range 2-98), 26 months (range 1-146) and 22 months (range 3-66) respectively. 5-and 8-year overall survival was 76.0% (95% CI: 68.8%-84.0%) and 64.4% (95% CI: 56.4%-73.5%) respectively. CONCLUSIONS: Though overall survival is better than with radiotherapy alone, recurrence occurs up to 10 years after treatment. This raises the issues of how to reduce late recurrence and the appropriateness of current follow-up protocols.

Distribution of the EQ-5D-5L Profiles and Values in Three Patient Groups.

BACKGROUND: The distribution of EQ-5D-3L values (health state profiles, weighted by value sets) often shows two distinct groups, arising from both the distribution of profiles and the characteristics of value sets. To date, there is little evidence about the distribution of EQ-5D-5L values. OBJECTIVES: To explore the distribution of EQ-5D-5L profiles; to compare the distributions of EQ-5D-5L values arising from the English value set (EVS) and a 'mapped' value set (MVS); and to develop further the methods used to investigate clustering within EQ-5D data. METHODS: We obtained data from Cambridgeshire Community Services NHS Trust containing EQ-5D-5L profiles before treatment for three patient groups: community rehabilitation (N=6919); musculoskeletal physiotherapy (N=19999); and specialist nursing services (N=3366). Values were calculated using the EVS and MVS. Clusters were examined using the k-means method and Calinski-Harabasz pseudo-F index stopping rule. RESULTS: We found no evidence for clustering of EQ-5D-5L values arising from the classification system and no strong or consistent evidence of clustering arising from the EVS. There was clearer evidence of clustering using the MVS, with two being the optimal number of clusters. The clusters that were found for the EVS were very different from the MVS clusters. CONCLUSIONS: Unlike the EQ-5D-3L, clustering of EQ-5D-5L values does not seem to be driven by clustering of its profile. This suggests the EQ-5D-5L is superior in that it is less likely to generate artefactual clusters - however, clusters may still result from using value sets such as MVS that have the tendency to generate them.

An economic analysis of human milk supplementation for very low birth weight babies in the USA.

BACKGROUND: An exclusive human milk diet (EHMD) using human milk based products (pre-term formula and fortifiers) has been shown to lead to significant clinical benefits for very low birth weight (VLBW) babies (below 1250 g). This is expensive relative to diets that include cow's milk based products, but preliminary economic analyses have shown that the costs are more than offset by a reduction in the cost of neonatal care. However, these economic analyses have not completely assessed the economic implications of EHMD feeding, as they have not considered the range of outcomes affected by it. METHODS: We conducted an economic analysis of EHMD compared to usual practice of care amongst VLBW babies in the US, which is to include cow's milk based products when required. Costs were evaluated from the perspective of the health care payer, with societal costs considered in sensitivity analyses. RESULTS: An EHMD substantially reduces mortality and improves other health outcomes, as well as generating substantial cost savings of $16,309 per infant by reducing adverse clinical events. Cost savings increase to $117,239 per infant when wider societal costs are included. CONCLUSIONS: An EHMD is dominant in cost-effectiveness terms, that is it is both cost-saving and clinically beneficial, for VLBW babies in a US-based setting.

Rationale and design of the SMaRT trial: A randomised, prospective, parallel, non-blinded, one-centre trial to evaluate the use of magnetic resonance imaging in acute setting in patients presenting with suspected scaphoid fracture.

Background Wrist injury is a common presentation to the Emergency Department in the United Kingdom. Among these injuries, the scaphoid is the most common fractured carpal bone. However, given the limited ability of conventional radiography to accurately diagnose a suspected scaphoid fracture on presentation, its diagnosis and management remain challenging. Despite the vast clinical evidence supporting the superior accuracy of magnetic resonance imaging, there is little to no evidence around the real-world clinical and economic impact of immediate magnetic resonance imaging in the management of suspected scaphoid fractures. Methods Review of design and implementation challenges associated with the identification and subsequent recruitment of eligible patients, implementation of a novel clinical pathway in an acute setting, rationale behind the primary and secondary outcomes selected and measurement of the primary outcome. Results The Scaphoid Magnetic Resonance Imaging in Trauma trial is a single-site prospective, randomised, non-blinded, parallel design trial that aims to evaluate the use of immediate magnetic resonance imaging in the management of patients presenting to the acute setting with suspected scaphoid fractures. The primary outcome is the total 3-month cost per patient associated with the diagnosis and treatment of suspected scaphoid fractures. It is hypothesised that the immediate use of magnetic resonance imaging, a more accurate but expensive imaging modality, in patients with negative findings in the initial four-view radiography, will reduce the overall National Health Service costs by promoting definitive care and avoiding unnecessary diagnostic and treatment procedures. Other rationale design considerations in the recruitment, randomisation, data acquisition and intervention implementation are also discussed. Several of these challenges derive from real-world operational issues associated with the provision of magnetic resonance imaging in an intrinsically complex acute setting. Staff engagement during the trial's planning phase, combined with an extensive training programme rolled out prior to the trial's launch, were essential to raise staff awareness and engagement. Given the acute nature of the clinical condition, the latter was deemed essential as the eligibility assessment, recruitment, randomisation and treatment allocation processes all need to happen in a very tight time frame. Limitations Findings from the Scaphoid Magnetic Resonance Imaging in Trauma trial might not be generalisable to other National Health Service hospitals, foreign healthcare systems nor patient presentations outside normal magnetic resonance imaging working hours. Conclusion The Scaphoid Magnetic Resonance Imaging in Trauma trial was designed to evaluate the costs, patient satisfaction and clinical outcomes around the management of suspected scaphoid fractures and ultimately provide solid evidence on which to base the United Kingdom and international clinical practice. This article discusses the steps considered in the design of this novel trial, with particular emphasis on the issues and lessons learned during the planning and implementation stages.

An exploration of differences between Japan and two European countries in the self-reporting and valuation of pain and discomfort on the EQ-5D.

PURPOSE: To investigate the systematic differences in the self-reporting and valuation of overall health and, in particular, pain/discomfort between three countries (England/UK, Japan, and Spain) on the EQ-5D. METHODS: Existing datasets were used to explore differences in responses on the EQ-5D descriptive system between Japan (3L and 5L), the UK (3L), England (5L), and Spain (5L), particularly on the dimension of pain/discomfort. The role of different EQ dimensions in determining self-reported overall health scores for the EuroQol visual analog scale (EQ-VAS) was investigated using ordinary least squares regression. Time trade-off (TTO) results from Japanese and UK respondents for the EQ-5D-3L as well as Japanese and English respondents for the EQ-5D-5L were compared using t tests. RESULTS: For the EQ-5D-3L, a higher percentage of respondents in Japan than in the UK reported 'no pain/discomfort' (81.6 vs 67.0%, respectively); for the EQ-5D-5L, the proportions were 79.2% in Spain, 73.2% in Japan, and 63-64% in England, after adjusting for age differences in samples. The 'pain/discomfort' dimension had the largest impact on respondents' self-reported EQ-VAS only for EQ-5D-3L in Japan. Using the EQ-5D-3L, Japanese respondents were considerably less willing to trade off time to avoid pain/discomfort than the UK respondents; for example, moving from health state, 11121 (some problems with pain/discomfort) to 11131 (extreme pain/discomfort) represented a decrement of 0.65 on the observed TTO value in the UK compared with 0.15 in Japan. Using the EQ-5D-5L, Japanese respondents were also less willing to trade off time to avoid pain/discomfort than respondents in England; however, the difference in values was much smaller than that observed using EQ-5D-3L data. CONCLUSIONS: This study provides evidence of between-country differences in the self-reporting and valuation of health, including pain/discomfort, when using EQ-5D in general population samples. The results suggest a need for caution when comparing or aggregating EQ-5D self-reported data in multi-country studies.

Adenosine/guanosine preferring nucleoside ribohydrolase is a distinct, druggable antitrichomonal target.

Nucleoside salvage pathway enzymes used by Trichomonas vaginalis are distinct from the pathway involved in activation of existing 5-nitroimidazole drugs. They thus represent excellent targets for developing novel, mechanism-based antitrichomonal agents. The purine-specific adenosine/guanosine preferring ribohydrolase (AGNH) was screened against the NIH Clinical Collection to assess its druggability. Eight compounds, including five flavonoids, were identified with IC50 values ⩽10 µM and confirmed in counter screens run in the presence of detergent. The inhibitors are structurally distinct from inhibitors of the pyrimidine-specific uridine ribohydrolase (UNH) thus indicating that AGNH is a distinct, druggable target from UNH.

Inter-provider comparison of patient-reported outcomes: developing an adjustment to account for differences in patient case mix.

This paper describes the development of a methodology for the case-mix adjustment of patient-reported outcome measures (PROMs) data permitting the comparison of outcomes between providers on a like-for-like basis. Statistical models that take account of provider-specific effects form the basis of the proposed case-mix adjustment methodology. Indirect standardisation provides a transparent means of case mix adjusting the PROMs data, which are updated on a monthly basis. Recently published PROMs data for patients undergoing unilateral knee replacement are used to estimate empirical models and to demonstrate the application of the proposed case-mix adjustment methodology in practice. The results are illustrative and are used to highlight a number of theoretical and empirical issues that warrant further exploration. For example, because of differences between PROMs instruments, case-mix adjustment methodologies may require instrument-specific approaches. A number of key assumptions are made in estimating the empirical models, which could be open to challenge. The covariates of post-operative health status could be expanded, and alternative econometric methods could be employed.

The Influence of Cost-Effectiveness and Other Factors on Nice Decisions.

The National Institute for Health and Care Excellence (NICE) emphasises that cost-effectiveness is not the only consideration in health technology appraisal and is increasingly explicit about other factors considered relevant but not the weight attached to each. The objective of this study is to investigate the influence of cost-effectiveness and other factors on NICE decisions and whether NICE's decision-making has changed over time. We model NICE's decisions as binary choices for or against a health care technology in a specific patient group. Independent variables comprised of the following: clinical and economic evidence; characteristics of patients, disease or treatment; and contextual factors potentially affecting decision-making. Data on all NICE decisions published by December 2011 were obtained from HTAinSite [www.htainsite.com]. Cost-effectiveness alone correctly predicted 82% of decisions; few other variables were significant and alternative model specifications had similar performance. There was no evidence that the threshold has changed significantly over time. The model with highest prediction accuracy suggested that technologies costing £40 000 per quality-adjusted life-year (QALY) have a 50% chance of NICE rejection (75% at £52 000/QALY; 25% at £27 000/QALY). Past NICE decisions appear to have been based on a higher threshold than £20 000-£30 000/QALY. However, this may reflect consideration of other factors that cannot be easily quantified. © 2014 The Authors. Health Economics published by John Wiley & Sons Ltd.

Identification of proton-pump inhibitor drugs that inhibit Trichomonas vaginalis uridine nucleoside ribohydrolase.

Trichomonas vaginalis continues to be a major health problem with drug-resistant strains increasing in prevalence. Novel antitrichomonal agents that are mechanistically distinct from current therapies are needed. The NIH Clinical Compound Collection was screened to find inhibitors of the uridine ribohydrolase enzyme required by the parasite to scavenge uracil for its growth. The proton-pump inhibitors omeprazole, pantoprazole, and rabeprazole were identified as inhibitors of this enzyme, with IC50 values ranging from 0.3 to 14.5 µM. This suggests a molecular mechanism for the in vitro antitrichomonal activity of these proton-pump inhibitors, and may provide important insights toward structure-based drug design.

Assessing the performance of the EQ-VAS in the NHS PROMs programme.

OBJECTIVES: The study aims to increase knowledge about the performance of the EuroQol-visual analogue scales (EQ-VAS) in the UK NHS patient-reported outcome measures (PROMs) programme, which covers groin hernia, hip and knee replacement and varicose vein surgery, and make suggestions for improved collection, coding and analysis of data. METHODS: Four hundred scanned images of matched before-and-after EQ-VAS PROMs responses were selected at random. These were classified according to the different ways in which they were completed. Patient-level PROMs programme data linked to Hospital Episode Statistics for all patients from April 2009 to February 2011 were used to analyse the relationship between the EQ-VAS and the EQ-5D profile, index-weighted profile and condition-specific instruments. The linked PROMs and HES data comprise 331,951 anonymised patient records. RESULTS: A large majority (95 %) of EQ-VAS responses were completed in an unambiguous way, but only a minority (45 %) conformed strictly to the instructions given, posing challenges for data coding. The EQ-VAS data have a predictable and consistent relationship with the EQ-5D profile, although the correlations between the EQ-VAS and other measures of patient-reported health, both before and after surgery and in the change between them, are weak. CONCLUSIONS: EQ-VAS data might be improved by providing better guidance on collection and coding. It is argued that the observed differences in results from EQ-VAS and other measures of health reflect the fact that it measures a broader underlying construct of health, arguably providing a means of summarising overall health that is closer to the patient's perspective.

Truly inefficient or providing better quality of care? Analysing the relationship between risk-adjusted hospital costs and patients' health outcomes.

Observed variation in hospital costs may be attributable to differences in patients' health outcomes. Previous studies have resorted to inherently incomplete outcome measures such as mortality or re-admission rates to assess this claim. This study makes use of a novel dataset of routinely collected patient-reported outcome measures (PROMs) linked to inpatient records to (i) access the degree to which cost variation is associated with variation in patients' health gain and (ii) explore how far judgement about hospital cost performance changes when health outcomes are accounted for. We use multilevel modelling to address the clustering of patients in providers and isolate unexplained cost variation. We find some evidence of a U-shaped relationship between risk-adjusted costs and outcomes for hip replacement surgery. For three other procedures (knee replacement, varicose vein and groin hernia surgery), the estimated relationship is sensitive to the choice of PROM instrument. We do not observe substantial changes in cost performance estimates when outcomes are explicitly accounted for.

Medical crises and therapeutic talk.

Coexisting medical traditions operate at different levels of scale. In rural eastern Africa there are diviners and herbalists whose clients are drawn from the immediate neighbourhood. Some develop healing reputations more widely over a region or nation, sometimes with prophetic and witch-finding powers. Biomedical clinics and hospitals are also interlinked regionally, nationally and internationally. Patients or carers may seek healthcare by moving through these different levels, sometimes beginning with a neighbourhood healer and sometimes trying out different therapies simultaneously. Sicknesses and misfortunes are often first discussed within a family or homestead, with concern for the victim extending to all its members. The talk is based on assumed trust among its members. However, if unresolved, the affliction may trigger a crisis that breaks the trust, so that healers beyond the neighbourhood are sought, whether prophetic/witch-finding or biomedical. Taken out of the context of family and homestead intimacy, the talk blames the ailment on the malevolence or negligence of individuals in the community. Talk about sickness among sufferers and between them and healers, is thus transformed from that which seeks resolution in amity to that which seeks culpability and, sometimes, retribution. A similar process of sickness talk changing through its appropriation by wider scale and more powerful medical authority also occurs in western biomedical hospitals and clinics.

Early diffusion weighted magnetic resonance imaging can predict survival in women with locally advanced cancer of the cervix treated with combined chemo-radiation.

OBJECTIVES: To assess the predictive value of diffusion weighted imaging (DWI) for survival in women treated for advanced cancer of the cervix with concurrent chemo-radiotherapy. METHODS: Twenty women treated for advanced cancer of the cervix were recruited and followed up for a median of 26 (range <1 to 43) months. They each had DWI performed before treatment, 2 weeks after beginning therapy (midtreatment) and at the end of treatment. Apparent diffusion coefficient (ADC) values were calculated from regions of interest (ROI). All participants were reviewed for follow-up data. ADC values were compared with mortality status (Mann-Whitney test). Time to progression and overall survival were assessed (Kaplan-Meier survival graphs). RESULTS: There were 14 survivors. The median midtreatment ADC was statistically significantly higher in those alive compared to the non-survivors, 1.55 and 1.36 (×10(-3)/mm(2)/s), respectively, P = 0.02. The median change in ADC 14 days after treatment commencement was significantly higher in the alive group compared to non-survivors, 0.28 and 0.14 (×10(-3)/mm(2)/s), respectively, P = 0.02. There was no evidence of a difference between survivors and non-survivors for pretreatment baseline or post-therapy ADC values. CONCLUSION: Functional DWI early in the treatment of advanced cancer of the cervix may provide useful information in predicting survival. KEY POINTS : • Diffusion weighted magnetic resonance imaging (DWI) is increasingly used in cervical cancer. • Functional DWI early in treatment of cervical cancer may help predict survival. • DWI may help clinicians to tailor or individualise treatment appropriately. • This may limit toxicity from ineffective treatment and allow early alternative therapy.

EQ-5D-3L and quality of life in total knee arthroplasty (TKA) patients: beyond the index scores.

BACKGROUND: Many patient reported outcome measures (PROMs) generate single number index scores that summarise responses to different questions within a questionnaire. Although these are valuable as unambiguous indicators of ill-health and changes in health, further information can be gained from examining the questionnaire responses themselves. This has additional importance since the patients' reports are those responses and not the index scores. This paper reanalyses data from two prospective multicentre clinical studies assessing patients' quality of life before and after total knee arthroplasty (TKA) using the EQ-5D-3L. Patients who completed EQ-5D-3L questionnaires at 3 time periods were included from 4 countries (USA, UK, Australia, New Zealand) operated on by the same surgeons using two different knee replacement systems. Descriptive analyses included levels within EQ-5D dimensions and profiles (combinations of dimensions and levels) at baseline and follow-up, including changes over time and differences between implants. Regression analysis quantified the relationship between the profiles and the EQ VAS. RESULTS: Problems with mobility, usual activities and pain & discomfort, in that order, were most frequent for pre-operative patients. There were large improvements in every dimension after surgery, but the time that this was observed differed: for mobility, self-care and anxiety & depression, most of the improvement occurred during the first 10 months; for usual activities and pain & discomfort, over 11-22 months. Analysing profiles, 85% of patients experienced an unequivocal improvement, 5.9% had no change, 3.5% worsened and 5.5% a mixed change at 11-22 months follow-up. Anxiety & depression had the greatest impact on EQ VAS scores; while mobility and usual activities were also important; usual activities was particularly important post-surgery. CONCLUSIONS: The value of analysing patients' responses to PROMs questionnaires without using summary scores was confirmed. The results add further detail to existing knowledge about the health problems that TKA patients experience before surgery, improvements after surgery, residual problems that some have, and the time at which improvements are experienced. This was a small study, but its methods may be easily replicated in other studies that use the EQ-5D-3L. It may also be possible to adapt them for other PROMs.

Longitudinal study of patients' health-related quality of life using EQ-5D-3L in 11 Swedish National Quality Registers.

OBJECTIVE: To compare problems reported in the five EQ-5D-3L dimensions and EQ VAS scores at baseline and at 1-year follow-up among different patient groups and specific diagnoses in 11 National Quality Registers (NQRs) and to compare these with the general population. DESIGN: Longitudinal, descriptive study. PARTICIPANTS: 2 66 241 patients from 11 NQRs and 49 169 participants from the general population were included in the study. PRIMARY AND SECONDARY OUTCOME MEASURES: Proportions of problems reported in the five EQ-5D-3L dimensions, EQ VAS scores of participants' own health and proportions of participants and mean/median EQ VAS score in the Paretian Classification of Health Change (PCHC) categories. RESULTS: In most of the included registers, and the general population, problems with pain/discomfort were the most frequently reported at baseline and at 1-year follow-up. Mean EQ VAS score (SD) ranged from 45.2 (22.4) among disc hernia patients to 88.1 (15.3) in wrist and hand fracture patients at baseline. They ranged from 48.9 (20.9) in pulmonary fibrosis patients to 83.3 (17.4) in wrist and hand fracture patients at follow-up. The improved category of PCHC, improvement in at least one dimension without deterioration in any other, accounted for the highest proportion in several diagnoses, corresponding with highest improvement in mean EQ VAS score. CONCLUSIONS: The study documented self-reported health of several different patient groups using the EQ-5D-3L in comparing with the general population. This demonstrated the important role of patient-reported outcomes in routine clinical care, to assess and follow-up health status and progress within different groups of patients. The EQ-5D-3L descriptive system and EQ VAS have an important role in providing a 'common denominator', allowing comparisons across NQRs and specific diagnoses. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov (NCT04359628).