DEMQOL and DEMQOL-Proxy: a Rasch analysis among those diagnosed with dementia.

BACKGROUND: In previous work we concluded that DEMQOL and DEMQOL-Proxy can provide robust measurement of HRQL in dementia when scores are derived from analysis using the Rasch model. As the study sample included people with mild cognitive impairment, we undertook a replication study in the subsample with a diagnosis of dementia (PWD). PWD constitute the population for whom DEMQOL and DEMQOL-Proxy were originally developed. METHODS: We conducted a Rasch model analysis using the RUMM2030 software to re-evaluate DEMQOL (441 PWD) and DEMQOL-Proxy (342 family carers). We evaluated scale to sample targeting, ordering of item thresholds, item fit to the model, and differential item functioning (sex, age, severity, relationship), local independence, unidimensionality and reliability. RESULTS: For both DEMQOL and DEMQOL-Proxy, results were highly similar to the results in the original sample. We found the same problems with content and response options. CONCLUSIONS: DEMQOL and DEMQOL-Proxy can provide robust measurement of HRQL in people with a diagnosis of dementia when scores are derived from analysis using the Rasch model. As in the wider sample, the problems identified with content and response options require qualitative investigation in order to improve the scoring of DEMQOL and DEMQOL-Proxy.

Caregiver burden and quality of life 2 years after attendance at a memory clinic.

OBJECTIVES: We aimed to describe (1) the burden and health-related quality of life (HRQL) of informal caregivers of new patients attending a memory assessment service (MAS), (2) changes in these outcomes over 2 years, and (3) satisfaction with services. METHODS: Informal caregivers of patients attending one of 73 MASs throughout England completed questionnaires at the patient's first appointment, and 6 and 12 months later. Participants from 30 of these MASs were also followed up at 24 months. Questionnaires covered caregivers' sociodemographic characteristics, Zarit Burden Interview, EQ-5D-3L, and satisfaction with services. We used multivariable linear regression to assess relationships between burden, HRQL, and caregiver and patient characteristics. RESULTS: Of 1020 caregivers at baseline, 569 were followed up at 6 months, 452 at 12 months, and 187 at 24 months. There was a small increase in caregiver burden over 2 years (effect size 0.30 SD). These changes were not associated with most caregiver or patient characteristics, except socio-economic deprivation, which was associated with larger increases in burden at 2 years. Caregivers' HRQL was weakly associated with burden and showed a small reduction over time (0.2 SD). Most caregivers were satisfied with services, but caregivers who were not satisfied with the services they received reported greater increases in burden. CONCLUSIONS: Increases in caregiver burden and reductions in HRQL appear to be small over the first 2 years after attending a MAS. However, the longer term impact on caregivers and those they care for needs investigating, as do strategies to reduce their burden.

Caregiver burden and quality of life two years after attendance at a memory clinic.

OBJECTIVES: We aimed to describe 1) the burden and HRQL of informal caregivers of new patients attending a memory assessment service (MAS), 2) changes in these outcomes over two years and 3) satisfaction with services. METHODS: Informal caregivers of patients attending one of 73 MASs throughout England completed questionnaires at the patient's first appointment, and 6 and 12 months later. Participants from 30 of these MASs were also followed up at 24 months. Questionnaires covered caregivers' sociodemographic characteristics, Zarit Burden Interview, EQ-5D-3L and satisfaction with services. We used multivariable linear regression to assess relationships between burden, HRQL and caregiver and patient characteristics. RESULTS: Of 1020 caregivers at baseline, 569 were followed up at 6 months, 452 at 12 months and 187 at 24 months. There was a small increase in caregiver burden over two years (effect size 0.30 SD). These changes were not associated with most caregiver or patient characteristics, except socioeconomic deprivation which was associated with larger increases in burden at two years. Caregivers' HRQL was weakly associated with burden and showed a small reduction over time (0.2 SD). Most caregivers were satisfied with services but caregivers who were not satisfied with the services they received reported greater increases in burden. CONCLUSIONS: Increases in caregiver burden and reductions in HRQL appear to be small over the first two years after attending a MAS. However, the longer-term impact on caregivers and those they care for needs investigating, as do strategies to reduce their burden.

Is the effectiveness of memory assessment services associated with their structural and process characteristics?

OBJECTIVES: The aim of this study was to investigate whether structural and process characteristics of memory assessment services (MASs) are associated with outcomes (changes in patients' health-related quality of life (HRQL), carers' HRQL and carers' burden) over the first 6 months following the first appointment. METHODS: Data from 785 patients referred to 69 MASs and 511 of their lay carers, collected at the first appointment and 6 months later. Data on MAS characteristics were collected using a questionnaire at baseline. We used multilevel linear regression models to explore the associations of patients' HRQL and carers' outcomes with structural and process characteristics of MASs. Analyses were conducted on the full sample of patients and carers, and separately on those patients diagnosed with dementia. RESULTS: None of the structural (skill mix, workload, volume, provision of clinical assessments and provision of psychosocial support) or process (waiting time, length and number of appointments, anti-dementia drug use and psychosocial interventions use) characteristics included in the analyses were associated with patients' or carers' outcomes at 6 months, apart from the presence of allied health professionals (AHPs), which was associated with a DEMQOL score 2.7 points higher. When only those with a diagnosis of dementia were considered, the association with presence of AHPs was no longer observed. CONCLUSIONS: Apart from involving AHPs, alterations to the way MASs are structured or function appear unlikely to improve their effectiveness in improving patients' and carers' HRQL. It is possible that the characteristics of MASs may influence patients' and carers' experience, but this was not studied. Copyright © 2017 John Wiley & Sons, Ltd.

Memory assessment services and health-related quality of life: 1-year follow-up.

OBJECTIVES: Our group has already demonstrated that patients' health-related quality of life (HRQL) improves in the first 6 months after their first appointment at memory assessment services (MASs), but the sustainability of such gains is unknown. We aimed to describe changes in patients' HRQL at 12 months after their first MAS appointment and to examine associations with patient and MAS characteristics. METHODS: We collected data from 702 patients and 452 lay caregivers at the first appointment and 12 months later. Multivariable linear regression was used to examine the relationships of change in HRQL (self-reported and proxy-reported) with patients' characteristics and use of post-diagnostic interventions, and multilevel models were used to analyse the relationships of HRQL with MAS characteristics. RESULTS: In the whole group, self-reported HRQL improved over 12 months (+3.5 points, 95% CI 2.7 to 4.2). Among people diagnosed with dementia, improvement in HRQL was more than double that among those with mild cognitive impairment or no diagnosis. Proxy-reported HRQL improved only in those diagnosed with dementia (+1.2 points, 95% CI 0.2 to 2.2). Changes in HRQL were not associated with any patient characteristics. The only feature of MASs associated with larger improvements in HRQL was the presence of advisory and support staff. CONCLUSIONS: Improvements in HRQL observed at 6 months are maintained up to 1 year after the first MAS appointment, more so among those who receive a diagnosis of dementia. Continued follow-up will determine if the improvement is even longer lasting.

Antibiotic prescribing in patients with self-reported sore throat.

Objectives: To investigate the predictors of general practitioner (GP) consultation and antibiotic use in those developing sore throat. Methods: We conducted a prospective population-based cohort study on 4461 participants in two rounds (2010-11) from 1897 households. Results: Participants reported 2193 sore throat illnesses, giving a community sore throat incidence of 1.57/ person-year. 13% of sore throat illnesses led to a GP consultation and 56% of these consultations led to antibiotic use. Participants most likely to have sore throats included women and children (e.g. school compared with retirement age); adjusted incidence rate ratio (aIRR) of 1.33 and 1.52, respectively. Participants with sore throat were more likely to consult their GP if they were preschool compared with retirement age [adjusted OR (aOR) 3.22], had more days of sore throat (aOR 1.11), reported more severe pain (aOR 4.24) or reported fever (aOR 3.82). Antibiotics were more often used by chronically ill individuals (aOR 1.78), those reporting severe pain (aOR 4.14), those reporting fever (aOR 2.58) or children with earache (aOR 1.85). Among those who consulted, males and adults who reported feeling anxious were more likely to use antibiotics; aOR 1.87 and 5.36, respectively. Conclusions: Only 1 in 10 people who have a sore throat see a doctor and more than half of those attending get antibiotics. Further efforts to curb antibiotic use should focus on reducing initial GP consultations through public information promoting safe self-management, targeted at groups identified above as most likely to attend with sore throats.

Patient-reported outcome (PRO) questionnaires for men who have radical surgery for prostate cancer: a conceptual review of existing instruments.

To critically review conceptual frameworks for available patient-reported outcome (PRO) questionnaires in men having radical prostatectomy (RP), psychometrically evaluate each questionnaire, and identify whether each is appropriate for use at the level of the individual patient. We searched PubMed, the Reports and Publications database of the University of Oxford Patient-Reported Outcomes Measurement Group and the website of the International Consortium for Health Outcomes Measurement (ICHOM) for psychometric reviews of prostate cancer-specific PRO questionnaires. From these we identified relevant questionnaires and critically appraised the conceptual content, guided by the Wilson and Cleary framework and psychometric properties, using well established criteria. The searches found four reviews and one recommendation paper. We identified seven prostate cancer-specific PROs: the Expanded Prostate Cancer Index Composite-26 (EPIC-26), Expanded Prostate Cancer Index Composite-50 (EPIC-50), University of California-Los Angeles Prostate Cancer Index (UCLA-PCI), Functional Assessment of Cancer Therapy - Prostate Cancer Subscale (FACT-P PCS), European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - prostate specific 25-item (EORTC QLQ-PR25), Prostate Cancer - Quality of Life (PC-QoL), and Symptom Tracking and Reporting (STAR). Six out of seven measures purported to measure health-related quality of life (HRQL), but items focused strongly on urinary and sexual symptoms/functioning. The remaining questionnaire (STAR) claimed to assess functional recovery after RP. The psychometric evidence for these questionnaires was incomplete and variable in quality; none had evidence that they were appropriate for use with individual patients. Several questionnaires provide the basis of measures of urinary and/or sexual symptoms/functioning. Further work should explore other aspects of HRQL that are important for men having RP. Further psychometric work is also needed to determine whether they can be used at the individual level.

Change in Health-related Quality of Life After Referral to Memory Assessment Services.

Despite strong support for the provision of memory assessment services (MASs) in England and other countries, their effectiveness in improving patient outcomes is uncertain. We aimed to describe change in patients' health-related quality of life (HRQL) 6 months after referral to MASs and to examine associations with patient characteristics and use of postdiagnostic interventions. Data from 883 patients referred to 69 MASs and their informal caregivers (n=569) were collected at referral and 6 months later. Multivariable linear regression was used to examine associations of change in HRQL (DEMQOL, DEMQOL-Proxy) with patient characteristics (age, sex, ethnicity, socioeconomic deprivation, and comorbidity) and use of postdiagnostic interventions (antidementia medications and nonpharmacological therapies). Mean HRQL improved, irrespective of diagnosis: self-reported HRQL increased 3.4 points (95% CI, 2.7-4.1) and proxy-reported HRQL 1.3 points (95% CI, 0.5-2.1). HRQL change was not associated with any of the patient characteristics studied. Patients with dementia (54%) receiving antidementia drugs reported greater improvement in their HRQL but those using nonpharmacological therapies reported less improvement compared with those note receiving therapy. HRQL improved in the first 6 months after referral to MASs. Research is needed to determine longer term sustainability of the benefits and the cost-effectiveness of MASs.

Sociodemographic Characteristics, Cognitive Function, and Health-related Quality of Life of Patients Referred to Memory Assessment Services in England.

National policy in England is to encourage referral of people with suspected dementia to Memory Assessment Services (MAS). However, little is known about the characteristics of new referrals, which limits our capacity to evaluate these services. The objectives were to: describe the characteristics (age, sex, ethnicity, socioeconomic deprivation, and comorbidity) of referred patients, and examine the relationships between these characteristics and cognitive function (tertiles of Mini-Mental State Examination score) and health-related quality of life (HRQL) (DEMQOL, DEMQOL-Proxy). We used multivariable regression methods to analyze data from 1420 patients from 73 MAS, and their lay carers (n=1020). The mean age of patients was 78 years; 42% had cognitive function equivalent to Mini-Mental State Examination <24. Characteristics associated with lower function were: older age, being female, deprivation, and nonwhite ethnicity. Deprivation and nonwhite ethnicity were also associated with lower self-reported HRQL, as was having multiple comorbidities; older age was associated with better self-reported HRQL. Lower proxy-reported HRQL was associated with being female, deprivation and comorbidities, but not age and ethnicity. A large proportion of study participants had moderate or high cognitive function scores, suggesting that these patients were referred early to MAS. Research is needed to identify why apparent sociodemographic inequalities in use of MAS exist.

DEMQOL and DEMQOL-Proxy: a Rasch analysis.

BACKGROUND: DEMQOL and DEMQOL-Proxy are widely used patient reported outcome measures (PROMs) of health related quality of life in people with dementia (PWD). Growing interest in routine use of PROMs in health care calls for more robust instruments that are potentially fit for reliable and valid comparisons at the micro-level (patients) and meso-level (clinics, hospitals, care homes). METHODS: We used modern psychometric methods (based on the Rasch model) to re-evaluate DEMQOL (1428 PWDs) and DEMQOL-Proxy (1022 carers) to ensure they are fit for purpose. We evaluated scale to sample targeting, ordering of item thresholds, item fit to the model, and differential item functioning (sex, age, relationship), local independence, unidimensionality and reliability on the full set of items and a smaller item set. RESULTS: For both DEMQOL and DEMQOL-Proxy the smaller item set performed better than the original item set. We developed revised scores using the items from the smaller set. CONCLUSIONS: We have improved the scoring of DEMQOL and DEMQOL-Proxy using the Rasch measurement model. Future work should focus on the problems identified with content and response options.

Reliability and validity of a self-administration version of DEMQOL-Proxy.

OBJECTIVE: This study aimed to investigate the reliability and validity of a self-administered version of DEMQOL-Proxy, a disease-specific instrument that measures health-related quality of life in people with dementia. METHODS: The sample consisted of 173 informal carers of people with dementia, aged 29 to 89 years old. Carers were mostly female, White/White British and closely related to the patient. They completed DEMQOL-Proxy (self-administered), EQ-5D-3L (proxy reported about the person with dementia), EQ-5D-3L (self-reported about their own health) and the Zarit Burden Interview. Using well-established methods from classical test theory, we evaluated scale level acceptability, reliability and convergent, discriminant and known-groups validity of DEMQOL-Proxy. RESULTS: DEMQOL-Proxy (self-administered) showed high acceptability (3.5% missing data and 0% scores at floor or ceiling), high internal consistency reliability (α = 0.93) and good convergent and discriminant validity. Amongst others, we found a moderately high correlation with EQ-5D-3L proxy reported (r = 0.52) and low to essentially zero correlations with EQ-5D-3L self-reported (r = 0.20) and carer and patient background variables (r ≤ 0.20). As predicted, DEMQOL-Proxy (self-administered) showed a modest correlation with DEMQOL (r = 0.32). Known-groups differences on health-related quality of life (comparing people with versus people without cognitive impairment) were of moderate effect size (d = 0.38) and in the expected direction. CONCLUSIONS: DEMQOL-Proxy (self-administered) has comparable acceptability, reliability and validity with DEMQOL-Proxy (interviewer administered). DEMQOL-Proxy (self-administered) can be used in a wider variety of contexts than its interviewer-administered version, including routine use in busy clinics. Copyright © 2016 John Wiley & Sons, Ltd.

Delirium risk stratification in consecutive unselected admissions to acute medicine: validation of a susceptibility score based on factors identified externally in pooled data for use at entry to the acute care pathway.

Background: recognition of prevalent delirium and prediction of incident delirium may be difficult at first assessment. We therefore aimed to validate a pragmatic delirium susceptibility (for any, prevalent and incident delirium) score for use in front-line clinical practice in a consecutive cohort of older acute medicine patients. Methods: consecutive patients aged ≥65 years over two 8-week periods (2010-12) were screened prospectively for delirium using the Confusion Assessment Method (CAM), and delirium was diagnosed using the DSM IV criteria. The delirium susceptibility score was the sum of weighted risk factors derived using pooled data from UK-NICE guidelines: age >80 = 2, cognitive impairment (cognitive score below cut-off/dementia) = 2, severe illness (systemic inflammatory response syndrome) = 1, infection = 1, visual impairment = 1. Score reliability was determined by the area under the receiver operating curve (AUC). Results: among 308 consecutive patients aged ≥65 years (mean age/SD = 81/8 years, 164 (54%) female), AUC was 0.78 (95% CI 0.71-0.84) for any delirium; 0.71 (0.64-0.79), for prevalent delirium; 0.81 (0.70-0.92), for incident delirium; odds ratios (ORs) for risk score 5-7 versus <2 were 17.9 (5.4-60.0), P < 0.0001 for any delirium, 8.1 (2.2-29.7), P = 0.002 for prevalent delirium, and 25.0 (3.0-208.9) P = 0.003 for incident delirium, with corresponding relative risks of 5.4, 4.7 and 13. Higher risk scores were associated with frailty markers, increased care needs and poor outcomes. Conclusions: the externally derived delirium susceptibility score reliably identified prevalent and incident delirium using clinical data routinely available at initial patient assessment and might therefore aid recognition of vulnerability in acute medical admissions early in the acute care pathway.

Delirium risk stratification in consecutive unselected admissions to acute medicine: validation of externally derived risk scores.

BACKGROUND: reliable delirium risk stratification will aid recognition, anticipation and prevention and will facilitate targeting of resources in clinical practice as well as identification of at-risk patients for research. Delirium risk scores have been derived for acute medicine, but none has been prospectively validated in external cohorts. We therefore aimed to determine the reliability of externally derived risk scores in a consecutive cohort of older acute medicine patients. METHODS: consecutive patients aged ≥65 over two 8-week periods (2010, 2012) were screened prospectively for delirium using the Confusion Assessment Method (CAM), and delirium was diagnosed using the DSM IV criteria. The reliability of existing delirium risk scores derived in acute medicine cohorts and simplified for use in routine clinical practice (USA, n = 2; Spain, n = 1; Indonesia, n = 1) was determined by the area under the receiver operating characteristic curve (AUC). Delirium was defined as prevalent (on admission), incident (occurring during admission) and any (prevalent + incident) delirium. RESULTS: among 308 consecutive patients aged ≥65 (mean age/SD = 81/8 years, 164 (54%) female), existing delirium risk scores had AUCs for delirium similar to those reported in their original internal validations ranging from 0.69 to 0.76 for any delirium and 0.73 to 0.83 for incident delirium. All scores performed better than chance but no one score was clearly superior. CONCLUSIONS: externally derived delirium risk scores performed well in our independent acute medicine population with reliability unaffected by simplification and might therefore facilitate targeting of multicomponent interventions in routine clinical practice.

Adeno-associated virus Rep represses the human integration site promoter by two pathways that are similar to those required for the regulation of the viral p5 promoter.

UNLABELLED: Adeno-associated virus serotype 2 (AAV2) can efficiently replicate in cells that have been infected with helper viruses, such as adenovirus or herpesvirus. However, in the absence of helper virus infection, AAV2 establishes latency by integrating its genome site specifically into PPP1R12C, a gene located on chromosome 19. This integration target site falls into one of the most gene-dense regions of the human genome, thus inviting the question as to whether the virus has evolved mechanisms to control this complex transcriptional environment in order to facilitate integration, maintain an apparently innocuous latency, and/or establish conditions that are conducive to the rescue of the integrated viral genome. The viral replication (Rep) proteins control and direct every known aspect of the viral life cycle and have been shown to tightly control all AAV2 promoters. In addition, a number of heterologous promoters are repressed by the AAV2 Rep proteins. Here, we demonstrate that Rep proteins efficiently repress expression from the target site PPP1R12C promoter. We find evidence that this repression employs mechanisms similar to those described for Rep-mediated AAV2 p5 promoter regulation. Furthermore, we show that the repression of the cellular target site promoter is based on two distinct mechanisms, one relying on the presence of a functional Rep binding motif within the 5' untranslated region (UTR) of PPP1R12C, whereas the second pathway requires only an intact nucleoside triphosphate (NTP) binding site within the Rep proteins, indicating the possible reliance of this pathway on interactions of the Rep proteins with cellular proteins that mediate or regulate cellular transcription. IMPORTANCE: The observation that repression of transcription from the adeno-associated virus serotype 2 (AAV2) p5 and integration target site promoters is mediated by shared mechanisms highlights the possible coevolution of virus and host and could lead to the identification of host factors that the virus exploits to navigate its life cycle.

Urinary and Sexual Impact of Robotic Radical Prostatectomy: Reporting of Patient-reported Outcome Measures in the First Year after Radical Prostatectomy in a Contemporary Multicentre Cohort in the United Kingdom.

Background and objective: Radical prostatectomy (RP) is an established treatment for localised prostate cancer that can have a significant impact on urinary and sexual function, with recovery over time. Our aim was to describe functional recovery in the first year after RP, reporting descriptive outcomes alongside validated patient-reported outcome measure scores (Expanded Prostate Cancer Index Composite, EPIC-26). Methods: Men undergoing RP between September 2015 and November 2019 completed EPIC-26 at baseline and 1, 3, 6, and 12 mo. Key findings and limitations: Overall, 2030 men consented to participation, underwent RP, and completed EPIC-26. At baseline, 97% were pad-free (1928/1996; 95% confidence interval [CI] 96-97%) and 77% were leak-free and pad-free (1529/1996; 95% CI 75-78), with a median EPIC-26 incontinence domain score of 100 (interquartile range [IQR] 86-100). At 12 mo, 65% were pad-free (904/1388; 95% CI 63-68%) and 42% were leak-free and pad-free (583/1388; 95% CI 39-45%), with a median EPIC-26 score of 76 (IQR 61-100). While one in three men reported wearing a pad at 12 mo, fewer than one in ten men needed more than 1 pad/d. At baseline, 1.9% reported a "moderate or big problem" with urine leakage, which increased to 9.7% at 12 mo. At baseline, the median sexual domain score among 1880 men was 74 (IQR 43-92) and 52% had erections sufficient for intercourse without medication (975/1880; 95% CI 50-54%). Among these 975 men, 630 responded at 12 mo, of whom 17% reported sufficient erections for intercourse (105/630; 95% CI 14-20%), without medication in 6% (37/630; 95% CI 4-8%) and needing medication in 11% (68/630; 95% CI 9-13%); the median EPIC-26 domain score was 26 (IQR 13-57). Conclusions and clinical implications: Reporting of functional outcomes after RP in terms of easily understood concepts such as pad-free and leak-free status, and erections with and with medication, alongside the classical report using EPIC-26 domain scores, increases the understanding of RP recovery patterns over the first year. Patient summary: At 12 months after surgery for prostate cancer, one in ten men reported a moderate or big problem with urine leakage and one in five men reported sufficient erections.

Anesthetics interfere with axon guidance in developing mouse neocortical neurons in vitro via a γ-aminobutyric acid type A receptor mechanism.

BACKGROUND: The finding that exposure to general anesthetics (GAs) in childhood may increase rates of learning disabilities has raised a concern that anesthetics may interfere with brain development. The generation of neuronal circuits, a complex process in which axons follow guidance cues to dendritic targets, is an unexplored potential target for this type of toxicity. METHODS: GA exposures were conducted in developing neocortical neurons in culture and in early postnatal neocortical slices overlaid with fluorescently labeled neurons. Axon targeting, growth cone collapse, and axon branching were measured using quantitative fluorescence microscopy. RESULTS: Isoflurane exposure causes errors in Semaphorin-3A-dependent axon targeting (n = 77 axons) and a disruption of the response of axonal growth cones to Semaphorin-3A (n = 2,358 growth cones). This effect occurs at clinically relevant anesthetic doses of numerous GAs with allosteric activity at γ-aminobutyric acid type A receptors, and it was reproduced with a selective agonist. Isoflurane also inhibits growth cone collapse induced by Netrin-1, but does not interfere branch induction by Netrin-1. Insensitivity to guidance cues caused by isoflurane is seen acutely in growth cones in dissociated culture, and errors in axon targeting in brain slice culture occur at the earliest point at which correct targeting is observed in controls. CONCLUSIONS: These results demonstrate a generalized inhibitory effect of GAs on repulsive growth cone guidance in the developing neocortex that may occur via a γ-aminobutyric acid type A receptor mechanism. The finding that GAs interfere with axon guidance, and thus potentially with circuit formation, represents a novel form of anesthesia neurotoxicity in brain development.

Psychometric performance of the Chichewa versions of the EQ-5D-Y-3L and EQ-5D-Y-5L among healthy and sick children and adolescents in Malawi.

OBJECTIVES: The EuroQol Group has developed an extended version of the EQ-5D-Y-3L with five response levels for each of its five dimensions (EQ-5D-Y-5L). The psychometric performance has been reported in several studies for the EQ-5D-Y-3L but not for the EQ-5D-Y-5L. This study aimed to psychometrically evaluate the EQ-5D-Y-3L and EQ-5D-Y-5L Chichewa (Malawi) versions. METHODS: The EQ-5D-Y-3L, EQ-5D-Y-5L and PedsQL™ 4.0 Chichewa versions were administered to children and adolescents aged 8-17 years in Blantyre, Malawi. Both of the EQ-5D-Y versions were evaluated for missing data, floor/ceiling effects, and validity (convergent, discriminant, known-group and empirical). RESULTS: A total of 289 participants (95 healthy, and 194 chronic and acute) self-completed the questionnaires. There was little problem with missing data (< 5%) except in children aged 8-12 years particularly for the EQ-5D-Y-5L. Ceiling effects was generally reduced in moving from the EQ-5D-Y-3L to the EQ-5D-Y-5L. For both EQ-5D-Y-3L and EQ-5D-Y-5L, convergent validity tested with PedsQL™ 4.0 was found to be satisfactory (correlation ≥ 0.4) at scale level but mixed at dimension /sub-scale level. There was evidence of discriminant validity (p > 0.05) with respect to gender and age, but not for school grade (p < 0.05). For empirical validity, the EQ-5D-Y-5L was 31-91% less efficient than the EQ-5D-Y-3L at detecting differences in health status using external measures. CONCLUSIONS: Both versions of the EQ-5D-Y-3L and EQ-5D-Y-5L had issues with missing data in younger children. Convergent validity, discriminant validity with respect to gender and age, and known-group validity of either measures were also met for use among children and adolescents in this population, although with some limitations (discriminant validity by grade and empirical validity). The EQ-5D-Y-3L seems particularly suited for use in younger children (8-12 years) and the EQ-5D-Y-5L in adolescents (13-17 years). However, further psychometric testing is required for test re-test reliability and responsiveness that could not be carried out in this study due to COVID-19 restrictions.

Development of consensus-based considerations for use of adult proxy reporting: an ISOQOL task force initiative.

AIMS: Many large-scale population-based surveys, research studies, and clinical care allow for inclusion of proxy reporting as a strategy to collect outcomes when patients are unavailable or unable to provide reliable self-report. Prior work identified an absence of methodological guidelines regarding proxy reporting in adult populations, including who can serve as a proxy, and considerations for data collection, analysis, and reporting. The primary objective of this work by the ISOQOL Proxy Task Force was to review documents and clinical outcome assessment measures with respect to proxy reporting and to develop, through consensus, considerations for proxy reporting. METHODS: We assembled an international group with clinically relevant and/or methodological expertise on proxy use in adult populations. We conducted a targeted review of documentation based on regulatory, non-regulatory, professional society, and individual measure sources. Using a standardized collection form, proxy-related information was extracted from each source including definitions of a proxy, characteristics of a proxy, domains addressable or addressed by a proxy, and observer-reporting. RESULTS: The definition of proxy was inconsistent across 39 sources, except regulatory documents which defined a proxy as a person other than the patient who reports on an outcome as if she/he were the patient. While proxy report was discouraged in regulatory documentation, it was acknowledged there were instances where self-report was impossible. Many documentation sources indicated proxies would be well-justified in certain contexts, but did not indicate who could act as a proxy, when proxies could be used, what domains of patient health they could report on, or how data should be reported. Observer-reported outcomes were typically defined as those based on observed behaviors, however there was not a consistent differentiation between proxy and observer reporting. Based on information extracted from these resources, we developed a checklist of considerations when including proxy-reported measures or using proxies in study design, data collection, analysis, interpretation and reporting of proxy reported data. CONCLUSION: Our targeted review highlights a lack of clarity in capturing, interpreting and reporting data from proxies in adult populations. We provide a checklist of considerations to assist researchers and clinicians with including proxies in research studies and clinical care. Lastly, our review identified areas where further guidance and future research are necessary.

Estimating preference-based single index measures for dementia using DEMQOL and DEMQOL-Proxy.

OBJECTIVE: Although condition-specific measures are commonly used in dementia, they cannot be used in analyses of cost per quality-adjusted life-year because they do not incorporate preferences. We addressed this gap by estimating two preference-based single index measures: the DEMQOL-U from the self-report DEMQOL (mild-to-moderate dementia severity) and the DEMQOL-Proxy-U from the carer-report DEMQOL-Proxy (all levels of dementia severity). METHODS: We conducted valuation studies on 593 members of the general population (306 for the DEMQOL-U, 287 for the DEMQOL-Proxy-U) using the time trade-off elicitation technique. We then fitted a range of mean and individual-level multivariate regression models to the valuation data to derive preference weights for each measure. We applied the estimated weights to a large, clinically representative sample. RESULTS: Mean observed time trade-off values ranged from 0.18 to 0.95 for DEMQOL-U and from 0.33 to 0.96 for DEMQOL-Proxy-U. The best performing models for each measure were main effects models estimated using individual-level data. DEMQOL-Proxy-U had inconsistent but insignificant coefficient estimates for one dimension. Models were estimated to remove these inconsistencies. CONCLUSION: Preference-based single index measures from DEMQOL and DEMQOL-Proxy for use in economic evaluation will enable economic evaluation using quality-adjusted life-years to be undertaken for people across the full range of dementia severity. Future research will examine how the utilities from each measure can be used and combined to populate cost-effectiveness models.