Tracey Young

Quality of life four years after acute myocardial infarction: short form 36 scores compared with a normal population

OBJECTIVES To assess the impact of myocardial infarction on quality of life in four year survivors compared to data from “community norms”, and to determine factors associated with a poor quality of life. DESIGN Cohort study based on the Nottingham heart attack register. SETTING Two district general hospitals serving a defined urban/rural population. SUBJECTS All patients admitted with acute myocardial infarction during 1992 and alive at a median of four years. MAIN OUTCOME MEASURES Short form 36 (SF 36) domain and overall scores. RESULTS Of 900 patients with an acute myocardial infarction in 1992, there were 476 patients alive and capable of responding to a questionnaire in 1997. The response rate was 424 (89.1%). Compared to age and sex adjusted normative data, patients aged under 65 years exhibited impairment in all eight domains, the largest differences being in physical functioning (mean difference 20 points), role physical (mean difference 23 points), and general health (mean difference 19 points). In patients over 65 years mean domain scores were similar to community norms. Multiple regression analysis revealed that impaired quality of life was closely associated with inability to return to work through ill health, a need for coronary revascularisation, the use of anxiolytics, hypnotics or inhalers, the need for two or more angina drugs, a frequency of chest pain one or more times per week, and a Rose dyspnoea score of ⩾ 2. CONCLUSIONS The SF 36 provides valuable additional information for the practising clinician. Compared to community norms the greatest impact on quality of life is seen in patients of working age. Impaired quality of life was reported by patients unfit for work, those with angina and dyspnoea, patients with coexistent lung disease, and those with anxiety and sleep disturbances. Improving quality of life after myocardial infarction remains a challenge for physicians.

Trends in healthcare incident reporting and relationship to safety and quality data in acute hospitals: results from the National Reporting and Learning System

Background: Internationally, there is increasing recognition of the need to collect and analyse data on patient safety incidents, to facilitate learning and develop solutions. The National Patient Safety Agency (NPSA) for England and Wales has been capturing incident data from acute hospitals since November 2003. Objectives: This study analyses patterns in reporting of patient safety incidents from all acute hospitals in England to the NPSA National Reporting and Learning System, and explores the link between reporting rates, hospital characteristics, and other safety and quality datasets. Methods: Reporting rates to the NPSA National Reporting and Learning System were analysed as trends over time, from the point at which each hospital became connected to the system. The relationships between reporting rates and other safety and quality datasets were assessed using correlation and regression analyses. Results: Reporting rates increased steadily over the 18 months analysed. Higher reporting rates correlated with positive data on safety culture and incident reporting from the NHS Staff Survey, and with better risk-management ratings from the NHS Litigation Authority. Hospitals with higher overall reporting rates had a lower proportion of their reports in the “slips, trips and falls” category, suggesting that these hospitals were reporting higher numbers of other types of incident. There was no apparent association between reporting rates and the following data: standardised mortality ratios, data from other safety-related reporting systems, hospital size, average patient age or length of stay. Conclusions: Incident reporting rates from acute hospitals increase with time from connection to the national reporting system, and are positively correlated with independently defined measures of safety culture, higher reporting rates being associated with a more positive safety culture.

Deriving a Preference-Based Measure for Cancer Using the EORTC QLQ-C30

OBJECTIVE The European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30) is one of the most commonly used measures in cancer care but in its current form cannot be used in economic evaluation because it does not incorporate preferences. We address this gap by estimating a preference-based measure for cancer from the EORTC QLQ-C30. METHODS Factor analysis, Rasch analysis, and other psychometric analyses were undertaken on a clinical trial dataset of 655 patients with multiple myeloma to derive a health state classification system amenable to valuation. Second a valuation study was conducted of 350 members of the UK general population using time trade-off. Mean and individual-level multivariate regression models were fitted to derive preference weights for the classification system. RESULTS The health state classification system has eight dimensions (physical functioning, role functioning, social functioning, emotional functioning, pain, fatigue and sleep disturbance, nausea, constipation, and diarrhea) with four or five levels each. Regression models have few inconsistencies (0 to 2) in estimated preference weights and small mean absolute error ranges (0.046 to 0.054). CONCLUSIONS It is feasible to derive a preference-based measure from the EORTC QLQ-C30 for use in economic evaluation. Future research will extend this to other countries and replicate across other patient groups.

Development of DEMQOL-U and DEMQOL-PROXY-U: generation of preference-based indices from DEMQOL and DEMQOL-PROXY for use in economic evaluation.

BACKGROUND Dementia is one of the most common and serious disorders in later life and the economic and personal cost of caring for people with dementia is immense. There is a need to be able to evaluate interventions in dementia using cost-effectiveness analyses, but the generic preference-based measures typically used to measure effectiveness do not work well in dementia. Existing dementia-specific measures can effectively measure health-related quality of life but in their current form cannot be used directly to inform cost-effectiveness analysis using quality-adjusted life-years as the measure of effectiveness. OBJECTIVES The aim was to develop two brief health-state classifications, one from DEMQOL and one from DEMQOL-Proxy, to generate health states amenable to valuation. These classification systems consisted of items taken from DEMQOL and DEMQOL-Proxy so they can be derived from any study that has used these instruments. DATA SOURCES In the first stage of the study we used a large, clinically representative sample aggregated from two sources: a sample of patients and carers attending a memory service in south London and a sample of patients and carers from other community services in south London. This included 644 people with a diagnosis of mild/moderate dementia and 689 carers of those with mild/moderate dementia. For the valuation study, the general population sample of 600 respondents was drawn to be representative of the UK general population. Households were sampled in urban and rural areas in northern England and balanced to the UK population according to geodemographic profiles. In the patient/carer valuation study we interviewed a sample of 71 people with mild dementia and 71 family carers drawn from a memory service in south London. Finally, the instruments derived were applied to data from the HTA-SADD (Study of Antidepressants for Depression in Dementia) trial. REVIEW METHODS This was a complex multiphase study with four linked phases: phase 1 - derivation of the health-state classification system; phase 2 - general population valuation survey and modelling to produce values for every health state; phase 3 - patient/carer valuation survey; and phase 4 - application of measures to trial data. RESULTS All four phases were successful and this report details this development process leading to the first condition-specific preference-based measures in dementia, an important new development in this field. LIMITATIONS The first limitation relates to the lack of an external data set to validate the DEMQOL-U and DEMQOL-Proxy-U classification systems. Throughout the development process we have made decisions about which methodology to use. There are other valid techniques that could be used and it is possible to criticise the choices that we have made. It is also possible that the use of a mild to moderate dementia sample has resulted in classification systems that do not fully reflect the challenges of severe dementia. CONCLUSION The results presented are sufficiently encouraging to recommend that the DEMQOL instruments be used alongside a generic measure such as the European Quality of Life-5 Dimensions (EQ-5D) in future studies of interventions in dementia as there was evidence that they can be more sensitive for patients at the milder end of disease and some limited evidence that the person with dementia measure may be able to reflect deterioration. FUNDING The National Institute for Health Research Health Technology Assessment programme.

Resuscitation from out-of-hospital cardiac arrest: is survival dependent on who is available at the scene?

Objective To determine whether survival from out-of-hospital cardiac arrest is influenced by the on-scene availability of different grades of ambulance personnel and other health professionals. Design Population based, retrospective, observational study. Setting County of Nottinghamshire with a population of one million. Subjects All 2094 patients who had resuscitation attempted by Nottinghamshire Ambulance Service crew from 1991 to 1994; study of 1547 patients whose arrest were of cardiac aetiology. Main outcome measures Survival to hospital admission and survival to hospital discharge. Results Overall survival from out-of-hospital cardiac arrest remains poor: 221 patients (14.3%) survived to reach hospital alive and only 94 (6.1%) survived to be discharged from hospital. Multivariate logistic regression analysis showed that the chances of those resuscitated by technician crew reaching hospital alive were poor but were greater when paramedic crew were either called to assist technicians or dealt with the arrest themselves (odds ratio 6.9 (95% confidence interval 3.92 to 26.61)). Compared to technician crew, survival to hospital discharge was only significantly improved with paramedic crew (3.55 (1.62 to 7.79)) and further improved when paramedics were assisted by either a health professional (9.91 (3.12 to 26.61)) or a medical practitioner (20.88 (6.72 to 64.94)). Conclusions Survival from out-of-hospital cardiac arrest remains poor despite attendance at the scene of the arrest by ambulance crew and other health professionals. Patients resuscitated by a paramedic from out-of-hospital cardiac arrest caused by cardiac disease were more likely to survive to hospital discharge than when resuscitation was provided by an ambulance technician. Resuscitation by a paramedic assisted by a medical practitioner offers a patient the best chances of surviving the event.

Estimating a Preference-Based Index for a 5-Dimensional Health State Classification for Asthma Derived from the Asthma Quality of Life Questionnaire

Background: This article presents a valuation study to estimate a preference-based index for a 5-dimensional health state classification for asthma (AQL-5D) derived from the Asthma Quality of Life Questionnaire (AQLQ). Methods: A sample of 307 members of the UK general population valued 99 asthma health states selected from the AQL-5D using the time tradeoff technique. Models were estimated to predict all possible 3125 health states defined by the AQL-5D, and the models were compared in terms of their ability to predict mean values for the 99 states. Results: Mean health state values ranged from 0.39 to 0.94 based on an average of 22 valuations per state. A main effects model estimated on mean health state values and adjusted for consistency had the best predictive ability (mean absolute error of 0.047 and only 9/98 states with errors >0.1) and the most logical consistency with levels of the AQL-5D. The low number of valuations per state may have resulted in unreliable estimates for the models. Preference-based condition specific measures are limited in their ability to make cross-disease comparisons. Conclusion: This is the first study to derive a condition-specific preference-based measure from an existing measure of health-related quality of life in asthma for use in economic evaluation.

Inpatient deaths from acute myocardial infarction, 1982-92 : Analysis of data in the Nottingham heart attack register

Abstract Objective: To assess longitudinal trends in admissions, management, and inpatient mortality from acute myocardial infarction over 10 years. Design: Retrospective analysis based on the Nottingham heart attack register. Setting: Two district general hospitals serving a defined urban and rural population. Subjects: All patients admitted with a confirmed acute myocardial infarction during 1982-4 and 1989-92 (excluding 1991, when data were not collected). Main outcome measures: Numbers of patients, background characteristics, time from onset of symptoms to admission, ward of admission, treatment, and inpatient mortality. Results: Admissions with acute myocardial infarction increased from 719 cases in 1982 to 960 in 1992. The mean age increased from 62.1 years to 66.6 years (P<0.001), the duration of stay fell from 8.7 days to 7.2 days (P<0.001), and the proportion of patients aged 75 years and over admitted to a coronary care unit increased significantly from 29.1% to 61.2%. A higher proportion of patients were admitted to hospital within 6 hours of onset of their symptoms in 1989-92 than in 1982-4, but 15% were still admitted after the time window for thrombolysis. Use of ß blockers increased threefold between 1982 and 1992, aspirin was used in over 70% of patients after 1989, and thrombolytic use increased 1.3-fold between 1989 and 1992. Age and sex adjusted odds ratios for inpatient mortality remained unchanged over the study period. Conclusions: Despite an increasing uptake of the “proved” treatments, inpatient mortality from myocardial infarction did not change between 1982 and 1992. Key messages During 1982-92 major changes in management of myocardial infarction in an unselected population have been guided by the results of randomised trials Adjusted odds ratios for deaths in hospital from acute myocardial infarction did not change over this period despite an overall fall in recorded deaths from ischaemic heart disease in Nottingham The use of existing treatments needs to be optimised and new management strategies need to be introduced if inpatient mortality from myocardial infarction is to be reduced

A Simulation Modelling Approach to Evaluating Alternative Policies for the Management of the Waiting List for Liver Transplantation

A shortage of donor liver grafts unfortunately results in approximately 10% of patients dying whilst listed for a liver transplant in Europe and the United States. Thus it is imperative that all available organs are used as efficiently as possible. This paper reports upon the application of a simulation modelling approach to assess the impact of several alternative allocation policies upon the cost effectiveness of this technology at one liver transplant centre in the UK. The impact of changes in allocation criteria on the estimated net life expectancy, average net costs and overall cost effectiveness of the transplantation programme were evaluated. The incremental cost effectiveness ratio (ICER) for the base case allocation policy, based upon the time spent on the waiting list (i.e., longest wait first) was £11,557 at 1999 prices. The ICERs associated with an allocation policy based upon age (lowest age first), and an allocation policy based upon the severity of the pre-transplant condition of the patient (with most severely ill patients given a lower priority) were lower than the base case at £10,424 and £9077, respectively. The results of this modelling study suggest that the overall cost effectiveness of the liver transplantation programme could be improved if the current allocation policy were modified to give more weight to the age of the patient and the reduced chances of success of the most severely ill patients.

The first stage of developing preference-based measures: constructing a health-state classification using Rasch analysis.

ObjectiveTo set out the methodological process for using Rasch analysis alongside classical psychometric methods in the development of a health-state classification that is amenable to valuation.MethodsThe overactive bladder questionnaire is used to illustrate a five step process for deriving a reduced health-state classification from an existing non-preference-based health-related quality-of-life instrument. Step I uses factor analysis to establish instrument dimensions, step II excludes items that do not meet the initial validation process and step III uses criteria based on Rasch analysis and other psychometric testing to select the final items for the health-state classification. In step IV, item levels are examined and Rasch analysis is used to explore the possibility of reducing the number of item levels. Step V repeats steps I–IV on alternative data sets in order to validate the selection of items for the health-state classification.ResultsThe techniques described enable the construction of a five-dimension health-state classification, the OAB-5D, amenable to valuation tasks that will allow the derivation of preference weights.ConclusionsThe health-related quality of life of patients with conditions like overactive bladder can be valued and quality adjustment weights estimated for calculation of quality-adjusted life years.

Folate Status and Aberrant DNA Methylation Are Associated With HPV Infection and Cervical Pathogenesis

Aberrant DNA methylation is a recognized feature of human cancers, and folate is directly involved in DNA methylation via one-carbon metabolism. Previous reports also suggest that folate status is associated with the natural history of human papillomavirus (HPV) infection. A cross-sectional study was conducted to test the hypothesis that folate status and aberrant DNA methylation show a progressive change across stages of cervical pathology from normal cells to cervical cancer. Additionally, we postulated that a gene-specific hypermethylation profile might be used as a predictive biomarker of cervical cancer risk. DNA hypermethylation of seven tumor suppressor genes, global DNA hypomethylation, systemic folate status, and HPV status were measured in 308 women with a diagnosis of normal cervix (n = 58), low-grade cervical intraepithelial neoplasia (CIN1; n = 68), high-grade cervical intraepithelial neoplasia (CIN2, n = 56; and CIN3, n = 76), or invasive cervical cancer (ICC; n = 50). Lower folate status was associated with high-risk HPV infection (P = 0.031) and with a diagnosis of cervical intraepithelial neoplasia or invasive cervical cancer (P < 0.05). Global DNA hypomethylation was greater in women with invasive cervical cancer than all other groups (P < 0.05). A cluster of three tumor suppressor genes, CDH1, DAPK, and HIC1, displayed a significantly increased frequency of promoter methylation with progressively more severe cervical neoplasia (P < 0.05). These findings are compatible with a role for folate in modulating the risk of cervical cancer, possibly through an influence over high-risk HPV infection. DAPK, CDH1, and HIC1 genes are potential biomarkers of cervical cancer risk. (Cancer Epidemiol Biomarkers Prev 2009;18(10):2782–9)