[Show abstract][Hide abstract] ABSTRACT: Objectives:
Misinterpretation of radiological examinations is an important contributing factor to diagnostic errors. Double reading reduces interpretation errors and increases sensitivity. Consultant radiologists in Norwegian hospitals submit 39% of computed tomography (CT) reports for quality assurance by double reading. Our objective was to estimate the proportion of radiology reports that were changed during double reading and to assess the potential clinical impact of these changes.
Materials and methods:
In this retrospective cross-sectional study we acquired preliminary and final reports from 1023 consecutive double read chest CT examinations conducted at five public hospitals. The preliminary and final reports were compared for changes in content. Three experienced pulmonologists independently rated the clinical importance of these changes. The severity of the radiological findings in clinically important changes was classified as increased, unchanged, or decreased.
Changes were classified as clinically important in 91 (9%) of 1023 reports. Of these: 3 were critical (demanding immediate action), 15 were major (implying a change in treatment) and 73 were intermediate (affecting subsequent investigations). More clinically important changes were made to urgent examinations and less to female first readers. Chest radiologist made more clinically important changes than other second readers. The severity of the radiological findings was increased in 73 (80%) of the clinically important changes.
A 9% rate of clinically important changes made during double reading may justify quality assurance of radiological interpretation. Using expert second readers and targeting a selection of urgent cases prospectively may increase the yield of discrepant cases and reduce harm to patients.
Full-text · Article · Nov 2015 · European Journal of Radiology
[Show abstract][Hide abstract] ABSTRACT: Background:
Traumatic brain injury (TBI) is classified into mild, moderate and severe, based on the Glasgow Coma Score (GCS). However, TBI patients are often influenced by ethanol, which in itself can attenuate the level of consciousness. This study investigated the effect of ethanol on the GCS group classification in TBI patients.
The Oslo University Hospital trauma database was searched for all patients admitted with a head injury where the blood ethanol concentration (BEC) had been measured (n = 1004). The effect of BEC on GCS groups was analysed using multivariate ordinal logistic regression.
This study identified 546, 142 and 316 patients in the mild, moderate and severe groups, respectively. Increasing BEC by 1 g kg(-1) and pre-hospital intubation had OR = 1.34 and 16.34 for being in a more severe GCS group, respectively. Increasing head abbreviated injury scale (head-AIS) was significantly associated with being in a more severe GCS group. The modelled probability of detecting a head-AIS of 4 or 5 in a patient with BEC of 2.0 g kg(-1) was 20%, 38% and 65% in the mild, moderate and severe groups, respectively.
Increasing BEC was associated with increasing odds of being in a more severe GCS group. However, because the modelled probability of significant brain injury was high in patients with high levels of BEC, a reduced level of consciousness in intoxicated patients mandates further radiological investigations.
[Show abstract][Hide abstract] ABSTRACT: Objectives: The objectives of the present study were to compare a simplified and a comprehensive method of estimating the index of microvascular resistance (IMR) and assess the changes from 7-11 weeks to 1 year after heart transplant (HTx). Background: he IMR is specific to the microvasculature and reflects the status of the microcirculation in cardiac patients and can be estimated via a simplified method (IMRs) or a comprehensive method (IMRc). The calculation for the latter includes coronary wedge pressure and central venous pressure. Methods: Consecutively transplanted patients (n=48) underwent left and right heart catheterization including physiological evaluation at two time points post-HTx. The agreement between the values of IMR obtained using the IMRs and IMRc methods were assessed using Bland-Altman analysis. The agreements and differences were assessed using mixed model analysis. Results: The mean bias between IMRs and IMRc was 1.3 mm Hg·s (95% limits of agreement: -1.2, 3.8 mm Hg). Between 7-11 weeks and 1 year post-HTx there was a significant decline in IMRs values (P=0.03) but a smaller and statistically nonsignificant decline in IMRc values (P=0.13). The significant difference (P=0.04) between IMRc and IMRs 7-11 weeks post-HTx was no longer present at 1 year (P=0.24). Conclusions: The IMRs method resulted in slightly higher IMR estimates and exhibited a somewhat larger change over the 10-month follow-up period than the IMRc method. However, the differences between the methods were small and unlikely to be of clinical importance.
No preview · Article · Oct 2015 · Journal of the American College of Cardiology
[Show abstract][Hide abstract] ABSTRACT: The Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) clinical trial, including 1,873 patients found an increased risk for cancer with lipid-lowering therapy with ezetimibe/simvastatin 10/40 mg/day, relative to placebo. In a registry-based follow-up study over 21 months from the conclusion of the SEAS trial, new incident cancer and total mortality were investigated in the SEAS study cohort from Denmark, Finland, Norway, Sweden, and the United Kingdom. Among 1,359 subjects eligible for follow-up (73% of the original total cohort), 1,194 had no history of cancer (primary follow-up cohort). New cancers and deaths were identified in the national cancer and mortality registries and classified by an Expert Review Committee. Data were analyzed using Cox proportional-hazards models of new cancers and mortality during follow-up according to treatment group assigned in the SEAS base study and with age, gender, smoking history, and previous cancers as covariates. The primary follow-up cohort had 12 patients with new cancers in the ezetimibe/simvastatin group and 22 in the placebo group (hazard ratio 0.55, 95% confidence interval 0.27 to 1.11), indicating no significant difference between the treatment groups. During follow-up, 43 patients assigned to ezetimibe/simvastatin and 33 assigned to placebo died (hazard ratio 1.29, 95% confidence interval 0.82 to 2.03). In conclusion, in this registry-based observational follow-up study of the original SEAS study patient population, treatment with ezetimibe/simvastatin was not associated with an increased risk for cancer or mortality in the 21-month period after the completion of the original SEAS study.
Full-text · Article · Aug 2014 · The American Journal of Cardiology
[Show abstract][Hide abstract] ABSTRACT: Aims: The index of microvascular resistance (IMR) is a relatively new tool that is used to assess microvascular function during routinely performed left heart catheterisations. In order to establish a reference interval for IMR, we investigated a subset of arrhythmia patients with structurally normal hearts and no or minimal coronary artery disease. Methods and results: Physiological variables, including IMR, were measured in 20 otherwise healthy patients aged 40-60 years (10 males and 10 females) who had been referred for electrophysiological evaluation of suspected atrioventricular nodal re-entry tachycardia. IMR values were non-normally distributed with a median value of 12.6. We established a reference interval, that would be relevant to 95% of the population, of 7.3 (90% CI: 6.6-8.0) - 27.2 (90% CI: 20.8-33.7), using Box-Cox transformation and the robust Horn method. Spearman's rank correlation analysis revealed no significant relationship between IMR and several different variables. Conclusions: A reference interval for IMR was established in a population of patients aged 40-60 years with structurally normal hearts, considered to be representative of the general population. IMR was not related to sex, age or any of the other variables tested, suggesting that this reference range can be applied to the general population.
No preview · Article · Jan 2014 · EuroIntervention: journal of EuroPCR in collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology
[Show abstract][Hide abstract] ABSTRACT: Early identification of patients with a prolonged stay due to acute exacerbation of chronic obstructive pulmonary disease (COPD) may reduce risk of adverse event and treatment costs. This study aimed to identify predictors of prolonged stay after acute exacerbation of COPD based on variables on admission; the study also looked to establish a prediction model for length of stay (LOS).
We extracted demographic and clinical data from the medical records of 599 patients discharged after an acute exacerbation of COPD between March 2006 and December 2008 at Oslo University Hospital, Aker. We used logistic regression analyses to assess predictors of a length of stay above the 75th percentile and assessed the area under the receiving operating characteristic curve to evaluate the model's performance.
We included 590 patients (54% women) aged 73.2±10.8 years (mean ± standard deviation) in the analyses. Median LOS was 6.0 days (interquartile range [IQR] 3.5-11.0). In multivariate analysis, admission between Thursday and Saturday (odds ratio [OR] 2.24 [95% CI 1.60-3.51], P<0.001), heart failure (OR 2.26, 95% CI 1.34-3.80), diabetes (OR 1.90, 95% CI 1.07-3.37), stroke (OR 1.83, 95% CI 1.04-3.21), high arterial PCO2 (OR 1.26 [95% CI 1.13-1.41], P<0.001), and low serum albumin level (OR 0.92 [95% CI 0.87-0.97], P=0.001) were associated with a LOS >11 days. The statistical model had an area under the receiver operating characteristic curve of 0.73.
Admission between Thursday and Saturday, heart failure, diabetes, stroke, high arterial PCO2, and low serum albumin level were associated with a prolonged LOS. These findings may help physicians to identify patients that will need a prolonged LOS in the early stages of admission. However, the predictive model exhibited suboptimal performance and hence is not ready for clinical use.
Full-text · Article · Jan 2014 · International Journal of COPD
[Show abstract][Hide abstract] ABSTRACT: To withhold and withdraw treatment are important and difficult decisions made in the intensive care unit (ICU). The aim of this study was to investigate the incidence of withholding or withdrawing treatment, characteristics of the patients, and how these decision processes were handled and documented in a general ICU from 2007 to 2009 in a university hospital in Norway.
Patient characteristics and outcomes of treatment were prospectively registered. We retrospectively reviewed the medical records for information on limitations in treatment.
In total, 1287 patients were admitted to the ICU. The ICU mortality was 208 (16%), and the hospital mortality was 341 (26%). In total, 301 patients (23%) had treatment withheld or withdrawn. Medical and unscheduled surgical patients with limitations in treatment had higher Simplified Acute Physiology Score II (P < 0.001) and were older (P < 0.001) than those without limitations in treatment. The most common main reason for withdrawing treatment was poor prognosis. According to the medical records, the patient was involved in the decision-making regarding withdrawal of treatment in only 2% of the cases, and the patient's relatives were involved in the decision-making in 77% of the cases. In 12% of the cases, type of treatment withdrawn was not documented.
Withholding or withdrawing treatment in the ICU was common. Medical and unscheduled surgical patients with limitations in treatment were older and more severely ill than patients without limitations. There is a potential for better documentation of the processes regarding withholding or withdrawing life-sustaining intensive care treatment.
No preview · Article · Jan 2014 · Acta Anaesthesiologica Scandinavica
[Show abstract][Hide abstract] ABSTRACT: Bakground: The objectives of this study were; (1) to assess the prevalence and frequency of headache in patients referred to polysomnography (PSG) due to a clinical suspicion of obstructive sleep apnea (OSA) or another sleep disturbance and compare with a reference population, and (2) to assess the association of OSA severity with headache and headache frequency.
A total of 784 participants filled in a headache questionnaire between 2003 and 2009 at the Department of Clinical Neurophysiology, Akershus University Hospital. Of these patients 477 were suspected to have OSA, and 307 had other sleep complaints. We assessed the prevalence of headache and monthly headache frequencies, as well as sleep apnea severity using an apnea-hypopnea index (AHI). The association of headache and monthly headache frequencies with PSG subgroups was assessed using multivariate logistic and ordered logistic regression analysis.
The frequency of headache was not associated with the severity of OSA. Patients referred to a sleep study for any reason had higher odds ratio (OR) for having experienced headache during the past year than population controls after adjustment for age, gender and education, i.e. patients with normal AHI had OR of 3.56, patients with OSA had OR of 3.51, and patients with other sleep disturbances had OR of 3.33. Similarly, the adjusted OR of being in a higher category of monthly headache frequency compared to controls was higher in those with normal AHI (OR 3.42), OSA (OR 3.29), and other sleep disturbances (OR 3.00).
The odds of headache and headache frequency were higher in subjects referred to a PSG for any sleep disturbance independently of OSA, compared to general population controls. However, there was no association between experiencing headache during the past year or headache frequency with OSA severity.
Preview · Article · Nov 2013 · The Journal of Headache and Pain
[Show abstract][Hide abstract] ABSTRACT: For clinical trial design and for clinical practice, it is of importance to assess factors associated with placebo response in patients with refractory epilepsy. We determined factors associated with placebo response in 359 adult patients with refractory focal epilepsy participating in three randomized placebo-controlled trials of the new antiepileptic drug lacosamide. At the end of the randomized 12-week maintenance period, 81 (23%) of the 359 patients randomized to placebo achieved at least a 50% seizure reduction (responders) compared to baseline. In contrast, 278 (77%) patients did not achieve a 50% seizure reduction (non-responders) compared to baseline. In multivariate analysis, five factors, which were present prior to the exposure to placebo, were found to be associated with placebo response. Higher age at study entry improved the chances of placebo response for each year [p=0.023, odds ratio (OR) 1.034 (95% confidence interval (95% CI): 1.005-1.063)]. In contrast, a lower chance of placebo response was seen with age at diagnosis of epilepsy of 6-20years compared to ≤5years [p=0.041, OR 0.475 (95% CI: 0.232-0.971)]. A history of 7 or more prior lifetime AEDs lowered the chance of achieving placebo response compared to 1-3 prior lifetime AEDs [p<0.001, OR 0.224 (95% CI: 0.101-0.493)] as did a baseline seizure frequency >10 seizures per 28days compared to ≤5 seizures per 28days [p=0.026, OR 0.431 (95% CI: 0.205-0.904)]. Prior epilepsy surgery lowered the likelihood of placebo response [p=0.02, OR 0.22 (95% CI: 0.062-0.785)]. We suggest that age at exposure to placebo, age at diagnosis of epilepsy, the number of prior lifetime AEDs, baseline seizure frequency and a history of epilepsy surgery appear to be associated with placebo response in adults with refractory focal epilepsy.
No preview · Article · Mar 2013 · Epilepsy & Behavior
[Show abstract][Hide abstract] ABSTRACT: IntroductionAcute exacerbation of chronic obstructive pulmonary disease (AECOPD) is a common cause of hospitalisation, and the readmission rate is high. We aimed to determine whether patients discharged from a pulmonary department (PD) after an AECOPD episode had a lower COPD-related readmission rate during the next 12 months than comparable patients discharged from other internal medicine departments (ODs). Methods
The medical records of 566 patients discharged after an episode of AECOPD between March 2006 and December 2008 at Oslo University Hospital, Aker, were reviewed retrospectively. Demographic and medical data, together with number of readmissions because of AECOPD during 12 months following the index admission were extracted. We matched patients discharged from the PD and the ODs using a propensity score and used the paired t-test to compare COPD-related readmission rates between the matched patients. ResultsIn total, 481 patients were included in the analysis, 247 patients discharged from the PD and 234 from ODs. The propensity score matching process resulted in 155 well-matched pairs. The mean (standard deviation) number of readmissions within 1 year was 0.8 (1.3) for the PD versus 1.1 (1.9) for ODs (P=0.09). After adjusting for exposure time, the corresponding readmission rates were 1.1 (2.3) and 1.6 (4.0) per year, respectively (P=0.17). Conclusion
There was little difference in COPD-related readmission rates between comparable patients discharged from the PD and the ODs after an AECOPD during 1 year following the index admission.
No preview · Article · Jan 2013 · The Clinical Respiratory Journal
[Show abstract][Hide abstract] ABSTRACT: Background
National EQ-5D value sets are developed because preferences for health may vary in different populations. UK values are lower than US values for most of the 243 possible EQ-5D health states. Although similar protocols were used for data collection, analytic choices regarding how to model values from the collected data may also influence national value sets. Participants in the UK and US studies assessed the same subset of 42 EQ-5D health states using the time trade-off (TTO) method. However, different methods were used to transform negative values to a range bounded by 0 and −1, and values for all 243 health states were estimated using two different regression models. The transformation of negative values is inconsistent with expected utility theory, and the choice of which transformation method to use lacks a theoretical foundation.
Our objectives were to assess how much of the observed difference between the UK and US EQ-5D value sets may be explained by the choice of transformation method for negative values relative to the choice of regression model and the differences between elicited TTO values in the respective national studies (datasets).
We applied both transformation methods and both regression models to each of the two datasets, resulting in eight comparable value sets. We arranged these value sets in pairs in which one source of difference (transformation method, regression model or dataset) was varied. For each of these paired value sets, we calculated the mean difference between the two matching values for each of the 243 health states. Finally, we calculated the mean utility gain for all possible transitions between pairs of EQ-5D health states within each value set and used the difference in transition scores as a measure of impact from changing transformation method, regression model or dataset.
The mean absolute difference in values was 1.5 times larger when changing the transformation method than when using different datasets. The choice of transformation method had a 3.2 times larger effect on the mean health gain (transition score) than the choice of dataset. The mean health gain in the UK value set was 0.09 higher than in the US value set. Using the UK transformation method on the US dataset reduced this absolute difference to 0.02. The choice of regression model had little overall impact on the differences between the value sets.
Most of the observed differences between the UK and US value sets were caused by the use of different transformation methods for negative values, rather than differences between the two study populations as reflected in the datasets. Changing the regression model had little impact on the differences between the value sets.
No preview · Article · Nov 2012 · PharmacoEconomics
[Show abstract][Hide abstract] ABSTRACT: Purpose: A frequently used valuation method for health state valuation is the time trade- off (TTO) method. Typically, valuation studies control for individual characteristics focusing on demographic variables like age, sex, education, and geography. We hypothesized that valuation of hypothetical health states are more prone to variance along other individual variables, including personality, beliefs, attitudes, and personal experience. The purpose of the study was to compare the impact of typical demographic variables to the impact of candidate variables from these other domains.
Method: 511 respondents participated in a web survey. The participants were fairly representative for the Norwegian population with respect to age and sex. Each participant valued eight health states of varying severity as described with the EQ-5D system. Additionally we asked questions about factors we hypothesized could affect their general willingness to trade away time: Agreement with euthanasia, number of children, the personality trait neuroticism, and the extent to which they considered themselves to be religious, to which extent they believed in a life after death. In a multivariate regression we used the TTO value as dependent variable and demographic variables and the other factors with potential influence as independent variables.
Linear regression of TTO scores on individual variables
sex (1 = female)
9-12 years of education
>12 years of education
Marital status (single vs. attached)
Children under 18 (dummy)
Belief in life after death (dummy)
Religiousity (5 point scale of agreement)
Attitudes toward euthanasia (mean of three 5 point scales)
Neuroticism (normalized Z scores)
Conclusion: Typical demographic variables did not significantly influence TTO values. However, having children in the home, attitudes toward euthanasia, and the personality trait neuroticism appear to significantly influence valuation of hypothetical health states. These variables were selected from their respective domains as likely candidates, and suggest that valuation of health states may be informed more by attitudes, personality, and experiences than the usual demographic variables. Variable relevance should be carefully considered.
[Show abstract][Hide abstract] ABSTRACT: Purpose: In population health surveys, national representativeness is of the utmost importance. Due to increased availability of online computers and increased computer literacy, the current gold standard of using postal surveys is challenged. The objective of this study was to compare the population representativeness of web-based and postal survey modes in a health survey setting where national representativeness is vital.
Method: We developed postal and web variants of a health valuation survey with intended to maximize representativeness in the adult Norwegian population. The postal version was mailed to a random sample of 5000 persons over the age of 18 drawn from the Norwegian Population Registry. For the web-survey, we invited 1936 respondents from the market research company Synovate’s standing panel of willing survey participants. We compared the two surveys in terms of distribution of respondents’ demographic characteristics and EQ-5D self-ratings.
Result: 4899 (postal) and 1936 (web) respondents were reached, of whom 1276 (26%) and 1003 (50,2%), respectively, submitted complete forms. Characteristics are listed in the table:
Table: Demographics and EQ-5D self-ratings, percentages
Conclusion: The web survey outperformed the postal in terms of demographic representativeness, particularly for education, albeit with low participation rates over the age of 70. The distributions of reported EQ-5D problems were similar, but web respondents reported more problems, possibly due to lower mean education levels. Severe health problems are likely to be underrepresented. Web surveys may already be superior to postal surveys in terms of representativeness, and may be recommended for use in studies in countries with widespread access to computers and high levels of computer literacy.
[Show abstract][Hide abstract] ABSTRACT: Background: Several countries have now passed laws that place limitations on where smokers may smoke. A range of smoking-cessation treatments have become available, many of which have documented increased quit rates. Population surveys show that most smokers wish to quit, and most nonsmokers would prefer to reduce the prevalence of smoking in society. The strengths of these preferences, however, as measured by their willingness to pay (WTP), have not yet been investigated.
Objective: This study aims to identify variables that explain variations in people’s answers to WTP questions on smoking-cessation treatments.
Methods: A representative sample of the Norwegian population was asked their WTP in terms of an earmarked contribution to a public smokingcessation programme. A sub-group of daily smokers was, in addition, asked about their WTP for a hypothetical treatment that would remove their urge to smoke. The impact of variation in the question format (different opening bids) on stated WTP was compared with that of factors suggested by economic theory, such as quit-rate effectiveness, degree of addiction as measured by the 12-item Cigarette Dependence Scale (CDS-12), and degree of peer group influence as measured by the proportion of one’s friends who smoke.
Results: In both programmes, the most important determinant for explaining variations in WTP was the size of the opening bid. Differences in quit-rate effectiveness did not matter for people’s WTP for the smoking-cessation programme. Addiction, and having a small proportion of friends who smoke, were positively associated with smokers’ WTP to quit smoking.
Conclusion: Variations in WTP were influenced more by how the question was framed in terms of differences in opening bids, than by variables reflecting the quality (effectiveness) and need (addiction level) for the good in question. While the WTP method is theoretically attractive, the findings that outcomes in terms of different quit rates did not affect WTP, and that WTP answers can be manipulated by the chosen opening bid, should raise further doubts on the ability of this method to provide valid and reliable answers that reflect true preferences for health and healthcare.
No preview · Article · Sep 2012 · Applied Health Economics and Health Policy
[Show abstract][Hide abstract] ABSTRACT: Purpose:
Health state values are by convention anchored to 'perfect health' and 'death.' Attitudes toward death may consequently influence the valuations. We used attitudes toward euthanasia (ATE) as a sub-construct for attitudes toward death. We compared the influence on values elicited with time trade-off (TTO), lead-time TTO (LT-TTO) and visual analogue scale (VAS).Since the 'death' anchor is most explicit in TTO, we hypothesized that TTO values would be most influenced by ATE.
Respondents valued eight EQ-5D health states with VAS, then TTO (n = 328) or LT-TTO (n = 484). We measured ATE on a scale from -2 (fully disagree) to 2 (fully agree) and used multiple linear regressions to predict VAS, TTO, and LT-TTO values by ATE, sex, age, and education.
A one-point increase on the ATE scale predicted a mean TTO value change of -.113 and LT-TTO change of -.072. Demographic variables, but not ATE, predicted VAS values.
TTO appears to measure ATE in addition to preferences for health states. Different ways of incorporating death in the valuation may impact substantially on the resulting values. 'Death' is a metaphysically unknown concept, and implications of attitudes toward death should be investigated further to evaluate the appropriateness of using 'death' as an anchor.
No preview · Article · Jun 2012 · Quality of Life Research
[Show abstract][Hide abstract] ABSTRACT: Background The use of moist snuff (snus) in young Norwegians is increasing, while smoking rates are declining. It is not clear whether snus facilitates smoking.
Objective To assess whether 16-year-old men who were never-smokers, but snus users in 2001, had an increased risk of smoking 3 years later.
Methods In a prospective school-based cohort study, 1440 men, who responded to questionnaires in 2001 and 2004, were included in the analyses. The participation rate was 89% in 2001 and 50% in 2004. Multinomial logistic regression models were used to assess the OR of snus users, smokers and dual users of cigarettes and snus, compared with non-tobacco users at baseline, to be smokers at follow-up.
Results Snus use at baseline was associated with increased odds of dual use at follow-up when the outcome was (1) current dual use versus no tobacco (OR 3.49, 95% CI 1.8 to 6.8) and when the outcome was (2) current dual use versus no smoking but including snus-only use (OR 1.88, 95% CI 1.1 to 3.3). Baseline snus users who were dual users at follow-up seemed to prefer using snus daily and cigarettes occasionally. Use of snus only at baseline was not associated with increased odds of smoking only at follow-up, after adjusting for known risk factors.
Conclusions Young men who only used snus at baseline had an increased risk of being dual users at follow-up. Snus use may therefore facilitate smoking.
[Show abstract][Hide abstract] ABSTRACT: Given serious concerns over the adverse effects of enzyme induction, modern nonenzyme-inducing antiepileptic drugs (AEDs) may be preferable, provided they have similar efficacy as enzyme-inducing AEDs. This is currently unclear.
Therefore, we performed a meta-analysis of the evidence to determine the placebo-corrected efficacy of adjunctive treatment with modern nonenzyme-inducing AEDs versus modern enzyme-inducing AEDs that are on the market for refractory focal epilepsy.
Of 322 potentially eligible articles reviewed in full text, 129 (40%) fulfilled eligibility criteria. After excluding 92 publications, 37 studies dealing with a total of 9,860 patients with refractory focal epilepsy form the basis for the evidence. The overall weighted pooled-risk ratio (RR) in favor of enzyme-inducing AEDs over placebo was 2.37 (95% confidence interval [CI] 1.77-3.18, p < 0.001) for at least 50% seizure reduction and 4.45 (2.26-8.76, p < 0.001) for seizure freedom. The corresponding weighted pooled RR in favor of nonenzyme-inducing AEDs over placebo was 2.28 (95% CI 2.03-2.57, p < 0.001) for at least 50% seizure reduction and 3.23 (95% CI 2.23-4.67, p < 0.001) for seizure freedom. In a meta-regression analysis in the same sample with at least 50% seizure reduction as outcome, the ratio of RRs for enzyme-inducing AEDs (eight studies) versus nonenzyme-inducing AEDs (29 studies) was 1.01 (95% CI 0.77-1.34, p = 0.92)). Similarly, the ratio of RRs for a seizure-free outcome for enzyme-inducing AEDs (six studies) versus nonenzyme-inducing AEDs (19 studies) was 1.38 (95% CI 0.60-3.16, p = 0.43).
Although the presence of moderate heterogeneity may reduce the validity of the results and limit generalizations from the findings, we conclude that the efficacy of adjunctive treatment with modern nonenzyme-inducing AEDs is similar to that of enzyme-inducing AEDs. Given the negative consequences of enzyme induction, our data suggest that nonenzyme-inducing AEDs may be useful alternatives to enzyme-inducing AEDs for treatment of refractory focal epilepsy.
[Show abstract][Hide abstract] ABSTRACT: In EuroQol five-dimensional questionnaire valuation studies, each participant typically assesses more than 10 hypothetical health states by using the time trade-off (TTO) method. We wanted to explore potential learning effects when using the TTO method, that is, whether the valuations were affected by the number of previously rated health states (the sequence number).
We included 3773 respondents from the US EQ-5D valuation study, each of whom valued 12 health states (plus unconscious) in random order. With linear regression, we used sequence number to predict mean and standard deviations across all health states. We repeated the analysis separately for TTO responses indicating a state better than death and a state worse than death. Each TTO value requires a specific number of choice iterations. To test whether respondents used fewer iterations with experience, we used linear regression with sequence number as the independent variable and number of iterations as the dependent variable.
Mean TTO values were fairly stable across the sequence number, but analyzing state better than death and state worse than death values separately revealed a tendency toward more extreme values: state better than death values increased by 0.02, while state worse than death values decreased by 0.21 (P < 0.0001) over the full sequence. The standard deviations increased slightly, while the number of choice iterations was the same over the sequence number. The findings were stable across the levels of health state severity, age, and sex.
TTO values become more extreme with increasing experience. Because of the randomized valuation order, these effects do not bias specific health states; however, they reduce the overall validity and reliability of TTO values.
[Show abstract][Hide abstract] ABSTRACT: EQ-5D valuation studies are usually performed using the time tradeoff (TTO) method, which is costly and time consuming. We focused on 2 properties that particularly characterize TTO: the initial choice task categorizing health states as better than death (BTD), worse than death (WTD), or equal to death (ETD), and unwillingness to trade (UTT) lifetime to improve health. The aim of this study was to estimate the value of the information to be gained from continuing the conventional TTO tasks beyond the initial question and the extent to which mean-based EQ-5D tariff values could be predicted through a simplified method of categorizing health states into BTD, WTD, ETD, and UTT.
We used data from the UK EQ-5D valuation study (n = 2997). We designed an abbreviated system with only 4 values (collapsed TTO [cTTO]) based on the 4 response categories and assigned values as follows: WTD = -.5, ETD = 0, BTD = .5, and UTT = 1. Based on the mean cTTO scores for the valued health states, we created a regression-based cTTO tariff, which was compared with the conventional (full) TTO tariff (fTTO) by regressing 1) the fTTO means on cTTO means and 2) the fTTO tariff on the cTTO tariff.
WTD values were unrelated to health state severity. Correlation between the means of fTTO and means of cTTO was >.999, and tariff values from fTTO correlated with tariff values from cTTO at r > .999.
Once respondents have classified health states as UTT, BTD, ETD, or WTD, the TTO procedure adds little further information to the tariff values. The WTD task fails to discriminate between good and bad health states. TTO valuation could likely be simplified using cTTO.
No preview · Article · Jan 2012 · Medical Decision Making