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1.

Purpose

Different health state utility (HSU) instruments produce different utilities for the same individuals, thereby compromising the intended comparability of economic evaluations of health care interventions. When developing crosswalks, previous studies have indicated nonlinear relationships. This paper inquires into the degree of nonlinearity across the four most widely used HSU-instruments and proposes exchange rates that differ depending on the severity levels of the health state utility scale.

Methods

Overall, 7933 respondents from six countries, 1760 in a non-diagnosed healthy group and 6173 in seven disease groups, reported their health states using four different instruments: EQ-5D-5L, SF-6D, HUI-3 and 15D. Quantile regressions investigate the degree of nonlinear relationships between these instruments. To compare the instruments across different disease severities, we split the health state utility scale into utility intervals with 0.2 successive decrements in utility starting from perfect health at 1.00. Exchange rates (ERs) are calculated as the mean utility difference between two utility intervals on one HSU-instrument divided by the difference in mean utility on another HSU-instrument.

Results

Quantile regressions reveal significant nonlinear relationships across all four HSU-instruments. The degrees of nonlinearities differ, with a maximum degree of difference in the coefficients along the health state utility scale of 3.34 when SF-6D is regressed on EQ-5D. At the lower end of the health state utility scale, the exchange rate from SF-6D to EQ-5D is 2.11, whilst at the upper end it is 0.38.

Conclusion

Comparisons at different utility levels illustrate the fallacy of using linear functions as crosswalks between HSU-instruments. The existence of nonlinear relationships between different HSU-instruments suggests that level-specific exchange rates should be used when converting a change in utility on the instrument used, onto a corresponding utility change had another instrument been used. Accounting for nonlinearities will increase the validity of the comparison for decision makers when faced with a choice between interventions whose calculations of QALY gains have been based on different HSU-instruments.
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2.

Purpose

To explore the comparative performance including discriminative and longitudinal validity of EQ-5D-5L and SF-6D index scores in adults with type 2 diabetes.

Methods

Data from an on-going cohort study of adults with type 2 diabetes in Alberta, Canada, were used. Known-groups approach was used to examine discriminative validity. Correlation and agreement indices and scatter and Bland–Altman plots were used to examine the relationship between the two measures. Longitudinal validity was explored using Wilcoxon signed-rank test, effect size, and standardized response mean.

Results

In 1832 participants at baseline (age 64.3, standard deviation 10.6 years; 45% female), median EQ-5D-5L score was 0.85 [interquartile range (IQR) 0.17], and floor and ceiling effects of 0.1 and 16.1%, respectively; median SF-6D score was 0.72 (IQR 0.24), and floor and ceiling effects of 0.1 and 3.2%, respectively. EQ-5D-5L and SF-6D index scores were significantly correlated with an overall Spearman correlation coefficient of 0.73, and an ICC of 0.62 (95% CI 0.42–0.74). Both EQ-5D-5L and SF-6D scores demonstrated statistically significant differences in self-reported chronic conditions, depressive symptoms, and diabetes-related distress, and were able to detect changes in depressive symptoms and diabetes distress across all change groups.

Conclusions

Both EQ-5D-5L and SF-6D index scores provide valid measurement in this patient population. Considerable overlap between the measures means it is not necessary to include both in surveys, however, the advantages and disadvantages of each should be considered.
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3.

Objectives

Depression is associated with considerable impairments in health-related quality-of-life. However, the relationship between different health states related to depression severity and utility scores is unclear. The aim of this study was to evaluate whether utility scores are different for various health states related to depression severity.

Methods

We gathered individual participant data from ten randomized controlled trials evaluating depression treatments. The UK EQ-5D and SF-6D tariffs were used to generate utility scores. We defined five health states that were proposed from American Psychiatric Association and National Institute for Clinical Excellence guidelines: remission, minor depression, mild depression, moderate depression, and severe depression. We performed multilevel linear regression analysis.

Results

We included 1629 participants in the analyses. The average EQ-5D utility scores for the five health states were 0.70 (95% CI 0.67–0.73) for remission, 0.62 (95% CI 0.58–0.65) for minor depression, 0.57 (95% CI 0.54–0.61) for mild depression, 0.52 (95%CI 0.49–0.56) for moderate depression, and 0.39 (95% CI 0.35–0.43) for severe depression. In comparison with the EQ-5D, the utility scores based on the SF-6D were similar for remission (EQ-5D?=?0.70 vs. SF-6D?=?0.69), but higher for severe depression (EQ-5D?=?0.39 vs. SF-6D?=?0.55).

Conclusions

We observed statistically significant differences in utility scores between depression health states. Individuals with less severe depressive symptoms had on average statistically significant higher utility scores than individuals suffering from more severe depressive symptomatology. In the present study, EQ-5D had a larger range of values as compared to SF-6D.
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4.

Objective

To assess the evidence on the validity and responsiveness of five commonly used preference-based instruments, the EQ-5D, SF-6D, HUI3, 15D and AQoL, by undertaking a review of reviews.

Methods

Four databases were investigated using a strategy refined through a highly sensitive filter for systematic reviews. References were screened and a search for grey literature was performed. Identified citations were scrutinized against pre-defined eligibility criteria and data were extracted using a customized extraction template. Evidence on known group validity, convergent validity and responsiveness was extracted and reviewed by narrative synthesis. Quality of the included reviews was assessed using a modified version of the AMSTAR checklist.

Results

Thirty reviews were included, sixteen of which were of excellent or good quality. The body of evidence, covering more than 180 studies, was heavily skewed towards EQ-5D, with significantly fewer studies investigating HUI3 and SF-6D, and very few the 15D and AQoL. There was also lack of head-to-head comparisons between GPBMs and the tests reported by the reviews were often weak. Where there was evidence, EQ-5D, SF-6D, HUI3, 15D and AQoL seemed generally valid and responsive instruments, although not for all conditions. Evidence was not consistently reported across reviews.

Conclusions

Although generally valid, EQ-5D, SF-6D and HUI3 suffer from some problems and perform inconsistently in some populations. The lack of head-to-head comparisons and the poor reporting impedes the comparative assessment of the performance of GPBMs. This highlights the need for large comparative studies designed to test instruments’ performance.
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5.

Purpose

The aim of this study was to examine the validity of the EuroQOL five dimensions questionnaire (EQ-5D) using a nationally representative data from the National Health Interview Survey (NHIS) through comparison with short-form 36 (SF-36).

Methods

Data for this study came from the 2009 NHIS in Taiwan. The study sample was the 4007 participants aged 20–64 years who completed the survey. We used SUDAAN 10.0 (SAS-Callable) to carry out weighed estimation and statistical inference. The EQ index was estimated using norm values from a Taiwanese study as well as from Japan and the United Kingdom (UK). The SF-36 score was standardized using American norm values.

Results

In terms of concurrent validity, the EQ-5D met the five hypotheses. The results did not fulfill hypothesis that women would have lower visual analogue scale (EQ-VAS) scores. In terms of discriminant validity, the EQ-5D fulfilled two hypotheses. Our results approached but did not fulfill hypothesis that there would be a weak association between the physical and psychological dimensions of the EQ-5D and the mental component summary score of the SF-36. Results were comparable regardless of whether the Japanese or UK norm value sets were used.

Conclusions

We were able to fulfill many, not all of our validity hypotheses regardless of whether the established Japanese or UK norm value sets or the Taiwanese norm values were used. The EQ-5D is an effective and simple instrument for assessing health-related quality of life of general population in Taiwan.
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6.

Purpose

The purpose of the study was to compare alternative statistical techniques to find the best approach for converting QLQ-C30 scores onto EQ-5D-5L and SF-6D utilities, and to estimate the mapping algorithms that best predict these health state utilities.

Methods

772 cancer patients described their health along the cancer-specific instrument (QLQ-C30) and two generic preference-based instruments (EQ-5D-5L and SF-6D). Seven alternative regression models were applied: ordinary least squares, generalized linear model, extended estimating equations (EEE), fractional regression model, beta binomial (BB) regression, logistic quantile regression and censored least absolute deviation. Normalized mean absolute error (NMAE), normalized root mean square error (NRMSE), r-squared (r2) and concordance correlation coefficient (CCC) were used as model performance criteria. Cross-validation was conducted by randomly splitting internal dataset into two equally sized groups to test the generalizability of each model.

Results

In predicting EQ-5D-5L utilities, the BB regression performed best. It gave better predictive accuracy in terms of all criteria in the full sample, as well as in the validation sample. In predicting SF-6D, the EEE performed best. It outperformed in all criteria: NRMSE?=?0.1004, NMAE?=?0.0798, CCC?=?0.842 and r2?=?72.7% in the full sample, and NRMSE?=?0.1037, NMAE?=?0.0821, CCC?=?0.8345 and r2?=?71.4% in cross-validation.

Conclusions

When only QLQ-C30 data are available, mapping provides an alternative approach to obtain health state utility data for use in cost-effectiveness analyses. Among seven alternative regression models, the BB and the EEE gave the most accurate predictions for EQ-5D-5L and SF-6D, respectively.
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7.
8.
9.

Purpose

This study aims to explore the changes in pain intensity and quality of life (QoL) experienced by patients with painful diabetic neuropathy (PDN) treated with spinal cord stimulation (SCS) and conventional medical practice (CMP).

Methods

Patient-reported pain intensity and QoL data were obtained from participants in an international multicentre randomised controlled trial comparing SCS versus CMP. Data were collected at randomisation and 6 month follow up by means of a visual analogue scale for pain intensity, the EuroQoL Visual Analogue Scale (EQ VAS) and the EuroQol EQ-5D index. Quality-adjusted life years (QALYs) were calculated for each treatment using the ‘area under the curve’ method. Differences in QALYs were calculated after adjusting for between-treatment imbalances in baseline QoL.

Results

At 6 months, patients allocated to SCS reported larger reductions in pain intensity and improvements in QoL measured by the EQ-5D utility score and EQ VAS as compared to those allocated to CMP. Initial calculations of QALYs for the SCS and CMP groups suggested no statistical differences between the groups. Adjusting for imbalances in baseline EQ-5D scores showed SCS to be associated with significantly higher QALYs compared to CMP.

Conclusions

SCS resulted in significant improvement in pain intensity and QoL in patients with PDN, offering further support for SCS as an effective treatment for patients suffering from PDN. From a methodological point of view, different results would have been obtained if QALY calculations were not adjusted for baseline EQ-5D scores, highlighting the need to account for imbalances in baseline QoL.
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10.

Purpose

Economic evaluations of mental health interventions often measure health benefit in terms of utility values derived from the EQ-5D. For the five-level version of the EQ-5D, there are two methods of estimating utility [crosswalk and stated preference (5L-SP)]. This paper explores potential impacts for researchers and decision-makers when comparing utility values derived from either method in the specific context of mental health.

Methods

Baseline EQ-5D-5L data from three large randomised controlled trials of interventions for mental health conditions were analysed. Utility values were generated using each method. Mean utility values were compared using a series of t tests on pooled data and subgroups. Scenario analyses explored potential impacts on cost-effectiveness decisions.

Results

EQ-5D data were available for 1399 participants. The mean utility value for each trial was approximately 0.08 higher when estimated using the 5L-SP approach compared to crosswalk (p?<?0.0001). The difference was greatest among people reporting extreme anxiety/depression (mean utility 5L-SP 0.309, crosswalk 0.084; difference?=?0.225; p?<?0.0001). Identical improvements in health status were associated with higher costs to gain one QALY with the 5L-SP approach; this is more pronounced when improvements are across all domains compared to improvements on the anxiety/depression domain only.

Conclusions

The two approaches produce significantly different utility values in people with mental health conditions. Resulting differences in cost per QALY estimates suggest that thresholds of cost-effectiveness may also need to be reviewed. Researchers and decision-makers should exercise caution when comparing or synthesising data from trials of mental health interventions using different utility estimation approaches.
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11.

Background

The Audit of Diabetes-Dependent Quality of Life (ADDQoL) questionnaire is an individualized instrument that measures the impact of diabetes mellitus on quality of life (QOL). With the worldwide increase in the number of Chinese people diagnosed with diabetes, we anticipated that a Chinese-language version of the ADDQoL would be urgently needed.

Objective

To evaluate the reliability and validity of the ADDQoL (Chinese version for Singapore) among Chinese-speaking Singaporeans with type 2 diabetes mellitus (T2DM).

Methods

Chinese versions of the ADDQoL, EuroQoL-Visual Analogue Scale (EQ-VAS), EQ-5D and SF-6D were administered to Chinese-speaking participants with T2DM (aged ≥21 years) at a tertiary acute-care hospital by convenience sampling. The ADDQoL was assessed for the following: internal consistency (Cronbach’s alpha); test-retest reliability (intraclass correlation coefficient [ICC]); factor structure; known-groups validity (insulin requiring vs non-insulin requiring, with vs without diabetes-related complications, overweight/obese vs not overweight/obese); and convergent and divergent validity (with EQ-VAS, EQ-5D and SF-6D). The usefulness of weighting and ‘not applicable’ (NA) options (key features of ADDQoL) were also evaluated.

Results

In 88 participants (58% male, mean [SD] age 56.6 [11.74] years), the mean (SD) ADDQoL average weighted impact (AWI) score was ?2.613 (1.899). Cronbach’s alpha was 0.941 and the ICC was 0.955 (95% CI 0.812, 0.990). In confirmatory factor analysis, the hypothesized one-factor solution was supported. ADDQoL AWI scores correlated strongly with ADDQoL diabetes-dependent global QOL scores (Spearman’s rank correlation coefficient [rs] = 0.5983) and weakly with generic measures (rs = ?0.028 for ADDQoL present global QOL scores, 0.310 for EQ-VAS, 0.164 for EQ-5D and 0.281 for SF-6D). Participants who required insulin, those with diabetes-related complications and those who were overweight/obese reported lower AWI scores, but the differences were not statistically significant. Importance scores of zero were assigned 1–28% of the time and the NA options were selected 3–49% of the time.

Conclusions

The ADDQoL is reliable and probably valid for assessing QOL among Chinese-speaking Singaporeans with T2DM, although known-groups validity warrants further investigation.
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12.
13.

Purpose

Premenstrual dysphoric disorder (PMDD) refers to the depression that occurs during the premenstrual phase and remits soon after the onset of menses. It affects the quality of life (QOL) of patients with PMDD. Therefore, this preliminary survey from chart recordings aimed to understand the symptom appearance and QOL reduction patterns in patients with PMDD, and to examine the extent of the loss of their quality-adjusted life years (QALYs).

Methods

Participants were 66 untreated female patients with PMDD. Data on symptom appearance and QOL reduction during the menstrual cycle, and the EuroQoL-5D (EQ-5D) scores during the premenstrual phase and immediately after the completion of a menstrual period were collected.

Results

The mean EQ-5D score of the 66 patients with PMDD was 0.795 ± 0.120 (range 0.362–0.949), indicating that their expected mean loss of QALYs was about 0.14 years.

Conclusions

If untreated, PMDD is expected to cause a mean loss of QALYs of about 0.14 years. However, on accounting for the period from disease development to menopause, and subtracting the menstruation-free periods such as pregnancy and breastfeeding, patients with untreated PMDD are expected to experience a QALY loss of about 3 years during their lifetime.
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14.

Objectives

The Health-Related Quality of Life Short Form 6D (HRQoL SF-6D) provides utility values for health status. Utilities generated have a number of potentially valuable applications in economic evaluations and not only to ensure comparability between studies. Reference values can be useful to estimate the effect on patients’ HRQoL as a result of interventions in the absence of control groups. Thus, the purpose of this study was to provide normative values in the SF-6D in relation to the Chilean population.

Methods

A cross-sectional study was conducted evaluating 5293 people. SF-6D utilities were derived from the SF-12 questions.

Results

Mean SF-6D utility index for the whole sample was 0.74. It was better for men (0.78) than for women (0.71). The ceiling effect was much higher for men (11.16%) than for women (5.31%). Women were more likely to show problems in any dimension than were men.

Conclusions

Chilean population norms for the SF-6D help in the decision-making process around health policies. Men reported higher health status than women in all subcategories analyzed. Likewise, men also reported higher scores than women in overall SF-6D dimensions.
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15.

Purpose

Health-related quality of life (HRQoL) of pulmonary TB patients has not been assessed in Pakistan. We assessed self-reported HRQoL of pulmonary TB patients in Karachi, Pakistan utilizing the EQ-5D and EQ-VAS prior to, during, and after completion of TB treatment.

Methods

We enrolled 226 pulmonary TB patients in a longitudinal cohort study. Health-utility scores were estimated by the EQ-5D five dimensions and the EQ-Visual Analogue Scale (VAS) at baseline (month 0) and each monthly follow-up visit until treatment completion at month 6. Repeated-measures ANOVA was used to investigate effect of time into treatment on EQ-5D and EQ-VAS scores.

Results

EQ-5D health utility and EQ-VAS scores increase with treatment progression. For the enrolled TB patients, the mean EQ-5D utility scores more than doubled from 0.43 to 0.88, p?<?.001, effect size η2?=?0.40 from treatment initiation to treatment completion.

Conclusion

Perceived HRQoL of TB patients improves with treatment progression. This can inform targeted treatment plans as well as TB policy and funding for high-burden countries.
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16.

Background

In economic evaluation, cost per quality-adjusted life year (QALY) is generally used as an indicator for cost-effectiveness. Although JPY 5 million to 6 million (USD 60, 000 to 75,000) per QALY is frequently referred to as a threshold in Japan, do all QALYs have the same monetary value?

Methods

To examine the relationship between severity of health status and monetary value of a QALY, we obtained willingness to pay (WTP) values for one additional QALY in eight patterns of health states. We randomly sampled approximately 2,400 respondents from an online panel. To avoid misunderstanding, we randomly allocated respondents to one of 16 questionnaires, with 250 responses expected for each pattern. After respondents were asked whether they wanted to purchase the treatment, double-bounded dichotomous choice method was used to obtain WTP values.

Results

The results clearly show that the WTP per QALY is higher for worse health states than for better health states. The slope was about JPY ?1 million per 0.1 utility score increase. The mean and median WTP values per QALY for 16 health states were JPY 5 million, consistent with our previous survey. For respondents who wanted to purchase the treatment, WTP values were significantly correlated with household income.

Conclusion

This survey shows that QALY based on the EQ-5D does not necessarily have the same monetary value. The WTP per QALY should range from JPY 2 million (USD 20,000) to JPY 8 million (USD 80,000), corresponding to the severity of health states.
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17.

Purpose

To refine two subscales of the health-related quality of life comorbidity index (HRQoL-CI) into a single index measure.

Methods

The 2010 and 2012 Medical Expenditure Panel Surveys were utilized as development and validation datasets, respectively. The least absolute shrinkage and selection operator was applied to select important comorbidity candidates associated with HRQoL. Exploratory factor analysis and confirmatory factor analysis (CFA) were used to assess dimensionality in comorbidity. Statistical weights were derived based on standardized factor loadings from CFA and regression coefficients from the model predicting HRQoL. Prediction errors and model R2 values were compared between HRQoL-CI and Charlson CI (CCI).

Results

Eighteen comorbid conditions were identified. CFA models indicated that the second-order multidimensional comorbidity structure had a better fit to the data than did the first-order unidimensional structure. The predictive performance of the refined scale under a multidimensional structure utilizing statistical weights outperformed the original scale and CCI in terms of average prediction error and R2 in the prediction models (R2 values from refined scale model are 0.25, 0.30, and 0.28 versus those from CCI of 0.10, 0.09, and 0.06 for general health, SF-6D, and EQ-5D, respectively).

Conclusion

The dimensionality of comorbidity and the weight scheme significantly improved the performance of the refined HRQoL-CI. The refined single HRQoL-CI measure appears to be an appropriate and valid instrument specific for risk adjustment in studies of HRQoL. Future research that validates the refined scales for different cultures, age groups, and healthcare settings is warranted.
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18.

Purpose

The Veterans RAND 12-Item Health Survey (VR-12) is currently the major endpoint used in the Medicare managed care outcomes measure in the Healthcare Effectiveness Data and Information Set (HEDIS®), referred to as the Health Outcomes Survey (HOS). The purpose of this study is to adapt the Brazier SF-6D utility measure to the VR-12 to generate a single utility index.

Methods

We used the HOS cohorts 2 and 3 for SF-36 data and 9 for VR-12 data. We calculated SF-6D scores from the SF-36 using the algorithms developed by Brazier and colleagues. The values of the Brazier SF-6D were used to estimate utility scores from the VR-12 using a mapping approach based on a 2-stage mapping procedure, named as VR-6D.

Results

The VR-6D derived from the VR-12 has similar distributional properties as the SF-6D. The change in VR-6D showed significant variations across disease groups with different levels of morbidity and mortality.

Conclusions

This study produced a utility measure for the VR-12 that is comparable to the SF-6D and responsive to change. The VR-6D can be used in evaluations of health care plans and cost-effectiveness analysis to compare the health gains that health care interventions can achieve.
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19.

Background

Conventionally, models used for health state valuation data have been frequentists. Recently a number of researchers have investigated the use of Bayesian methods in this area. The aim of this paper is to put on the map of modelling a new approach to estimating SF-6D health state utility values using Bayesian methods. This will help health care professionals in deriving better health state utilities of the original UK SF-6D for their specialized applications.

Methods

The valuation study is composed of 249 SF-6D health states valued by a representative sample of the UK population using the standard gamble technique. Throughout this paper, we present four different models, including one simple linear regression model and three random effect models. The predictive ability of these models is assessed by comparing predicted and observed mean SF-6D scores, R2/adjusted R2 and RMSE. All analyses were carried out using Bayesian Markov chain Monte Carlo (MCMC) simulation methods freely available in the specialist software WinBUGS.

Results

The random effects model with interaction model performs best under all criterions, with mean predicted error of 0.166, R2/adjusted R2 of 0.683 and RMSE of 0.218.

Conclusions

The Bayesian models provide flexible approaches to estimate mean SF-6D utility estimates, including characterizing the full range of uncertainty inherent in these estimates. We hope that this work will provide applied researchers with a practical set of tools to appropriately model outcomes in cost-effectiveness analysis.
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20.

Background

Clinical and radiological outcomes of operatively treated unstable pelvic ring fractures are well documented, whereas little is known about the patient’s related outcome. The purpose of this study is to evaluate the patient-reported outcome after minimal invasive treatment of pelvic ring fractures using the SF-36 and EQ-5D medical outcome scores.

Methods

Patients with unstable pelvic ring fractures treated in our trauma department with a minimal invasive screw-rod system between 01/2004 and 12/2014 were included. Next to patient data (sex, age), injury related details (fracture type, additional injuries, Injury Severity Score (ISS)) as well as operation details (method, time to operation, general complications, adverse events associated with the surgical procedure, revision surgery, fracture reduction) were assessed. The patient related outcome was evaluated using the SF-36 and the EQ-5D score.

Results

A total of 105 patients (57 men; 48 women; mean age 56?±?21 years) were identified as candidates for the study. 60 patients completed the SF-36 and EQ-5D score after a mean follow-up of five years (60.5 months (14-142 months)). Of these patients 77% were multiply injured with a mean ISS of 26?±?19. Within the respondent group 22% showed type B and 78% type C pelvic ring fractures. In 82% the dorsal pelvic ring fracture was stabilized using a minimally invasive transiliac internal fixator, in 18% an iliolumbar fixation was performed respectively. The mean physical component score of the SF-36 was 37.9?±?12.0, the mean mental component score was 49.8?±?12.5. The mean EQ-5D VAS reached 70.5?±?24.4.

Conclusion

Patients being multiply injured and treated with minimal invasive treated dorsal pelvic ring fractures were suffering more especially concerning physical domains compared to the healthy reference population. Nevertheless, the overall patient-related outcome is comparable to pelvic ring fractures in general.

Trial Registration Number

Clinical Trial Registry University of Regensburg Z-2017-0878-3. Registered 22. July 2017. Retrospectively registered.
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