Randomized Controlled Trial of a Spectacle Lens for Macular Degeneration.

SIGNIFICANCE: E-Scoop, a spectacle lens, provides no clinically relevant improvements on quality of life, visual acuity, and contrast sensitivity for patients with AMD. Because patients' burden is high and therapeutic options are scarce, the incentive to develop effective vision rehabilitation interventions remains. PURPOSE: Patients with AMD experience low quality of life due to vision loss, despite angiogenesis inhibitor interventions that slow down progression for some patients. E-Scoop, which includes low-power prisms, 6% magnification, yellow tint, and antireflection coating, might aid in daily activities by improving distance viewing. Separately, these features have little proven effectiveness. E-Scoop has not been formally tested. This study aimed to determine the impact of E-Scoop on quality of life and the effect on visual acuity and contrast sensitivity. METHODS: In this randomized controlled, open-label trial, 190 of 226 eligible patients were included. The primary outcome was quality of life measured with the 25-item National Eye Institute Visual Function Questionnaire. Secondary outcomes were visual acuity and contrast sensitivity. The follow-up for quality of life was after 6 weeks for controls and after 3 weeks of use for E-Scoop wearers. The visual measures were repeated after 6 weeks, with optimal refractive correction, with and without E-Scoop. RESULTS: Randomization resulted in 99 E-Scoop and 86 control group patients for intention-to-treat analysis. No differential change was found between the E-Scoop and control groups on the 25-item National Eye Institute Visual Function Questionnaire using Rasch analysis (Cohen d = -0.07, P = .53). Statistically significant but small effects were found in favor of E-Scoop on binocular visual acuity (mean difference, 0.05 logMAR [2.5 letters, P < .001]) and contrast sensitivity (mean difference, 0.10 logCS [2 letters, P < .001]). CONCLUSIONS: No effect of E-Scoop on quality of life was found. E-Scoop showed effects that were statistically significant, although not clinically meaningful and within typical variability, on visual measures.

Six and eight weeks injection frequencies of bevacizumab are non-inferior to the current four weeks injection frequency for quality of life in neovascular age-related macular degeneration: a randomized controlled trial.

PURPOSE: Patients with neovascular age-related macular degeneration (nARMD) will not deteriorate on visual acuity and retinal thickness when treated with bevacizumab injection frequencies of 6 or 8 weeks compared to 4 weeks. This study aimed to investigate this non-inferiority in quality of life (QoL). We hypothesized that less frequent bevacizumab injections are not inferior regarding patients reported QoL. METHODS: Patients were randomized to bevacizumab every 4 (n = 64), 6 (n = 63), and 8 weeks (n = 64). Patients were at least 65 years old, have a best-corrected visual acuity of 20/200 to 20/20, no previous ARMD treatment and active leakage. Vision-related QoL questionnaire NEI VFQ-39 was used to assess QoL at baseline and after 1 year. General QoL questionnaire SF-36 was included for secondary analysis. Multilevel analyses were performed, correcting for age, gender and baseline. RESULTS: The 6 (3.68; 95% CI - 0.63 to 8.00) and 8 (2.15; 95% CI - 2.26 to 6.56) weeks bevacizumab regimens resulted in non-inferior QoL differences compared to 4 weeks on the NEI VFQ-39. Also on the SF-36 the differences were well within the non-inferiority limits. CONCLUSION: Non-inferiority of the 6 and 8 weeks frequencies was demonstrated compared to 4 weeks on vision-related and general QoL in patients with nARMD. These results are in line with previously published results of lower frequency injections regarding visual acuity and central retinal thickness. Lower injection frequency may reduce burden, side effects, and treatment costs. In consideration of these results, 8 weeks frequency injections of intravitreal bevacizumab could be considered in patients with nARMD.

A very short version of the Visual Function Questionnaire (VFQ-3oo7) for use as a routinely applied Patient-Reported Outcome Measure.

BACKGROUND: Patient-reported outcome measures (PROMs) are valuable supplements in regular care to facilitate routine monitoring of quality of life from the patient's perspective. The 25-item National Eye Institute Visual Function Questionnaire (NEI-VFQ-25) is a widely used PROM in ophthalmology. However, the NEI-VFQ-25 is too time-consuming and cumbersome for routine evaluations in regular care. The aim of this study is to construct a 7-item questionnaire of which only 3 items are presented to the patient, by means of routing. This VFQ 3 out of 7 (VFQ-3oo7) should have a minimal loss of information compared with the NEI-VFQ-25. METHODS: An historical database including 3293 administrations of the NEI-VFQ-25 was constructed involving patients with retinal detachment, cataract, corneal diseases, glaucoma, macular degeneration, uveal melanoma and a normal population sample. The data were subjected to Rasch analyses, in particular a generalized partial credit model. Items were sorted on the latent trait and divided into seven categories. From each category, the item with the highest discriminative value was selected. Through routing, only three out of the seven remaining questions are used, where the answers navigate patients to a fitting trait level. RESULTS: A one-dimensional structure was considered fitting. The VFQ-3oo7 showed a small loss of information compared with the total score of the NEI-VFQ-25: correlation 0.927 and a relative precision of 0.868. CONCLUSION: The very short, but valid, VFQ-3oo7 can be applied to evaluate the patient's perceived vision-related health status in routine evaluations of treatments in regular care, with a small burden for patients.

Cost-effectiveness of a home-based group educational programme on renal replacement therapies: a study protocol.

INTRODUCTION: Living donor kidney transplantation (LDKT) is the optimal treatment for most patients with end-stage renal disease (ESRD). However, there are numerous patients who cannot find a living kidney donor. Randomised controlled trials have shown that home-based education for patients with ESRD and their family/friends leads to four times more LDKTs. This educational intervention is currently being implemented in eight hospitals in the Netherlands. Supervision and quality assessment are being employed to maintain the quality of the intervention. In this study, we aim to: (1) conduct a cost-effectiveness analysis of the educational programme and its quality assurance system; (2) investigate the relationship between the quality of the implementation of the intervention and the outcomes knowledge, communication and LDKT activities; and (3) investigate policy implications. METHODS AND DESIGN: Patients with ESRD who do not have a living kidney donor are eligible to receive the home-based educational intervention. This is carried out by allied health transplantation professionals and psychologists across eight hospitals in the Netherlands. The cost-effectiveness analysis will be conducted with a Markov model. Cost data will be obtained from the literature. We will obtain the quality of life data from the patients who participate in the educational programme. Questionnaires on knowledge and communication will be used to measure the outcomes of the programme. Data on LDKT activities will be obtained from medical records up to 24 months after the education. A protocol adherence measure will be assessed by a third party by means of a telephone interview with the patients and the invitees. ETHICS AND DISSEMINATION: Ethical approval was obtained through all participating hospitals. Results will be disseminated through peer-reviewed publications and scientific presentations. Results of the cost-effectiveness of the educational programme will also be disseminated to the Dutch National Health Care Institute. TRIAL REGISTRATION NUMBER: NL6529.

"The validity of the EQ-5D-5L in measuring quality of life benefits of breast reconstruction".

BACKGROUND: The EuroQol EQ-5D-5L instrument is the most widely used quality of life (QoL) measure in health economic evaluations. It is unclear whether such a generic instrument is valid enough to estimate the benefits of breast reconstruction (BR), given the specific changes observed in QoL after BR. Hence, we aimed to evaluate the validity of the EQ-5D-5L in patients who had undergone postmastectomy BR. METHODS: In a 10-year cross-sectional cohort study, 463 mastectomy patients completed an online survey: 202 patients with autologous-BR (A-BR), 103 with implant-based-BR (I-BR), and 158 without BR (MAS). The results were used to evaluate the psychometric performance of the EQ-5D-5L with respect to the ceiling effect and to known-group, convergent, and discriminant validity, by comparing it with the Breast-Q, the cancer-specific (EORTC-QLQ-C30), and breast cancer-specific (EORTC-QLQ-BR23) questionnaires. RESULTS: The EQ-5D-5L was able to discriminate between patients with and without complications, MAS with or without BR and MAS versus the general population. It was, however, not able to discriminate between A-BR vs. I-BR as well as BR vs. general population. It is not clear whether this was due to the insensitivity of the instrument, insufficient sample sizes, or because there were no actual differences in QoL between these groups. Good convergent and discriminant validity of both the EQ-5D-5L and its individual dimensions were demonstrated. Additional support for the instrument's validity was revealed by moderate correlations between the generic EQ-5D-5L and specific QoL aspects of BR such as sexuality and body image. CONCLUSIONS: The results of this study support the validity of the EQ-5D-5L as an outcome measure in health economic evaluations of BR.

Evaluation of Split Version and Feedback Module on the Improvement of Time Trade-Off Data.

BACKGROUND: EQ-5D-5L valuation studies previously reported many inconsistent responses in time trade-off (TTO) data. A number of possible elements, including ordering effects of the valuation tasks, mistakes at the sorting question, and interviewers' (learning) effects, may contribute to their inconsistency. OBJECTIVES: This study aimed to evaluate the effect of two modifications on consistency of TTO data in The Netherlands (NL) and Hong Kong (HK): (1) separating the valuation of the Better than Dead (BTD) and Worse than Dead (WTD) states; and (2) Implementation of feedback (FB) module by offering an opportunity to review TTO responses. METHODS: A crossover design with two study arms was used to test the effect of the modifications. In each jurisdiction, six interviewers were involved where half the interviewers started using the standard version, and the other half started with the split version. Each version was switched after every 25 (NL) or 30 (HK) interviews until 400 interviews were completed. RESULTS: In the NL and HK, 404 and 403 respondents participated, respectively. With the use of the FB module, the proportion of respondents with inconsistent responses was lowered from 17.8% to 10.6% (P < 0.001) in NL and from 31.8% to 22.3% (P = 0.003) in HK. The result of separating the valuation of BTD and WTD states was not straightforward because it reduced the inconsistency rate in NL but not in HK. CONCLUSIONS: The results support implementation of the FB module to promote the consistency of the data. The separation of the BTD and WTD task is not supported.

Novel, Moon and Mars, partial gravity simulation paradigms and their effects on the balance between cell growth and cell proliferation during early plant development.

Clinostats and Random Positioning Machine (RPM) are used to simulate microgravity, but, for space exploration, we need to know the response of living systems to fractional levels of gravity (partial gravity) as they exist on Moon and Mars. We have developed and compared two different paradigms to simulate partial gravity using the RPM, one by implementing a centrifuge on the RPM (RPMHW), the other by applying specific software protocols to driving the RPM motors (RPMSW). The effects of the simulated partial gravity were tested in plant root meristematic cells, a system with known response to real and simulated microgravity. Seeds of Arabidopsis thaliana were germinated under simulated Moon (0.17 g) and Mars (0.38 g) gravity. In parallel, seeds germinated under simulated microgravity (RPM), or at 1 g control conditions. Fixed root meristematic cells from 4-day grown seedlings were analyzed for cell proliferation rate and rate of ribosome biogenesis using morphometrical methods and molecular markers of the regulation of cell cycle and nucleolar activity. Cell proliferation appeared increased and cell growth was depleted under Moon gravity, compared with the 1 g control. The effects were even higher at the Moon level than at simulated microgravity, indicating that meristematic competence (balance between cell growth and proliferation) is also affected at this gravity level. However, the results at the simulated Mars level were close to the 1 g static control. This suggests that the threshold for sensing and responding to gravity alteration in the root would be at a level intermediate between Moon and Mars gravity. Both partial g simulation strategies seem valid and show similar results at Moon g-levels, but further research is needed, in spaceflight and simulation facilities, especially around and beyond Mars g levels to better understand more precisely the differences and constrains in the use of these facilities for the space biology community.

Effects of clinical parameters on patient-reported outcome in cataract patients: a multicentre study.

PURPOSE: Ophthalmologists tend to evaluate the results of cataract surgery by focusing on the clinical visual and refractive outcomes and the incidence of complications, where patients' main interest might be their ability to perform daily activities. Therefore, there appears to be a need for optimizing effective communication between patients and ophthalmologist about the outcome of cataract surgery. The aim of this multicentre study was to determine the effects of whether the surgery was performed in one or two eyes, ocular comorbidity and per- and postoperative complications on visual function experienced by patients measured with the Catquest-9SF. METHODS: To measure patient-reported outcomes, Catquest-9SF data were collected between 2014 and 2015 in five Dutch hospitals. Data from 870 pairs of questionnaires - completed before and after cataract surgery - were compared with clinical data. Clinical data, retrieved from patients' medical files, consisted of one or two eye surgery, ocular comorbidity and per- and postoperative complications. RESULTS: Quality of vision improved more in patients who had surgery in both eyes and had fewer postoperative complications (both p < 0.001). We found a nonsignificant trend that quality of vision was worse when ocular comorbidity was present. No significant effect of peroperative complications was observed. CONCLUSION: Our results emphasize the added value of the Catquest-9SF as a tool for visual function experienced by patients; the additional information can complement clinical parameters to improve patient-centred approaches in clinical practice.

SF-6D utility values for the better- and worse-seeing eye for health states based on the Snellen equivalent in patients with age-related macular degeneration.

OBJECTIVE: Economic evaluations in wet age-related macular degeneration (ARMD) is hampered as often utility values for solely one eye are used, mostly the better-seeing eye (BSE). Moreover, frequently chosen methods rely on patient values and/or disease specific measures, while economic evaluations prefer generic quality of life (QoL) measures based on societal preferences. The generic QoL utility instrument EQ-5D has shown to be insensitive for differences in visual acuity. The aim of this study was therefore to provide societal utility values, using the generic SF-6D, for health states acknowledging both BSE and worse-seeing eye (WSE). METHODS: SF-6D utility values of 191 ARMD patients (≥65 years) with 153 follow-up measures at 1 year were used to fill health states defined by the combination of BSE and WSE using Snellen equivalents; no visual loss (≥20/40), mild-moderate (<20/40->20/200) and severe (≤20/200). RESULTS: QoL utilities were estimated for the SF-6D, ranging from 0.740 for ARMD patients without visual loss to 0.684 for patients with a combination of mild-moderate visual loss in their BSE and severe visual loss in their WSE. CONCLUSION: Societal utility values are provided for ARMD patients using the generic QoL instrument SF-6D for visual acuity health states based on both BSE and WSE. The range of the values is smaller than previous elicited utilities with the disease-specific VisQoL. Besides, the utility values are placed on a more realistic position on the utility scale, and SF-6D utility values avoid the problem associated with the interpretation of disease-specific utility values.

Validation, test-retest reliability and norm scores for the Dutch Catquest-9SF.

PURPOSE: The Catquest-9SF questionnaire is a unidimensional, reliable, valid and short patient-reported outcome measure for quantifying benefits in visual functioning from cataract surgery. Our aim was to develop a formal Dutch translation, calculate norm scores, assess its validity and test-retest reliability and provide an easy way for use in clinical practice. METHODS: Translation of the questionnaire was performed according to guidelines of the International Society for Pharmacoeconomics and Outcomes Research. Catquest-9SF was obtained in 657 patients pre- and postcataract surgery. We applied Rasch and classical analyses to determine the questionnaire performance with characteristics such as unidimensionality, reliability, separation and differential item functioning. Test-retest reliability was assessed in another group of 145 patients. A cut-off value to discriminate between people with and without cataract, norm scores and a reliable change index (RCI) were calculated using data from a sample of 916 'healthy' persons from the normal population. RESULTS: The Dutch Catquest-9SF was unidimensional, and both person and item reliability were high; 0.87 and 0.99, respectively. Cronbach's alpha was 0.94, test-retest reliability was 0.85 and the intraclass correlation coefficient was 0.93. Catquest-9SF showed to be responsive to the effect of cataract surgery (effect size = 1.27; p < 0.001). The cut-off value was -1.90, and RCI was 2.27. A quick-access table with norm scores and percentiles was established to facilitate clinical interpretation. CONCLUSION: This investigation provides validity and reliability of the Dutch Catquest-9SF as well as norm scores and a new tool to facilitate the clinical interpretation of patient scores. This makes Catquest-9SF suitable for routine use in clinical practice.

The Cost-Effectiveness of Cognitive-Behavioral Group Training for Patients with Unexplained Physical Symptoms.

OBJECTIVE: The aim of the study was to evaluate the cost-effectiveness of a cognitive-behavioral group training compared with a wait-list control for patients with unexplained physical symptoms (UPS). METHODS: A probabilistic decision-analytic Markov model was developed with three health states (poor health, average health, and death) based on a cutoff score of the Physical Component Summary of the short-form 36 health survey. To assess the cost-effectiveness in terms of cost per quality-adjusted life-year (QALY), a societal perspective was adopted. The model consisted of cycles of 3 months and a time horizon of 4 years. Data for the model were derived from a randomized controlled trial, in which 162 patients with UPS were randomized either to cognitive-behavioral group training or to the wait-list control. Data were assessed at baseline and after the training of 3 months or after a wait-list period of 3 months. In addition, the training group was followed in an uncontrolled phase and assessed at 3 months and 1 year after the training. RESULTS: After 4 years, the group training was in terms of cost-effectiveness "dominant" compared with the wait-list control; there was a positive effect of 0.06 QALYs and a €828 reduction in costs. The cost-effectiveness improved with a longer time horizon. A threshold of €30,000/QALY was passed after 18 months. The group training was cost saving after 33 months. CONCLUSIONS: Cognitive-behavioral group training is a cost-effective treatment compared with the wait-list control for patients with UPS.

Solution focused therapy: a promising new tool in the management of fatigue in Crohn's disease patients psychological interventions for the management of fatigue in Crohn's disease.

BACKGROUND: Crohn's disease patients have a decreased Quality of Life (QoL) which is in part due to extreme fatigue. In a pilot study we prospectively assessed the feasibility and effect of psychological interventions in the management of fatigue. METHODS: Patients with quiescent Crohn's disease and a high fatigue score according to the Checklist Individual Strength were randomized to Problem Solving Therapy (PST), Solution Focused Therapy (SFT) or to a control group (treatment as usual, TAU). Patients completed the Inflammatory Bowel Disease Questionnaire, the EuroQol-5D, and the Trimbos questionnaire for Costs. RESULTS: Twenty-nine patients were included (12 TAU, 9 PST, 8 SFT), of these 72% were female, mean age was 31 years (range 20-50). The SFT group improved on the fatigue scale in 85.7% of the patients, in the PST group 60% showed improved fatigue scores and in the TAU group 45.5%. Although not significant, in both intervention groups the QoL increased. Medical costs lowered in 57.1% of the patients in the SFT group, in the TAU 45.5% and the in PST group 20%. The drop out rate was highest in the PST group (44%; SFT 12.5%; TAU 8.3%). CONCLUSIONS: PST and SFT both positively affect the fatigue and QoL scores in patients with Crohn's disease. SFT seems most feasible with fewer dropouts and is therefore a promising new tool in the management of fatigue in Crohn's disease patients.

On the correlation between bibliometric indicators and peer review: reply to Opthof and Leydesdorff.

Opthof and Leydesdorff (Scientometrics, 2011) reanalyze data reported by Van Raan (Scientometrics 67(3):491-502, 2006) and conclude that there is no significant correlation between on the one hand average citation scores measured using the CPP/FCSm indicator and on the other hand the quality judgment of peers. We point out that Opthof and Leydesdorff draw their conclusions based on a very limited amount of data. We also criticize the statistical methodology used by Opthof and Leydesdorff. Using a larger amount of data and a more appropriate statistical methodology, we do find a significant correlation between the CPP/FCSm indicator and peer judgment.

Severe language effect in university rankings: particularly Germany and France are wronged in citation-based rankings.

We applied a set of standard bibliometric indicators to monitor the scientific state-of-arte of 500 universities worldwide and constructed a ranking on the basis of these indicators (Leiden Ranking 2010). We find a dramatic and hitherto largely underestimated language effect in the bibliometric, citation-based measurements of research performance when comparing the ranking based on all Web of Science (WoS) covered publications and on only English WoS covered publications, particularly for Germany and France.

Towards a new crown indicator: an empirical analysis.

We present an empirical comparison between two normalization mechanisms for citation-based indicators of research performance. These mechanisms aim to normalize citation counts for the field and the year in which a publication was published. One mechanism is applied in the current so-called crown indicator of our institute. The other mechanism is applied in the new crown indicator that our institute is currently exploring. We find that at high aggregation levels, such as at the level of large research institutions or at the level of countries, the differences between the two mechanisms are very small. At lower aggregation levels, such as at the level of research groups or at the level of journals, the differences between the two mechanisms are somewhat larger. We pay special attention to the way in which recent publications are handled. These publications typically have very low citation counts and should therefore be handled with special care.

Bibliometric analysis of psychotherapy research: performance assessment and position in the journal landscape.

The authors provide an overview of advanced bibliometric methods for (a) an objective and transparent assessment of journal performance and (b) positioning of a journal in relation to other journals. These methods are applied to Psychotherapy Research, an international journal within the field of clinical psychology. In the first analysis, the authors focus on journal performance in an international comparative perspective (i.e., the performance of the journal in relation to all other journals in the same field of science) and introduce a novel type of journal impact factor. In the second analysis, the authors position the journal on the basis of total citation relations among all relevant journals, including those outside the specific field of science to which the journal belongs. A multitude of interdisciplinary relations between the journal under investigation and many other journals is revealed. The investigators discuss briefly the potential of such a "journal citation mapping" for unraveling interdisciplinary developments and "interfaces" between different fields of science.