Clinical and cost-effectiveness of internal limiting membrane peeling for patients with idiopathic full thickness macular hole. Protocol for a Randomised Controlled Trial:FILMS (Full-thickness macular hole and Internal Limiting Membrane peeling Study)

Background: A full-thickness macular hole (FTMH) is a common retinal condition associated with impaired vision. Randomised controlled trials (RCTs) have demonstrated that surgery, by means of pars plana vitrectomy and post-operative intraocular tamponade with gas, is effective for stage 2, 3 and 4 FTMH. Internal limiting membrane (ILM) peeling has been introduced as an additional surgical manoeuvre to increase the success of the surgery; i.e. increase rates of hole closure and visual improvement. However, little robust evidence exists supporting the superiority of ILM peeling compared with no-peeling techniques. The purpose of FILMS (Full-thickness macular hole and Internal Limiting Membrane peeling Study) is to determine whether ILM peeling improves the visual function, the anatomical closure of FTMH, and the quality of life of patients affected by this disorder, and the cost-effectiveness of the surgery. Methods/Design: Patients with stage 2-3 idiopathic FTMH of less or equal than 18 months duration (based on symptoms reported by the participant) and with a visual acuity = 20/40 in the study eye will be enrolled in this FILMS from eight sites across the UK and Ireland. Participants will be randomised to receive combined cataract surgery (phacoemulsification and intraocular lens implantation) and pars plana vitrectomy with postoperative intraocular tamponade with gas, with or without ILM peeling. The primary outcome is distance visual acuity at 6 months. Secondary outcomes include distance visual acuity at 3 and 24 months, near visual acuity at 3, 6, and 24 months, contrast sensitivity at 6 months, reading speed at 6 months, anatomical closure of the macular hole at each time point (1, 3, 6, and 24 months), health related quality of life (HRQOL) at six months, costs to the health service and the participant, incremental costs per quality adjusted life year (QALY) and adverse events. Discussion: FILMS will provide high quality evidence onthe role of ILM peeling in FTMH surgery. © 2008 Lois et al; licensee BioMed Central Ltd.

Internal limiting membrane peeling versus no peeling for idiopathic full-thickness macular hole: A pragmatic randomized controlled trial

PURPOSE. To determine whether internal limiting membrane (ILM) peeling is effective and cost effective compared with no peeling in patients with idiopathic stage 2 or 3 full-thickness maculay hole (FTMH). METHODS. This was a pragmatic multicenter randomized controlled trial. Eligible participants from nine centers were randomized to ILM peeling or no peeling (1:1 ratio) in addition to phacovitrectomy, including detachment and removal of the posterior hyaloid and gas tamponade. The primary outcome was distance visual acuity (VA) at 6 months after surgery. Secondary outcomes included hole closure, distance VA at other time points, near VA, contrast sensitivity, reading speed, reoperations, complications, resource use, and participant-reported health status, visual function, and costs. RESULTS. Of 141 participants randomized in nine centers, 127 (90%) completed the 6-month follow-up. Nonstatistically significant differences in distance visual acuity at 6 months were found between groups (mean difference, 4.8; 95% confidence interval [CI], -0.3 to 9.8; P = 0.063). There was a significantly higher rate of hole closure in the ILM-peel group (56 [84%] vs. 31 [48%]) at 1 month (odds ratio [OR], 6.23; 95% CI, 2.64-14.73; P <0.001) with fewer reoperations (8 [12%] vs. 31 [48%]) performed by 6 months (OR, 0.14; 95% CI, 0.05- 0.34; P <0.001). Peeling the ILM is likely to be cost effective. CONCLUSIONS. There was no evidence of a difference in distance VA after the ILM peeling and no-ILM peeling techniques. An important benefit in favor of no ILM peeling was ruled out. Given the higher anatomic closure and lower reoperation rates in the ILM-peel group, ILM peeling seems to be the treatment of choice for idiopathic stage 2 to 3 FTMH. © 2011 The Association for Research in Vision and Ophthalmology, Inc.

Cost-effectiveness of internal limiting membrane peeling versus no peeling for patients with an idiopathic full-thickness macular hole:Results from a randomised controlled trial

Aim: To determine whether internal limiting membrane (ILM) peeling is cost-effective compared with no peeling for patients with an idiopathic stage 2 or 3 full-thickness macular hole. Methods: A cost-effectiveness analysis was performed alongside a randomised controlled trial. 141 participants were randomly allocated to receive macular-hole surgery, with either ILM peeling or no peeling. Health-service resource use, costs and quality of life were calculated for each participant. The incremental cost per quality-adjusted life year (QALY) gained was calculated at 6 months. Results: At 6 months, the total costs were on average higher (£424, 95% CI -182 to 1045) in the No Peel arm, primarily owing to the higher reoperation rate in the No Peel arm. The mean additional QALYs from ILM peel at 6 months were 0.002 (95% CI 0.01 to 0.013), adjusting for baseline EQ-5D and other minimisation factors. A mean incremental cost per QALY was not computed, as Peeling was on average less costly and slightly more effective. A stochastic analysis suggested that there was more than a 90% probability that Peeling would be cost-effective at a willingness-to-pay threshold of £20 000 per QALY. Conclusion: Although there is no evidence of a statistically significant difference in either costs or QALYs between macular hole surgery with or without ILM peeling, the balance of probabilities is that ILM Peeling is likely to be a cost-effective option for the treatment of macular holes. Further long-term follow-up data are needed to confirm these findings.

Internal Limiting Membrane Peeling in Vitreo-retinal Surgery

Peeling the internal limiting membrane of the retina has become a very common procedure performed by vitreo-retinal surgeons. The combination of new microsurgical instrumentation with the availability of different dyes to stain this thin and transparent membrane has facilitated the performance of internal limiting membrane peeling, reducing the time and trauma associated with this maneuver. Internal limiting membrane peeling has been used to treat a variety of retinal pathologies, including full-thickness macular hole, epiretinal membrane, macular edema, vitreomacular traction syndrome, and Terson syndrome, among others. Although it appears that peeling the internal limiting membrane in these retinal conditions may be associated with better anatomical and visual outcomes following surgery, further evidence through randomized controlled clinical trials is still needed to guide the vitreo-retinal surgeon on the appropriate use of this surgical maneuver. © 2008 Elsevier Inc. All rights reserved.

Use of perfluorohexyloctane as a long-term internal tamponade agent in complicated retinal detachment surgery

PURPOSE: To report the use of perfluorohexyloctane, a liquid semifluorinated alkane that is heavier than water, as an internal tamponade agent in surgery for complicated retinal detachments. DESIGN: A consecutive interventional case series from three study centers. METHODS: In 23 consecutive eyes (23 patients, 19 men and four women, mean ± standard deviation (SD) age of 58.5 years ± 16.1) perfluorohexyloctane was used for long-term internal tamponade. Included were eyes with complicated retinal detachment involving the lower two quadrants of the fundus. Excluded were patients with diseases in the fellow eye or severe systemic disease. A pars plana vitrectomy was performed, including membrane peeling and retinotomy where necessary. RESULTS: The mean duration for perfluorohexyloctane being left in situ was 76 days (SD 37.64) (range, 35-202 days). Four weeks following the removal of perfluorohexyloctane 19 of the 23 patients had total reattachment of the retina; three eyes had a recurrence of retinal detachment. One patient was lost to follow-up. The mean follow-up after perfluorohexyloctane removal was 97 days (range, 48 to 169 days). Cataract formation or progression was noted in nine of the 10 eyes. There were two cases with high intraocular pressures. Dispersion into small droplets was observed as early as 3 days postoperatively in three of the 23 patients. At least 12 of the 23 patients had an obvious dispersion by the time of perfluorohexyloctane removal. There was no sign of optic atrophy, retinal necrosis, or retinal vascular occlusion. CONCLUSION: Perfluorohexyloctane was tolerated as a long-term internal tamponade agent without obvious signs of damage to the retina or optic disk. Of all the complications noted, the most common was that of dispersion of the perfluorohexyloctane bubble into droplets. © 2002 by Elsevier Science Inc. All rights reserved.

Fault Diagnostics for Internal Combustion Engines – Current and Future Techniques

The adoption of each new level of automotive emissions legislation often requires the introduction of additional emissions reduction techniques or the development of existing emissions control systems. This, in turn, usually requires the implementation of new sensors and hardware which must subsequently be monitored by the on-board fault detection systems. The reliable detection and diagnosis of faults in these systems or sensors, which result in the tailpipe emissions rising above the progressively lower failure thresholds, provides enormous challenges for OBD engineers. This paper gives a review of the field of fault detection and diagnostics as used in the automotive industry. Previous work is discussed and particular emphasis is placed on the various strategies and techniques employed. Methodologies such as state estimation, parity equations and parameter estimation are explained with their application within a physical model diagnostic structure. The utilization of symptoms and residuals in the diagnostic process is also discussed. These traditional physical model based diagnostics are investigated in terms of their limitations. The requirements from the OBD legislation are also addressed. Additionally, novel diagnostic techniques, such as principal component analysis (PCA) are also presented as a potential method of achieving the monitoring requirements of current and future OBD legislation.

Nonclassicality Criteria from Phase-Space Representations and Information-Theoretical Constraints Are Maximally Inequivalent

We consider two celebrated criteria for defining the nonclassicality of bipartite bosonic quantum systems, the first stemming from information theoretic concepts and the second from physical constraints on the quantum phase space. Consequently, two sets of allegedly classical states are singled out: (i) the set C composed of the so-called classical-classical (CC) states—separable states that are locally distinguishable and do not possess quantum discord; (ii) the set P of states endowed with a positive P representation (P-classical states)—mixtures of Glauber coherent states that, e.g., fail to show negativity of their Wigner function. By showing that C and P are almost disjoint, we prove that the two defining criteria are maximally inequivalent. Thus, the notions of classicality that they put forward are radically different. In particular, generic CC states show quantumness in their P representation, and vice versa, almost all P-classical states have positive quantum discord and, hence, are not CC. This inequivalence is further elucidated considering different applications of P-classical and CC states. Our results suggest that there are other quantum correlations in nature than those revealed by entanglement and quantum discord.

Immune complexes containing modified lipoproteins are related to the progression of internal carotid intima-media thickness in patients with type 1 diabetes

Modified lipoproteins induce autoimmune responses including the synthesis of autoantibodies with pro-inflammatory characteristics. Circulating modified lipoprotein autoantibodies combine with circulating antigens and form immune complexes (IC). We now report the results of a study investigating the role of circulating IC containing modified lipoproteins in the progression of carotid intima-media thickness (IMT) in patients enrolled in the Epidemiology of Diabetes Interventions and Complications (EDIC) Trial, a follow-up study of the Diabetes Control and Complications Trial (DCCT). This cohort includes 1229 patients with type 1 diabetes in whom B-mode ultrasonography of internal and common carotid arteries was performed in 1994-1996 and in 1998-2000. Conventional CHD risk factors, antibodies against modified forms of LDL and modified lipoprotein IC were determined in 1050 of these patients from blood collected in 1996-1998. Cholesterol and apolipoprotein B content of IC (surrogate markers of modified ApoB-rich lipoproteins) were significantly higher in patients who showed progression of the internal carotid IMT than in those showing no progression, regression or mild progression. Multivariate linear and logistic regression modeling using conventional and non-conventional risk factors showed that the cholesterol content of IC was a significant positive predictor of internal carotid IMT progression. In conclusion these data demonstrate that increased levels of modified ApoB-rich IC are associated with increased progression of internal carotid IMT in the DCCT/EDIC cohort of type 1 diabetes.

Vitrectomy with internal limiting membrane (ILM) peeling versus vitrectomy with no peeling for idiopathic full-thickness macular hole (FTMH)

Several observational studies have suggested the potential benefit of internal limiting membrane (ILM) peeling to treat idiopathic full-thickness macular hole (FTMH). However, no strong evidence is available on the potential benefit(s) of this surgical manoeuvre and uncertainty remains among vitreoretinal surgeons about the indication for peeling the ILM, whether to use it in all cases or in long-standing and/or larger holes. 

EEG decoding of semantic category reveals distributed representations for single concepts

Achieving a clearer picture of categorial distinctions in the brain is essential for our understanding of the conceptual lexicon, but much more fine-grained investigations are required in order for this evidence to contribute to lexical research. Here we present a collection of advanced data-mining techniques that allows the category of individual concepts to be decoded from single trials of EEG data. Neural activity was recorded while participants silently named images of mammals and tools, and category could be detected in single trials with an accuracy well above chance, both when considering data from single participants, and when group-training across participants. By aggregating across all trials, single concepts could be correctly assigned to their category with an accuracy of 98%. The pattern of classifications made by the algorithm confirmed that the neural patterns identified are due to conceptual category, and not any of a series of processing-related confounds. The time intervals, frequency bands and scalp locations that proved most informative for prediction permit physiological interpretation: the widespread activation shortly after appearance of the stimulus (from 100. ms) is consistent both with accounts of multi-pass processing, and distributed representations of categories. These methods provide an alternative to fMRI for fine-grained, large-scale investigations of the conceptual lexicon. © 2010 Elsevier Inc.