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Background Several mapping algorithms have been published with the EORTC-QLQ-C30 for estimating EQ-5D-3L utilities. However, none are available with EQ-5D-5L. Moreover, a comparison between mapping algorithms in the same set of patients has not been performed for these two instruments simultaneously. In this prospective data set of 100 non-small cell lung cancer (NSCLC) patients, we investigate three mapping algorithms using the EQ-5D-3L and EQ-5D-5L and compare their performance. Methods A prospective non-interventional cohort of 100 NSCLC patients were followed up for 12 months. EQ-5D-3L, EQ-5D-5L and EORTC-QLQ-C30 were assessed monthly. EQ-5D-5L was completed at least 1 week after EQ-5D-3L. A random effects linear regression model, a beta-binomial (BB) and a Limited Variable Dependent Mixture (LVDM) model were used to determine a mapping algorithm between EQ-5D-3L, EQ-5D-5L and QLQ-C30. Simulation and cross validation and other statistical measures were used to compare the performances of the algorithms. Results Mapping from the EQ-5D-5L was better: lower AIC, RMSE, MAE and higher R 2 were reported with the EQ-5D-5L than with EQ-5D-3L regardless of the functional form of the algorithm. The BB model proved to be more useful for both instruments: for the EQ-5D-5L, AIC was –485, R 2 of 75 %, MAE of 0.075 and RMSE was 0.092. This was –385, 69 %, 0.099 and 0.113 for EQ-5D-3L respectively. The mean observed vs. predicted utilities were 0.572 vs. 0.577 and 0.515 vs. 0.523 for EQ-5D-5L and EQ-5D-3L respectively, for OLS; for BB, these were 0.572 vs. 0.575 and 0.515 vs. 0.518 respectively and for LVDMM 0.532 vs 0.515 and 0.569 vs 0.572 respectively. Less over-prediction at poorer health states was observed with EQ-5D-5L. Conclusions The BB mapping algorithm is confirmed to offer a better fit for both EQ-5D-3L and EQ-5D-5L. The results confirm previous and more recent results on the use of BB type modelling approaches for mapping. It is recommended that in studies where EQ-5D utilities have not been collected, an EQ-5D-5L mapping algorithm is used.

Background Vitiligo is reported to affect 2% of the world’s population and has a significant impact on health related quality of life (HRQoL). The relationship between HRQoL and clinical outcomes used in vitiligo require further examination. Mapping condition specific measures of HRQoL: vitiligo specific quality of life instrument (VitiQoL), vitiligo noticeability scale (VNS) and vitiligo re-pigmentation scores (RPS) to the EQ-5D have not yet been reported. Methods Data collected from a randomised clinical trial (HI-Light) in vitiligo was used to develop mapping algorithms for the EQ-5D-5 L and the relationship between HRQoL, clinical outcomes and EQ-5D were investigated. Two EQ-5D-5 L value sets (Van Hout and Alava) using linear and non-linear models were considered. Logistic regression models were used to model the probability of vitiligo noticeability (VNS) in terms of RPS, EQ-5D and VitiQoL scores. Results Mapping from RPS appeared to perform better followed by VNS for the Alava crosswalks using polynomial models: Mean observed vs. predicted utilities of 0.9008 (0.005) vs. 0.8984 (0.0004) were observed for RPS. For VNS, mean observed vs. predicted utilities of 0.9008 (0.005) vs. 0.8939 (0.0003) were observed. For VitiQoL, mean observed vs. predicted utilities of 0.9008 (0.005) vs. 0.8912 (0.0002) were observed. For patients with the least re-pigmentation (RPS < 25%), a Total VitiQoL score of about 20 points gives around an 18% chance of vitiligo being no longer or a lot less noticeable. Conclusion The algorithm based on RPS followed by VNS performed best. The relationship between effects from vitiligo specific HRQoL instruments and clinical RPS was established allowing for plausible clinically relevant differences to be identified, although further work is required in this area.

The ability to manipulate a liquid meniscus using electrowetting has many applications. In any electrowetting design, at least two electrodes are required: one forms the field to change the contact angle and the other functions as a ground electrode. The contribution of the ground electrode (GE) to the dynamics of electrowetting has not yet been thoroughly investigated. In this paper, we discovered that with a bare ground electrode, the contact angle of a sessile drop increases instead of decreases when a direct current (DC) voltage varying from zero to the threshold voltage is applied. This phenomenon is opposite to what occurs when the GE is coated with a dielectric, where the contact-angle change follows the Lippmann–Young equation above the threshold voltage of electrowetting. However, this behaviour is not observed with either a dielectric-coated electrode using direct current (DC) or a bare ground electrode using alternating current (AC) voltage electrowetting. This study explains this phenomenon with finite element simulation and theory. From previous research work, the ground electrode configuration is inconsistent. In some studies, the ground electrode is exposed to water; in other studies, the ground electrode is covered with dielectric. This study identified that an exposed ground electrode is not required in electrowetting. Moreover, this research work suggests that for applications where precise control of the contact angle is paramount, a dielectric-coated ground electrode should be used since it prevents the increase in the contact angle when increasing the applied potential from zero to the threshold voltage. This study also identified that contact angle hysteresis is lower with a Cytop-coated ground electrode and DC voltage than with a bare ground electrode using AC or DC voltages.

Many patients with advanced non-small-cell lung cancer (NSCLC) receive only active supportive care because of poor performance status or presence of several comorbidities. We investigated whether erlotinib improves clinical outcome in these patients. TOPICAL was a double-blind, randomised, placebo-controlled, phase 3 trial, done at 78 centres in the UK. Eligibility criteria were newly diagnosed, pathologically confirmed NSCLC; stage IIIb or IV; chemotherapy naive; no symptomatic brain metastases; deemed unsuitable for chemotherapy because of poor (≥2) Eastern Cooperative Oncology Group performance status or presence of several comorbidities, or both; and estimated life expectancy of at least 8 weeks. Patients were randomly assigned (by phone call, in a 1:1 ratio, stratified by disease stage, performance status, smoking history, and centre, block size 10) to receive oral placebo or erlotinib (150 mg per day) until disease progression or unacceptable toxicity. Investigators, clinicians, and patients were masked to assignment. The primary endpoint was overall survival. Analyses were by intention to treat, and prespecified subgroup analyses included development of a rash due to erlotinib within 28 days of starting treatment. This study is registered, number ISRCTN 77383050. Between April 14, 2005, and April 1, 2009, we randomly assigned 350 patients to receive erlotinib and 320 to receive placebo. We followed up patients until March 31, 2011. 657 patients died; median overall survival did not differ between groups (erlotinib, 3·7 months, 95% CI 3·2–4·2, vs placebo, 3·6 months, 3·2–3·9; unadjusted hazard ratio [HR] 0·94, 95% CI 0·81–1·10, p=0·46). 59% (178 of 302) of patients assigned erlotinib and who were assessable at 1 month developed first-cycle rash, which was the only independent factor associated with overall survival. Patients with first-cycle rash had better overall survival (HR 0·76, 95% CI 0·63–0·92, p=0·0058), compared with placebo. Compared with placebo, overall survival seemed to be worse in the group that did not develop first-cycle rash (1·30, 1·05–1·61, p=0·017). Grade 3 or 4 diarrhoea was more common with erlotinib than placebo (8% [28 of 334] vs 1% [four of 313], p=0·0001), as was high-grade rash (23% [79 of 334] vs 2% [five of 313], p<0·0001); other adverse events were much the same between groups. Patients with NSCLC who are deemed unsuitable for chemotherapy could be given erlotinib. Patients who develop a first-cycle rash should continue to receive erlotinib, whereas those who do not have a rash after 28 days should discontinue erlotinib, because of the possibility of decreased survival. Cancer Research UK, Roche.

The corrosion resistance of anodized and composite‐coated aluminum alloys is rigorously examined in this review with an emphasis on the 5xxx and 6xxx series, which are extensively utilized in the transportation and structural industries. The study starts with a historical review of corrosion prevention before delving into the development and fundamental ideas of anodization and describing the impact of important operational factors, such as alloy composition, post‐treatment techniques, anodization time, and current density. The cutting‐edge techniques, such as multistep anodization and plasma electrolytic oxidation (PEO), improve the oxide layer, enhancing corrosion potentials augmented by +200 to +400 mV, and impedance values exceeding 10 6 Ω·cm 2 . In addition, a critical review is conducted on how different electrolytes and their concentrations can be used to customize corrosion performance. When combined with anodized substrates, composite coatings, an emerging class of surface protection, are evaluated for their synergistic activity. Composite coatings that integrate graphene, MXenes, and h‐BN significantly improve barrier efficacy, achieving corrosion inhibition efficiencies up to 99% and ensuring an enhancement in adhesion strength by 30%–40%. The study highlights important obstacles to developing long‐lasting, eco‐friendly, and alloy‐specific protection techniques. A forward‐looking viewpoint highlights the need for multifunctional coatings, complex characterization, and predictive modeling, which are being investigated to optimize performance in real‐world situations.

Cediranib, an oral pan-vascular endothelial growth factor (VEGF) receptor tyrosine kinase inhibitor, failed to show benefit over lomustine in relapsed glioblastoma. One resistance mechanism for cediranib is up-regulation of epidermal growth factor receptor (EGFR). This study aimed to determine if dual therapy with cediranib and the oral EGFR inhibitor gefitinib improved outcome in recurrent glioblastoma. This was a multi-center randomized, two-armed, double-blinded phase II study comparing cediranib plus gefitinib versus cediranib plus placebo in subjects with first relapse/first progression of glioblastoma following surgery and chemoradiotherapy. The primary outcome measure was progression free survival (PFS). Secondary outcome measures included overall survival (OS) and radiologic response rate. Recruitment was terminated early following suspension of the cediranib program. 38 subjects (112 planned) were enrolled with 19 subjects in each treatment arm. Median PFS with cediranib plus gefitinib was 3.6 months compared to 2.8 months for cediranib plus placebo (HR; 0.72, 90% CI; 0.41 to 1.26). Median OS was 7.2 months with cediranib plus gefitinib and 5.5 months with cediranib plus placebo (HR; 0.68, 90% CI; 0.39 to 1.19). Eight subjects (42%) had a partial response in the cediranib plus gefitinib arm versus five patients (26%) in the cediranib plus placebo arm. Cediranib and gefitinib in combination is tolerated in patients with glioblastoma. Incomplete recruitment led to the study being underpowered. However, a trend towards improved survival and response rates with the addition of gefitinib to cediranib was observed. Further studies of the combination incorporating EGFR and VEGF inhibition are warranted. ClinicalTrials.gov NCT01310855.

Traditional tracking devices for solar energy applications have several disadvantages, such as bulky mechanical structure, large wind loads, and ease of misalignment. This study aims to design a flat, thin, and adaptive beam steering device to eliminate these drawbacks. A proof of concept device was fabricated to demonstrate this design. The novelty of the proof of concept device is the hexagonal structure of the electrowetting cell design. The hexagonal cell was dosed with two immiscible liquids with different refractive indices. The hypothesis of this design is that by deforming the liquid shape with the application of voltage, light can be steered and concentrated for solar energy applications. A maximum contact angle change of 44° was observed with the application of 26 V to one of the electrodes of the hexagonal cell. The device demonstrated a 4.5° change of laser beam path with only a 0.2 refractive index difference of the liquids. The 3D simulation model developed in this study shows that a tilted and flat interface can be achieved using higher dielectric constant dielectric materials. The device can facilitate the planer steering and concentration of sunlight for rooftop applications without moving mechanical parts.

Background Assessing the long term effects of many surgical interventions tested in pragmatic RCTs may require extended periods of participant follow-up to assess effectiveness and use patient-reported outcomes that require large sample sizes. Consequently the RCTs are often perceived as being expensive and time-consuming, particularly if the results show the test intervention is not effective. Adaptive, and particularly group sequential, designs have great potential to improve the efficiency and cost of testing new and existing surgical interventions. As a means to assess the potential utility of group sequential designs, we re-analyse data from a number of recent high-profile RCTs and assess whether using such a design would have caused the trial to stop early. Methods Many pragmatic RCTs monitor participants at a number of occasions (e.g. at 6, 12 and 24 months after surgery) during follow-up as a means to assess recovery and also to keep participants engaged with the trial process. Conventionally one of the outcomes is selected as the primary (final) outcome, for clinical reasons, with others designated as either early or late outcomes. In such settings, novel group sequential designs that use data from not only the final outcome but also from early outcomes at interim analyses can be used to inform stopping decisions. We describe data from seven recent surgical RCTs (WAT, DRAFFT, WOLLF, FASHION, CSAW, FIXDT, TOPKAT), and outline possible group sequential designs that could plausibly have been proposed at the design stage. We then simulate how these group sequential designs could have proceeded, by using the observed data and dates to replicate how information could have accumulated and decisions been made for each RCT. Results The results of the simulated group sequential designs showed that for two of the RCTs it was highly likely that they would have stopped for futility at interim analyses, potentially saving considerable time (15 and 23 months) and costs and avoiding patients being exposed to interventions that were either ineffective or no better than standard care. We discuss the characteristics of RCTs that are important in order to use the methodology we describe, particularly the value of early outcomes and the window of opportunity when early stopping decisions can be made and how it is related to the length of recruitment period and follow-up. Conclusions The results for five of the RCTs tested showed that group sequential designs using early outcome data would have been feasible and likely to provide designs that were at least as efficient, and possibly more efficient, than the original fixed sample size designs. In general, the amount of information provided by the early outcomes was surprisingly large, due to the strength of correlations with the primary outcome. This suggests that the methods described here are likely to provide benefits more generally across the range of surgical trials and more widely in other application areas where trial designs, outcomes and follow-up patterns are structured and behave similarly.

IntroductionPain and disability after meniscectomy can be a substantial lifelong problem. There are few treatment options, especially for young people. Non-surgical management (rehabilitation) is an option but increasingly surgeons are performing meniscal allograft transplants (MATs) for these individuals. However, this is still an uncommon procedure, and availability and usage of MAT vary widely both in the UK and internationally. It is not known which treatment option is the most effective and cost-effective.Methods and analysisThe Meniscal Transplant surgery or Optimised Rehabilitation trial is an international, multicentre, randomised controlled trial. The aim is to compare the clinical and cost effectiveness of MAT versus an optimised package of individualised, progressive, rehabilitation that we have called personalised knee therapy (PKT).Participants will be recruited from sites across the UK, Australia, Canada and Belgium. The planned 144 participants provide at least 90% power to detect a 10-point difference in the Knee injury and Osteoarthritis Outcome Score (KOOS4) at 24-months post randomisation (primary outcome). A prospectively planned economic evaluation will be conducted from a healthcare system and personal social services perspective. Secondary outcome data including health utility, occupational status, sports participation, mental well-being, further treatment, and adverse events will be collected at 3, 6, 12, 18, and 24 months. Analysis will be on an intention-to-treat basis and reported in-line with the Consolidated Standards of Reporting Trials statement.Ethics and disseminationThe trial was approved by the London—Bloomsbury Research Ethics Committee on 19 August 2022 (22/LO/0327) and Northern Sydney Local Health District Human Research Ethics Committee, NSW, Australia on the 13 March 2023 (2022/ETH01890).Trial results will be disseminated via peer-reviewed publications, presentations at international conferences, in lay summaries and using social media as appropriate.This protocol adheres to the recommended Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) checklist.Trial registration number ISRCTN87336549.