Dental adhesives are vital for the success of dental restorations. The objective of this study is to make strong and durable dental adhesives that are free from 2 symbolic methacrylate-based dental ...resins—2-bis4-(2-hydroxy-3-methacryl-oxypropoxy)-phenyl-propane (Bis-GMA) and 2-hydroxyethyl-methacrylate (HEMA)—and have equivalent/improved bonding strength and durability. We formulated, prepared, and evaluated 2 dental adhesives using mixtures of a hydrolytically stable ether-based monomer, triethylene glycol divinylbenzyl ether (TEG-DVBE), with urethane dimethacrylate (UDMA) or pyromellitic glycerol dimethacrylate. These adhesives were composed of equimolar ester-/ether-based vinyl functional groups. They were compared with Bis-GMA/HEMA-based commercial and experimental dental adhesives in terms of shear bond strength and microtensile bond strength (µTBS) to human dentin and the µTBS bond stability under extended thermocycling challenges. In addition, the resins’ infiltration to dentin tubules, mechanical performance, and chemical properties were assessed by scanning electron microscopy, ISO standard flexural strength and modulus measurements, contact angle measurements, and water sorption/solubility measurements. The hybrid TEG-DVBE-containing dental adhesives generated equivalent shear bond strength and µTBS in comparison with the controls. Significantly, these adhesives outperformed the controls after being challenged by 10,000 thermocycles between 5 °C and 55 °C. Water contact angle measurements suggested that the hybrid dental adhesives were relatively more hydrophobic than the Bis-GMA/HEMA controls. However, both TEG-DVBE-containing adhesives developed more and deeper resin tags in dentin tubules and formed thicker hybrid layers at the composite-dentin interface. Furthermore, the water solubility of UDMA/TEG-DVBE resins was reduced approximately 89% in comparison with the Bis-GMA/HEMA controls. The relatively hydrophobic adhesives that achieved equivalent/enhanced bonding performance suggest great potentials in developing dental restoration with extended service life. Furthermore, the TEG-DVBE-containing materials may find wider dental applications and broader utility in medical device development.
Acute rheumatic fever (ARF) is an acute inflammatory process resulting in rheumatic carditis, one of the most common acquired heart diseases in youth. Among the clinical manifestations of carditis, ...pathologic valve regurgitation and atrioventricular block are included in the criteria for the diagnosis of ARF. Besides atrioventricular block, ARF may often present with other arrhythmias, such as junctional tachycardia (JT). However, JT is currently not recognized as a criterion for the diagnosis of ARF. Three adolescents presented in our hospital with JT, polyarthralgia, and laboratory signs of inflammation with evidence of preceding group A
infection. None of the patients fulfilled the diagnostic criteria of ARF. On the basis of the presumed diagnosis of ARF, all 3 patients were treated with intravenous steroids. Steroid therapy was given, and JT converted to sinus rhythm within an average of 62 hours. Subsequent electrocardiograms revealed variable degree of atrioventricular block in all 3 patients, providing clinical evidence and fulfilling the diagnostic criteria of ARF. Patients were monitored for a total 2 to 8 days before discharge on standard antiinflammatory treatment. Follow-up electrocardiograms and Holter monitoring revealed resolution of the atrioventricular block and lack of JT recurrence in all patients. On the basis of these sentinel cases, we propose that JT should be included as a diagnostic criterion for the diagnosis of ARF.
Summary
Background The tumour necrosis factor‐α antagonist etanercept and the interleukin (IL)‐12/23p40 antagonist ustekinumab have been shown to be effective psoriasis therapies. The IL‐12/23p40 ...antagonist briakinumab was shown to be effective psoriasis treatment in a phase II study.
Objectives To assess the efficacy, safety and tolerability of briakinumab compared with etanercept and placebo in patients with moderate to severe psoriasis.
Methods Three hundred and fifty patients were enrolled in this phase III, 12‐week study (M10‐315, NCT00710580) and randomized in the following 2:2:1 ratio: 139 patients received 200 mg briakinumab at weeks 0 and 4 followed by 100 mg briakinumab at week 8; 139 patients received 50 mg of etanercept twice weekly 3–4 days apart at weeks 0–11; 72 patients received placebo injections matching active treatment. The co‐primary efficacy endpoints were the proportion of patients achieving a Physician’s Global Assessment (PGA) of 0/1 at week 12, and the proportion of patients achieving a Psoriasis Area and Severity Index (PASI) 75 response at week 12.
Results Of the briakinumab‐treated patients, 72·7% achieved a PGA of 0/1 at week 12 as compared with 29·5% of etanercept‐treated patients and 4·2% of placebo‐treated patients (P < 0·001, for both comparisons). Of the briakinumab‐treated patients, 80·6% achieved a PASI 75 response at week 12 as compared with 39·6% of etanercept‐treated and 6·9% of placebo‐treated patients (P < 0·001, for both comparisons). Serious adverse events were reported in two (1·4%) briakinumab‐treated patients, one (0·7%) etanercept‐treated patient and two (2·8%) placebo‐treated patients.
Conclusions In patients with moderate to severe psoriasis, briakinumab had superior efficacy to both placebo and etanercept at 12 weeks as administered in this study.
Fast microtomography combined with local crack driving force analysis has been employed to analyze crack-tip stress/strain singularities in an aluminum alloy. The application of fast microtomography ...has made it possible to observe real crack initiation and propagation behaviors without intermediate unloading. The details of a crack and its local propagation behaviors are readily observed with this technique along with evidence of microstructure/crack interactions. After a preliminary investigation of the achieved spatial resolution, we show that conventional stationary and growing crack singularities can be quantitatively validated by deriving the local crack opening displacement. This is to our knowledge the first three-dimensional validation of conventional fracture mechanics during a real time continuous experiment that has been mainly developed via surface observations so far. We also reveal that there is a spatial transition from a stationary crack singularity to a growing crack singularity in addition to the well-known temporal transition that occurs with the onset of crack propagation. Local crack propagation behaviors are also discussed on the basis of this validation. To separate the effects of complex crack geometry from those of microstructure, we also perform an image-based numerical simulation.
Background Tumor necrosis factor (TNF) antagonists have improved outcomes for patients with psoriasis, but some patients are unresponsive to treatment (primary failure) or lose an initially effective ...response (secondary failure). Objective We sought to systematically investigate the efficacy and safety of a second TNF antagonist after failure of a first TNF antagonist. Methods Published primary studies evaluating the efficacy of switching TNF antagonists after failure were systematically extracted. Results Fifteen studies were included. Although response rates to a second TNF antagonist were lower than for a first, a substantial proportion of patients in every study achieved treatment success. Week-24 response rates for a second antagonist were 30% to 74% for a 75% improvement in Psoriasis Area and Severity Index score and 20% to 70% for achieving a Physician Global Assessment score of 0/1; mean improvements in Dermatology Life Quality Index ranged from −3.5 to −13. In general, patients who experienced secondary failure achieved better responses than patients with primary failure. Adverse event incidences ranged from 20% to 71%, without unexpected adverse events; 0% to 11% of patients experienced serious adverse events. Limitations There was no common definition of treatment failure across these studies of varied design. Conclusions Some patients benefit from switching to a second TNF antagonist after failure of a first TNF antagonist, with improved quality of life.
In this study, we investigated the differences in physical activity before and after transplantation, and the relationship between physical activity and physical function and health‐related quality ...of life (QOL) in 30 patients who underwent allogeneic haematopoietic stem cell transplantation (allo‐HSCT). Duration and intensity of physical activity were quantified using a three‐dimensional accelerometer. Physical function was quantified by handgrip and knee‐extensor strength, with the 6‐minute walk test (6MWT) used as a measure of exercise capacity. Health‐related QOL was assessed using the 36‐item Short‐Form Health Survey. The proportion of daily activities performed at an intensity >3.0 metabolic equivalents (METs) increased significantly after allo‐HSCT (p < .05). Daily activity time performed at an intensity of 1.6–2.9 METs significantly correlated only with left knee strength (p < .05). In contrast, the total number of daily steps and the proportion of activity performed at 1.6–2.9 METs and >3.0 METs were positively correlated with the 6MWT (p < .05). Additionally, physical functioning and general health subscales in health‐related QOL positively correlated with daily activities performed at >3.0 METs (p < .05). Physical activity was associated with 6MWT and health‐related QOL. These findings have implications for rehabilitation planning for patients undergoing allo‐HSCT.
In this paper, we propose and evaluate six methods for the segmentation of skin lesions in dermoscopic images. This set includes some state of the art techniques which have been successfully used in ...many medical imaging problems (gradient vector flow (GVF) and the level set method of Chan et al.(C-LS). It also includes a set of methods developed by the authors which were tailored to this particular application (adaptive thresholding (AT), adaptive snake (AS), EM level set (EM-LS), and fuzzy-based split-and-merge algorithm (FBSM). The segmentation methods were applied to 100 dermoscopic images and evaluated with four different metrics, using the segmentation result obtained by an experienced dermatologist as the ground truth. The best results were obtained by the AS and EM-LS methods, which are semi-supervised methods. The best fully automatic method was FBSM, with results only slightly worse than AS and EM-LS.
Summary
Background
Phase III studies showed that some patients maintained response for ≥ 6 months following ustekinumab discontinuation.
Objectives
To assess clinical responses with extended ...ustekinumab maintenance dosing intervals.
Methods
Adults with moderate‐to‐severe plaque psoriasis received ustekinumab at weeks 0, 4 and 16 during open‐label treatment. Patients achieving a week‐28 Physician's Global Assessment (PGA) score of cleared/minimal (PGA = 0/1) were randomized 1 : 4 to group 1 approved every 12 weeks (q12 wk) maintenance or group 2 (q12–24 wk; response‐based dosing determined by time to loss of PGA = 0/1). Key end points included the number of visits with PGA = 0/1 (primary end point) and ≥ 75% improvement in Psoriasis Area and Severity Index (PASI 75) between weeks 88 and 112, and PGA/PASI responses between weeks 28 and 112.
Results
Overall, 378 patients achieved PGA = 0/1 at week 28 and were randomized to group 1 (n = 76) or group 2 (n = 302). Patients in group 1 had numerically greater mean numbers of visits with PGA = 0/1 than group 2 and also with PASI 75 from week 88 to 112. A higher proportion of patients in group 1 (55%) than group 2 (39%) had PGA = 0/1 at all seven visits from week 88 to 112. Maintenance of response was observed with dose‐interval extension beyond q12 wk in a subset of patients. Extending the dosing interval did not affect antibody development or safety.
Conclusions
Efficacy was better maintained among week‐28 PGA responders randomized to continue q12 wk ustekinumab vs. extending maintenance dosing based on clinical response, although some patients maintained high levels of efficacy with up to q24 wk dosing.
What's already known about this topic?
Ustekinumab maintenance doses are typically administered every 12 weeks, although earlier studies and clinical practice suggest that some patients may maintain high levels of efficacy with extended dosing intervals.
What does this study add?
Patients better maintained higher levels of efficacy when ustekinumab was given every 12 weeks compared with longer dosing intervals.
A subset of patients, however, continued to achieve high levels of efficacy with dosing intervals as long as every 24 weeks.
Overall, these findings further our understanding of clinical response to ustekinumab in patients with moderate‐to‐severe psoriasis.
Respond to this article
It is unclear whether primary efficacy outcomes in plaque psoriasis clinical trials represent residual disease during treatment.
To evaluate supplementing dichotomous efficacy with residual disease ...activity.
This post hoc analysis used pooled, patient-level data after tildrakizumab 100 mg (N = 616) or placebo (N = 309) treatment from reSURFACE 1/2 (NCT01722331/NCT01729754) phase 3 clinical trials of patients with moderate to severe plaque psoriasis.
Median baseline Psoriasis Area and Severity Index (PASI) was 17.9 for patients receiving tildrakizumab 100 mg. At Week 12, median PASI was 2.9, whereas dichotomous PASI 90 response rate was 36.9%, and absolute PASI <5.0, <3.0, and <1.0 were 64.0%, 50.8%, and 23.3%, respectively. At Week 28, median PASI was 1.7, whereas PASI 90 response rate was 51.9%, and absolute PASI <5.0, <3.0, and <1.0 were 75.3%, 62.8%, and 38.0%, respectively. Dermatology Life Quality Index and PASI scores were correlated through Week 28 (r = 0.51, p ≤ .0001).
Disease activity was more reliably estimated by PASI scores than percentage PASI improvement; this may partially explain efficacy disparities between clinical trials and practice. These results suggest supplementing dichotomous PASI improvement with PASI scores and consideration of patient treatment goals could facilitate clinical decisions.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
PDF
