Secukinumab demonstrates high sustained efficacy and a favourable safety profile in patients with moderate-to-severe psoriasis through 5 years of treatment (SCULPTURE Extension Study).

BACKGROUND: Secukinumab, a fully human monoclonal antibody that selectively neutralizes IL-17A, has been shown to have significant efficacy and a favourable safety profile in the treatment of moderate-to-severe psoriasis and psoriatic arthritis. OBJECTIVE: To assess the efficacy and safety of secukinumab through 5 years of treatment in moderate-to-severe psoriasis. METHODS: In the core SCULPTURE study, Psoriasis Area and Severity Index (PASI) 75 responders at Week 12 continued receiving subcutaneous secukinumab until Year 1. Thereafter, patients entered the extension phase and continued treatment as per the core trial. Treatment was double-blinded until the end of Year 3 and open-label from Year 4. Here, we focus on the 300 mg fixed-interval (every 4 weeks) treatment, the recommended per label dose. Efficacy data are primarily reported as observed, but multiple imputation (MI) and last observation carried forward (LOCF) techniques were also undertaken as supportive analyses. RESULTS: At Year 1, 168 patients entered the extension study and at the end of Year 5, 126 patients completed 300 mg (every 4 weeks) treatment. PASI 75/90/100 responses at Year 1 (88.9%, 68.5% and 43.8%, respectively) were sustained to Year 5 (88.5%, 66.4% and 41%). PASI responses were consistent regardless of the analysis undertaken (as observed, MI, or LOCF). The average improvement in mean PASI was approximately 90% through 5 years compared with core study baseline. DLQI (dermatology life quality index) 0/1 response also sustained through 5 years (72.7% at Year 1 and 65.5% at Year 5). The safety profile of secukinumab remained favourable, with no cumulative or unexpected safety concerns identified. CONCLUSION: Secukinumab 300 mg treatment delivered high and sustained levels of skin clearance and improved quality of life through 5 years in patients with moderate-to-severe psoriasis. Favourable safety established in the secukinumab phase 2/3 programme was maintained through 5 years.

Annihilation of exceptional points from different Dirac valleys in a 2D photonic system.

Topological physics relies on Hamiltonian's eigenstate singularities carrying topological charges, such as Dirac points, and - in non-Hermitian systems - exceptional points (EPs), lines or surfaces. So far, the reported non-Hermitian topological transitions were related to the creation of a pair of EPs connected by a Fermi arc out of a single Dirac point by increasing non-Hermiticity. Such EPs can annihilate by reducing non-Hermiticity. Here, we demonstrate experimentally that an increase of non-Hermiticity can lead to the annihilation of EPs issued from different Dirac points (valleys). The studied platform is a liquid crystal microcavity with voltage-controlled birefringence and TE-TM photonic spin-orbit-coupling. Non-Hermiticity is provided by polarization-dependent losses. By increasing the non-Hermiticity degree, we control the position of the EPs. After the intervalley annihilation, the system becomes free of any band singularity. Our results open the field of non-Hermitian valley-physics and illustrate connections between Hermitian topology and non-Hermitian phase transitions.

The influence of surface standardization of lithium disilicate glass ceramic on bond strength to a dual resin cement.

In vitro studies to assess bond strength between resins and ceramics have used surfaces that have been ground flat to ensure standardization; however, in patients, ceramic surfaces are irregular. The effect of a polished and unpolished ceramic on bond strength needs to be investigated. Sixty ceramic specimens (20×5×2 mm) were made and divided into two groups. One group was ground with 220- to 2000-grit wet silicon carbide paper and polished with 3-, 1-, and »-µm diamond paste; the other group was neither ground nor polished. Each group was divided into three subgroups: treated polished controls (PC) and untreated unpolished controls (UPC), polished (PE) and unpolished specimens (UPE) etched with hydrofluoric acid, and polished (PS) and unpolished specimens (UPS) sandblasted with alumina. Resin cement cylinders were built over each specimen. Shear bond strength was measured, and the fractured site was analyzed. Analysis of variance (ANOVA) and Tukey post hoc tests were performed. PE (44.47 ± 5.91 MPa) and UPE (39.70 ± 5.46 MPa) had the highest mean bond strength. PS (31.05 ± 8.81 MPa), UPC (29.11 ± 8.11 MPa), and UPS (26.41 ± 7.31 MPa) were statistically similar, and PC (24.96 ± 8.17 MPa) was the lowest. Hydrofluoric acid provides the highest bond strength regardless of whether the surface is polished or not.

Extravasation (Paravasation) of Chemotherapy Drugs - Recommendations for Standard Care in the Czech Republic based on Consolations between Representatives of the Supportive Care Group of the Czech Society for Oncology, Oncology Section of the Czech Nurses Association, and the Society for Ports and Permanent Catheters.

BACKGROUND: Extravasation (paravasation) of chemotherapy drugs is a very significant complication in the treatment of cancer patients. Preventive and therapeutic interventions reduce the risk of this complication or the extent of its consequences. A working group of authors from expert groups prepared recommendations for standard care. PURPOSE: To prepare a basic summary of recommended interventions for daily practice, based on knowledge from long-term, proven, evidence-based practice or on consensus opinions of representatives of expert groups. RESULTS: Preventive measures are essential and include early consideration of long-term venous access device indications, choice of injection site, venous line control before each chemotherapy drug application, and patient education. Interventions in cases of extravasation mainly involve the application of antidotes (dimethylsulfoxide, hyaluronidase, and dexrazoxane) and the application of dry cold or heat, depending on the type of cytostatic drug. Corticosteroids injected subcutaneously, moist heat or cooling, and compression, are not recommended. CONCLUSION: The recommended procedures will contribute to reducing the risk and consequences of extravasation. The range of recommended interventions can be expanded depending on individual clinical workplace policy and needs. The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers. Submitted: 28. 9. 2019 Accepted: 13. 10. 2019.

Effect of Chlorhexidine Treatment Prior to Fiber Post Cementation on Long-Term Resin Cement Bond Strength.

The purpose of this study was to evaluate the push-out bond strength of two different adhesive cements (total etch and self-adhesive) for glass fiber post (GFP) cementation in simulated, long-term service (thermocycling) when the root canal is treated with chlorhexidine before cementation. One hundred twenty premolar specimens with a single root canal were selected, endodontically treated, and shaped for GFP cementation (n=120). The specimens were randomly placed into one of 12 groups (10 specimens each) according to cement (T = total-etch RelyX ARC or S = self-adhesive RelyX Unicem), treatment with chlorhexidine (N or Y: without or with), and number of thermal cycles (00, 20, or 40: 0, or 20,000 or 40,000 cycles): 1. TN00, 2. TN20, 3. TN40, 4. TY00, 5. TY20, 6. TY40, 7. SN00, 8. SN20, 9. SN40, 10. SY00, 11. SY20, 12. SY40. The root of each specimen was cut perpendicular to the vertical axis, yielding six 1.0 mm-thick sections. A push-out bond strength test was performed followed by statistical analysis using a factorial analysis of variance. Pairwise comparisons of significant factor interactions were adjusted using the Tukey test. Significant differences of push-out bond strengths were found in the four main effects (resin cement [ p<0.0001], treatment with chlorhexidine [ p<0.0001], number of cycles [ p<0.0001], and root third [ p<0.0001]) and all interactions ( p<0.05 for all). Both resin cements produced higher bond strength in the cervical third followed by the middle third, and lower values were detected in the apical third. Additionally, the results suggest that the use of an additional disinfection treatment with chlorhexidine before the cement application produced the highest push-out bond strength regardless of root third. Further, the thermocycling simulation decreased the bond strength for both resin cements long-term when the chlorhexidine was not applied before cementation. However, when the root canal was treated with chlorhexidine and the fiber post was cemented with self-adhesive cement, the bond strength increased after 0, 20,000 and 40,000 cycles.

Marginal Adaptation and Quality of Interfaces in Lithium Disilicate Crowns - Influence of Manufacturing and Cementation Techniques.

PURPOSE: To evaluate the cement line thickness and the interface quality in milled or injected lithium disilicate ceramic restorations and their influence on marginal adaptation using different cement types and different adhesive cementation techniques. METHODS AND MATERIALS: Sixty-four bovine teeth were prepared for full crown restoration (7.0±0.5 mm in height, 8.0 mm in cervical diameter, and 4.2 mm in incisal diameter) and were divided into two groups: CAD/CAM automation technology, IPS e.max CAD (CAD), and isostatic injection by heat technology, IPS e.max Press (PRESS). RelyX ARC (ARC) and RelyX U200 resin cements were used as luting agents in two activation methods: initial self-activation and light pre-activation for one second (tack-cure). Next, the specimens were stored in distilled water at 23°C ± 2°C for 72 hours. The cement line thickness was measured in micrometers, and the interface quality received scores according to the characteristics and sealing aspects. The evaluations were performed with an optical microscope, and scanning electron microscope images were presented to demonstrate the various features found in the cement line. For the cement line thickness, data were analyzed with three-way analysis of variance (ANOVA) and the Games-Howell test (α=0.05). For the variable interface quality, the data were analyzed with the Mann-Whitney U-test, the Kruskal-Wallis test, and multiple comparisons nonparametric Dunn test (α=0.05). RESULTS: The ANOVA presented statistical differences among the ceramic restoration manufacturing methods as well as a significant interaction between the manufacturing methods and types of cement (p<0.05). The U200 presented lower cement line thickness values when compared to the ARC with both cementation techniques (p<0.05). With regard to the interface quality, the Mann-Whitney U-test and the Kruskal-Wallis test demonstrated statistical differences between the ceramic restoration manufacturing methods and cementation techniques. The PRESS ceramics obtained lower scores than did the CAD ceramics when using ARC cement (p<0.05). CONCLUSIONS: Milled restorations cemented with self-adhesive resin cement resulted in a thinner cement line that is statistically different from that of CAD or pressed ceramics cemented with resin cement with adhesive application. No difference between one-second tack-cure and self-activation was noted.

Push-Out Bond Strength Evaluation of Glass Fiber Posts With Different Resin Cements and Application Techniques.

The purpose of this study was to evaluate the push-out strength of two different adhesive cements (total etch and self-adhesive) for glass fiber post (GFP) cementation using two different techniques (microbrush and elongation tip) of cement application. In addition, this study evaluated the effect of total-etch conditioning before the use of a self-adhesive cement. Sixty premolar specimens with a single root canal were selected, endodontically treated, and shaped for GFP cementation. The specimens were randomly placed into one of six groups according to the cement and technique used: RelyX ARC (ARC): ARC + microbrush, ARC + elongation tip; RelyX Unicem (RU): RU + microbrush, RU + elongation tip; or RelyX Unicem + 37% phosphoric acid (RUE): RUE + microbrush, RUE + elongation tip. Each specimen root was cut perpendicular to the vertical axis yielding six 1.0-mm-thick sections. Push-out strength test was performed, followed by statistical analysis using three-way analysis of variance and the Games-Howell test (p<0.05). Statistically significant differences between the groups were found (p< 0.05). The cervical third of the roots had the highest mean push-out strength values, while the apical third had the lowest mean values regardless of the technique used. The elongation technique produced higher mean push-out strength values compared to the microbrush technique. The self-etch adhesive cement had the highest mean push-out strength value in all thirds. The addition of a conditioning step before the self-etch adhesive cementation appears to be effective in enhancing push-out strength with GFPs.

Bradykinin analogues containing N alpha-methyl amino acids.

Analogues of bradykinin were synthesized containing single substitutions by N alpha-methyl amino acids in the 1, 4, 5, 5, and 9 positions. [MeArg]Bradykinin possessed 60% of the muscle-contracting activity of the parent compound in a guinea pig ileum assay. The other analogues were very weak agonists (less than 2%) and, disappointingly, failed to show blocking activity except at very high doses.

Accuracy of pedicle screw placement in lumbar fusions by plain radiographs and computed tomography.

STUDY DESIGN: Postoperative radiographs and computed tomography scans were used to evaluate 74 pedicle screws in 16 consecutive patients who underwent lumbar spine fusion with pedicle screw fixation. OBJECTIVE: To evaluate pedicle screw placement using plain radiographs versus computed tomographic scans. SUMMARY OF BACKGROUND DATA: Plain radiographs are the primary means of assessing pedicle screw placement. Comparison of plain radiographs and computed tomography has not been done. METHODS: Screws were graded as IN, OUT, or QUESTIONABLE; the direction of misplacement was noted. All evaluations were performed independently by three observers. RESULTS: Fewer screws were clearly within the pedicle on computed tomography when compared with plain radiographs. Computed tomography showed 10 times as many screws violating the medial cortex as did radiographs. Interobserver differences were not statistically significant. Intraobserver differences approached statistical significance when the two tests were compared. No recognized neurologic complications resulted from pedicle screw placement. CONCLUSIONS: Plain radiographs alone may not accurately reveal pedicle screw placement. Plain radiographs and thin section computed tomographic scans should be used to evaluate postoperative neurologic deficits in patients undergoing instrumented lumbar spine fusion with pedicle screws.

Reversal of migration in the labor reserves of Zimbabwe? Prospects for change.

PIP: Changing patterns of migration in Zimbabwe over time are reviewed, with particular reference to rural-urban migration and the government's efforts to slow out-migration from rural areas. The author notes that the recently established resettlement schemes are achieving a level of success in lowering rates of out-migration. However, he also observes that adequate credit for the purchase of equipment and cattle is necessary if out-migration is to be reduced.^ieng

Migration dynamics and development in rural South Africa: demographic and socioeconomic perspectives.

"This paper addresses five key questions related to migration dynamics and development in rural South Africa: (1) Which individual and household level factors are particularly important in understanding migration patterns? (2) Taken together, are sociodemographic or socioeconomic factors more influential? (3) Do present patterns of migration and remittance flows reflect strategies that connote survival, or do they represent household efforts to advance their well-being and their position in society? (4) Which segments of the population appear to gain or lose from contemporary patterns of migration and remittance flows? and (5) How might remittances shape trends in local level development and equality, or inequality?... The data source is the nationwide representative sample survey ¿Project for Statistics on Living Standards and Development' undertaken in the latter part of 1993."

Effects of preheating and precooling on the hardness and shrinkage of a composite resin cured with QTH and LED.

The aim of this study was to evaluate in vitro the hardness and shrinkage of a pre-cooled or preheated hybrid composite resin cured by a quartz-tungsten-halogen light (QTH) and light-emitting diode (LED) curing units. The temperature on the tip of the devices was also investigated. Specimens of Charisma resin composite were produced with a metal mold kept under 37°C. The syringes were submitted to 4°C, 23°C, and 60°C (n=20) before light-curing, which was carried out with the Optilux 501 VCL and Elipar FreeLight 2 units for 20 seconds. The specimens were kept under 37°C in a high humidity condition and darkness for 48 hours. The Knoop hardness test was carried out with a 50 gram-force (gf) load for 10 seconds, and the measurement of the shrinkage gap was carried out using an optical microscope. The data were subjected to analysis of variance and the Games-Howell test (α=0.05). The mean hardness of the groups were similar, irrespective of the temperatures (p>0.05). For 4°C and 60°C, the top surface light-cured by LED presented significantly reduced shrinkage when compared with the bottom and to both surfaces cured by QTH (p<0.05). It was concluded that the hardness was not affected by pre-cooling or preheating. However, polymerization shrinkage was slightly affected by different pre-polymerization temperatures. The QTH-curing generated greater shrinkage than LED-curing only when the composite was preheated. Different temperatures did not affect the composite hardness and shrinkage when cured by a LED curing unit.