Network meta-analysis of biologic treatments for psoriasis using absolute Psoriasis Area and Severity Index values ≤1, 2, 3 or 5 derived from a statistical conversion method.

BACKGROUND: In practice, the goal of treatment for patients with psoriasis is to achieve almost clear or clear skin and maintain disease control, regardless of baseline disease severity. However, identifying absolute Psoriasis Area and Severity Index (PASI) values for new treatment goals is challenging, as most clinical trials report relative PASI 50, 75, 90 or 100 improvements but rarely absolute PASI values achieved. OBJECTIVE: Our objective was to illustrate a statistical conversion method that was developed to derive absolute PASI values from available clinical trial data on relative PASI improvements. The results of network meta-analyses (NMAs) based on these derived data were then compared with those of NMAs based on the corresponding relative PASI improvement data for selected biologics for moderate-to-severe psoriasis. METHODS: The PASI statistical conversion method was applied to relative PASI improvement data for 11 biologic treatment regimens and placebo at 12 weeks using data from 50 published studies. The respective proportions of patients reaching absolute PASI values ≤1, 2, 3 or 5 were then calculated. Frequentist NMAs (Rücker method) were subsequently used to compare efficacy results across relative and absolute PASI data. RESULTS: The ranking of included treatment regimens for patients achieving absolute PASI 0 to 8 was aligned with results for relative PASI scores (from 100 to 60) at end of induction therapy. Across the range of PASI scores considered, the most effective treatment regimens based on both absolute and relative PASI NMAs were brodalumab 210 mg every 2 weeks and ixekizumab 80 mg every 2 weeks, followed by guselkumab 100 mg every 8 weeks and risankizumab 150 mg every 12 weeks. CONCLUSION: Data generated using this mathematical model will be useful to inform ongoing scientific discussions on treatment goals in the absence of primary absolute PASI data for all available treatments for moderate-to-severe plaque psoriasis.

Matching-adjusted indirect comparison of efficacy in patients with moderate-to-severe plaque psoriasis treated with ixekizumab vs. secukinumab.

BACKGROUND: Head-to-head randomized studies comparing ixekizumab and secukinumab in the treatment of psoriasis are not available. OBJECTIVES: To assess efficacy and quality of life using matching-adjusted indirect comparisons for treatment with ixekizumab vs. secukinumab. METHODS: Psoriasis Area and Severity Index (PASI) improvement of at least 75%, 90% and 100% and Dermatology Life Quality Index (DLQI) 0/1 response rates for approved dosages of ixekizumab (160 mg at Week 0, then 80 mg every two weeks for the first 12 weeks) and secukinumab (300 mg at Weeks 0, 1, 2, 3 and 4, then 300 mg every 4 weeks) treatment were compared using data from active (etanercept and ustekinumab) and placebo-controlled studies. Comparisons were made using the Bucher (BU) method and two modified versions of the Signorovitch (SG) method (SG total and SG separate). Subsequently, results based on active treatment common comparators were combined using generic inverse-variance meta-analysis. RESULTS: In the meta-analysis of studies with active comparators, PASI 90 response rates were 12·7% [95% confidence interval (CI) 5·5-19·8, P = 0·0005], 10·0% (95% CI 2·1-18·0, P = 0·01) and 11·2% (95% CI 3·2-19·1, P = 0·006) higher and PASI 100 response rates were 11·7% (95% CI 5·9-17·5, P < 0·001), 12·7% (95% CI 6·0-19·4, P < 0·001) and 13·1% (95% CI 6·3-19·9, P < 0·001) higher for ixekizumab compared with secukinumab using BU, SG total and SG separate methods. PASI 75 results were comparable when SG methods were used and favoured ixekizumab when the BU method was used. Week 12 DLQI 0/1 response rates did not differ significantly. CONCLUSIONS: Ixekizumab had higher PASI 90 and PASI 100 responses at week 12 compared with secukinumab using adjusted indirect comparisons.

Psychosocial impact, perceived stress and learning effect in undergraduate dental students during transition from pre-clinical to clinical education.

INTRODUCTION: This study aimed to develop a suitable instrument for a comprehensive quantitative and qualitative assessment of perceived psychosocial impact, levels of stress and learning effect in undergraduate dental students during the transition from pre-clinical to clinical education. These findings might improve curricular structures and didactic organisation during this period. MATERIALS AND METHODS: At the beginning of their first clinical year, undergraduate dental students were asked to complete an anonymous forty-item questionnaire. Two hundred and seventy-six undergraduate dental students were willing to participate and completed the questionnaire and participated during the years 2011-2016. RESULTS: The response rate was between 45% and 96%. Correlational analysis (Spearman-Rho) in the field of psychosocial impact showed the dental teacher to be the most important multiplier of students' feelings. If the students feel that their teacher acts cooperatively, positive items increase and negative items decrease significantly (P < .0001). Also, students who report high levels of stress are affected significantly in their psychosocial interaction (P < .0001). Wilcoxon test yielded highest levels of stress in endodontology during the first weeks (P < .0001). During the same period, the greatest learning increment was seen for diagnostics and caries excavation. CONCLUSION: In conclusion, teaching of undergraduate dental students during the transition period from pre-clinical to clinical education can be positively influenced by a supportive learning environment and by specific chronological modifications in the curriculum. Students should start their clinical training with diagnostics, preventive dentistry and initial periodontal treatment. Due to high levels of perceived stress, endodontology should be introduced later in the clinical curriculum.

Effect of enamel sealants on tooth bleaching and on the color stability of the result.

The purpose of this in vitro study was to evaluate the effect of enamel sealants on bleaching of natural teeth by use of 40 % hydrogen peroxide in a dental surgery. The color stability of the results from bleaching was, furthermore, determined 10 months after the bleaching procedure. In a standardized setting, four sealants (Pro Seal®, Light Bond™ Sealant, Protecto®, and Clinpro™ XT Varnish) were applied to and removed from human teeth in accordance with the manufacturer's instructions. Natural teeth served as medium; half of the teeth were sealed and the others served as controls. Hydrogen peroxide gel (40 %; Opalescence Boost; Ultradent Products, South Jordan, UT, USA) was used as bleaching agent. Color measurement was performed with a spectroradiometer (Photoresearch PR670) before the bleaching process (T1) and 24 h (T2) and 10 months (T3) after bleaching. The spectroradiometer results were expressed by use of the Commission Internationale de l'Éclairage (CIE) L*a*b* color notation. The L*, a*, and b* values of the sealed and the unsealed surfaces were not significantly different at any time during the study (p > 0.05), irrespective of the sealant used. Ten months after the bleaching process, mean L*, a*, and b* values were lower than at 1-day post-bleaching; the mean value of ΔE between 1-day post-bleaching and 10 months post-bleaching was 2.46 (±3.1). The results of the study suggest that the effectiveness of professional tooth whitening is not appreciably affected by the application of the four sealants tested.

Effect of endurance training on dental erosion, caries, and saliva.

The aim of this investigation was to give insights into the impact of endurance training on oral health, with regard to tooth erosion, caries, and salivary parameters. The study included 35 triathletes and 35 non-exercising controls. The clinical investigation comprised oral examination, assessment of oral status with special regard to caries and erosion, saliva testing during inactivity, and a self-administered questionnaire about eating, drinking, and oral hygiene behavior. In addition, athletes were asked about their training habits and intake of beverages and sports nutrition. For saliva assessment during exercise, a subsample of n = 15 athletes volunteered in an incremental running field test (IRFT). Athletes showed an increased risk for dental erosion (P = 0.001). No differences were observed with regard to caries prevalence and salivary parameters measured during inactivity between athletes and controls. Among athletes, a significant correlation was found between caries prevalence and the cumulative weekly training time (r = 0.347, P = 0.04). In athletes after IRFT and at maximum workload, saliva flow rates decreased (P = 0.001 stimulated; P = 0.01 unstimulated) and saliva pH increased significantly (P = 0.003). Higher risk for dental erosions, exercise-dependent caries risk, and load-dependent changes in saliva parameters point out the need for risk-adapted preventive dental concepts in the field of sports dentistry.

Diagnostic Value of the Basic Erosive Wear Examination for the Assessment of Dental Erosion on Patients, Dental Photographs, and Dental Casts.

OBJECTIVES: The aim of this trial was to investigate the diagnostic value of the basic erosive wear examination (BEWE) in clinical use, on dental photographs, and on dental casts over a two-year follow-up period (2013-2015). According to the main hypothesis for longitudinal monitoring of dental erosion, the BEWE is equally reproducible by the three assessment methods. METHODS AND MATERIALS: The clinical assessment included intraoral photographic documentation, dental impressions, oral examination, and assessment of BEWE. Clinical assessment of BEWE was done by one blinded examiner, whereas assessment on photographs and dental casts was performed by three calibrated examiners and repeated after 14 days. The three assessment methods were analyzed separately by longitudinal agreement and inter- and intrarater reliability (intraclass correlation coefficient) alongside 95% confidence intervals (CIs). RESULTS: Comparing the longitudinal data of the years 2013-2015, clinical use and photographs showed no significant difference (p=0.0681-0.9963), whereas the statistical analysis showed a significant difference for dental casts by comparing data from 2013 vs 2014 (p=0.0266) as well as data from 2013 vs 2015 (p=0.0001). Statistical evaluation of overall BEWE showed an intrarater reliability of 0.79-0.91 for photographs and 0.60-0.87 for dental casts. The interrater reliability was 0.77 (95% CI=[0.69; 0.84]) for photographs and 0.63 (95% CI=[0.52; 0.72]) for dental casts. CONCLUSION: This investigation showed that in longitudinal clinical monitoring, the assessment of the BEWE on patients and dental photographs yielded comparable results. In addition, based on these findings, the assessment of the BEWE on dental casts showed moderate reproducibility. Therefore, dental casts may be better used for laboratory assessment techniques.

High oblique sagittal split osteotomy of the mandible: assessment of the positions of the mandibular condyles after orthognathic surgery based on cone-beam tomography.

High oblique sagittal split osteotomy is an orthognathic technique to move the mandible. Our aim was to evaluate changes in the position of the condyle in the glenoid fossa and its angulation before and after high oblique sagittal split osteotomy (HSSO). Fifty patients (32 women and 18 men, mean age 26.3 (SD 7.4) years) had cone-beam computed tomographyic (CT) scans before operation, immediately postoperatively, and before removal of the osteosynthesis nine months postoperatively. The images were analysed to look for changes in the sagittal, coronal, and axial positions of the condyles. Twenty-four patients with class II malocclusion had a mean (SD) mandibular advancement of 6.51 (2.41) mm, and 26 patients with class III malocclusion had a mean (SD) mandibular setback of 4.16 (2.77) mm. The joint space increased significantly (p<0.05) relative to baseline immediately postoperatively, but there was no significant increase at the nine-month follow-up. The changes in position in the sagittal, coronal, and axial planes were comparable. Despite there being a short proximal joint-bearing segment, the results indicate that this technique allows free-hand condylar positioning into the fossa safely without any clinically relevant dislocations.

In vitro studies on the cytotoxic potential of surface sealants.

OBJECTIVE: The objective of this in vitro study was an initial screening of the cytotoxic potential of widely used smooth enamel surface sealants. MATERIALS AND METHODS: A total of 20 products were allocated to four groups based on their chemical composition: (1) filled resin-based sealants, (2) unfilled resin-based sealants, (3) a resin-modified, glass ionomer-based sealant, and (4) silicone-based sealants. All materials were applied to human enamel slices both in accordance with manufacturers' instructions and in additional experiments applying 50% undercuring and 50% overcuring. An agar overlay assay was then used to test the specimens following ISO 10933. The cytotoxic potential of each material was interpreted based on a reaction index that summarized the decolorization and lysis scores obtained. RESULTS: The cytotoxic potential decreased as follows: unfilled resin-based sealants > filled resin-based sealants > resin-modified, glass ionomer-based sealant > silicone-based sealants. In 75% of the resin-based products, deliberate undercuring was associated with more extensive decolorization zones, leading to higher rates of cytotoxic potential in two of those products. Overcuring, by contrast, was associated with a tendency for smaller decolorization zones in 50% of the resin-based products. CONCLUSION: Surface sealants derived from resin monomers exhibited cytotoxic potential in the agar overlay assay. There is also evidence of a possible association with curing, as undercuring can increase the cytotoxic potential, whereas normal curing (as per manufacturers' instructions) or overcuring may help minimize such effects. More research into the biological implications of these materials is needed, especially with regard to their potential impact on the adjacent gingiva.

[Influence of corneal pachymetric changes on functional results after cataract surgery]. / Einfluss der Hornhautdickenveränderung auf die funktionellen Ergebnisse nach Kataraktchirurgie.

BACKGROUND: In the early postoperative period following uncomplicated cataract surgery, the correlation of corrected distance visual acuity (CDVA) and the increase in corneal thickness and anterior chamber depth (ACD) are investigated. PATIENTS AND METHODS: A total of 54 cataract patients with a mean age of 70 ± 8.4 years were included in this prospective study. Surgery was carried out on one eye of each patient according to the study protocol. Refraction, CDVA and ACD were evaluated 1 day and 1 week postoperatively and compared with the pachymetry results measured with the Pentacam. RESULTS: The mean postoperative CDVA significantly improved from 0.31 ± 0.24 logMAR to 0.18 ± 0.22 logMAR after one day and up to 0.06 ± 0.13 logMAR one week after surgery (p < 0.05). The mean spherical equivalent was - 0.52 ± 0.69 D after one day and - 0.50 ± 0.82 D one week after surgery and showed only minimal differences compared to the mean target refraction of - 0.39 ± 0.70 D. Postoperative corneal thickness showed a significant increase compared to the preoperative results (p < 0.05) on both visits: the mean difference was 33.26 ± 50.20 µm (- 17 to 315 µm) on the first day and 20.22 ± 23.15 µm (- 10 to 99 µm) one week after surgery. Up to 7 days postoperatively the increase in corneal thickness and CDVA showed only moderate or no correlations (r = 0.465 vs. r = 0.072, respectively). Regarding pachymetry and ACD values, no or only low correlations were found. CONCLUSION: The significant increase in corneal thickness on the first and seventh day shows no to moderate correlation to the CDVA. Nevertheless, a good and early rehabilitation of visual acuity following uncomplicated cataract surgery is possible. Intraocular pressure measurement can lead to false high results due to an increase in corneal thickness.

[Fibrous metaphyseal defect (fibrous cortical defect, non-ossifying fibroma) (author's transl)]. / Der fibröse metaphysäre Defekt (fibröser Kortikalisdefekt, nicht ossifizierendes Knochenfibrom).

Fibrous cortical defect and non-ossifying fibromas can be classified together as fibrous metaphyseal defects (FMD) since they have the same pathological substrate, with a tendency to the same localisation around the knee, and occurring at the same age. They have a tendency to spontaneous healing, are clinically silent and are usually discovered accidentally during radiological examination. A radiological survey of 5.674 metaphyseal regions in the upper and lower extremities of 2.065 unselected patients aged one to 20 years revealed an incidence of 1.8%; exclusive examination of the distal femur showed an incidence of 2.7%. 96% of all lesions were in the lower extremities and only 4% in the upper. The marked discrepancy in the incidence rate between American and German publications is discussed.

[Fibrous metaphyseal defect (fibrous cortical defect, non-ossifying fibroma). Paper II: differential diagnosis (author's transl)]. / Der fibröse metaphysäre Defekt (fibröser Kortikalisdefekt, nicht-ossifizierendes Knochenfibrom).

FMD, whether in the stage of a fibrous cortical defect or a non-ossifying fibroma, possesses very characteristic radiological appearances which rarely make it necessary to resort to biopsy. In order to avoid mistakes, it is necessary to observe strictly the known radiological features: metaphyseal position, clearcut relationships to the cortex, well defined margins, maximal size 6 to 7 cm., presence during growth, rarely observed in the upper extremity. The differential diagnosis, which needs to be considered only rarely, is discussed.

[New intensifying screens in clinical radiology. II. Examinations in clinical practice]. / Neue Verstärkerfolien in der klinischen Radiologie. II. Praktisch-klinische Untersuchungen

A clinically applicable procedure for testing new intensifying rare earth screens, as well as the special Siemens' screen is described. The results are related to universal screens. The film-screen combination alpha 4XD (gadolinium oxysulphide with normal, green sensitive film) results in a reduction of radiation dose to half with detail comparable with universal screens. The Siemens' special screen has similar advantages. Screens with a higher intensification factor and reduction of the mAs to one sixth results in loss of detail. This does not necessarily reduce their clinical use if they are used for appropriate purposes. The results of this clinically orientated technique agreed well with physically objective methods using lead grids. The advantages of the new screens are discussed in terms of their practical application.

[New aspects concerning exposure factors during direct geometrical X-ray magnification (author's transl)]. / Neue Aspekte zur Belichtungstechnik bei der direkten geometrischen Röntgenvergrösserung.

The paper is concerned with the use of rare-earth intensifying screens in order to overcome some of the exposure problems during magnification techniques using very small focal spots. Theoretical experiments and tests with biological objects indicate that the use of high intensifying screens under these circumstances is acceptable and useful. A comparison has been carried out between the results of conventional techniques without magnification and magnification techniques using very small focal spots and rare-earth intensifying screens.

[Dose reduction during radiological examination using high intensity rare earth screens or increased kV (author's transl)]. / Zum Problem der Dosiseinsparung bei Röntgenaufnahmen durch Einsatz hochverstärkender Seltene-Erden-Folien oder durch Erhöhung der Aufnahmespannung.

Using a procedure which resembles actual practice, it has been shown that an increase in kV. results in a reduction of radiation dose similar to that obtained by using the new high intensity rare earth screens while maintaining similar detail. In practical terms this means that there is only limited usefulness for the new rare earth screens. An exception to this is the screen which reduces dose while producing similar, or better, detail than a standard screen. We could demonstrate this for the film-screen combination Trimax alpha4XD.

[New intensifying screens in clinical radiology. Paper I-Experimental investigations (author's transl)]. / Neue Verstärkerfolien in der klinischen Radiologie. I. Mitteilung; Experimentelle Untersuchungen

The degree of intensification and resolution was compared using rare-earth-screens and conventional calcium tungstate screens. -In order to approximate usual phantom (DIN 6, 815) was equipped with a lead grid at a depth of 6 cm. Nine screen-film combinations were exposed at 70 to 80 kv., using a 12-pulse generator and Bucky grid till blackening of S = 1 was obtained. -Resolution depends substantially on the inherent noise of the system and improves from 0.6 Lp/mm. for the most sensitive combinations (intensitification factor 8.0) to 1.15 Lp/mm (intensification factor 1.7). Compared with the standard combination with a resolution of about 0.9 Lp/mm., dose was reduced by more than 40% with an increase in resolution of 45% (combination 3M-Trimax A4/XD).

[Anastomosis prolapse of the gastric mucosa]. / Der Anastomosenprolaps der Magenschleimhaut.

X-rays of 91 patients who underwent gastric surgery between 1973 and 1977 were retrospectively evaluated. We found 16 large mucosal prolapses through the gastroduodenal anastomosis and another six with a so-called anastomosis bulge. Of these patients, 77% presented complaints in relation to delayed gastric emptying. When analyzing the prolapse frequency, patient age at the time of surgery, type of surgery, and suture technique, we found that mucosal prolapse occurred mostly in older patients with an extensive gastric resection after oralis-partialis anastomosis and after employing the two-layered suture technique.

[New intensifier screens in pediatric radiology (authors transl)]. / Neue Verstärkerfolien in der Kinderradiologie

On the basis of the physical and clinical findings of this investigation, the characteristics of new screens made of rare earths were described. The possibilities of application for pediatric radiology and those advantages which can be achieved with the new screens were discussed. Possible technical difficulties were mentioned.

[Are conventional roentgen technics for tbc diagnosis still acceptable?]. / Ist die konventionelle Röntgenaufnahmetechnik für Tbc-Diagnostik noch vertretbar?

Image quality in chest radiography has to be high enough that even subtle pulmonary abnormalities can be easily visualised. Conventional screen/film radiographs obtained with 200 to 400 speed systems fulfil this requirement well enough. Large screen and slit beam image intensifier systems that have replaced fluoroscopy screens, yield equivalently good results. The amber system and storage phosphor digital radiography systems are efficient alternatives. Radiation exposure is generally low and decreased further if image intensifiers are used. Conventional technique with highly sensitive film/screen combinations has been approved for diagnosis of pulmonary tuberculosis.

[Quality criteria in diagnostic radiology, goals and reality]. / Qualitätskriterien in der diagnostischen Radiologie, Ziel und Realität.

Quality criteria describe the medical standards (guidelines) with respect to the different aspects of radiological diagnosis. The indication does not seem to be justified in 20-50% of studies. Indication lists should be developed. Image quality has generally improved--with the exclusion of barium studies of the gastrointestinal tract. In 60% of patient studies, radiation exposure has been lowered to 25% due to the use of low-dose film-screen systems (speed class 400), higher exposure voltages, and improved constancy of the technical equipment. Over the last years diagnostically valuable computed tomography studies have been performed with considerably higher organs and effective doses. Technical restrictions in this field are necessary without compromising the diagnostic information. The benefit-risk ratio underscores the fact that the diagnostic and therapeutic benefit for the patient exceeds the nominal stochastic radiation risk by several orders of magnitude.