Methods used for indirect comparisons of systemic treatments for psoriasis. A systematic review.

Background: Indirect comparisons (including network meta-analyses [NMAs]) allow us to compare benefits and risks of multiple interventions for the same clinical condition when head-to-head comparisons are not feasible. Objective: To provide guidance to the clinical community on better understanding indirect comparison methods to help them to interpret their results by applying two quality standards to published indirect comparisons of systemic biologics for moderate to severe psoriasis. Methods: A systematic literature review (SLR) of published indirect comparisons of biologics for the treatment of moderate to severe psoriasis in adults was conducted. Data extraction was performed using a predefined subset of NICE TSD7 (National Institute for Health and Care Excellence Technical Support Document 7) checklist questions and methods used to perform each analysis were descriptively compared. Methodological quality of the SLR underlying each indirect comparison was assessed using AMSTAR 2 (A MeaSurement Tool to Assess systematic Reviews version 2). Results: Twenty-two NMAs and four adjusted indirect comparisons (AICs) were identified. Although there were some similarities, for example, application of Bayesian random-effects models, several important methodological aspects varied considerably across NMAs identified, for example, classes of drugs, number of treatments and studies included, reporting and handling of different doses, and reporting of both checks for and investigations of inconsistency. Methodological comparisons across AICs were limited by the small number. The quality of most underlying SLRs described, assessed as overall level of confidence in the results, was 'critically low'. Conclusions: Understanding that there are different methodologies employed to answer differing research questions is key to helping clinicians to interpret the indirect evidence currently available in psoriasis.

Validating the Assumptions of Population Adjustment: Application of Multilevel Network Meta-regression to a Network of Treatments for Plaque Psoriasis.

BACKGROUND: Network meta-analysis (NMA) and indirect comparisons combine aggregate data (AgD) from multiple studies on treatments of interest but may give biased estimates if study populations differ. Population adjustment methods such as multilevel network meta-regression (ML-NMR) aim to reduce bias by adjusting for differences in study populations using individual patient data (IPD) from 1 or more studies under the conditional constancy assumption. A shared effect modifier assumption may also be necessary for identifiability. This article aims to demonstrate how the assumptions made by ML-NMR can be assessed in practice to obtain reliable treatment effect estimates in a target population. METHODS: We apply ML-NMR to a network of evidence on treatments for plaque psoriasis with a mix of IPD and AgD trials reporting ordered categorical outcomes. Relative treatment effects are estimated for each trial population and for 3 external target populations represented by a registry and 2 cohort studies. We examine residual heterogeneity and inconsistency and relax the shared effect modifier assumption for each covariate in turn. RESULTS: Estimated population-average treatment effects were similar across study populations, as differences in the distributions of effect modifiers were small. Better fit was achieved with ML-NMR than with NMA, and uncertainty was reduced by explaining within- and between-study variation. We found little evidence that the conditional constancy or shared effect modifier assumptions were invalid. CONCLUSIONS: ML-NMR extends the NMA framework and addresses issues with previous population adjustment approaches. It coherently synthesizes evidence from IPD and AgD studies in networks of any size while avoiding aggregation bias and noncollapsibility bias, allows for key assumptions to be assessed or relaxed, and can produce estimates relevant to a target population for decision-making. HIGHLIGHTS: Multilevel network meta-regression (ML-NMR) extends the network meta-analysis framework to synthesize evidence from networks of studies providing individual patient data or aggregate data while adjusting for differences in effect modifiers between studies (population adjustment). We apply ML-NMR to a network of treatments for plaque psoriasis with ordered categorical outcomes.We demonstrate for the first time how ML-NMR allows key assumptions to be assessed. We check for violations of conditional constancy of relative effects (such as unobserved effect modifiers) through residual heterogeneity and inconsistency and the shared effect modifier assumption by relaxing this for each covariate in turn.Crucially for decision making, population-adjusted treatment effects can be produced in any relevant target population. We produce population-average estimates for 3 external target populations, represented by the PsoBest registry and the PROSPECT and Chiricozzi 2019 cohort studies.

Indirect comparisons of ixekizumab versus three interleukin-23 p19 inhibitors in patients with moderate-to-severe plaque psoriasis - efficacy findings up to week 12.

BACKGROUND: It is challenging to select the most appropriate biologic treatment for patients with moderate-to-severe plaque psoriasis. OBJECTIVE: To compare speed of onset and level of skin improvement between the interleukin (IL)-17A antagonist ixekizumab and the IL-23 p19 inhibitors guselkumab, tildrakizumab, and risankizumab in patients with moderate-to-severe plaque psoriasis. METHODS: Using data from controlled clinical trials, both adjusted indirect comparisons (AICs) and matching adjusted indirect comparisons (MAICs) were performed to determine the risk difference (RD) between ixekizumab and each IL-23 p19 inhibitor for the proportion of patients with ≥75%/90%/100% improvement compared with baseline in Psoriasis Area and Severity Index (PASI 75/90/100) up to week 12. Placebo, etanercept, or ustekinumab were used as the comparator bridge. RESULTS: In all (M)AICs, RDs generally significantly favored ixekizumab over guselkumab (placebo bridge), tildrakizumab (placebo or etanercept bridge), and risankizumab (placebo or ustekinumab bridge) from the earliest assessment time (≥ week 2) to week 12 when considering PASI 75/90/100 responses. CONCLUSION: Ixekizumab provides a faster onset of effect and earlier clinical benefits than guselkumab, tildrakizumab, or risankizumab in patients with moderate-to-severe psoriasis, as reflected by higher levels of skin improvement than with these IL-23 p19 inhibitors up to week 12.

Impact of clinical and demographic characteristics on patient preferences for psoriasis treatment features: Results from a discrete-choice experiment in a multicountry study.

OBJECTIVES: This study aimed to elicit preferences for psoriasis treatment features and to test for preference heterogeneity across groups of respondents. MATERIALS AND METHODS: A discrete-choice experiment was employed to elicit preferences of patients with plaque psoriasis in multiple countries. The survey instrument included a series of choice questions between three hypothetical treatments, each characterized by varying levels of six attributes (namely, lesion reduction, risk of impairing side effects, time to reach results, mode and frequency of administration, itching reduction, and side effects). Random parameters logit was used to model the data. Results were compared across a total of 18 subgroup sets. RESULTS: The data analysis from 1,123 respondents showed that, on average, respondents receive more utility gain from higher levels of lesion reduction and lower risks of impairing side effects than changes in other attributes included in the study. Systematic differences were detected for 13 sets; the most pronounced differences were observed based on disease severity, nail psoriasis, biologic experience, and quality-of-life scores. CONCLUSION: These many sources of preference heterogeneity identified by our analysis suggest that to improve patient satisfaction and, probably, adherence and persistence, clinicians should discuss options with patients when prescribing their treatment.

Cardiac Rehabilitation in German Speaking Countries of Europe-Evidence-Based Guidelines from Germany, Austria and Switzerland LLKardReha-DACH-Part 2.

BACKGROUND: Scientific guidelines have been developed to update and harmonize exercise based cardiac rehabilitation (ebCR) in German speaking countries. Key recommendations for ebCR indications have recently been published in part 1 of this journal. The present part 2 updates the evidence with respect to contents and delivery of ebCR in clinical practice, focusing on exercise training (ET), psychological interventions (PI), patient education (PE). In addition, special patients' groups and new developments, such as telemedical (Tele) or home-based ebCR, are discussed as well. METHODS: Generation of evidence and search of literature have been described in part 1. RESULTS: Well documented evidence confirms the prognostic significance of ET in patients with coronary artery disease. Positive clinical effects of ET are described in patients with congestive heart failure, heart valve surgery or intervention, adults with congenital heart disease, and peripheral arterial disease. Specific recommendations for risk stratification and adequate exercise prescription for continuous-, interval-, and strength training are given in detail. PI when added to ebCR did not show significant positive effects in general. There was a positive trend towards reduction in depressive symptoms for "distress management" and "lifestyle changes". PE is able to increase patients' knowledge and motivation, as well as behavior changes, regarding physical activity, dietary habits, and smoking cessation. The evidence for distinct ebCR programs in special patients' groups is less clear. Studies on Tele-CR predominantly included low-risk patients. Hence, it is questionable, whether clinical results derived from studies in conventional ebCR may be transferred to Tele-CR. CONCLUSIONS: ET is the cornerstone of ebCR. Additional PI should be included, adjusted to the needs of the individual patient. PE is able to promote patients self-management, empowerment, and motivation. Diversity-sensitive structures should be established to interact with the needs of special patient groups and gender issues. Tele-CR should be further investigated as a valuable tool to implement ebCR more widely and effectively.

Cardiac Rehabilitation in German Speaking Countries of Europe-Evidence-Based Guidelines from Germany, Austria and Switzerland LLKardReha-DACH-Part 1.

BACKGROUND: Although cardiovascular rehabilitation (CR) is well accepted in general, CR-attendance and delivery still considerably vary between the European countries. Moreover, clinical and prognostic effects of CR are not well established for a variety of cardiovascular diseases. METHODS: The guidelines address all aspects of CR including indications, contents and delivery. By processing the guidelines, every step was externally supervised and moderated by independent members of the "Association of the Scientific Medical Societies in Germany" (AWMF). Four meta-analyses were performed to evaluate the prognostic effect of CR after acute coronary syndrome (ACS), after coronary bypass grafting (CABG), in patients with severe chronic systolic heart failure (HFrEF), and to define the effect of psychological interventions during CR. All other indications for CR-delivery were based on a predefined semi-structured literature search and recommendations were established by a formal consenting process including all medical societies involved in guideline generation. RESULTS: Multidisciplinary CR is associated with a significant reduction in all-cause mortality in patients after ACS and after CABG, whereas HFrEF-patients (left ventricular ejection fraction <40%) especially benefit in terms of exercise capacity and health-related quality of life. Patients with other cardiovascular diseases also benefit from CR-participation, but the scientific evidence is less clear. There is increasing evidence that the beneficial effect of CR strongly depends on "treatment intensity" including medical supervision, treatment of cardiovascular risk factors, information and education, and a minimum of individually adapted exercise volume. Additional psychologic interventions should be performed on the basis of individual needs. CONCLUSIONS: These guidelines reinforce the substantial benefit of CR in specific clinical indications, but also describe remaining deficits in CR-delivery in clinical practice as well as in CR-science with respect to methodology and presentation.

Dynamic Visual Representation of Clinical Efficacy of Ixekizumab in Psoriasis.

INTRODUCTION: Ixekizumab, a high-affinity monoclonal antibody that selectively targets interleukin-17A, is an approved treatment for plaque psoriasis. This study aimed to use animated visualizations as a tool to simplify complex data from ixekizumab clinical trials. METHODS: Animated visualizations were developed to show outcomes from ixekizumab clinical trials and a Bayesian network meta-analysis of 11 approved biologics. The visualizations simultaneously highlighted both aggregate scores and the individual progression of patients over the course of treatment. RESULTS: The animations provided key messages and information from the complex data in efficient and scientific ways that were also visually pleasing and simple to understand. The animations highlighted (1) rapid reduction in disease severity from baseline; (2) sustained efficacy of ixekizumab in the treatment of skin and nail psoriasis; (3) side-by-side comparisons of treatment efficacy and clinical improvement across trials; (4) simultaneous visual presentation of individual results with summary response over time; and (5) indirect comparison of relative treatment effects with other biologics based on Bayesian network meta-analysis. CONCLUSION: The rapid and sustained efficacy of ixekizumab in the treatment of psoriasis was demonstrated using multiple dynamic visualizations with different clinical endpoints. Animated visualizations provided a simpler and more comprehensive understanding of complex data than conventional static figures.

Posttraumatic Perfusion Analysis of Quadriceps, Patellar, and Achilles Tendon Regeneration With Dynamic Contrast-Enhanced Ultrasound and Dynamic Contrast-Enhanced Magnetic Resonance Imaging: Preliminary Results.

OBJECTIVES: The healing process of tendons after surgical treatment of tendon ruptures mainly depends on the perfusion of the tendon and its surrounding tissue. Dynamic contrast-enhanced ultrasound (DCE-US) and dynamic contrast-enhanced MRI (DCE-MRI) can provide additional information about the local microperfusion. In this pilot study, the feasibility of these techniques to assess the vascularization during tendon regeneration was evaluated. METHODS: Between 2013 and 2015, 23 patients with surgical treatment of traumatic rupture of quadriceps, patellar, and Achilles tendons were involved. All patients received clinical follow-up examinations at 6, 12, and at least 52 weeks postoperatively. Dynamic contrast-enhanced US and DCE-MRI examinations were performed 6 and 12 weeks postoperatively. Dynamic contrast-enhanced US perfusion was quantified by the parameters peak enhancement, wash-in area under the curve, rise time, and initial area under the curve. Correlations between these parameters were examined via the Spearman rank correlation. The clinical and functional outcomes were assessed via the Lysholm Knee Score and Knee and Osteoarthritis Outcome Score at 12 and 52 weeks postoperatively. RESULTS: Fourteen patients with quadriceps (n = 8), patellar (n = 4) and Achilles (n = 2) tendon ruptures with complete follow-up were available. The microperfusion could be successful assessed. We could detect a strong correlation of DCE-US (peak enhancement) parameters with DCE-MRI (initial area under the curve) parameters after 6 and 12 weeks. CONCLUSIONS: In this pilot study, DCE-US was able to visualize the microperfusion of healing tendons with a strong correlation with DCE-MRI. Our initial results are in favor of DCE-US as a potential quantitative imaging tool for evaluating the vascularization in tendon regeneration as a complementary method.

Multilevel network meta-regression for population-adjusted treatment comparisons.

Standard network meta-analysis (NMA) and indirect comparisons combine aggregate data from multiple studies on treatments of interest, assuming that any effect modifiers are balanced across populations. Population adjustment methods relax this assumption using individual patient data from one or more studies. However, current matching-adjusted indirect comparison and simulated treatment comparison methods are limited to pairwise indirect comparisons and cannot predict into a specified target population. Existing meta-regression approaches incur aggregation bias. We propose a new method extending the standard NMA framework. An individual level regression model is defined, and aggregate data are fitted by integrating over the covariate distribution to form the likelihood. Motivated by the complexity of the closed form integration, we propose a general numerical approach using quasi-Monte-Carlo integration. Covariate correlation structures are accounted for by using copulas. Crucially for decision making, comparisons may be provided in any target population with a given covariate distribution. We illustrate the method with a network of plaque psoriasis treatments. Estimated population-average treatment effects are similar across study populations, as differences in the distributions of effect modifiers are small. A better fit is achieved than a random effects NMA, uncertainty is substantially reduced by explaining within- and between-study variation, and estimates are more interpretable.

Survival and success of implants in a private periodontal practice: a 10 year retrospective study.

BACKGROUND: To assess long-term results of implants (XiVE/Frialit-2 Synchro) in a private periodontal practice according to survival and success rates (biological and technical complications) and to detect possible influencing factors, retrospectively. METHODS: Implant placement of at least one implant took place 10 years ±6 months before clinical and radiographic re-examination. Incidence of implant loss as main and incidence of mucositis/ peri-implantitis as secondary outcome were detected. Also, patient-related and implant-related influencing factors were determined by regression analyses. RESULTS: 100 patients (59.0% female) with 242 implants were included into analysis. Survival rate was 94.0% (XiVE: 97.7%; Frialit-2-Synchro: 66.7%). Mucositis was found in 77.6% of all patients, moderate/severe peri-implantitis in 16.3%. In logistic regression analyses statistically significant influencing factors for implant loss was implant type (p < 0.001), for mucositis a wider implant diameter (p = 0.0438) and a high modified Plaque Index (p = 0.0253), for peri-implantits number of implants per patient (p = 0.0075) and a wider implant diameter (p = 0.0079). Technical complications were found in 47 implants (19.4%). CONCLUSIONS: XiVE implants showed a high survival rate over a 10-year follow-up, on the other hand Frialit-2 Synchro implants had worse survival rates. Success rates regarding biological complications are in line with other implant systems.

Modeling Heterogeneity in Patients' Preferences for Psoriasis Treatments in a Multicountry Study: A Comparison Between Random-Parameters Logit and Latent Class Approaches.

BACKGROUND: Either a random-parameters logit (RPL) or latent class (LC) model can be used to model or explain preference heterogeneity in discrete-choice experiment (DCE) data. The former assumes continuous distribution of preferences across the sample, while the latter assumes a discrete distribution. This study compared RPL and LC models to explore preference heterogeneity when analyzing patient preferences for psoriasis treatments. METHODS: Using DCE data collected from respondents with moderate-to-severe plaque psoriasis, we calculated and compared preference weights derived from RPL and LC models. We then compared how RPL and LC explain preference heterogeneity by exploring differences across subgroups defined by observed characteristics (i.e., country, age, gender, marital status, and psoriasis severity). RESULTS: While RPL and LC models resulted in the same mean preference weights, different preference-heterogeneity patterns emerged from the two approaches. In both models, country of residence and self-reported disease severity could be linked to systematic differences in preferences. The RPL also identified gender and marital status, but not age, as sources of heterogeneity; the LC membership probability model indicated that age was a significant factor, but not gender or marital status. CONCLUSIONS: Using data from a psoriasis patient survey to compare two widely used methods for exploring heterogeneity identified differences in results between stated-preferences: subgroup analysis in the RPL model and inclusion of subgroup characteristics in the class membership probability function of the LC model. Researchers should model data using the most adaptable approach to address the initial study question.

Combination of several matching adjusted indirect comparisons (MAICs) with an application in psoriasis.

In health technology assessment (HTA), beside network meta-analysis (NMA), indirect comparisons (IC) have become an important tool used to provide evidence between two treatments when no head-to-head data are available. Researchers may use the adjusted indirect comparison based on the Bucher method (AIC) or the matching-adjusted indirect comparison (MAIC). While the Bucher method may provide biased results when included trials differ in baseline characteristics that influence the treatment outcome (treatment effect modifier), this issue may be addressed by applying the MAIC method if individual patient data (IPD) for at least one part of the AIC is available. Here, IPD is reweighted to match baseline characteristics and/or treatment effect modifiers of published data. However, the MAIC method does not provide a solution for situations when several common comparators are available. In these situations, assuming that the indirect comparison via the different common comparators is homogeneous, we propose merging these results by using meta-analysis methodology to provide a single, potentially more precise, treatment effect estimate. This paper introduces the method to combine several MAIC networks using classic meta-analysis techniques, it discusses the advantages and limitations of this approach, as well as demonstrates a practical application to combine several (M)AIC networks using data from Phase III psoriasis randomized control trials (RCT).

Alternative Weighting Approaches for Anchored Matching-Adjusted Indirect Comparisons via a Common Comparator.

BACKGROUND: Adjusted indirect comparisons (anchored via a common comparator) are an integral part of health technology assessment. These methods are challenged when differences between studies exist, including inclusion/exclusion criteria, outcome definitions, patient characteristics, as well as ensuring the choice of a common comparator. OBJECTIVES: Matching-adjusted indirect comparison (MAIC) can address these challenges, but the appropriate application of MAICs is uncertain. Examples include whether to match between individual-level data and aggregate-level data studies separately for treatment arms or to combine the arms, which matching algorithm should be used, and whether to include the control treatment outcome and/or covariates present in individual-level data. RESULTS: Results from seven matching approaches applied to a continuous outcome in six simulated scenarios demonstrated that when no effect modifiers were present, the matching methods were equivalent to the unmatched Bucher approach. When effect modifiers were present, matching methods (regardless of approach) outperformed the Bucher method. Matching on arms separately produced more precise estimates compared with matching on total moments, and for certain scenarios, matching including the control treatment outcome did not produce the expected effect size. The entropy balancing approach was used to determine whether there were any notable advantages over the method proposed by Signorovitch et al. When unmeasured effect modifiers were present, no approach was able to estimate the true treatment effect. CONCLUSIONS: Compared with the Bucher approach (no matching), the MAICs examined demonstrated more accurate estimates, but further research is required to understand these methods across an array of situations.

Effects of staining and polishing on different types of enamel surface sealants.

OBJECTIVE: To assess surface discoloration of four enamel sealants based on different chemical compositions after exposure to artificial aging and staining solutions. Furthermore, their cleanability after polishing will be evaluated. MATERIALS AND METHODS: Selected sealants were a composite resin-based sealant with fillers (Pro Seal), a composite resin-based sealant without fillers (Light BondSealant), a resin-modified glass ionomer-based sealant (ClinproXT Varnish) and a silicon-based sealant (Protecto). Natural teeth served as medium. Immersion solutions were water, juice, tea, and turmeric. In a standardized setting, all samples were measured seven times with a spectroradiometer (Photoresearch PR670) at baseline, after thermocycling; 7 days; 2 and 4 weeks of immersion; and after finally polishing. RESULTS: Thermocycling had no significant effect on color stability. After exposure to staining solutions, all sealed surfaces showed significant color changes. Color change predominately occurred for all sealants in the first week of staining (P ≤ .01). Best resistance to staining decreased as follows: Protecto > Light Bond Sealant > ProSeal > Clinpro XT Varnish. Surface cleaning by polishing significantly reduced the color change. CONCLUSION: Sealed enamel surfaces are prone to discoloration, which is most prominent in filled composite and glass-ionomer-based sealants. Staining can be reduced by polishing; however, in this in vitro setting the original color could not be restored. CLINICAL SIGNIFICANCE: Enamel sealants might exert adverse effects in terms of discoloration. This should be taken into consideration by clinicians and patients, particularly when sealants are applied in esthetically critical areas.

Association of trauma, Posttraumatic Stress Disorder and Conduct Disorder: A systematic review and meta-analysis.

OBJECTIVE: To summarize findings of previous studies on the prevalence of trauma and Posttraumatic Stress Disorder (PTSD) in Conduct Disorder (CD). METHOD: We conducted a systematic review and meta-analysis following the PRISMA guidelines. EBSCOhost, PubMed, CDSR and ARIF databases were searched in October 2016, employing relevant keywords. RESULTS: 19 studies met inclusion criteria. Meta-analysis resulted in a lifetime PTSD prevalence of 11% (95% CI: 7-17%) in children and adolescents with CD, 14% (95% CI: 12-15%) in adults with pre-existing CD and 32% (95% CI: 25-40%) in juvenile offenders with CD. Higher lifetime PTSD prevalence was observed in individuals with than without CD, and in females compared to males with CD. CONCLUSIONS: Studies focusing on the association of trauma, PTSD and CD are still relatively rare. Possible comorbidity models are discussed considering psychological and biological risk factors in a comprehensive model. The high rate of PTSD in CD may be due to shared risk factors; furthermore, CD might increase the risk for comorbid PTSD due to CD inherent risk taking behavior. To study pathways of risk, especially longitudinal studies are necessary.

Fiber-reinforced composite fixed dental prostheses: A 4-year prospective clinical trial evaluating survival, quality, and effects on surrounding periodontal tissues.

STATEMENT OF PROBLEM: Although fiber-reinforced composite fixed dental prostheses (FRC FDPs) are a reliable treatment option for the restoration of single missing teeth, comparatively few prospective clinical trials (PCT) exist. PURPOSE: The purpose of this PCT was to evaluate the survival, quality outcome, and effect of FRC FDPs on periodontal health over 4 years. MATERIAL AND METHODS: Twenty-six consecutive patients (16 men, 10 women) receiving FRC FDPs with preimpregnated unidirectional fiber reinforcement were included in the trial. Eighteen FRC FDPs were placed in the maxilla and 8 in the mandible. Data from baseline, 12-, 36-, and 48-months of follow-up were recorded, and the prostheses were classified as "success," "survival," or "failure." Periodontal parameters (probing depth, clinical attachment level, plaque index, and bleeding index were assessed, and the quality was rated according to modified United States Public Health Service (USPHS)/Ryge or World Dental Federation (FDI) criteria. RESULTS: Functional survival at 4 years was 73.5% (95% confidence interval [CI], 52.9-87.3) with 17 FRC FDPs still functioning. Twelve of these were classified as "success" and 5 as "survival." Overall survival was 53.0% (95% CI, 30.4-74.4). Six FRC FPDs failed completely. Periodontal parameters did not change over the observation period. Regression analysis showed that probing depth and clinical attachment level did not influence the survival of FRC FDPs. According to USPHS/Ryge/FDI criteria only "wear" and "surface luster" increased significantly over 4 years. CONCLUSIONS: The survival rate of FRC FPDs confirms existing data. Negative effects on periodontal health were not seen over the period of observation. Aging effects such as wear were recorded and indicated that FRC FPDs are at risk of disintegration, as they are composed of a fiber framework and veneering composite resin.

Surgery-first approach in orthognathic surgery: Psychological and biological aspects - A prospective cohort study.

INTRODUCTION: The aim of this pilot study was to investigate psychological and biological changes after application of a surgery-first orthognathic treatment approach. METHODS: A prospective cohort study of 9 patients (6 women and 3 men; mean age 26.7 years) suffering from skeletal Class II and III deformities was conducted. Skeletal changes from pre-to post-treatment were analyzed based on data acquired by use of cone-beam computed tomography (CBCT). Psychological changes were analyzed using the orthognathic quality of life (OQLQ) questionnaire, Sense of Coherence 29-item scale (SOC-29) and longitudinal day-to-day questionnaire. For biological evaluation, concentrations of IL-1 ß, IL-6, TGF ß 1-3, MMP-2 and VEGF were assessed in crevicular fluid by bead-based multiplex assays at one preoperative and various postoperative time points. RESULTS: A significant improvement (P = 0.015) in quality of life, as measured with the OQLQ, was observed between baseline and 3 months post-surgery. The most affected dimensions were: facial aesthetics (p = 0.022), oral function (p = 0.051) and social aspects (p = 0.057). Sense of coherence (SOC) significantly improved after treatment by 9 points (P = 0.029). Despite the significant improvement in OQLQ and SOC during the course of the study, the personal experience of appearance varied distinctly in course and intensity. In accordance with the temporal pattern of fracture healing, the analysis of crevicular fluid revealed an increase in pro-resorptive factors (IL-1 ß, IL-6 and MMP-2) at early postoperative time points, while remodeling factors (members of the TGF-ß superfamily) were detected at later postoperative time points. CONCLUSIONS: Orthognathic treatment using the surgery-first approach has a positive impact on patient's psychosocial status. Accelerated tooth movement after surgery might, to a certain extent, be due to elevated levels of bone remodeling factors with overlapping functions during fracture healing and tooth movement.

Long-term stability of splinted anterior mandibular teeth during supportive periodontal therapy.

OBJECTIVE: The aim of the study was to retrospectively assess the survival rate and stability of periodontally compromised and mobile anterior mandibular teeth after splinting in patients under supportive periodontal therapy (SPT). MATERIALS AND METHODS: Thirty-nine patients with splinted anterior mandibular teeth and SPT (≥1 visit/year) for 3-15 years were re-examined. Periodontal status, patient and tooth-related factors were assessed retrospectively before (baseline) and 3 years after splinting (n = 39 patients, 162 splinted teeth). For patients with splints inserted for more than 3 years, retrospective data after 5 (n = 30), 7 (n = 24), 10 (n = 16), 12 (n = 8) and 15 years (n = 4) was included, if available. At baseline, splinted teeth included at least one tooth with increased mobility combined with clinical attachment loss (CAL) ≥ 5 mm and ≥50% relative bone loss (RBL). Baseline RBL of splinted teeth was assessed for all patients. Change in RBL was assessed after 10 years, if available. RESULTS: No splinted tooth was lost within the first 3 years after splinting. One splinted tooth was lost 7 years after baseline and one 12 years after baseline. After 3 years mean(SD) periodontal probing depth of splinted teeth decreased from 3.39(1.41) mm to 2.12(0.37) mm and mean(SD) CAL from 5.61(1.66) mm to 5.09(1.67) mm and remained stable over the observation period. No change in RBL was observed over a 10-year period (p = .213). The survival rate of the splints until fracture or debonding was 74.4% after 3 years. CONCLUSIONS: Periodontally compromised splinted teeth show a high survival-rate and periodontal stability during SPT.

Yield of active screening for tuberculosis among asylum seekers in Germany: a systematic review and meta-analysis.

All asylum seekers in Germany undergo upon-entry screening for tuberculosis TB, but comprehensive evidence on the yield is lacking. We compared the national estimates with the international literature in a systematic review and meta-analysis of studies reporting the yield of TB, defined as the fraction of active TB cases detected among asylum seekers screened in Germany upon entry. We searched 11 national and international databases for empirical studies and the internet for grey literature published in English or German without restrictions on publication time. Among 1,253 screened articles, we identified six articles reporting the yield of active TB based on German data, ranging from 0.72 (95% confidence interval (CI): 0.45-1.10) to 6.41 (95% CI: 4.19-9.37) per 1,000 asylum seekers. The pooled estimate across all studies was 3.47 (95% CI: 1.78-5.73; I2 = 94.9%; p < 0.0001) per 1,000 asylum seekers. This estimate was in line with international evidence (I2 = 0%; p for heterogeneity 0.55). The meta-analysis of available international estimates resulted in a pooled yield of 3.04 (95% CI: 2.24-3.96) per 1,000. This study provides an estimate across several German federal states for the yield of TB screening in asylum seekers. Further research is needed to develop more targeted screening programmes.