MDCT-based longitudinal automated airway and air trapping analysis in school-age children with mild cystic fibrosis lung disease.

Objectives: Quantitative computed tomography (QCT) offers some promising markers to quantify cystic fibrosis (CF)-lung disease. Air trapping may precede irreversible bronchiectasis; therefore, the temporal interdependencies of functional and structural lung disease need to be further investigated. We aim to quantify airway dimensions and air trapping on chest CT of school-age children with mild CF-lung disease over two years. Methods: Fully-automatic software analyzed 144 serial spirometer-controlled chest CT scans of 36 children (median 12.1 (10.2-13.8) years) with mild CF-lung disease (median ppFEV1 98.5 (90.8-103.3) %) at baseline, 3, 12 and 24 months. The airway wall percentage (WP5-10), bronchiectasis index (BEI), as well as severe air trapping (A3) were calculated for the total lung and separately for all lobes. Mixed linear models were calculated, considering the lobar distribution of WP5-10, BEI and A3 cross-sectionally and longitudinally. Results: WP5-10 remained stable (P = 0.248), and BEI changed from 0.41 (0.28-0.7) to 0.54 (0.36-0.88) (P = 0.156) and A3 from 2.26% to 4.35% (P = 0.086) showing variability over two years. ppFEV1 was also stable (P = 0.276). A robust mixed linear model showed a cross-sectional, regional association between WP5-10 and A3 at each timepoint (P < 0.001). Further, BEI showed no cross-sectional, but another mixed model showed short-term longitudinal interdependencies with air trapping (P = 0.003). Conclusions: Robust linear/beta mixed models can still reveal interdependencies in medical data with high variability that remain hidden with simpler statistical methods. We could demonstrate cross-sectional, regional interdependencies between wall thickening and air trapping. Further, we show short-term regional interdependencies between air trapping and an increase in bronchiectasis. The data indicate that regional air trapping may precede the development of bronchiectasis. Quantitative CT may capture subtle disease progression and identify regional and temporal interdependencies of distinct manifestations of CF-lung disease.

Mental Health Specialist Video Consultations Versus Treatment-as-Usual for Patients With Depression or Anxiety Disorders in Primary Care: Randomized Controlled Feasibility Trial.

BACKGROUND: Most people affected by depression or anxiety disorders are treated solely by their primary care physician. Access to specialized mental health care is impeded by patients' comorbidity and immobility in aging societies and long waiting times at the providers' end. Video-based integrated care models may leverage limited resources more efficiently and provide timely specialized care in primary care settings. OBJECTIVE: The study aims to evaluate the feasibility of mental health specialist video consultations with primary care patients with depression or anxiety disorders. METHODS: Participants were recruited by their primary care physicians during regular practice visits. Patients who had experienced at least moderate symptoms of depression and/or anxiety disorders were considered eligible for the study. Patients were randomized into 2 groups receiving either treatment-as-usual as provided by their general practitioner or up to 5 video consultations conducted by a mental health specialist. Video consultations focused on systematic diagnosis and proactive monitoring using validated clinical rating scales, the establishment of an effective working alliance, and a stepped-care algorithm within integrated care adjusting treatments based on clinical outcomes. Feasibility outcomes were recruitment, rate of loss to follow-up, acceptability of treatment, and attendance at sessions. Effectiveness outcomes included depression (Patient Health Questionnaire-9), anxiety (Generalized Anxiety Disorder-7), burden of specific somatic complaints (Somatic Symptom Disorder-B Criteria Scale-12), recovery (Recovery Assessment Scale-German [RAS-G]), and perception of chronic illness care (Patient Assessment of Chronic Illness Care), which were measured at baseline and 16 weeks postallocation by assessors blinded to the group allocation. RESULTS: A total of 50 patients with depression and/or anxiety disorders were randomized, 23 in the intervention group and 27 in the treatment-as-usual group. The recruitment yield (number randomized per number screened) and the consent rate (number randomized per number eligible) were 69% (50/73) and 86% (50/58), respectively. Regarding acceptability, 87% (20/23) of the participants in the intervention group completed the intervention. Of the 108 planned video consultations, 102 (94.4%) were delivered. Follow-up rates were 96% (22/23) and 85% (23/27) for the intervention and control groups, respectively. The change from baseline scores at postmeasurement for the No Domination by Symptoms domain of recovery (RAS-G) was somewhat higher in the intervention group than in the control group (Mann-Whitney U test: rank-biserial r=0.19; 95% CI -0.09 to 0.46; P=.18). We did not detect any notable differences between the intervention and control groups in terms of other effectiveness outcomes. We did not observe any serious adverse events related to the trial. CONCLUSIONS: The intervention and study procedures were found to be feasible for patients, primary care practice staff, and mental health specialists. A sufficiently powered pragmatic trial on mental health specialist video consultations should be conducted to investigate their effectiveness in routine care. TRIAL REGISTRATION: German Clinical Trials Register DRKS00015812; https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00015812.

Isolated femoral artery revascularisation with or without iliac inflow improvement - a less invasive surgical option in critical limb ischemia.

Background: Isolated femoral artery revascularisation (iFAR) represents a well-established surgical method in the treatment of peripheral arterial disease (PAD) involving common femoral artery disease. Data for iFAR in multilevel PAD are inconsistent, particularly in patients with critical limb ischemia (CLI). The aim of the study was to evaluate the outcome of iFAR in CLI regarding major amputation and reintervention and to identify associated risk factors for this outcome. Patients and methods: The data used have been derived from the German Registry of Firstline Treatment in Critical Limb Ischemia (CRITISCH). A total of 1200 patients were enrolled in 27 vascular centres. This sub-analysis included patients, which were treated with iFAR with/without concomitant iliac intervention. For detection of risk factors for the combined endpoint of major amputation and/or reintervention, selection of variables for multiple regression was conducted using stepwise forward/backward selection by Akaike's information criterion. Results: 95 patients were included (mean age: 72 years ± 10.82; 64.2% male). Of those, 32 (33.7%) participants reached the combined endpoint. Risk factor analysis revealed continued tobacco use (odds ratio [OR] 2.316, confidence interval [CI] 0.832-6.674), TASC D-lesion (OR: 2.293, CI: 0.869-6.261) and previous vascular intervention in the trial leg (OR: 2.720, CI: 1.037-7.381) to be associated with reaching the combined endpoint. Conclusions: iFAR provides a reasonable, surgical option to treat CLI. Lesion length (TASC D) seems to have a negative impact on outcome. Further research is required to better define the future role of iFAR for combined femoro-popliteal lesions in CLI - best in terms of a randomised controlled trial.

Outcomes of thoracic endovascular aortic repair in thoracic aortic aneurysm and penetrating aortic ulcer using the Conformable Gore TAG within and outside the instructions for use.

OBJECTIVE: To describe the outcome of thoracic endovascular aortic repair (TEVAR) in thoracic aortic aneurysm and penetrating aortic ulcer with respect to instructions for use status. METHODS: Between October 2009 and September 2017, a total of 532 patients underwent TEVAR; of which 195 have been treated using the Conformable GORE® TAG® thoracic endoprosthesis (CTAG). Fifty-six patients of this cohort underwent TEVAR for thoracic aortic aneurysm/penetrating aortic ulcer using the CTAG. Depending on the preoperative computed tomography angiography findings, patients were classified as inside or outside the device's instructions for use. All inside instruction for use patients underwent postoperative reclassification regarding the instructions for use status. Study endpoints included TEVAR-related reintervention, exclusion of the pathology (endoleak type I/III), TEVAR-related mortality, and graft-related serious adverse events. The median duration of follow-up was 29.7 months (range: 0-109.4 months). RESULTS: Of the 56 patients, 17 were primarily classified as outside instruction for use, and in additional 13 patients, TEVAR was performed outside instruction for use, leading to 30 outside instruction for use patients (53.6%). Twenty-six patients (46.4%) were treated inside instruction for use. Reintervention-free survival was lower in outside instruction for use patients (P = 0.016) with a hazard ratio of 9.74 (confidence interval 1.2-80.2; P = 0.034) for TEVAR-related reintervention. With respect to endoleak type I/III, relevant difference was detected between inside/outside instruction for use status (P = 0.012). The serious adverse event rate was 30.4%, mainly in outside instruction for use patients (P = 0.004). Logistic regression analysis indicated an association between graft-related serious adverse event/instructions for use status (odds ratio 6.11; confidence interval 1.6-30.06; P = 0.012). In-hospital death was seen more frequently in outside instruction for use patients (P = 0.12) as was procedure-related death (log-rank test: P = 0.21). CONCLUSION: TEVAR for thoracic aortic aneurysm/penetrating aortic ulcer is frequently performed outside instruction for use despite preoperative inside instruction for use eligibility, leading to important consequences for technical/clinical outcome. Instructions for use adherence in TEVAR should be of interest for further large-scale studies.

Consolidation Immunotherapy After Platinum-Based Chemoradiotherapy in Patients With Unresectable Stage III Non-Small Cell Lung Cancer-Cross-Sectional Study of Eligibility and Administration Rates.

INTRODUCTION: The PACIFC trial demonstrated a significant benefit of durvalumab consolidation immunotherapy (CIT) after definitive platinum-based chemoradiotherapy (P-CRT) for survival in stage III non-small cell lung cancer (NSCLC). It is unknown how many patients are eligible in clinical practice to receive CIT according to PACIFIC criteria compared to real administration rates and what influencing factors are. PATIENTS AND METHODS: We analyzed 442 patients with unresectable stage III NSCLC who received P-CRT between 2009 and 2019 regarding CIT eligibility rates according to PACIFIC criteria and administration rates since drug approval. RESULTS: Sixty-four percent of 437 patients were male, median age was 63 years [interquartile range (IQR): 57-69]. The most common histologic subtypes were adenocarcinoma (42.8%) and squamous cell carcinoma (41.1%), most tumors were in stage IIIB (56.8%). Mean PD-L1 tumor proportion score (TPS) was 29.8% (IQR: 1-60). The median total RT dose was 60 Gy (IQR: 60-66). Platinum component of P-CRT was evenly distributed between cisplatin (51.4%) and carboplatin (48.6%). 50.3% of patients were eligible for CIT according to PACIFIC criteria. Observed contraindications were progressive disease according to RECIST (32.4%), followed by a PD-L1 TPS < 1% (22.3%), pneumonitis CTCAE ≥ 2 (12.6%) and others (4.9%). One year after drug approval, 85.6% of patients who were eligible according to PACIFIC criteria actually received CIT. Time interval between chemotherapy start and radiation therapy start (OR 0.9, 95% CI: [0.9; 1.0] p = 0.009) and probably cisplatin as platinum-component of P-CRT (OR 1.5, 95% CI: [1.0; 2.4] p < 0.061) influence CIT eligibility. Highly positive PD-L1 TPS (≥50%; (OR 2.4, 95% CI: [1.3; 4.5] p = 0.004) was associated to a better chance for CIT eligibility. CONCLUSION: Eighty-five percent of potentially eligible patients received CIT one year after drug approval. Fifty percent of patients did not meet PACIFIC criteria for durvalumab eligibility, this was mainly caused by disease progression during platinum-based CRT, followed by therapy-related pneumonitis and PD-L1 TPS < 1% (in view of the EMA drug approval).

Comparison of Methods for Estimating Therapy Effects by Indirect Comparisons: A Simulation Study.

Objective. In evidence synthesis, therapeutic options have to be compared despite the lack of head-to-head trials. Indirect comparisons are then widely used, although little is known about their performance in situations where cross-trial differences or effect modification are present. Methods. We contrast the matching adjusted indirect comparison (MAIC), simulated treatment comparison (STC), and the method of Bucher using a simulation study. The different methods are evaluated according to their power and type I error rate as well as with respect to the coverage, bias, and the root mean squared error (RMSE) of the effect estimate for practically relevant scenarios using binary and time-to-event endpoints. In addition, we investigate how the power planned for the head-to-head trials influences the actual power of the indirect comparison. Results. Indirect comparisons are considerably underpowered. None of the methods had substantially superior performance. In situations without cross-trial differences and effect modification, MAIC and Bucher led to similar results, while Bucher has the advantage of preserving the within-study randomization. MAIC and STC could enhance power in some scenarios but at the cost of a potential type I error inflation. Adjusting MAIC and STC for confounders that did not modify the effect led to higher bias and RMSE. Conclusion. The choice of effect modifiers in MAIC and STC influences the precision of the indirect comparison. Therefore, a careful selection of effect modifiers is warranted. In addition, missed differences between trials may lead to low power and partly high bias for all considered methods, and thus, results of indirect comparisons should be interpreted with caution.

Tooth-related factors for tooth loss 20 years after active periodontal therapy-A partially prospective study.

AIM: To assess factors contributing to tooth loss 20 years after active periodontal therapy (APT) on tooth level. MATERIALS AND METHODS: After an initial retrospective analysis 10 years after APT, patients were monitored for 10 more years. At clinical re-evaluation 20 years after APT, tooth-related factors (tooth type, location, bone loss, furcation involvement, abutment status) and patient-related factors (gender, smoking, adherence) were investigated. Descriptive statistical analysis and a mixed logistic regression analysis were performed with tooth loss as primary outcome variable. RESULTS: The study included 69 patients (42 female/27 male). 39 patients were non-adherent (56.5%), and 11 were active smokers (15.9%). A total of 198 out of 1611 teeth were lost. Tooth loss was significantly highest (p < .01) in molars (21.1%), multi-rooted teeth with furcation involvement (23.5%) and abutment teeth (fixed: 27.6%, removable: 36.4%). 37.6% of teeth with initial bone loss >60% were lost during 20 years. Adherent patients showed less frequent tooth loss than non-adherent patients (OR 0.371; p <  .01). CONCLUSION: Even teeth with an initial bone loss over 60% could be retained in approximately two thirds for 20 years. This should be kept in mind when assigning prognosis and establishing a treatment plan.

Stereotactic Cavity Irradiation or Whole-Brain Radiotherapy Following Brain Metastases Resection-Outcome, Prognostic Factors, and Recurrence Patterns.

Introduction: Following the resection of brain metastases (BM), whole-brain radiotherapy (WBRT) is a long-established standard of care. Its position was recently challenged by the less toxic single-session radiosurgery (SRS) or fractionated stereotactic radiotherapy (FSRT) of the resection cavity, reducing dose exposure of the healthy brain. Patients and Methods: We analyzed 101 patients treated with either SRS/FSRT (n = 50) or WBRT (n = 51) following BM resection over a 5-year period. Propensity score adjustment was done for age, total number of BM, timepoint of BM diagnosis, controlled primary and extracranial metastases. A Cox Proportional Hazards model with univariate and multivariate analysis was fitted for overall survival (OS), local control (LC) and distant brain control (DBC). Results: Median patient age was 61 (interquartile range, IQR: 56-67) years and the most common histology was non-small cell lung cancer, followed by breast cancer. 38% of the patients had additional unresected BM. Twenty-four patients received SRS, 26 patients received FSRT and 51 patients received WBRT. Median OS in the SRS/FSRT subgroup was not reached (IQR NA-16.7 months) vs. 12.6 months (IQR 21.3-4.4) in the WBRT subgroup (hazard ratio, HR 3.3, 95%-CI: [1.5; 7.2] p < 0.002). Twelve-months LC-probability was 94.9% (95%-CI: [88.3; 100.0]) in the SRS subgroup vs. 81.7% (95%-CI: [66.6; 100.0]) in the WBRT subgroup (HR 0.2, 95%-CI: [0.01; 0.9] p = 0.037). Twelve-months DBC-probabilities were 65.0% (95%-CI: [50.8; 83.0]) and 58.8% (95%-CI: [42.9; 80.7]), respectively (HR 1.4, 95%-CI: [0.7; 2.7] p = 0.401). In propensity score-adjusted multivariate analysis, incomplete resection negatively impacted OS (HR 3.9, 95%-CI: [2.0;7.4], p < 0.001) and LC (HR 5.4, 95%-CI: [1.3; 21.9], p = 0.018). Excellent clinical performance (HR 0.4, 95%-CI: [0.2; 0.9], p = 0.030) and better graded prognostic assessment (GPA) score (HR 0.4, 95%-CI: [0.2; 1.0], p = 0.040) were prognostic of superior OS. A higher number of BM was associated with a greater risk of developing new distant BM (HR 5.6, 95%-CI: [1.0; 30.4], p = 0.048). In subgroup analysis, larger cavity volume (HR 1.1, 95%-CI: [1.0; 1.3], p = 0.033) and incomplete resection (HR 12.0, 95%-CI: [1.2; 118.3], p = 0.033) were associated with inferior LC following SRS/FSRT. Conclusion: This is the first propensity score-adjusted direct comparison of SRS/FSRT and WBRT following the resection of BM. Patients receiving SRS/FSRT showed longer OS and LC compared to WBRT. Future analyses will address the optimal choice of safety margin, dose and fractionation for postoperative stereotactic RT of the resection cavity.

Single-Isocenter Volumetric Modulated Arc Therapy vs. CyberKnife M6 for the Stereotactic Radiosurgery of Multiple Brain Metastases.

Introduction: Stereotactic radiosurgery (SRS) is becoming more frequently used for patients with multiple brain metastases (BMs). Single-isocenter volumetric modulated arc therapy (SI-VMAT) is an emerging alternative to dedicated systems such as CyberKnife (CK). We present a dosimetric comparison between CyberKnife M6 and SI-VMAT, planned at RayStation V8B, for the simultaneous SRS of five or more BM. Patients and Methods: Twenty treatment plans of CK-based single-session SRS to ≥5 brain metastases were replanned using SI-VMAT for delivery at an Elekta VersaHD linear accelerator. Prescription dose was 20 or 18 Gy, conformally enclosing at least 98% of the total planning target volume (PTV), with PTV margin-width adapted to the respective SRS technique. Comparatively analyzed quality metrics included dose distribution to the healthy brain (HB), including different isodose volumes, conformity, and gradient indices. Estimated treatment time was also compared. Results: Median HB isodose volumes for 3, 5, 8, 10, and 12 Gy were consistently smaller for CK-SRS compared to SI-VMAT (p < 0.001). Dose falloff outside the target volume, as expressed by the gradient indices GI_high and GI_low, was consistently steeper for CK-SRS compared to SI-VMAT (p < 0.001). CK-SRS achieved a median GI_high of 3.1 [interquartile range (IQR), 2.9-1.3] vs. 5.0 (IQR 4.3-5.5) for SI-VMAT (p < 0.001). For GI_low, the results were 3.0 (IQR, 2.9-3.1) for CK-SRS vs. 5.6 (IQR, 4.3-5.5) for SI-VMAT (p < 0.001). The median conformity index (CI) was 1.2 (IQR, 1.1-1.2) for CK-SRS vs. 1.5 (IQR, 1.4-1.7) for SI-VMAT (p < 0.001). Estimated treatment time was shorter for SI-VMAT, yielding a median of 13.7 min (IQR, 13.5-14.0) compared to 130 min (IQR, 114.5-154.5) for CK-SRS (p < 0.001). Conclusion: SI-VMAT offers enhanced treatment efficiency in cases with multiple BM, as compared to CyberKnife, but requires compromise regarding conformity and integral dose to the healthy brain. Additionally, delivery at a conventional linear accelerator (linac) may require a larger PTV margin to account for delivery and setup errors. Further evaluations are warranted to determine whether the detected dosimetric differences are clinically relevant. SI-VMAT could be a reasonable alternative to a dedicated radiosurgery system for selected patients with multiple BM.

A matched-pair analysis comparing stereotactic radiosurgery with whole-brain radiotherapy for patients with multiple brain metastases.

INTRODUCTION: Stereotactic radiosurgery (SRS) is an emerging treatment for patients with multiple brain metastases (BM). The present work compares the SRS of multiple brain metastases with whole-brain radiotherapy (WBRT). METHODS: We performed a matched-pair analysis for 128 patients with multiple BM treated with either SRS or WBRT over a 5-year period. Patients were matched pairwise for seven potential prognostic factors. A mixed Cox Proportional Hazards model with univariate and multivariate analysis was fitted for overall survival (OS). Distant intracranial progression-free survival (icPFS) and local control were assessed using a Fine and Gray subdistribution hazard model and considering death as competing event. RESULTS: Patients undergoing SRS had a median of 4 BM (range 3-16). 1-year local control of individual BM following SRS was 91.7%. Median OS in the SRS subgroup was 15.7 months (IQR 9.7-36.4) versus 8.0 months (interquartile range, IQR 3.8-18.0) in the WBRT subgroup (HR 2.25, 95% CI [1.5; 3.5], p < 0.001). Median icPFS was 8.6 (IQR 3.4-18.0) versus 22.4 (IQR 5.6-28.6) months, respectively (HR for WBRT 0.41, 95% CI [0.24; 0.71], p = 0.001). Following SRS, synchronous BM diagnosis (HR 2.51, 95% CI [1.30; 4.70], p = 0.004), higher initial number of BM (HR 1.21, 95% CI [1.10; 1.40], p = 0.002) and lung cancer histology (HR 2.05, 95% CI [1.10; 3.80], p = 0.024) negatively impacted survival. Excellent clinical performance (KPI 90%) was a positive prognosticator (HR 0.38, 95% CI [0.20; 0.72], p = 0.003), as was extracerebral tumor control (HR 0.48, 95% CI [0.24; 0.97], p = 0.040). Higher initial (HR 1.19, 95% CI [1.00; 1.40], p < 0.013) and total number of BM (HR 1.23, 95% CI [1.10; 1.40], p < 0.001) were prognostic for shorter icPFS. CONCLUSION: This is the first matched-pair analysis to compare SRS alone versus WBRT alone for multiple BM. OS was prolonged in the SRS subgroup and generally favorable in the entire cohort. Our results suggest SRS as a feasible and effective treatment for patients with multiple BM.

In vivo comparison of MRI- and CBCT-based 3D cephalometric analysis: beginning of a non-ionizing diagnostic era in craniomaxillofacial imaging?

OBJECTIVES: To evaluate whether magnetic resonance imaging (MRI) can serve as an alternative diagnostic tool to the "gold standard" cone-beam computed tomography (CBCT) in 3D cephalometric analysis. METHODS: In this prospective feasibility study, 12 patients (8 males, 4 females; mean age ± SD, 26.1 years ± 6.6) underwent 3D MRI and CBCT before orthognathic surgery. 3D cephalometric analysis was performed twice by two independent observers on both modalities. For each dataset, 27 cephalometric landmarks were defined from which 35 measurements (17 angles, 18 distances) were calculated. Statistical analyses included the calculation of Euclidean distances, intraclass correlation coefficients (ICCs), Bland-Altman analysis, and equivalence testing (linear mixed effects model) with a predefined equivalence margin of ± 1°/1 mm. RESULTS: Analysis of reliability for CBCT vs. MRI (intra-rater I/intra-rater II/inter-rater) revealed Euclidean distances of 0.86/0.86/0.98 mm vs. 0.93/0.99/1.10 mm for landmarks, ICCs of 0.990/0.980/0.986 vs. 0.982/0.978/0.980 for angles, and ICCs of 0.992/0.988/0.989 vs. 0.991/0.985/0.988 for distances. Bland-Altman analysis showed high levels of agreement between CBCT and MRI with bias values (95% levels of agreement) of 0.03° (- 1.49; 1.54) for angles and 0.02 mm (- 1.44; 1.47) for distances. In the linear mixed effects model, the mean values of CBCT and MRI measurements were equivalent. CONCLUSION: This feasibility study indicates that MRI enables reliable 3D cephalometric analysis with excellent agreement to corresponding measurements on CBCT. Thus, MRI could serve as a non-ionizing alternative to CBCT for treatment planning and monitoring in orthodontics as well as oral and maxillofacial surgery. KEY POINTS: • Clinically established 3D cephalometric measurements performed on MRI are highly reliable and show an excellent agreement with CBCT (gold standard). • The MRI technique applied in this study could be used as a non-ionizing diagnostic tool in orthodontics as well as oral and maxillofacial surgery. • Since most patients benefiting from 3D cephalometry are young in age, the use of MRI could substantially contribute to radiation protection and open up new possibilities for treatment monitoring.

Tooth loss in aggressive periodontitis: Results 25 years after active periodontal therapy in a private practice.

AIM: To assess tooth loss in patients with aggressive periodontitis (AgP) 10-35 years after active periodontal therapy (APT) in a private practice and to detect possible factors influencing tooth loss. MATERIAL AND METHODS: In 100 patients with AgP, tooth loss was recorded over a median follow-up period of 25.5 years after APT, retrospectively. Patient- and tooth-level factors were assessed with a Cox frailty regression model. RESULTS: Of 2,380 teeth, 227 were lost during a median follow-up time of 25.5 years (2.3 ± 3.6 teeth/patient, range 0-17 teeth), resulting in a mean tooth loss rate of 0.09 teeth/patient/year. At patient-level, statistically significant factors for tooth loss were smoking (p = .039) and the baseline diagnosis generalized AgP (p < .001). Influencing factors at tooth-level were location in the maxilla (p = .003), baseline bone loss (p < .001), molars (p < .001) and premolars (p < .001) as well as abutment teeth (p = .009). CONCLUSION: Tooth loss occurred rarely in patients with AgP treated in a private practice over a long-time period. Annual tooth loss rates are comparable with those described in university settings. Smoking, generalized form of AgP, location/type of tooth, baseline bone loss and abutment status could be detected as factors impacting upon tooth loss.

In vitro diagnostic accuracy of low-dose CBCT for evaluation of peri-implant bone lesions.

OBJECTIVES: To investigate the in vitro diagnostic accuracy of low-dose cone-beam computed tomography (LD-CBCT) for the detection, classification, and measurement of peri-implant bone lesions. MATERIAL AND METHODS: Titanium dental implants with all-ceramic single crowns (n = 24) were inserted into bovine bone. At twelve implants, four types of peri-implant bone lesions were created. Radiographic imaging was performed using three techniques: LD-CBCT, high-definition CBCT (HD-CBCT), and intraoral radiography (IR). The datasets were presented twice to four observers in a random order. Diagnostic accuracy was measured by calculating sensitivity and specificity, and analyzed using the McNemar's test at a significance level of 0.05. Absolute agreement between the defect sizes was assessed by means of intraclass correlation coefficients (ICC). RESULTS: For all three techniques, diagnostic accuracy and reliability for the detection of defects were almost perfect. The following order was found for classification of the different defect types (sensitivity/specificity): HD-CBCT (0.96/0.99) > LD-CBCT (0.93/0.98) > IR (0.71/0.95). No significant difference was found between the two CBCT techniques. Their performance was superior to that of IR. With regard to absolute agreement of defect size, LD-CBCT agreement with HD-CBCT (ICC, 95% confidence interval) was slight for defect depth (0.342, 0.181-0.625) and substantial for defect width (0.911, 0.775-0.963). CONCLUSION: Intraoral radiography is useful for detecting peri-implant bone lesions. LD-CBCT provides additional information regarding the geometry of defects. The even higher diagnostic accuracy of the HD-CBCT protocol tested needs to be carefully weighed against its radiation dose, which is 14 times higher than that of LD-CBCT.

Adaptive propensity score procedure improves matching in prospective observational trials.

BACKGROUND: Randomized controlled trials are the gold-standard for clinical trials. However, randomization is not always feasible. In this article we propose a prospective and adaptive matched case-control trial design assuming that a control group already exists. METHODS: We propose and discuss an interim analysis step to estimate the matching rate using a resampling step followed by a sample size recalculation. The sample size recalculation is based on the observed mean resampling matching rate. We applied our approach in a simulation study and to a real data set to evaluate the characteristics of the proposed design and to compare the results to a naive approach. RESULTS: The proposed design achieves at least 10% higher matching rate than the naive approach at final analysis, thus providing a better estimation of the true matching rate. A good choice for the interim analysis seems to be a fraction of around [Formula: see text] to [Formula: see text] of the control patients. CONCLUSION: The proposed resampling step in a prospective matched case-control trial design leads to an improved estimate of the final matching rate and, thus, to a gain in power of the approach due to sensible sample size recalculation.

In vivo accuracy of tooth surface reconstruction based on CBCT and dental MRI-A clinical pilot study.

OBJECTIVES: Guided implant surgery (GIS) requires alignment of virtual models to reconstructions of three-dimensional imaging. Accurate visualization of the tooth surfaces in the imaging datasets is mandatory. In this prospective clinical study, in vivo tooth surface accuracy was determined for GIS using cone-beam computed tomography (CBCT) and dental magnetic resonance imaging (dMRI). MATERIALS AND METHODS: CBCT and 3-Tesla dMRI were performed in 22 consecutive patients (mean age: 54.4 ± 15.2 years; mean number of restorations per jaw: 6.7 ± 2.7). Altogether, 92 teeth were included (31 incisor, 29 canines, 20 premolars, and 12 molars). Surfaces were reconstructed semi-automatically and registered to a reference standard (3D scans of stone models made from full-arch polyether impressions). Reliability of both methods was assessed using intraclass correlation coefficients. Accuracy was evaluated using the two one-sided tests procedure with a predefined equivalence margin of ±0.2 mm root mean square (RMS). RESULTS: Inter- and intrarater reliability of tooth surface reconstruction were comparable for CBCT and dMRI. Geometric deviations were 0.102 ± 0.042 mm RMS for CBCT and 0.261 ± 0.08 mm RMS for dMRI. For a predefined equivalence margin, CBCT and dMRI were statistically equivalent. CBCT, however, was significantly more accurate (p ≤ .0001). For both imaging techniques, accuracy did not differ substantially between different tooth types. CONCLUSION: Cone-beam computed tomography is an accurate and reliable imaging technique for tooth surfaces in vivo, even in the presence of metal artifacts. In comparison, dMRI in vivo accuracy is lower. Still, it allows for tooth surface reconstruction in satisfactory detail and within acceptable acquisition times.

Impact of social support on psychosocial symptoms and quality of life in cancer patients: results of a multilevel model approach from a longitudinal multicenter study.

Background: This prospective multicenter study aimed to investigate the courses of positive support (PS) and detrimental interaction (DI), two different aspects of social support, and the relation between social support and psychosocial distress and/or health-related quality of life (HRQOL) in a large sample of patients with different cancers. Methods: For this observational study, we enrolled adult patients with cancer from 13 comprehensive cancer centers (CCCs) in Germany. We included a total of 1087 patients in our analysis. We assessed the outcomes via standardized self-report questionnaires at three measurement points: at admission for acute care (T1), 6 (T2) and 12 months (T3) thereafter. Our outcome variables included PS and DI, depression and anxiety symptoms, distress, mental quality of life (MQoL) and physical QoL (PQoL). Data were analyzed using three-level hierarchical linear modeling (HLM) and group-based trajectory modeling. Results: During the first year after the cancer diagnosis, both PS and DI decreased in our sample. Baseline depression symptom severity was a significant predictor of PS and DI. Further analyses revealed significant associations between PS, DI and the course of depression and anxiety symptoms, and MQoL. PS buffered the negative effects of DI with regards to these variables. Low DI was associated with better PQoL, whereas PS was not. In general, the impact of social support on psychosocial outcomes was weak to moderate. Conclusions: Our findings provide evidence for the influence of PS and DI on psychosocial symptoms and HRQOL, and emphasize the importance of psycho-oncological interventions that strengthen PS and prevent or reduce DI for patients with cancer and their relatives.

Primary care physicians' satisfaction after health care reform: a cross-sectional study from two cities in Central Java, Indonesia.

BACKGROUND: In 2014, Indonesia launched a mandatory national health insurance system called Jaminan Kesehatan Nasional (JKN). The reform introduced new conditions for primary care physicians (PCPs) that could influence their job satisfaction. This study assessed PCPs' satisfaction and its predictors in two cities in Central Java, Indonesia, following the reform. METHODS: In this exploratory, cross-sectional study, we recruited 276 PCPs from the selected area. The data were all collected in 2016 using self-report questionnaires and interviews. PCPs' satisfaction was measured using a modified version of the Warr-Cook-Wall Job Satisfaction Scale which contains 19 items and uses a Likert-type response scale. Analysis of variance, the Kruskal-Wallis H test, both with Bonferroni corrections for post hoc testing, and Cochran-Mantel-Haenszel tests were used to compare overall job satisfaction between participant groups. We used simple and multiple linear regression analyses to identify the predictors of PCP satisfaction. Furthermore, a logistic regression analysis for binary outcome was applied to model the PCPs intention to leave practice. RESULTS: PCPs' mean overall satisfaction level was 3.19 out of 5. They tended to be very satisfied with their relationship with colleagues, working hours, and physical working conditions. However, the PCPs were dissatisfied with the new referral system, the JKN health services standards, and JKN policy. The factors significantly associated with job satisfaction (p <  0.001) included type of practice, performance of managerial tasks, and PCPs' perceptions of and experiences with patients. PCP satisfaction was negatively associated (p = 0.004) with PCPs' intention to leave their practice. CONCLUSIONS: The PCPs investigated in these two cities in Central Java had moderate satisfaction after the Indonesian health care reform. PCPs who worked in solo practices, performed managerial tasks, and had good experiences with patients tended to have higher satisfaction scores, which in turn prevented them from developing an intention to leave their practice. The three aspects that PCPs with which most dissatisfied were related with the JKN reform. Because of that, the government and BPJS for Health should aim to improve the JKN system in order to increase PCPs' satisfaction.

Transient N-glycosylation abnormalities likely due to a de novo loss-of-function mutation in the delta subunit of coat protein I.

Accurate glycosylation of proteins is essential for their function and their intracellular transport. Numerous diseases have been described, where either glycosylation or intracellular transport of proteins is impaired. Coat protein I (COPI) is involved in anterograde and retrograde transport of proteins between endoplasmic reticulum and Golgi, where glycosylation takes place, but no association of defective COPI proteins and glycosylation defects has been described so far. We identified a patient whose phenotype at a first glance was reminiscent of PGM1 deficiency, a disease that also affects N-glycosylation of proteins. More detailed analyses revealed a different disease with a glycosylation deficiency that was only detectable during episodes of acute illness of the patient. Trio-exome analysis revealed a de novo loss-of-function mutation in ARCN1, coding for the delta-COP subunit of COPI. We hypothesize that the capacity of flow through Golgi is reduced by this defect and at high protein synthesis rates, this bottleneck also manifests as transient glycosylation deficiency.

Pre-Operative Versus Post-Operative Radiosurgery of Brain Metastases-Volumetric and Dosimetric Impact of Treatment Sequence and Margin Concept.

BACKGROUND: Pre-operative radiosurgery (SRS) preceding the resection of brain metastases promises to circumvent limitations of post-operative cavity SRS. It minimizes uncertainties regarding delineation and safety margins and could reduce dose exposure of the healthy brain (HB). METHODS: We performed a systematic treatment plan comparison on 24 patients who received post-operative radiosurgery of the resection cavity at our institution. Comparative treatment plans were calculated for hypofractionated stereotactic radiotherapy (7 × 5 Gray (Gy)) in a hypothetical pre-operative (pre-op) and two post-operative scenarios, either with (extended field, post-op-E) or without the surgical tract (involved field, post-op-I). Detailed volumetric comparison of the resulting target volumes was performed, as well as dosimetric comparison focusing on targets and the HB. RESULTS: The resection cavity was significantly smaller and different in morphology from the pre-operative lesion, yielding a low Dice Similarity Coefficient (DSC) of 53% (p = 0.019). Post-op-I and post-op-E targets showed high similarity (DSC = 93%), and including the surgical tract moderately enlarged resulting median target size (18.58 ccm vs. 22.89 ccm, p < 0.001). Dosimetric analysis favored the pre-operative treatment setting since it significantly decreased relevant dose exposure of the HB (Median volume receiving 28 Gy: 6.79 vs. 10.79 for pre-op vs. post-op-E, p < 0.001). Dosimetrically, pre-operative SRS is a promising alternative to post-operative cavity irradiation that could furthermore offer practical benefits regarding delineation and treatment planning. Comparative trials are required to evaluate potential clinical advantages of this approach.

Converting habits of antibiotic use for respiratory tract infections in German primary care - study protocol of the cluster-randomized controlled CHANGE-3 trial.

BACKGROUND: The overuse of antibiotics is a major cause for the worldwide rise of antibiotic resistance. Although it is well known that acute respiratory tract infections (ARTI) are mainly caused by viruses and are often self limiting, antibiotics are too frequently prescribed in primary care. CHANGE-3 examines whether a complex intervention focusing on improving communication and provision of prescribing feedback reduces antibiotic use in patients suffering from ARTI. METHODS/DESIGN: The CHANGE-3 trial is a cluster-randomized controlled trial nested within a web-based public campaign conducted in two regions in Germany. A total of 114 medical practices will be included. Practices randomized to the intervention will receive a practice-specific antibiotic-prescription feedback and an educational outreach visit. During the visit the whole practice team will receive an introduction to e-learning modules addressing patient-centered communication on antibiotics. Furthermore, the practices will receive tablet PCs with information on antibiotics and the treatment of ARTI to be presented to patients. Practices randomized to the control will provide care as usual. The primary outcome measure is the antibiotic prescribing rate for patients with a history of ARTI. Data collected before the intervention, during the intervention and after the intervention will be compared. The use of narrow- vs. broad-spectrum antibiotics will be analyzed as a secondary outcome. A process evaluation is also part of the trial. DISCUSSION: This study should contribute to the growing body of research on reducing antibiotic prescription. TRIAL REGISTRATION: ISRCTN, ISRCTN15061174 . Registered retrospectively on 13 July 2018.