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Background and Objective: Objective of this study was to determine whether the diagnostic accuracy of the Diagnostic Criteria for Temporomandibular Disorders (DC/TMD) is sufficient for use among schoolchildren aged 8‐12 years. Methods: This prospective cohort study on diagnostic accuracy with calibrated examiners was conducted among 533 children of both sexes aged 8‐12 years, with and without TMD symptoms, selected randomly from the Rhein‐Neckar district. Self‐reporting of non‐dental facial pain was used as the reference standard, against which we calculated the following for the pain‐related items of the DC/TMD (index test): sensitivity, specificity, positive and negative likelihood ratios, diagnostic odds ratio, accuracy and 95% Wilson Score confidence intervals. We also calculated the area under the receiver‐operating characteristic (AUROC) curve displaying sensitivity and specificity. Results: Our final sample consisted of 282 children, half of whom reported having facial pain and 3.2% reported sounds from the temporomandibular joints (TMJs). Despite high specificity (90.78%; 95% confidence interval (CI): [84.86%; 94.53%]), sensitivity of the adapted DC/TMD for pain on maximum jaw opening was poor (37.59%; 95% CI: [30.02%; 45.81%]). For pain on palpation, more similar values were recorded for sensitivity (74.47%; 95% CI: [66.69%; 80.95%]) and specificity (70.21%; 95% CI: [62.21%; 77.14%]). The diagnostic odds ratio was >1 for both examinations. The AUROC for pain on opening was 68.39% (95% CI: [62.62%; 74.16%]), and for pain on palpation, it was 74.63% (95% CI: [69.45%; 79.81%]), whereas the combination of both resulted to an AUROC of 74.09% (95% CI: [68.96%; 79.21%]). It was not possible to measure the diagnostic accuracy of the DC/TMD regarding TMJ sounds or jaw‐opening limitations, as they occurred too rarely in our sample. Conclusion: In this study, the diagnostic accuracy of the DC/TMD for TMD‐related pain in children was lower than that recorded for adults in previous studies. [ABSTRACT FROM AUTHOR]

Abstract Background Quality of life in tumour patients following combined ablative and reconstructive head and neck surgery varies significantly. This is at least partially due to differences in speech and swallowing function. A tool to objectively evaluate articulation by magnetic resonance imaging (MRI) has now been tested alongside ultrasound examination. Patients and methods A standardized sequence of phonemes from the German language was established in 20 healthy volunteers and recorded in different planes by MRI and ultrasound. Phonemes were identified through recognition of typical tongue configurations by two different observers. An algorithm for metric analysis of articulation in terms of distances and angles for five extreme points on the tongue (anterior, posterior, cranial and two basal corners) was designed. The findings in these volunteers were subsequently compared with the results of an examination of a tumour patient. Results Physiological articulation was visualized and evaluated both by MRI and ultrasound. There was a high intra-class correlation coefficient for measurements between independent observers. Tongue position for certain phonemes was mostly constant in healthy patients of different age groups, with gender-specific differences. In a first comparison, tongue position in a patient with tongue cancer differed significantly from this position, both pre- and postoperatively. In agreement with clinical articulation quality, the tongue position of the patient returned to almost normal within 12 months postoperatively. Conclusion Both ultrasound and MRI are appropriate instruments for visualization of articulation and objective measurements to evaluate speech in tumour patients. Whilst MRI is more precise and can identify more subtle differences, ultrasound is a valid alternative due to its wider availability and broader applicability. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: The purpose of this work was to investigate the long‐term effectiveness of oral health education of caregivers in nursing homes with care‐dependent and cognitively impaired residents. Methods: Fourteen nursing homes with a total of 269 residents were allocated to a control group, with continued normal care, or to an intervention group. Allocation was performed at nursing home level. In the intervention group, caregivers were given oral health education, and ultrasonic cleaning devices were provided to clean removable prostheses. Oral health was assessed at baseline and after 6 and 12 months by use of the Plaque Control Record (PCR), Gingival Bleeding Index (GBI), Community Periodontal Index of Treatment Needs (CPITN) and Denture Hygiene Index (DHI). Mixed models for repeated measures were performed for each target variable, with possible confounding factors (intervention/control group, age, sex, residence location and care‐dependence). Results: In the control group, no changes of target variables were observed between baseline and the 6‐ and 12‐month follow‐ups. After 6 and 12 months, PCR and DHI were significantly improved in the intervention group. For PCR, the intergroup difference of improvements was −14.4 (95% CI: −21.8; −6.9) after 6 months. After 12 months, the difference was −16.2 (95% CI: −27.7; −4.7). For DHI, the intergroup difference compared to baseline was −15 (95% CI: −23.6; −6.5) after 6 months and −13.3 (95% CI: −24.9; −1.8) after 12 months. There was neither a statistically significant effect on GBI nor on CPITN. Care‐dependency showed a substantial trend to smaller improvements in PCR (P = .074), while an inverse effect was apparent for DHI (P < .001). Conclusions: Education of caregivers improves and maintains the oral health of care‐dependent nursing home residents over longer periods. Use of ultrasonic devices is a promising means of improving denture hygiene among the severely care‐dependent. Such interventions can be easily and cheaply implemented in routine daily care. [ABSTRACT FROM AUTHOR]

Purpose To evaluate the short- and long-term impact of mandibular-only advancement on pharyngeal airway space (PAS) changes by using cone-beam computed tomography (CBCT) and a new segmentation software. Furthermore, to determine whether a correlation exists between forward movement and PAS gain. Materials and methods A retrospective evaluation of a homogeneous cohort of Class II patients who had undergone mandibular-only advancement was performed. Pre- (T0), post- (T1), and 1-year post-operative (T2) CBCT scans were obtained in each case, and the changes in PAS parameters (volume and smallest cross-sectional area) were compared with new segmentation software. Mandibular advancement was measured and correlated with PAS parameters. Results A significant postoperative gain in all airway parameters compared with baseline was shown for T1 (p = 0.02), with an additional increase for T2 (p < 0.001). No significant linear association between the movement of the measurement points and any other PAS parameters could be discerned (p > 0.05). Conclusion Our findings indicate that bilateral mandibular-only advancement surgery results in a significant widening of the PAS in Class II patients. Long-term adaption of the PAS also occurs after surgery implying an additional gain of PAS over time. Sicat Air® software seems to be a sufficient and promising tool for PAS evaluation. [ABSTRACT FROM AUTHOR]

Purpose Combined ablative and reconstructive oral maxillofacial surgery involves a multitude of anatomical and functional structures for speech and swallowing. Although there are a few methods to objectively examine swallowing function, this is not true for speech. We describe the development of an objective visualization and measurement tool for magnetic resonance imaging (MRI) to evaluate speech and its first application in a patient. Material and methods A total of 20 healthy patients and one patient with squamous cell carcinoma localized in the anterior floor of the mouth were included in the study. Examination included an MRI examination of a paced, defined set of fictive words representing all sounds of the German language. The patient underwent MRI preoperatively and 1, 3, 6 and 12 months postoperatively. MRI findings were correlated with speech intelligibility. Results In sagittal planes, the correct identification of vowels and consonants was feasible and showed a high accordance between two independent observers and repetitions. Measurements for the patient showed significant deviations 1 month postoperatively but gradually decreased over time. Aberrant values were persistent for sound /s/. Findings correlated with clinical findings of speech intelligibility. Conclusion The presented tool seems to be promising for evaluating articulation in (tumor) patients. [ABSTRACT FROM AUTHOR]

References 1 Bozorgmehr F, Chung I, Christopoulos P. Thoracic radiotherapy plus Durvalumab in elderly and/or frail NSCLC stage III patients unfit for chemotherapy - employing optimized (hypofractionated) radiotherapy to foster durvalumab efficacy: study protocol of the TRADE-hypo trial. After n = 18 patients have been enrolled to the HYPO- or CON-treatment arm, respectively, an interim efficacy analysis for the respective arm will be conducted based on the objective response rate (ORR) at 12 weeks after first durvalumab administration", the sentence was refined to "[...] the objective response rate (ORR), B when the 18th patient in each arm has undergone first radiographic assessment ( b at 12 weeks after first durvalumab administration B ) b .". [Extracted from the article]

Objectives: Treatment of the severely atrophic maxilla with dental implants is challenging due to the insufficient horizontal and vertical bone volume and centripetal resorption pattern of the maxilla. Bone-augmentation procedures are often necessary prior to implant placement. The objective of this study was to assess the suitability of using calvarial bone grafts to enable implant placement in severely atrophic maxillae. Material and Methods: Seventeen patients with severe atrophic edentulous maxillae were reconstructed with autogenous calvarial bone grafts. After a 4-month healing period, the patients received a total of 134 dental implants, which were left to heal in submerged positions for 3 months before prosthetic rehabilitation was performed. Patients were followed clinically and radiographically for an average observation period of 53.94 months. Results: At the intraoral recipient sites, two infections developed, causing partial loss of the respective bone grafts. Implant placement, however, was possible at all sites. No donor-site complications occurred. Two of 134 implants were lost in two patients prior to prosthetic loading. The implant survival rate was 98.51%. The implant success rate was 87.6%, and a mean marginal bone loss of 0.62 mm (SD 0.77 mm) was documented. Conclusions: Patients with severe bone atrophy of the edentulous maxilla can be successfully reconstructed with calvarial bone grafts and dental implants and show a stable clinical and radiographic situation after a mean observation period of 53 months. [ABSTRACT FROM AUTHOR]

Purpose Bone defects after resective tumor surgeries often require the use of microvascular reanastomized bone grafts for reconstruction. The decision as to which specific flap is most suitable for the particular patient is dependent on various factors. The aspects donor site morbidity and quality of life are rarely taken into account in this connection. The aim of this study was to analyze whether these factors, in the future, should influence the choice of donor site. Material and methods In this study, the donor sites of 46 patients with respect to deep-circumflex iliac artery (DCIA) and fibula flaps were analyzed using subjective and objective parameters. The primary outcome was postoperative pain measured by VAS. Postoperative complication evaluations as well as 2 orthopedic scores were implemented (American Orthopedic Foot and Ankle Society (AOFAS) Ankle-Hindfoot Score and Harris Hip Score) and the patients' quality of life was assessed using the 36-Item Short Form (SF-36) questionnaire to quantify donor site impairment. Results Postoperative pain was rated with a mean value of 42.4 mm (SD 34.8) for the DCIA group and 36.9 mm (SD 37.1) for the fibula group (p = 0.617). After a mean period of 13.72 months, pain was rated with a mean value of 15.3 mm (SD 21.7) for DCIA and 13.3 mm (SD 22.6 mm) for the fibula (p = 0.763). Persistent pain, however, was recorded only in 11.11% of DCIA patients and 5.26% of fibula patients. Furthermore pain intensity was higher in the DCIA group. A changed gait pattern was observed in 59.26% of DCIA patients and 21.05% of fibula patients. DCIA patients required walking aids for walking and stair climbing more often. Looking at the results of the 2 orthopedic scores, fibula patients showed slightly better results. Concerning quality of life, patients after reconstructive surgery with DCIA flaps showed slight better results than patients in the fibula group. Conclusions Taking the results of this study into account, the outcome in terms of pain, morbidity and quality of life did not show a significant superiority of any donor site. [ABSTRACT FROM AUTHOR]

The implementation of a bachelor degree in Interprofessional Health Care at the University of Heidelberg, Germany, has fostered the need to evaluate the impact of this innovative programme. The University of the West of England Interprofessional Questionnaire (UWE-IP) was developed for longitudinal evaluation of an interprofessional curriculum. The UWE-IP consists of 35 items in four scales: “Communication and Teamwork Scale,” “Interprofessional Learning Scale,” “Interprofessional Interaction Scale,” and “Interprofessional Relationships Scale.” The UWE-IP was translated to German according to international guidelines. Psychometrics were assessed: reliability of the four scales was tested with Cronbach‘s alpha and confirmatory factor analysis was performed to examine the underlying factor structure. The sample consisted of 326 datasets. Reliability for the scales was between 0.75 and 0.90. The underlying factor structure showed a good fit. We conclude that the German UWE-IP shows good psychometrics and recommend its use for evaluation of interprofessional learning activities. These results add to the body of knowledge on evaluation instruments in interprofessional education. [ABSTRACT FROM PUBLISHER]

The APROVE study is a prospective one-arm phase-2 study investigating the safety and treatment tolerability of postoperative proton beam therapy in women with uterine cervical or endometrial cancer. In this analysis, we report the primary study endpoint of safety and treatment tolerability as well as toxicity rates and progression-free survival (PFS). 25 patients were treated with postoperative proton beam therapy with a total dose of 45 to 50.4 Gy (RBE) in 5 to 6 × 1.8 Gy (RBE) fractions weekly using active raster-scanning intensity modulated proton beam therapy (IMPT). Sequential or simultaneous platinum-based chemotherapy was administered if indicated. The primary endpoint was defined as the lack of any acute ≥grade 3 gastrointestinal (GI) or urogenital (GU) toxicity according to the Common Terminology Criteria for Adverse Events v 4.0 or premature treatment abortion. Secondary endpoints were clinical symptoms and toxicity, quality of life, and PFS. All patients completed IMPT according to the protocol, with a median treatment duration of 43 days (range, 33 to 51 days). No patient developed gastrointestinal or genitourinary toxicity ≥grade 3, and the treatment tolerability rate was 100%. Therefore, the null hypothesis H0: Tolerability Rate ≤80% could be rejected in favor of the alternative hypothesis H1: Tolerability rate >80% using an exact binomial test with a one-sided significance level of α = 10% (one-sided P value P =.0059). The median follow-up time after the end of IMPT was 25.1 months (range, 20.2 to 50.3 months). 18 of 25 (75%) patients completed the study follow-up of 24 months. 7 patients had progressive disease. Kaplan-Meier-estimated mean PFS was 39.9 months (95% confidence interval: 33.37 to 46.5 months). Postoperative IMPT is a safe treatment option for cervical and endometrial cancer patients, with only low-grade acute and late toxicities. Larger randomized trials are necessary to further assess the potential of IMPT and improve patient selection. [ABSTRACT FROM AUTHOR]

Unlike in the field of visual scene recognition, where tremendous advances have taken place due to the availability of very large datasets to train deep neural networks, inference from medical images is often hampered by the fact that only small amounts of data may be available. When working with very small dataset problems, of the order of a few hundred items of data, the power of deep learning may still be exploited by using a pre-trained model as a feature extractor and carrying out classic pattern recognition techniques in this feature space, the so-called few-shot learning problem. However, medical images are highly complex and variable, making it difficult for few-shot learning to fully capture and model these features. To address these issues, we focus on the intrinsic characteristics of the data. We find that, in regimes where the dimension of the feature space is comparable to or even larger than the number of images in the data, dimensionality reduction is a necessity and is often achieved by principal component analysis or singular value decomposition (PCA/SVD). In this paper, noting the inappropriateness of using SVD for this setting we explore two alternatives based on discriminant analysis (DA) and non-negative matrix factorization (NMF). Using 14 different datasets spanning 11 distinct disease types we demonstrate that at low dimensions, discriminant subspaces achieve significant improvements over SVD-based subspaces and the original feature space. We also show that at modest dimensions, NMF is a competitive alternative to SVD in this setting. The implementation of the proposed method is accessible via the following link. [ABSTRACT FROM AUTHOR]

Background: When running a randomized controlled trial (RCT), a clinical site may face a situation when an eligible trial participant is to be randomized to the treatment that is not available at the site. In this case, there are two options: not to enroll the participant, or, without disclosing to the site, allocate the participant to a treatment arm with drug available at the site using a built-in feature of the interactive response technology (IRT). In the latter case, one has employed a "forced randomization" (FR). There seems to be an industry-wide consensus that using FR can be acceptable in confirmatory trials provided there are "not too many" instances of forcing. A better understanding of statistical properties of FR is warranted. Methods: We described four different IRT configurations with or without FR and illustrated them using a simple example. We discussed potential merits of FR and outlined some relevant theoretical risks and risk mitigation strategies. We performed a search using Cortellis Regulatory Intelligence database (IDRAC) (www.cortellis.com) to understand the prevalence of FR in clinical trial practice. We also proposed a structured template for development and evaluation of randomization designs featuring FR and showcased an application of this template for a hypothetical multi-center 1:1 RCT under three experimental settings ("base case", "slower recruitment", and "faster recruitment") to explore the effect of four different IRT configurations in combination with three different drug supply/re-supply strategies on some important operating characteristics of the trial. We also supplied the Julia code that can be used to reproduce our simulation results and generate additional results under user-specified experimental scenarios. Results: FR can eliminate refusals to randomize patients, which can cause frustration for patients and study site personnel, improve the study logistics, drug supply management, cost-efficiency, and recruitment time. Nevertheless, FR carries some potential risks that should be reviewed at the study planning stage and, ideally, prospectively addressed through risk mitigation planning. The Cortellis search identified only 9 submissions that have reported the use of FR; typically, the FR option was documented in IRT specifications. Our simulation evidence showed that under the considered realistic experimental settings, the percentage of FR is expected to be low. When FR with backfilling was used in combination with high re-supply strategy, the final treatment imbalance was negligibly small, the proportion of patients not randomized due to the lack of drug supply was close to zero, and the time to complete recruitment was shortened compared to the case when FR was not allowed. The drug overage was primarily determined by the intensity of the re-supply strategy and to a smaller extent by the presence or absence of the FR feature in IRT. Conclusion: FR with a carefully chosen drug supply/re-supply strategy can result in quantifiable improvements in the patients' and site personnel experience, trial logistics and efficiency while preventing an undesirable refusal to randomize a patient and a consequential unblinding at the site. FR is a useful design feature of multi-center RCTs provided it is properly planned for and carefully implemented. [ABSTRACT FROM AUTHOR]

Objectives: Primary objectives • To assess the time from randomisation until an improvement within 84 days defined as two points on a seven point ordinal scale or live discharge from the hospital in high-risk patients (group 1 to group 4) with SARS-CoV-2 infection requiring hospital admission by infusion of plasma from subjects after convalescence of SARS-CoV-2 infection or standard of care. Secondary objectives • To assess overall survival, and the overall survival rate at 28 56 and 84 days. • To assess SARS-CoV-2 viral clearance and load as well as antibody titres. • To assess the percentage of patients that required mechanical ventilation. • To assess time from randomisation until discharge.Trial Design: Randomised, open-label, multicenter phase II trial, designed to assess the clinical outcome of SARS-CoV-2 disease in high-risk patients (group 1 to group 4) following treatment with anti-SARS-CoV-2 convalescent plasma or standard of care.Participants: High-risk patients >18 years of age hospitalized with SARS-CoV-2 infection in 10-15 university medical centres will be included. High-risk is defined as SARS-CoV-2 positive infection with Oxygen saturation at ≤ 94% at ambient air with additional risk features as categorised in 4 groups: • Group 1, pre-existing or concurrent hematological malignancy and/or active cancer therapy (incl. chemotherapy, radiotherapy, surgery) within the last 24 months or less. • Group 2, chronic immunosuppression not meeting the criteria of group 1. • Group 3, age ≥ 50 - 75 years meeting neither the criteria of group 1 nor group 2 and at least one of these criteria: Lymphopenia < 0.8 x G/l and/or D-dimer > 1μg/mL. • Group 4, age ≥ 75 years meeting neither the criteria of group 1 nor group 2. Observation time for all patients is expected to be at least 3 months after entry into the study. Patients receive convalescent plasma for two days (day 1 and day 2) or standard of care. For patients in the standard arm, cross over is allowed from day 10 in case of not improving or worsening clinical condition. Nose/throat swabs for determination of viral load are collected at day 0 and day 1 (before first CP administration) and subsequently at day 2, 3, 5, 7, 10, 14, 28 or until discharge. Serum for SARS-Cov-2 diagnostic is collected at baseline and subsequently at day 3, 7, 14 and once during the follow-up period (between day 35 and day 84). There is a regular follow-up of 3 months. All discharged patients are followed by regular phone calls. All visits, time points and study assessments are summarized in the Trial Schedule (see full protocol Table 1). All participating trial sites will be supplied with study specific visit worksheets that list all assessments and procedures to be completed at each visit. All findings including clinical and laboratory data are documented by the investigator or an authorized member of the study team in the patient's medical record and in the electronic case report forms (eCRFs).Intervention and Comparator: This trial will analyze the effects of convalescent plasma from recovered subjects with SARS-CoV-2 antibodies in high-risk patients with SARS-CoV-2 infection. Patients at high risk for a poor outcome due to underlying disease, age or condition as listed above are eligible for enrollment. In addition, eligible patients have a confirmed SARS-CoV-2 infection and O2 saturation ≤ 94% while breathing ambient air. Patients are randomised to receive (experimental arm) or not receive (standard arm) convalescent plasma in two bags (238 - 337 ml plasma each) from different donors (day 1, day 2). A cross over from the standard arm into the experimental arm is possible after day 10 in case of not improving or worsening clinical condition.Main Outcomes: Primary endpoints: The main purpose of the study is to assess the time from randomisation until an improvement within 84 days defined as two points on a seven-point ordinal scale or live discharge from the hospital in high-risk patients (group 1 to group 4) with SARS-CoV-2 infection requiring hospital admission by infusion of plasma from subjects after convalescence of a SARS-CoV-2 infection or standard of care. Secondary endpoints: • Overall survival, defined as the time from randomisation until death from any cause 28-day, 56-day and 84-day overall survival rates. • SARS-CoV-2 viral clearance and load as well as antibody titres. • Requirement mechanical ventilation at any time during hospital stay (yes/no). • Time until discharge from randomisation. • Viral load, changes in antibody titers and cytokine profiles are analysed in an exploratory manner using paired non-parametric tests (before - after treatment).Randomisation: Upon confirmation of eligibility (patients must meet all inclusion criteria and must not meet exclusion criteria described in section 5.3 and 5.4 of the full protocol), the clinical site must contact a centralized internet randomization system ( https://randomizer.at/ ). Patients are randomized using block randomisation to one of the two arms, experimental arm or standard arm, in a 1:1 ratio considering a stratification according to the 4 risk groups (see Participants).Blinding (masking): The study is open-label, no blinding will be performed.Numbers To Be Randomised (sample Size): A total number of 174 patients is required for the entire trial, n=87 per group.Trial Status: Protocol version 1.2 dated 09/07/2020. A recruitment period of approximately 9 months and an overall study duration of approximately 12 months is anticipated. Recruitment of patients starts in the third quarter of 2020. The study duration of an individual patient is planned to be 3 months. After finishing all study-relevant procedures, therapy, and follow-up period, the patient is followed in terms of routine care and treated if necessary. Total trial duration: 18 months Duration of the clinical phase: 12 months First patient first visit (FPFV): 3rd Quarter 2020 Last patient first visit (LPFV): 2nd Quarter 2021 Last patient last visit (LPLV): 3rd Quarter 2021 Trial Report completed: 4th Quarter 2021 TRIAL REGISTRATION: EudraCT Number: 2020-001632-10, https://www.clinicaltrialsregister.eu/ctr-search/trial/2020-001632-10/DE , registered on 04/04/2020.Full Protocol: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (Additional file 2). The eCRF is attached (Additional file 3). [ABSTRACT FROM AUTHOR]

Background: Non-small cell lung cancer is the most common cause of cancer death worldwide, highlighting the need for novel therapeutic concepts. In particular, there is still a lack of treatment strategies for the group of elderly and frail patients, who are frequently not capable of receiving standard therapy regimens. Despite comprising the majority of lung cancer patients, this group is underrepresented in clinical trials. This applies also to elderly and frail patients suffering from unresectable stage III NSCLC, who are unfit for chemotherapy, and, therefore, cannot receive the standard therapy comprising of radiochemotherapy and the recently approved subsequent durvalumab consolidation therapy. These patients often receive radiotherapy only, which raises the concern of undertreatment. The TRADE-hypo trial aims at optimizing treatment of this patient group by combining radiotherapy with concomitant durvalumab administration, thereby employing the immune-promoting effects of radiotherapy, and determining safety, feasibility, and efficacy of this treatment.Methods/ Design: In this prospective phase II clinical trial, durvalumab therapy will be combined with either conventionally fractionated (CON-group) or hypofractionated (HYPO-group) thoracic radiotherapy. A safety stop-and-go lead-in phase will assess safety of hypofractionated radiotherapy with respect to severe pneumonitis in small patient cohorts before opening full enrollment. Tumor tissue, blood and stool samples will be collected before and during the study period to investigate the immunological mechanisms responsible for checkpoint inhibitor efficacy and immune-promoting effects of radiotherapy.Discussion: Preclinical data suggests that irradiation-induced immunogenicity can be further increased if applied in a hypofractionated setting, potentially boosting the expected synergistic effect with immune checkpoint inhibition in restoring the immune anti-tumor response. If proven safe and efficient, a hypofractionated radiation schedule can provide a considerably more practicable option for the patient. Taking into consideration the intend to develop a combination treatment strategy that can be made available to patients soon after proving to be efficient and the potentially elevated toxicity of a hypofractionated radiotherapy approach, this trial was designed as a two-trials-in-one design. An accompanying translational research program is planned striving to gain insights into the tumor-host biology and to identify suitable biomarkers to predict therapy response.Trial Registration: Clinicaltrials.gov , NCT04351256 . Registered 17 April 2020, Eudra-CT, 2019-002192-33 . Registered 24 October 2019. [ABSTRACT FROM AUTHOR]

Background: Elderly patients represent a major fraction of non-small cell lung cancer (NSCLC) patients in routine clinical practice, but they are still underrepresented in clinical trials. In particular, data regarding efficacy and safety in frail or elderly patients with respect to immunotherapy are lacking. Importantly, immunosenescence in elderly patients might interfere with activities of immune-modulating drugs such as PD-1/PD-L1 inhibitors. Thus, there is an urgent need to assess safety and efficacy of such inhibitors in this group.Methods/design: This prospective, open label, treatment stratified, randomized phase II study will enroll 200 patients with stage IV NSCLC amenable at least to single-agent chemotherapy (CT). Eligible patients must be aged 70 years or older and/or "frail" (Charlson Comorbidity Index > 1) or have a restricted performance status (Eastern Cooperative Oncology Group, ECOG > 1). Patients are stratified according to modified Cancer and Age Research Group (CARG) score: "fit" patients are allocated to combination CT (carboplatin/nab-paclitaxel) and "less fit" patients receive single-agent CT (gemcitabine or vinorelbine). After allocation to strata, patients are randomized 1:1 to receive either four cycles of CT or two cycles of CT followed by two cycles of durvalumab and subsequent maintenance treatment with durvalumab every 4 weeks. The primary endpoint is the rate of treatment-related grade III/IV adverse events (Common Terminology Criteria for Adverse Events (CTCAE) V4.03). As secondary endpoints, progression-free survival (PFS) according to Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1, response rate (RR), overall survival (OS), descriptive subgroup analyses according to PD-L1 expression, and quality of life are addressed. Geriatric screening assessments and functional tests will be performed to complete the phenotyping of a potential "frail" and "elderly" patient cohort. The trial is accompanied by a biomaterial repository to explore potential biomarkers.Discussion: The DURATION trial will prospectively investigate the safety and tolerability of anti-PD-L1 treatment with durvalumab after chemotherapy in elderly and frail patients and thereby provide new insights into the effect of PD-L1 blockade and the impact of immunosenescence in this cohort of patients.Trial Registration: ClinicalTrials.gov, NCT03345810; initially registered on 17 November 2017. Eudra-CT, 2016-003963-20; initially registered on 3 January 2017. [ABSTRACT FROM AUTHOR]

Background: To evaluate early failure and possible risk factors for failure of dental implants placed under practice-based conditions. Methods: To clarify the research question, anonymized data from 106 patients with 186 dental implants were analyzed. The presence of sucessful healing (yes/no) at the time of incorporation of the final prosthesis was assessed. Mixed models were compiled for each target variable to enable estimation of the effects of patient-related and implant-related conditions on the risk of early implant failure. Results: Nine out of 186 implants (4.8%) placed in 106 participants failed before incorporation of the final prosthesis. The use of shorter implants (< 10 mm) and the need for augmentation procedures were associated with a greater risk of early implant failure. For shorter implants, the risk was 5.8 times greater than that for longer implants (p = 0.0230). Use of augmentation procedures increased the risk by a factor of 5.5 (p = 0.0174). Conclusions: Implants placed in the dental practice with a specialization in implantology heal successfully. The use of augmentation procedures and of implants shorter than 10 mm seems to be associated with a greater risk of early implant failure. [ABSTRACT FROM AUTHOR]