Oral and Subcutaneous Anticancer Therapy Training Course for Non-physician Healthcare Professionals: a Survey Evaluating the Relevance of its Content and its Implications in the Practice of Cancer Care.

The creation of antitumor agents with an oral or subcutaneous route of administration has had important positive implications in the development of drugs to treat cancers, but issues such as false drug intake, uncontrolled side effects, and limited supervision may jeopardize the ability of these agents to improve treatment. A potential solution is the recruitment of non-physician healthcare professionals (i.e., nurses and physician assistants) and a special training course for them that focuses on the improvement of patient compliance. We developed and implemented three special professional training modules for non-physician healthcare professionals, which focus on the pharmacological aspects and side effects of oral and subcutaneous antitumor medications in regard to management strategies and communication issues that these non-physician healthcare professionals should address. Subsequently, we administered a questionnaire survey evaluating the course content and the implementation of the course in practice to the training participants to collect data for its implementation. Of 165 questionnaires that were administered, 44 (27%) were answered. The participants rated the course as being highly useful for their daily work. The participants reported a significant improvement in their professional expertise from the course. They emphasized the importance of medical topics and practical content to be included in the course delivery. The course encouraged 75% of the responders to start independent consultations with cancer patients that focused on questions of medication adherence for oral and subcutaneous antitumor medications, as well as the management of their side effects. Based on our results, at least a portion of the non-physician healthcare workforce is highly interested in engaging in active and autonomous co-supervision of patients who are treated with oral and subcutaneous antitumor medications. In addition to the theoretical basics of the treatment modalities, educational courses on oral and subcutaneous antitumor medications for non-physician healthcare professionals should focus on practical training and topics relevant to patient care.

Overdentures borne on less than four abutments with telescopic crowns: 5-year results of a retrospective clinical study.

OBJECTIVE: Retrospective evaluation of the clinical performance of tooth-supported overdentures retained by resilient telescopic crowns with occlusal clearance fit (ODRTC) in severely reduced dentition (1-3 remaining teeth). MATERIALS AND METHODS: A total of 313 ODRTCs were inserted in an undergraduate prosthodontic program (University Medical Center, Goettingen, Germany) between 2000 und 2012. Data regarding 263 ODRTCs in 221 patients were reevaluated (observational period: 64.5 ± 34.8 months), and time-dependent survival and success rates (Kaplan-Meier-Estimator) were calculated. The number of the abutment teeth was analyzed as an influencing factor (Cox regression model (p < 0.05)). RESULTS: The 5- and 8-year overdenture survival rates were 62% [CI: 0.55; 0.69] and 38% [CI: 0.30; 0.45]. The 5- and 8-year success-rates (biologically and technically event-free restorations) were 13% [CI: 0.09; 0.17] and 3% [CI: 0.01; 0.05]. On the abutment level, the 5- and 8-year survival rates were 55% [CI: 0.48; 0.62], and 34% [CI: 0.27; 0.42]. The number of abutment teeth significantly influenced the overdenture and abutment survival rates. Restorations with 1 or 2 abutments were significantly associated with an increased number of technical and biological complications (decementation of the primary crown, abutment fracture) compared to ODRTCs with 3 abutments. CONCLUSIONS: The survival and success rates of ODRTCs are significantly influenced by the number of abutments. CLINICAL RELEVANCE: For ODRTCs, reduced survival and success rates are expected, especially when only 1 or 2 abutment teeth are included.

Retrospective evaluation of extended heat-pressed ceramic veneers after a mean observational period of 7 years.

OBJECTIVES: Retrospective evaluation of extended anterior glass-ceramic veneers 7 years after placement in a private practice. MATERIALS AND METHODS: A total of 31 patients (20 females/11 males) underwent restoration with adhesively luted extended veneers that were fabricated using heat-pressed glass-ceramic (Cergo, Dentsply Sirona). A single dentist restored 101 teeth (maxilla, n = 65; mandible, n = 36). Adhesive cementation was performed using an etch-and-rinse adhesive (OptibondFL, Kerr Corporation), and two different dual-curing composite cements (Variolink, Ivoclar Vivadent/Calibra, Dentsply Sirona). RESULTS: After 7 years, the Kaplan-Meier survival rate (in situ criteria) was 93.6% (95% CI: 0.89; 0.98). The observed failures were caused by ceramic fractures for seven restorations and biological failure for one restoration. In total 80 of the 101 restorations were still in service and did not require any clinical intervention (7-year success rate: 84.3% [95% CI]: 0.76; 0.93). Interventions were necessary in 13 cases (8 recementations, 2 endodontic treatments, 2 composite fillings (caries), and 1 polishing of minor fractures). The clinical performance was not influenced by the veneer position (maxilla/mandible, survival P = .56/success P = .30). The veneers that covered large areas of exposed dentin (>50%) exhibited a significantly increased risk (hazard ratio 3.71, P = .0041) for requiring a clinical intervention; however, no effect on the survival rate was observed for these veneers (P = .35). CONCLUSIONS: Following 7 years of clinical service, extended anterior ceramic veneer restorations exhibited comparable survival and success rates for the upper and lower jaw. Large areas of exposed dentin (>50%) were associated with significantly lower success rates. CLINICAL SIGNIFICANCE: Dentin exposure (more than 50% of the preparation surface) during preparation significantly affects the clinical performance of extended heat-pressed glass-ceramic veneers.

Peripheral blood cytogenetics allows treatment monitoring and early identification of treatment failure to lenalidomide in MDS patients: results of the LE-MON-5 trial.

Transfusion-dependent patients with low- or intermediate-1-risk myelodysplastic syndrome, <5% bone marrow (BM) blasts and isolated 5q-deletion received lenalidomide within the German MDS study group phase-II clinical trial LE-MON-5 (EudraCT:2008-001866-10) of the University of Duesseldorf, Germany. Cytogenetic monitoring was performed by chromosome banding analyses (CBA) of BM cells and fluorescence in situ hybridization (FISH) analyses of peripheral blood (PB) mononuclear CD34+ cells using extended probe panels. Out of 144 patients screened for study enrollment, 24% failed to meet inclusion criteria due to cytogenetic findings. Eighty-seven patients were followed with a median observation time of 30 months. Cytogenetic response detected by FISH and CBA in 74 and 66% of patients, respectively, was predictive for hematologic response as well as of high prognostic relevance. After 2 years, AML rate was 8% for all patients. Karyotype evolution was detected in 21 (FISH)-34% (CBA) of patients associated with significantly shorter AML-free survival. Disease progression was first detectable on the cytogenetic level on average 5-6 months before recurrence of transfusion dependence. Our data show for the first time in a prospective setting that a cytogenetic monitoring from the PB helps to early identify treatment failure and progressive disease in lenalidomide-treated patients to improve clinical management. TRIAL REGISTRATION: EudraCT:2008-001866-10.

CatWalk gait analysis in a rat model of multiple sclerosis.

BACKGROUND: Myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis (EAE) is a widely used animal model for multiple sclerosis. The characteristic feature of the MOG-EAE model in Brown Norway rats is consistent involvement of the spinal cord resulting in limb paresis. The aim of the study was to investigate whether early subclinical gait abnormalities are present in this animal model and can be detected by CatWalk XT, a fully automated gait analysis system. Furthermore, we investigated the usability of CatWalk system for treatment studies. RESULTS: Our gait analysis showed no preclinical abnormalities in MOG-EAE animals. Nevertheless, we characterized a combination of gait parameters that display a high predictive capacity in regard to disease onset. Our detailed histopathological analysis of the spinal cord revealed that lesion formation starts in the lumbar region and propagates toward the cervical part of the spinal cord during the disease course. In the treatment study, the stabilization of gait parameters under the treatment with methylprednisolone was detected in CatWalk as well as in traditional EAE-scoring system. CONCLUSIONS: The results from CatWalk test indicate no benefit of lab-intensive automated gait system in EAE-model with chronic-progressive disease course as well as in therapeutic studies with pronounced effect on the severity of clinical symptoms. However, due to its quantitative and objective nature this system may display a refined test to detect small but functional relevant changes in regeneration-orientated studies.

Neutrophilic Epitheliotropism is a Histopathological Clue to Neutrophilic Urticarial Dermatosis.

BACKGROUND: Neutrophilic urticarial dermatosis (NUD) comprises a particular autoinflammatory condition within the spectrum of aseptic neutrophilic dermatoses characterized by a distinct urticarial eruption clinically and a neutrophilic dermatosis histopathologically. OBJECTIVE: In this study, we reviewed skin biopsies of lesional skin of patients seen in our outpatient clinic for autoimmune dermatoses and in allergy department from 1982 to 2014 that fulfilled these criteria. METHODS: A total of 77 biopsies from 50 patients were analyzed histopathologically. Included were cases of Schnitzler syndrome, Still disease, systemic lupus erythematosus, Sjögren syndrome, cryopyrin-associated periodic syndrome, primary biliary cirrhosis, inflammatory bowel disease, and those that had signs of systemic inflammation not otherwise specified, that is, fever, arthritis, leukocytosis, and elevated erythrocyte sedimentation rate. A control cohort was defined as including a total of 70 biopsies from 50 patients comprising neutrophilic urticaria (pressure-induced and not pressure-induced), conventional urticaria, lupus erythematosus expressing neutrophils, and exanthematous drug reaction of macular type expressing neutrophils. RESULTS: Skin biopsies of NUD revealed a perivascular and interstitial neutrophilic infiltrate focally extending into the epithelia of epidermis, hair follicles, sebaceous and sweat glands, a feature which we termed neutrophilic epitheliotropism. This neutrophilic epitheliotropism proved to be of high sensitivity (83.1%) and lower specificity (74.3%). The histological findings could be substantiated by immunohistochemical markers for leukocytes (elastase and myeloperoxidase), in particular in cases where neutrophils showed uncharacteristic band-like nuclei. CONCLUSIONS: Neutrophilic epitheliotropism is a new sensitive and specific histopathological clue for NUD, a histopathological reaction pattern within the spectrum of neutrophilic dermatoses that needs to be differentiated from conventional urticaria.

[A survey among family doctors on care reality of patients under oral tyrosine kinase inhibitor therapies]. / Befragung von Hausärzt*innen zur Versorgung von Patienten unter oralen Tyrosinkinaseinhibitoren.

INTRODUCTION: Oral tyrosine kinase inhibitor (TKI) therapies are becoming increasingly more important in the treatment of malignant diseases. Monitoring with focus on adherence, side effects and interactions poses new challenges for medical care. The role and capabilities of family doctors in the care of TKI patients are yet unclear and should be uncovered in a nationwide survey. METHODS: From April to July 2016, 3,000 family doctors in Germany were asked to complete a written questionnaire regarding their capabilities for co-supervision of TKI patients. RESULTS: The response rate was 18% (n=553). The peak age was between 50 and 60 years. 81% were specialists in general medicine, 14% specialists in internal medicine and 5% general practitioners. 98% cared for no or less than 10 TKI patients per quarter. Knowledge of side effects and interaction potential of TKIs was low in over 90%. 83% preferred monitoring by the treating oncologist and 93% felt uncertain about treatment monitoring. The control of adherence was of little importance in 66%. The number of treated TKI patients had a significant impact on knowledge and opportunities for treatment monitoring. There was a significant correlation between knowledge about TKIs and confidence in treatment monitoring. In general, younger doctors tended to be more confident in treatment monitoring, and specialists in internal medicine tended to have more knowledge than specialists in general medicine general practitioners and general practitioners. DISCUSSION: Currently, the low number of TKI patients, little knowledge about TKI, and the desire for specialist care are limiting the possibilities of co-caring for TKI patients by family doctors. CONCLUSION: Although family doctors are generally motivated to care for tumor patients, routine treatment controls of TKI patients conducted by family doctors seem hardly possible at the moment and should currently remain with the specialist.

Geometry of Torsional Malalignment Syndrome: Trochlear Dysplasia but Not Torsion Predicts Lateral Patellar Instability.

BACKGROUND: The clinical impact of increased torsion on patellar instability and patellofemoral pain syndrome (PFPS) has been suggested by several studies. HYPOTHESIS: The hypotheses of this study were that (1) torsional malalignment (TM) is characterized by a positive correlation between different malalignment parameters that represent an overall picture of the malalignment syndrome and (2) an increase in overall torsion is the underlying difference between patellar instability and isolated patellofemoral pain. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: Between April 2015 and July 2017, a total of 428 patients were treated for lateral patellar dislocation (LPD), and 333 patients were treated for PFPS. Sixty-two patients (14.5%) with patellar instability (LPD group) and 29 patients (8.7%) with patellofemoral pain (PFPS group) had additional TM and were included in this study. All patients underwent magnetic resonance imaging for torsional alignment and patellar tracking, including femoral antetorsion, tibial torsion, knee rotation, tibial tuberosity-trochlear groove (TT-TG) distance, tibial tuberosity-posterior cruciate ligament (TT-PCL) distance, Dejour classification of trochlear dysplasia, lateral trochlear inclination (LTI) angle, and patellar height. RESULTS: The LPD and PFPS groups differed significantly in terms of trochlear dysplasia (P < .001), LTI angle (P < .001), and TT-TG distance (P = .0167) but did not differ in terms of femoral antetorsion (20.02° ± 8.80° vs 20.03° ± 7.91°, respectively; P = .8545), tibial torsion (39.53° ± 9.23° vs 41.24° ± 7.28°, respectively; P = .3616), or knee rotation (10.42° ± 5.16° vs 8.48° ± 7.81°, respectively; P = .0163). Only measures of TT-TG distance and TT-PCL distance and measures of TT-TG distance and knee rotation were positively correlated. Trochlear dysplasia (type B-D) was identified as the only significant predictor of patellar instability. CONCLUSION: TM in patients with either PFPS or LPD does not appear to be characterized by a fixed constellation of different malalignment parameters. Between groups, the parameters differed significantly only in terms of trochlear dysplasia and the TT-TG distance, and trochlear dysplasia (type B-D) (but not torsion) was identified as a predictor of lateral patellar instability.

Prospective Evaluation of Posterior Fixed Zirconia Dental Prostheses: 10-Year Clinical Results.

PURPOSE: To investigate the clinical survival and success rates of conventionally luted three- and four-unit fixed dental prostheses (FDPs) with zirconia frameworks (Cercon Smart Ceramics, DeguDent) after a mean observation period of 119 ± 36 months. MATERIALS AND METHODS: A total of 75 patients were treated in the Department of Prosthodontics at the University of Goettingen, Germany, and a total of 99 posterior FDPs were inserted and luted with zinc phosphate cement. Time-dependent survival and success rates were calculated using Kaplan-Meier curves, and their relationships with the type of veneer (ceramic), location (maxilla vs mandible), and span length (three-unit vs four-unit) were analyzed with a Cox regression model (P < .05). RESULTS: Of the 99 inserted FDPs, 24 were lost to follow-up, 51 remained functional and passed the 10-year examination (overall survival rate: 75.0%; 95% confidence interval [CI]: 0.64, 0.85), and 13 were absolute failures caused by technical events (technical survival rate: 84%; 95% CI: 0.64, 0.85). In 50 FDPs, relative failure required a clinical intervention to maintain function (overall success rate: 40%; 95% CI: 0.29, 0.52). For 35 of these FDPs, the relative failure was caused by technical events (technical success rate: 61%; 95% CI: 0.49, 0.73). None of the evaluated factors showed an association with overall or technical survival or success. CONCLUSION: Zirconia-based posterior FDPs produced with a first-generation computer-assisted manufacturing (CAM) system revealed high rates of absolute and relative failure, mainly due to technical events, after a mean observational period of 10 years. Further clinical studies with updated computer-assisted design (CAD)/CAM systems are needed to determine the long-term performance of zirconia-based FDPs.

Impact of a Differential Learning Approach on Practical Exam Performance: A Controlled Study in a Preclinical Dental Course.

The aim of this study was to evaluate if differential learning in a preclinical dental course impacted the performance of dental students in a practical exam (preparation of a gold partial crown) immediately after the training session and 20 weeks later compared to conventional learning. This controlled study was performed in a preclinical course in operative dentistry at a dental school in Germany. Third-year students were trained in preparing gold partial crowns by using either the conventional learning (n=41) or the differential learning approach (n=32). The differential learning approach consisted of 20 movement exercises with a continuous change of movement execution during the learning session, while the conventional learning approach was mainly based on repetition, a methodological series of exercises, and correction of preparations during the training phase. Practical exams were performed immediately after the training session (T1) and 20 weeks later (T2, retention test). Preparations were rated by four independent and blinded examiners. At T1, no significant difference between the performance (exam passed) of the two groups was detected (conventional learning: 54.3%, differential learning: 68.0%). At T2, significantly more students passed the exam when trained by the differential learning approach (68.8%) than by the conventional learning approach (18.9%). Interrater reliability was moderate (Kappa: 0.57, T1) or substantial (Kappa: 0.67, T2), respectively. These results suggest that a differential learning approach can increase the manual skills of dental students.

High mast cell density indicates a longer overall survival in oral squamous cell carcinoma.

This study evaluates the effects of tumour-associated mast cells on the prognosis of patients suffering from oral squamous cell carcinoma (OSCC). Tryptase-positive (MCT+) and CD117-positive (CD117+) mast cells were immunohistochemically evaluated in tissue samples of 118 OSCC patients. Besides, various clinicopathological parameters, the influence of the MCT+ and CD117+ mast cell density on overall survival and the incidence of first local recurrence was analysed by Cox regression and competing risk regression. Among all investigated parameters, multiple Cox regression revealed a significant influence of the MCT+ (cut-off at 14.87 mast cells/mm2 stroma; p = 0.0027) and CD117+ mast cell density (cut-off at 33.19 mast cells/mm2 stroma; p = 0.004), the age at primary diagnosis, and the T and N stage (all p-values < 0.05) on overall survival. Patients with a low mast cell density showed a significantly poorer overall survival rate compared to those with a high mast cell density in the tumour-associated stroma. Competing risk regression revealed a significant influence of the resection status (R) on the incidence of first local recurrence (p = 0.0023). A high mast cell density in the tumour-associated stroma of oral squamous cell carcinoma indicates a longer patient survival.

Acute Levodopa Challenge Test in Patients with de novo Parkinson's Disease: Data from the DeNoPa Cohort.

BACKGROUND: The precise clinical diagnosis of Parkinson's disease (PD) can be difficult in the early stages. Diagnostic criteria include the response of key motor features to levodopa as a supportive prospective criterion. Data are sparse on the diagnostic value of the acute levodopa challenge test (LDCT) in patients with de novo PD. The objective of this study was to validate the LDCT as a tool in the early clinical diagnosis of PD. METHODS: We performed the standardized LDCT with 250 mg levodopa in the prospective longitudinal cohort study "DeNoPa," comprising 159 patients with de novo PD, and carried out longitudinal clinical follow-up for 24 months. Motor assessments at baseline using the motor part (part III) of the Unified Parkinson's Disease Rating Scale before and 1 hr after drug administration were documented. The optimal cutoff score on the LDCT was calculated using the Youden index. RESULTS: Clinical reassessment of 144 patients who returned for follow-up confirmed the diagnosis of PD in 120 patients (83%). In 24 patients (17%), the initial diagnoses were revised and classified as other neurologic disorders. The optimal cutoff at 33% improvement of motor symptoms on the part 3 of the Unified Parkinson's Disease Rating Scale during the LDCT reached a sensitivity of 70% a specificity of 71%. The positive and negative predictive values were 92% and 32%, respectively. Sensitivity (91%), specificity (79%), and positive/negative (96%/63%) predictive values improved with the addition of further clinical information (urinary incontinence, fainting, asymmetric tremor, and amount of further drug-intake). CONCLUSIONS: The LDCT is a reliable tool in the early diagnosis of PD. The accuracy of this test can be further improved by additional, easy-to-acquire clinical information provided by patients. © 2017 International Parkinson and Movement Disorder Society.

Primary stability and osseointegration of dental implants in polylactide modified bone - A pilot study in Goettingen minipigs.

The present study aimed to evaluate primary stability (PS) and osseointegration of dental implants in polylactide [70/30 poly(l-lactide-co-d, l-lactide); (PLDLA)] modified bone in 30 Goettingen minipigs. Each animal received three implants per jaw quadrant. In a split-mouth design, one side of the maxilla and mandible was randomly allocated to the experimental treatment (PLDLA applied into the drill hole before implantation), while the contralateral sides served as intraindividual controls (no PLDLA applied). The required insertion torque and the implant stability quotient (ISQ) were measured during implantation. ISQ, volume density (VD) of new bone formation (NBF), and the bone-implant contact (BIC) were evaluated at the end of the observation period (1, 3, 6, 12, and 24 months, respectively) in six animals each. Across all study groups, the PLDLA treatment resulted in a) a comparable insertion torque, b) an equivalent ISQ, c) a reduced BIC, and d) a reduced VD of NBF, as opposed to the untreated controls. In conclusion, the PLDLA treatment did not affect the PS, but rather led to an impaired osseointegration, which was particularly strong in the compact mandibular bone, and decreased in the spongious maxillary bone. PLDLA induced anchoring in spongious bone should be evaluated in further investigations.