Dental and Maxillofacial Cone Beam CT-High Number of Incidental Findings and Their Impact on Follow-Up and Therapy Management.

Cone beam computed tomography (CBCT) is increasingly used for dental and maxillofacial imaging. The occurrence of incidental findings has been reported, but clinical implications of these findings remain unclear. The study's aim was to identify the frequency and clinical impact of incidental findings in CBCT. A total of 374 consecutive CBCT examinations of a 3 year period were retrospectively evaluated for the presence, kind, and clinical relevance of incidental findings. In a subgroup of 54 patients, therapeutic consequences of CBCT incidental findings were queried from the referring physicians. A total of 974 incidental findings were detected, involving 78.6% of all CBCT, hence 2.6 incidental findings per CBCT. Of these, 38.6% were classified to require treatment, with an additional 25.2% requiring follow-up. Incidental findings included dental pathologies in 55.3%, pathologies of the paranasal sinuses and airways in 29.2%, osseous pathologies in 14.9% of all CBCT, and findings in the soft tissue or TMJ in few cases. Clinically relevant dental incidental findings were detected significantly more frequently in CBCT for implant planning compared to other indications (60.7% vs. 43.2%, p < 0.01), and in CBCT with an FOV ≥ 100 mm compared to an FOV < 100 mm (54.7% vs. 40.0%, p < 0.01). Similar results were obtained for paranasal incidental findings. In a subgroup analysis, 29 of 54 patients showed incidental findings which were previously unknown, and the findings changed therapeutical management in 19 patients (35%). The results of our study highlighted the importance of a meticulous analysis of the entire FOV of CBCT for incidental findings, which showed clinical relevance in more than one in three patients. Due to a high number of clinically relevant incidental findings especially in CBCT for implant planning, an FOV of 100 × 100 mm covering both the mandible and the maxilla was concluded to be recommendable for this indication

The ELSA trial: single versus combinatory effects of non-prohibited beta-2 agonists on skeletal muscle metabolism, cardio-pulmonary function and endurance performance—study protocol for a randomized 4-way balanced cross-over trial

Background Asthma and/or airway hyper-responsiveness (AHR) are common in elite endurance athletes with a high prevalence rate of beta-2 adrenoreceptor (beta-2) agonists use. Nevertheless, there are data on dose-dependent ergogenic effects of beta-2 agonists suggesting increased muscle strength, endurance and neuromuscular performance. Therefore, most beta-2 agonists belong to the World Anti Doping Agency (WADA) list of prohibited substances and it is tempting to speculate that illegitimate use of beta-2 agonists might be a common practice to boost performance in competitive sports. It is currently unknown whether or not inhaled beta-2 agonists enhance performance by stimulatory effects in skeletal and cardiac muscle. Methods The ELSA trial is a double-blinded, placebo-controlled, randomized, balanced, four-way cross-over study. Study participants (n=24, 12 ♀, 12 ♂) complete four study arms (i.e. periods with treatment A, placebo; B, salbutamol; C, formoterol; D, formoterol + salbutamol) in random order after an initial preliminary testing session. Participants inhale the study medication 20 min before the 10-min time trial (TT; exercise performance test), where participants cycle 10 min at the highest possible workload. Cardiac output is measured continuously. A skeletal muscle biopsy is collected 3 h after the TT. Study endpoints include measures of skeletal muscle expression of nuclear receptors, hormones and cytokine levels, urinary and plasma concentrations of salbutamol and formoterol, circulating cardiac markers, cardiopulmonary function and exercise performance (average power and peak power during the TT). Blood and urine are collected and respiratory testing is performed 24 h post TT. Summary/conclusions This clinical trial evaluates the potential performance-enhancing effects of non-prohibited, not medically indicated inhaled short- and long-acting beta-2 agonists on skeletal muscle gene expression, endocrine regulation, cardiac biomarkers, cardiopulmonary function and acute endurance exercise performance. These data will be used by WADA to adapt the annually published list of prohibited substances (WADA 2021) and will be published in scientific journals

Neurochemical markers in CSF of adolescent and adult SMA patients undergoing nusinersen treatment

Background: There is limited information on neurochemical markers being used to support and monitor the affection of motoneurons in patients with spinal muscular atrophy (SMA). The objective of this study was to examine neurochemical markers in cerebrospinal fluid (CSF) under treatment with the antisense-oligonucleotide (ASO), nusinersen. Methods: We measured markers of axonal degeneration [neurofilament light chain (NfL) and phosphorylated neurofilament heavy chain (pNfH)] along with basic CSF parameters in 25 adolescent and adult SMA type 2 and 3 patients at baseline and after four intrathecal injections of nusinersen. Neurochemical markers were compared with controls. In addition, neurochemical markers in SMA patients were related to the Hammersmith Functional Rating Scale Expanded (HFMSE). Results: No significant difference in neurofilament (Nf) values was observed between SMA and control group, neither at baseline nor after four injections of nusinersen. NfL, protein and quotients of albumin (Qalb) increased slightly in SMA patients after the fourth injection. The slight increase of NfL could be related to the development of mild CSF flow change. No relations were observed between changes in Nf and HFMSE. Conclusion: We assume that Nf levels in CSF in these patients may result from slow disease progression in this stage of disease, pre-existing loss of motoneurons due to long disease duration besides affection of the LMN only. Therefore, we conclude that Nf levels in CSF do not seem useful as diagnostic and monitoring markers in adolescent and adult SMA type 2 and 3 patients

A Randomized, Double Blind, Placebo-Controlled Trial of Pioglitazone in Combination with Riluzole in Amyotrophic Lateral Sclerosis

BACKGROUND: Pioglitazone, an oral anti-diabetic that stimulates the PPAR-gamma transcription factor, increased survival of mice with amyotrophic lateral sclerosis (ALS). METHODS/PRINCIPAL FINDINGS: We performed a phase II, double blind, multicentre, placebo controlled trial of pioglitazone in ALS patients under riluzole. 219 patients were randomly assigned to receive 45 mg/day of pioglitazone or placebo (one: one allocation ratio). The primary endpoint was survival. Secondary endpoints included incidence of non-invasive ventilation and tracheotomy, and slopes of ALS-FRS, slow vital capacity, and quality of life as assessed using EUROQoL EQ-5D. The study was conducted under a two-stage group sequential test, allowing to stop for futility or superiority after interim analysis. Shortly after interim analysis, 30 patients under pioglitazone and 24 patients under placebo had died. The trial was stopped for futility; the hazard ratio for primary endpoint was 1.21 (95% CI: 0.71-2.07, p = 0.48). Secondary endpoints were not modified by pioglitazone treatment. Pioglitazone was well tolerated. CONCLUSION/SIGNIFICANCE: Pioglitazone has no beneficial effects on the survival of ALS patients as add-on therapy to riluzole. TRIAL REGISTRATION: Clinicaltrials.gov NCT00690118

Evaluation of a health promotion program in children: Study protocol and design of the cluster-randomized Baden-Württemberg primary school study [DRKS-ID: DRKS00000494]

<p>Abstract</p> <p>Background</p> <p>Increasing prevalences of overweight and obesity in children are known problems in industrialized countries. Early prevention is important as overweight and obesity persist over time and are related with health problems later in adulthood. "Komm mit in das gesunde Boot - Grundschule" is a school-based program to promote a healthier lifestyle. Main goals of the intervention are to increase physical activity, decrease the consumption of sugar-sweetened beverages, and to decrease time spent sedentary by promoting active choices for healthy lifestyle. The program to date is distributed by 34 project delivery consultants in the state of Baden-Württemberg and is currently implemented in 427 primary schools. The efficacy of this large scale intervention is examined via the Baden-Württemberg Study.</p> <p>Methods/Design</p> <p>The Baden-Württemberg Study is a prospective, stratified, cluster-randomized, and longitudinal study with two groups (intervention group and control group). Measurements were taken at the beginning of the academic years 2010/2011 and 2011/2012. Efficacy of the intervention is being assessed using three main outcomes: changes in waist circumference, skinfold thickness and 6 minutes run. Stratified cluster-randomization (according to class grade level) was performed for primary schools; pupils, teachers/principals, and parents were investigated. An approximately balanced number of classes in intervention group and control group could be reached by stratified randomization and was maintained at follow-up.</p> <p>Discussion</p> <p>At present, "Komm mit in das Gesunde Boot - Grundschule" is the largest school-based health promotion program in Germany. Comparative objective main outcomes are used for the evaluation of efficacy. Simulations showed sufficient power with the existing sample size. Therefore, the results will show whether the promotion of a healthier lifestyle in primary school children is possible using a relatively low effort within a school-based program involving children, teachers and parents. The research team anticipates that not only efficacy will be proven in this study but also expects many other positive effects of the program.</p> <p>Trial registration</p> <p>German Clinical Trials Register (DRKS), DRKS-ID: DRKS00000494</p

Generelle Fallzahl- und Powerabschätzung über Simulation bei Studien mit komplexen hierarchischen Daten als Unterstützung der Studienplanung in der Versorgungsforschung

Studien stellen wichtige Instrumente im Erkenntnisgewinn in der Versorgungsforschung dar, wobei oft Studiendesigns mit hierarchischer Datenstruktur und zusätzlichen Kovariaten auftreten (Studiendesigns mit komplexer hierarchischer Datenstruktur). Werden konfirmatorische Fragestellungen untersucht, ist eine a-priori Abschätzung der Fallzahl bzw. statistischen Power erforderlich, wofür in komplexeren Situationen nur unzureichende oder keine Methoden verfügbar sind. Im Ergebnis eines vom Nachwuchsprogramm des Netzwerks "Versorgungsforschung Baden-Württemberg" unterstützten Projekts entstanden drei Berichte zu dieser Problematik: 1) Anwenderbroschüre zur nutzerfreundlichen Anwendung einer Spezialsoftware für Powersimulationen bei metrischen und binären Zielgrößen; 2) Formelsammlung für Fallzahl- und Powerberechnungen in einfachen Situationen; 3) Ein Dokument mit Hinweisen für Planung und Durchführung von Feasibility- oder Pilotstudien im Kontext komplexer hierarchischer Datenstrukturen. Das PDF enthält die drei Berichte. ---- english version---- Studies are an important source of knowledge in health service research. Here, designs with hierarchical data structures and additional consideration of covariates (complex hierarchical data structures) often occur. In case of confirmatory studies in such situations, a-priori power or sample size calculation is needed but available methods are limited. Three reports were developed as result of a project funded by the trainee program of the health services research network in Baden Wuerttemberg: 1) User brochure for a user-friendly application of a special software for power simulation for continuous and binary outcomes; 2) Formulary containing formulas for sample size or power calculation in some special situations; 3) A document which contains information for planning and carrying out feasibility or pilot studies in situations with complex hierarchical data structures. The PDF contains the three reports

Smoking exposure, loss of forced expiratory volume in one second and the risk of lung cancer among patients with malignant disease who present with cardiac or pulmonary symptoms: a cross-sectional study

Introduction Smokers with airway obstruction are at a higher risk of lung cancer than smokers without airway obstruction. Inflammation plays a key role in lung carcinogenesis. This single-center study prospectively assessed (i) the relationship between smoking exposure and the loss of forced expiratory volume in 1 s (FEV1) in determining lung cancer risk and (ii) the effect of lung cancer on systemic inflammation. Material and Methods The study group comprised 475 consecutively enrolled patients with cancer who presented with pulmonary or cardiac symptoms. The effects of smoking exposure and FEV1 loss on the predicted lung cancer risk were assessed using multiple logistic regression analysis. C-reactive protein (CRP) was used as a marker of inflammation. Results The prevalence of lung cancer was 0.23. The lung cancer risk increased with the number of pack years and FEV1 loss (p < 0.01). Moving from the 5th (−22% of the predicted value) to the 95th percentile of FEV1 loss (56% of the predicted value) increased lung cancer risk from 0.07 to 0.23 (Δ = 0.16) at 0 pack years and from 0.39 to 0.73 (Δ = 0.34) at 70 pack years (95th percentile). The values for Δ peaked at 61 pack years (0.34) and then decreased with a further increase in smoking exposure, without reaching the zero mark. Patients with lung cancer were more likely to have a CRP level above the median (4.05 mg/L) than patients with other cancers (adjusted odds ratio = 2.67). Conclusions Systemic inflammation is more pronounced in patients with lung cancer than in patients with other cancers. The effect of FEV1 loss on the patients’ predicted risks of lung cancer increases with increasing smoking exposure. Measurements of FEV1 loss are useful to identify patients facing an increased risk of developing lung cancer