In-depth analysis of data from the RAS-ALS study reveals new insights in rasagiline treatment for amyotrophic lateral sclerosis.

BACKGROUND AND PURPOSE: In 2016, we concluded a randomized controlled trial testing 1 mg rasagiline per day add-on to standard therapy in 252 amyotrophic lateral sclerosis (ALS) patients. This article aims at better characterizing ALS patients who could possibly benefit from rasagiline by reporting new subgroup analysis and genetic data. METHODS: We performed further exploratory in-depth analyses of the study population and investigated the relevance of single nucleotide polymorphisms (SNPs) related to the dopaminergic system. RESULTS: Placebo-treated patients with very slow disease progression (loss of Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised [ALSFRS-R] per month before randomization of ≤0.328 points) showed a per se survival probability after 24 months of 0.85 (95% confidence interval = 0.65-0.94). The large group of intermediate to fast progressing ALS patients showed a prolonged survival in the rasagiline group compared to placebo after 6 and 12 months (p = 0.02, p = 0.04), and a reduced decline of ALSFRS-R after 18 months (p = 0.049). SNP genotypes in the MAOB gene and DRD2 gene did not show clear associations with rasagiline treatment effects. CONCLUSIONS: These results underline the need to consider individual disease progression at baseline in future ALS studies. Very slow disease progressors compromise the statistical power of studies with treatment durations of 12-18 months using clinical endpoints. Analysis of MAOB and DRD2 SNPs revealed no clear relationship to any outcome parameter. More insights are expected from future studies elucidating whether patients with DRD2CC genotype (Rs2283265) show a pronounced benefit from treatment with rasagiline, pointing to the opportunities precision medicine could open up for ALS patients in the future.

Corneal cross-linking in patients with keratoconus: up to 13 years of follow-up.

INTRODUCTION: To evaluate long-term safety and efficacy of corneal collagen cross-linking (CXL) in patients with keratoconus up to 13 years. MATERIALS AND METHODS: In this mono-centre exploratory study, we included all consecutive patients who underwent CXL in our cornea centre from 01/01/2007 to 12/30/2011 and met the inclusion criteria. CXL was performed in all patients according to the Dresden protocol. Evaluation included best-corrected visual acuity (BCVA), topographic keratometry by Scheimpflug corneal tomography and endothelial cell count (ECC). Follow-up measurements were taken up to 13 years after treatment were compared with baseline values. RESULTS: The study enrolled 168 eyes. The mean age of our patients was 26.3 years ± 7.8 years. A complete topographic dataset was available 1 year postoperatively for 142 eyes, 5 years postoperatively for 105 eyes, 10 years postoperatively for 61 eyes and 13 years postoperatively for 9 eyes. BCVA increased statistically significant after 1 year, 5 years and 10 years and non-significantly after 13 years. All keratometric parameters with exception of posterior astigmatism showed a statistically significant decrease after 1 year, 5 years and 10 years. After 13 years, the decrease was statistically significant only in Kmax, K2 and thinnest cornea. No significant changes in ECC were detected. Three eyes received Re-CXL, none of the eyes received penetrating keratoplasty and no infections occurred in this cohort. CONCLUSIONS: CXL can slow down or even stop the progression of keratoconus in the majority of cases. The effect is long-lasting with excellent safety.

Fat-rich versus carbohydrate-rich nutrition in ALS: a randomised controlled study.

OBJECTIVE: There is growing evidence that the course of amyotrophic lateral sclerosis (ALS) may be influenced beneficially by applying high-caloric food supplements (HCSs). However, it is unknown which composition of nutrients offers optimal tolerability and weight gain. METHODS: We conducted a randomised controlled study (Safety and Tolerability of Ultra-high-caloric Food Supplements in Amyotrophic Lateral Sclerosis (ALS); TOLCAL-ALS study) in 64 patients with possible, probable or definite ALS according to El Escorial criteria. Patients were randomised into four groups: a high-caloric fatty supplement (HCFS; 405 kcal/day, 100% fat), an ultra-high-caloric fatty supplement (UHCFS; 810 kcal/day, 100% fat), an ultra-high-caloric, carbohydrate-rich supplement (UHCCS; 900 kcal/day, 49% carbohydrates) and an open control (OC) group without any supplement. The primary endpoint was tolerability. Patients were followed up over 4 weeks. RESULTS: Gastrointestinal side effects were most frequent in the UHCFS group (75.0%), while loss of appetite was most frequent in the UHCCS group (35.3%). During intervention, patients gained +0.9 kg/month of body weight (IQR -0.9 to 1.5; p=0.03) in the HCFS group and +0.9 kg/month (IQR -0.8 to 2.0; p=0.05) in the UHCFS group. A non-significant trend for weight gain (+0.6 kg/month (IQR -0.3 to 1.9; p=0.08)) was observed in the UHCCS group. Patients in OC group continued to lose body weight (-0.5 kg/month, IQR -1.4 to 1.3; p=0.42). INTERPRETATION: The findings suggest that HCSs frequently cause mild to moderate tolerability issues in patients with ALS, most notably gastrointestinal symptoms in high-fat supplements, and loss of appetite in high-carbohydrate supplements. All three HCSs tested are suited to increase body weight.

Blood-Based Targeted Metabolomics Discriminate Patients with Alcoholic Liver Cirrhosis from Those with Non-Cirrhotic Liver Damage: An Explorative Study.

BACKGROUND: Early detection of liver cirrhosis is crucial for secondary prevention of complications. However, noninvasive blood-based patient monitoring tools are lacking. In this explorative study, we conducted a targeted metabolomic analysis in order to identify possible serum markers indicating alcoholic liver cirrhosis (aLiC) with or without hepatocellular carcinoma (HCC). METHODS: Venous blood of 30 individuals was collected: healthy controls ("Con", n = 12), patients with aLiC without and with HCC ("aLiC": n = 6 and "aLiC + HCC": n = 6), and patients with other liver diseases ("oLiD": n = 6). A targeted metabolomic analysis was conducted using the AbsoluteIDQ® p180 Kit (Biocrates Life Sciences®, Innsbruck, Austria). Statistical analysis was performed by applying a one-way ANOVA on all subgroups followed by a t test for pairwise comparison of subgroups and logistic regression analysis. RESULTS: ANOVA revealed 29 metabolites that significantly discriminate between the different cohorts. Among these analytes, 25 were significantly altered in Con versus aLiC, as indicated by t test, most importantly SM C18:1 (p < 0.001), SM C20:2 (p = 0.001), SM (OH) C22:2 (p < 0.001), lysoPC a C20:4 (p < 0.001), and PC aa C36:5 (p < 0.001). To a similar extent, the metabolites discriminated also between the oLiD and aLiC but less between the Con or oLiD and aLiC + HCC cohorts. Most of these analytes were either lyso- and phosphatidylcholines or sphingomyelins. Results were not significant for comparison of Con versus oLiD and aLiC versus aLiC + HCC. CONCLUSION: Decreased lyso- and phosphatidylcholine as well as sphingomyelin species in venous blood could help to detect liver cirrhosis in patients with non-cirrhotic liver disease.

Effect of High-Caloric Nutrition on Survival in Amyotrophic Lateral Sclerosis.

OBJECTIVE: Weight loss has been identified as a negative prognostic factor in amyotrophic lateral sclerosis, but there is no evidence regarding whether a high-caloric diet increases survival. Therefore, we sought to evaluate the efficacy of a high-caloric fatty diet (HCFD) for increasing survival. METHODS: A 1:1 randomized, placebo-controlled, parallel-group, double-blinded trial (LIPCAL-ALS study) was conducted between February 2015 and September 2018. Patients were followed up at 3, 6, 9, 12, 15, and 18 months after randomization. The study was performed at 12 sites of the clinical and scientific network of German motor neuron disease centers (ALS/MND-NET). Eligible patients were randomly assigned (1:1) to receive either HCFD (405kcal/day, 100% fat) or placebo in addition to riluzole (100mg/day). The primary endpoint was survival time, defined as time to death or time to study cutoff date. RESULTS: Two hundred one patients (80 female, 121 male, age = 62.4 ± 10.8 years) were included. The confirmatory analysis of the primary outcome survival showed a survival probability of 0.39 (95% confidence interval [CI] = 0.27-0.51) in the placebo group and 0.37 (95% CI = 0.25-0.49) in the HCFD group, both after 28 months (point in time of the last event). The hazard ratio was 0.97, 1-sided 97.5% CI = -∞ to 1.44, p = 0.44. INTERPRETATION: The results provide no evidence for a life-prolonging effect of HCFD for the whole amyotrophic lateral sclerosis population. However, post hoc analysis revealed a significant survival benefit for the subgroup of fast-progressing patients. ANN NEUROL 2020;87:206-216.

A phase II study of the PI3K inhibitor copanlisib in combination with the anti-CD20 monoclonal antibody rituximab for patients with marginal zone lymphoma: treatment rationale and protocol design of the COUP-1 trial.

BACKGROUND: Advanced stage marginal zone lymphoma (MZL) is an incurable indolent B-cell lymphoma, for which a wide variety of treatments ranging from single agent rituximab to more dose intense immunochemotherapy exists. One of the major goals in this palliative setting is to develop chemotherapy-free treatments, which approach the efficacy of immunochemotherapies, but avoid chemotherapy associated toxicity in this often elderly patient population. The PI3K inhibitor copanlisib has recently shown remarkable clinical activity in refractory or relapsed indolent B-cell lymphomas, among them MZL. Based on these data, copanlisib monotherapy was granted breakthrough designation by the FDA for the treatment of adult patients with relapsed marginal zone lymphoma who have received at least two prior therapies. However, data are still limited in particular for MZL. Based on this, the COUP-1 trial aims at testing the toxicity and efficacy of copanlisib in combination with rituximab in treatment naive and relapsed MZL. METHODS: COUP-1 is a prospective, multicenter, single-arm, open-label, non-randomized phase II trial of 6 cycles (28 days cycle) of copanlisib (60 mg intravenous day 1, 8, 15) and rituximab (375 mg/m2 intravenous day 1) in the induction phase followed by a maintenance phase of copanlisib (d1, d15 every 4 weeks for a maximum of 12 cycles) and rituximab (d1 every 8 weeks for a maximum of 12 cycles) in patients aged ≥18 years with previously untreated or relapsed MZL in need of treatment. A total of 56 patients are to be enrolled. Primary endpoint is the complete response (CR) rate determined 12 months after start of induction therapy. Secondary endpoints include the overall response (OR) rate, progression free survival (PFS), overall survival (OS), safety and patient related outcome with quality of life. The study includes a translational bio-sampling program with the prospect to measure minimal residual disease. The study was initiated in November 2019. DISCUSSION: The COUP-1 trial evaluates the efficacy and toxicity of the treatment of copanlisib in combination with rituximab in patients with MZL and additionally offers the chance for translational research in this heterogenous type of lymphoma. TRIAL REGISTRATION: ClinicalTrials.gov : NCT03474744 . Registration date: 03/23/2018.

A complex intervention to promote prevention of delirium in older adults by targeting caregiver's participation during and after hospital discharge - study protocol of the TRAnsport and DElirium in older people (TRADE) project.

BACKGROUND: Among potentially modifiable risk factors for delirium, transfers between wards, hospitals and other facilities have been mentioned with low evidence. TRADE (TRAnsport and DElirium in older people) was set up to investigate i) the impact of transfer and/or discharge on the onset of delirium in older adults and ii) feasibility and acceptance of a developed complex intervention targeting caregiver's participation during and after hospital discharge or transfer on cognition and the onset of delirium in older adults. METHODS: The study is designed according to the guidelines of the UK Medical Research Council (MRC) for development and evaluation of complex interventions and comprises two steps: development and feasibility/piloting. The development phase includes i) a multicenter observational prospective cohort study to assess delirium incidence and cognitive decline associated with transfer and discharge, ii) a systematic review of the literature, iii) stakeholder focus group interviews and iv) an expert workshop followed by a Delphi survey. Based on this information, a complex intervention to better and systematically involve family caregivers in discharge and transport was developed. The intervention will be tested in a pilot study using a stepped wedge design with a detailed process and health economic evaluation. The study is conducted at four acute care hospitals in southwest Germany. Primary endpoints are the delirium incidence and cognitive function. Secondary endpoints include prevalence of caregiver companionship, functional decline, cost and cost effectiveness, quality of discharge management and quality of admission management in admitting hospitals or nursing homes. Data will be collected prior to discharge as well as after 3, 7 and 90 days. DISCUSSION: TRADE will help to evaluate transfer and discharge as a possible risk factor for delirium. In addition, TRADE evaluates the impact and modifiability of caregiver's participation during patient's transfer or discharge on delirium incidence and cognitive decline providing the foundation for a confirmatory implementation study. TRIAL REGISTRATION: DRKS (Deutsches Register für klinische Studien) DRKS00017828 . Registered on 17th September 2019. Retrospectively registered.

Rehabilitation of shortened dental arches: A fifteen-year randomised trial.

BACKGROUND: Few long-term studies on treatments in the shortened dental arch (SDA) are available. OBJECTIVE: The objective of this trial was to analyse the long-term success of two different treatment concepts. METHODS: Patients over 35 years of age with missing molars in one jaw and at least the canine and one premolar present on both sides were eligible. In the partial removable dental prosthesis (PRDP) group (N = 81), molars and missing second premolars were replaced by a precision attachment retained prosthesis. In the SDA group (N = 71), the dental arch ended with the second premolar that had to be present or replaced by a cantilever fixed dental prosthesis. Follow-up examinations were carried out over 15 years. RESULTS: A comprehensive outcome variable comprised four failure categories for which Kaplan-Meier survival (success) analyses were conducted. Half of the patients exhibited a continuous preservation of the per protocol prosthetic status that remained totally unaffected by complications for more than 10 years. The event-free success rates for moderate or worse failure implied a loss of the per protocol prosthetic status. The respective survival rates fell below 50% at 14.2 years in the PRDP group and 14.3 years in the SDA group. In none of the analyses, a significant group difference was found. CONCLUSIONS: In patients with an SDA condition, changes in the prosthetic status have to be expected. The affected proportion increases almost linearly from shortly after treatment and comprises the majority after 15 years. The influence of the examined treatments on success appears to be low.

Pattern of paresis in ALS is consistent with the physiology of the corticomotoneuronal projections to different muscle groups.

OBJECTIVE: A recent neuroanatomical staging scheme of amyotrophic lateral sclerosis (ALS) indicates that a cortical lesion may spread, as a network disorder, both at the cortical level and via corticofugal tracts, including corticospinal projections providing direct monosynaptic input to α-motoneurons. These projections are involved preferentially and early in ALS. If these findings are clinically relevant, the pattern of paresis in ALS should primarily involve those muscle groups that receive the strongest direct corticomotoneuronal (CM) innervation. METHODS: In a large cohort (N=436), we analysed retrospectively the pattern of muscle paresis in patients with ALS using the UK Medical Research Council (MRC) scoring system; we subsequently carried out two independent prospective studies in two smaller groups (N=92 and N=54). RESULTS: The results indicated that a characteristic pattern of paresis exists. When pairs of muscle groups were compared within patients, the group known to receive the more pronounced CM connections was significantly weaker. Within patients, there was greater relative weakness (lower MRC score) in thumb abductors versus elbow extensors, for hand extensors versus hand flexors and for elbow flexors versus elbow extensors. In the lower limb, knee flexors were relatively weaker than extensors, and plantar extensors were weaker than plantar flexors. CONCLUSIONS: These findings were mostly significant (p<0.01) for all six pairs of muscles tested and provide indirect support for the concept that ALS may specifically affect muscle groups with strong CM connections. This specific pattern could help to refine clinical and electrophysiological ALS diagnostic criteria and complement prospective clinicopathological correlation studies.

Thin Slices and Maximum Intensity Projection Reconstructions Increase Sensitivity to Hyperdense Middle Cerebral Artery Sign in Acute Ischemic Stroke.

INTRODUCTION: Cranial nonenhanced CT (NECT) imaging in hyperacute ischemic stroke is rarely used for assessing arterial obstruction of middle cerebral artery by identifying hyperdense artery sign (HAS). Considering, however, its growing importance due to its impact on the decision-making process of thrombolysis with or without mechanical thrombectomy improved sensitivity to HAS is necessary, particularly in the group of less experienced clinicians being frequently the first one assessing the presence of HAS on NECT. OBJECTIVE: The present study aimed to investigate the effect of different NECT image reconstructions on the correct detection of hyperdense middle cerebral artery sign in a cohort of observers with lower experience level on NECT. Particularly, MIP image reconstructions were expected to be useful for less experienced observers due to both strengthening of the hyperdensity of HAS and streamlining to less image slices. METHODS: Twenty-five of 100 patients' NECT image data presented with HAS. Sixteen observers with lower practice level on NECT (10 radiologists and 6 neurologists) evaluated independently the 3 image reconstructions of each data set with thin slice 1.5 mm, thick slab 5 mm, and 6-mm maximum intensity projection (MIP) and rated the presence of HAS in middle cerebral artery. A GEE model with random observer effect was used to examine the influence of the 3 image reconstructions on sensitivity to HAS. A linear mixed effects regression model was used to investigate the ranking of detectability of HAS. Interrater reliability was determined by Fleiss' kappa coefficient (κ). RESULTS: Recognition of HAS and sensitivity to HAS significantly differed between the 3 image reconstructions (p = 0.0106). MIP and thin slice reconstructions yielded each on average the highest sensitivities with 73% compared to thick slab reconstruction with 45% sensitivity. The interobserver reliability was fair (κ, 0.3-0.4). Detectability of HAS was significantly easier and better visible ranked on MIP and thin slice reconstructions compared to thick slab (p < 0.05). CONCLUSION: MIP and thin slice reconstructions increased the sensitivity to HAS (73%), whereas thick slab reconstructions seemed to be less appropriate (45%).

Phase II trial evaluating the efficacy and safety of the anti-CD20 monoclonal antibody obinutuzumab in patients with marginal zone lymphoma.

Marginal zone lymphoma (MZL) belongs to the group of indolent B-cell non-Hodgkin's lymphomas, which is characterized by an indolent course. In this mostly elderly patient population, the development of chemotherapy-free approaches is of particular interest. In this situation, single-agent treatment with the next-generation anti-CD20 antibody obinutuzumab is an attractive approach, which promises high efficacy without major toxicity. We describe here an open-label, multicentric Phase II trial evaluating the efficacy and safety of obinutuzumab in de novo MZL patients, who are treatment naive for systemic therapy and not eligible for or failed local treatment. ClinicalTrials.gov identifier NCT03322865.

Blue-Light Fundus Autofluorescence Imaging following Ruthenium-106 Brachytherapy for Choroidal Melanoma.

PURPOSE: To describe changes in blue-light fundus autofluorescence (FAF) and corresponding alterations in optical coherence tomography (OCT) within the irradiation field after ruthenium-106 brachytherapy (RBT) for choroidal melanoma. METHODS: Consecutive patients with choroidal melanoma were included in a retrospective case series. Patients were treated with RBT at a single institution. As part of their routine examination patients underwent multimodal imaging including ultrasonography, fundus photography, OCT, and FAF imaging (excitation = 488 nm). FAF images were analysed for changes within the irradiation field. RESULTS: 31 patients (mean age 65.7 years) were treated with RBT for unilateral choroidal melanoma. Mean tumour height before therapy was 2.7 mm (SD 1.0). Mean follow-up time was 23.3 months (SD 13.3). Main FAF characteristics attributable to RBT emerged as increased FAF with speckled decreased FAF (FAF mottling) within the irradiation field and a rim of increased FAF at its border. OCT scans demonstrated loss of the ellipsoid zone and the external limiting membrane, thinning of the neurosensory retina, and alterations of the retinal pigment epithelium like clumping, migration, and atrophy. CONCLUSIONS: FAF changes in the irradiation field after RBT of choroidal melanomas follow a characteristic pattern that correlates with distinct OCT alterations. FAF and OCT imaging give additional information to monitor effects of RBT and, therefore, complement multimodal imaging techniques after plaque therapy.

Comparison between Findings in Optical Coherence Tomography Angiography and in Fluorescein Angiography in Patients with Diabetic Retinopathy.

OBJECTIVE: To compare typical findings of diabetic retinopathy in optical coherence tomography angiography (OCTA) and fluorescein angiography (FA). SUBJECTS/METHODS: 42 patients were enrolled in this study. We performed FA and obtained en face 3 × 3 mm OCTA images of the macular region. The count of microaneurysms (MAs) and the size of the foveal avascular zone (FAZ) were compared. The assessability of the imaging modalities was graded in each eye. RESULTS: 53 eyes of 42 patients with a mean age of 61 years were included. 36/53 eyes revealed nonproliferative diabetic retinopathy, 17/53 eyes had proliferative diabetic retinopathy. The mean size of the FAZ was 0.39 mm2 in FA and 0.42 mm2 in OCTA. The mean MA count was 14 in FA and 13 in OCTA. The assessability was favorable to OCTA in 38-41/53 eyes regarding the FAZ and favorable to FA in 45-49/53 eyes regarding MAs. CONCLUSION: We found a good agreement for the size of the FAZ and a weak agreement regarding the count of MAs in both imaging modalities. The readers favored OCTA for the assessment of the FAZ and FA for the assessment of MAs. Complementary use of FA and OCTA ensures the best diagnostic approach in patients with diabetic retinopathy.

[Cluster-Randomized Trials: Methodical and Practical Implications]. / Cluster-randomisierte Studien: Methodische und praktische Aspekte.

Quite often critics demand more randomized studies in rehabilitation science to gather methodological evidence of high quality. However, it is also recognized that the design of double-blind, placebo-controlled, randomized studies often cannot simply be transferred into rehabilitation science. Validity concerning the health care is here in the focus. Thus, treatment as-usual is mostly used as placebo treatment and double-blinding is partly not definable. Additionally, it is often difficult to offer 2 similar forms of treatment in one rehabilitation hospital due to lack of capacity. Additionally, contamination effects are to be expected when patients of different study arms communicate. Here cluster-randomized studies may be helpful. However, in comparison to individual randomized studies they need often higher sample sizes, a more complex methodology of sample size calculation as well as extensive methods of statistical analysis.Within this article advantages and disadvantages as well as the characteristics of cluster randomization are described and information is given how they can be implemented into the field of rehabilitation science.

Alveolar ridge preservation and primary stability as influencing factors on the transfer accuracy of static guided implant placement: a prospective clinical trial.

BACKGROUND: The aim of this prospective clinical study was to investigate differences between virtually planned and clinically achieved implant positions in completely template-guided implant placements as a function of the tooth area, the use of alveolar ridge preservation, the implant length and diameter, and the primary implant stability. METHODS: The accuracy of 48 implants was analyzed. The implants were placed in a completely template-guided manner. The data of the planned implant positions were superimposed on the actual clinical implant positions, followed by measurements of the 3D deviations in terms of the coronal (dc) and apical distance (da), height (h), angulation (ang), and statistical analysis. RESULTS: The mean dc was 0.7 mm (SD: 0.3), the mean da was 1.4 mm (SD: 0.6), the mean h was 0.3 mm (SD: 0.3), and the mean ang was 4.1° (SD: 2.1). The tooth area and the use of alveolar ridge preservation had no significant effect on the results in terms of the implant positions. The implant length had a significant influence on da (p = 0.02). The implant diameter had a significant influence on ang (p = 0.04), and the primary stability had a significant influence on h (p = 0.02). CONCLUSION: Template-guided implant placement offers a high degree of accuracy independent of the tooth area, the use of measures for alveolar ridge preservation or the implant configuration. A clinical benefit is therefore present, especially from a prosthetic point of view. TRIAL REGISTRATION: German Clinical Trial Register and the International Clinical Trials Registry Platform of the WHO: DRKS00005978 ; date of registration: 11/09/2015.

Cross-sectional associations of objectively assessed sleep duration with physical activity, BMI and television viewing in German primary school children.

BACKGROUND: The global incidence of overweight and obesity has increased dramatically among children and adolescents over the past decades. Insufficient sleep duration and physical inactivity are known risk factors for overweight and obesity in children. To engage children in a healthier lifestyle knowledge about associations of sleep duration and behavioural aspects in children are vital. Therefore, this study investigated the mentioned associations in German primary school children. METHODS: Data of 308 first and second graders (7.1 ± 0.6 years) was used; children's anthropometric data were taken during a school visit. Children's physical activity (PA) and sleep duration were assessed objectively (Actiheart©, CamNtech Ltd., Cambridge, UK); children's daily television time and socio-demographic data were collected via parental questionnaire. Linear mixed-effects regression models as well as logistic regressions were used to determine associations of PA, television viewing, age, gender, BMI z-scores and socio-economic variables on sleep duration. RESULTS: In linear regression models young age and not having a migration background were significantly associated with long sleep duration (p < 0.001). In logistic regressions, long night time sleep (≥10:08 h; compared to medium and short sleep duration) was significantly associated with not reaching the PA guideline (OR 0.60 [0.36;0.99]), daily television viewing of less than one hour (OR 0.44 [0.24;0.80]), young age (OR 0.38 [0.21;067]), a high parental education level (OR 0.52 [0.27;0.99]) and the lack of migration background (OR 0.21 [0.10;0.48]). However, if controlling for age, gender, parental education level and migration background, reaching the PA guideline stayed no longer significantly associated with a tertiary sleep level. CONCLUSIONS: Children in the highest sleep category showed a negative association with reaching the PA guideline and a positive association with daily television viewing. This therefore adds to previously primarily subjectively assessed associations of sleep and risk factors for obesity (related behaviours) with a detailed insight based on objective data. Hence, interventions trying to decrease children's BMI and television viewing should also aim at extending children's night-time sleep and inform parents about the importance of sufficient sleep during childhood. TRIAL REGISTRATION: DRKS-ID: DRKS00000494 .

High sedentary time in children is not only due to screen media use: a cross-sectional study.

BACKGROUND: Sedentary behaviour has become a growing public health concern. Currently, it is a common belief that screen time (SCT) is a key factor in high overall sedentary time (ST) and is often used as a primary outcome. However, the evidence is lacking. Therefore, this study investigated the association of objectively assessed total ST with SCT among children. Further, SCT was investigated separately for sedentary level, weight status, gender, and migration background. METHODS: For 198 primary school children (7.1 ± 0.7 years, boys: 43.9%) ST was assessed objectively using a multi-sensor device (Actiheart®; CamNtech, Cambridge, UK). The sample was split into three groups (tertiles) to investigate SCT of children with low, medium and high ST. SCT and socio-demographic parameters, such as migration background, were assessed using a parental questionnaire; anthropometric data was collected at schools. RESULTS: Absolut SCT did not differ significantly among the three sedentary groups: Daily average of SCT was 83.8 ± 55.0 min (27.4% of ST) for children with high ST, 82.8 ± 50.5 min (39.8% of ST) for children with medium ST, and 77.2 ± 59.4 min (71.3% of ST) for those with low ST. However, relatively the SCT percentage of total ST was significantly higher among children with low ST (p < 0.01). Significantly higher SCT was found in children with migration background (p < 0.01), while underweight children had significantly less SCT (p < 0.05). An association of total SCT and overall ST was found for the whole sample (B = 17.11, [2.75; 31.48], p = 0.02), but did not remain when analysis were separated for the groups, except for normal weight children (B = 15.97, [0.13; 31.81], p = 0.05). CONCLUSIONS: The amount of SCT is the same among high, low and medium sedentary children, and high ST is largely independent of SCT. Therefore, SCT cannot be the key contributor to high ST and should not solely be used for predicting or changing children's sedentary behaviour. Moreover, children's weight status to classify activity levels and the role of possible compensation mechanisms should be considered in future research and when trying to intervene on ST. TRIAL REGISTRATION: German Clinical Trials Register (DRKS), DRKS-ID: DRKS00000494 DATE: 25/08/2010.

[Comparison Between Automated and Manual Measurement of Foveal Avascular Zone Retinopathy in Optical Coherence Tomography]. / Evaluation der automatisierten Messung von ischämischen Veränderungen der Makula bei diabetischer Makulopathie.

OBJECTIVE: A comparison between automated and manual measurements of a foveal avascular zone in optical coherence tomography angiography (OCTA) in patients with diabetic retinopathy (DR). MATERIAL AND METHODS: Consecutive patients with non-proliferative DR were included in this study. All patients received an OCTA, with a 3 × 3 mm scan of the macular region taken with the Zeiss OCT CIRRUS 5000 with the AngioPlex module. The size of the foveal avascular zone (FAZ) was determined both manually and with the help of the automated measurement metrics. Next, the measurements obtained using manual and automated methods were compared. In addition, the circularity index determined in metrics was examined for correlations with the size and area of the FAZ. RESULTS: Thirty-four eyes from 28 patients with non-proliferative diabetic retinopathy with a mean age of 63 years were included. The mean size of the foveal avascular zone was 0.34 ± 0.12 mm2 (0.08 - 0.65 mm2) for manual evaluation and 0.23 ± 0.11 mm2 (range 0.03 - 0.49 mm2) in metrics. The circularity index in metrics averaged 0.58 and showed a statistically significant correlation with the size of the manually measured FAZ. CONCLUSION: There was a comparable result for the size of the FAZ in both measurement methods. Automated measurements with metrics can reliably represent changes in the FAZ for most patients, based on the calculated area, as well as on the circumference and the circularity index.

[Visualization of Retinal Neovascularization with Optical Coherence Tomography Angiography in Comparison with Fluorescein Angiography]. / Darstellung von retinalen Neovaskularisationen mit der optischen Kohärenztomografie-Angiografie im Vergleich mit der Fluoreszeinangiografie.

OBJECTIVE: Comparison of retinal neovascularizations of the disc (NVD) and elsewhere (NVE) in optical coherence tomography angiography (OCTA) and fluorescein angiography (FA) in patients with proliferative diabetic retinopathy. MATERIALS AND METHODS: 15 consecutive patients were included in this study. All patients received an OCTA with a 3 × 3 mm scan of the region of interest with the ZEISS OCT Cirrus 5000 with the AngioPlex module. The size of the neovascularization (NV) was determined manually in OCTA and FA and compared between the two methods. RESULTS: 20 eyes of 15 patients with proliferative diabetic retinopathy with an average age of 57 years were included. The mean size of NVDs was 3.44 mm2 in OCTA and 3.75 mm2 in FA, the mean size of NVDs was 1.06 mm2 in OCTA and 1.54 mm2 in FA. Taking into account a generally larger area measured in the FA, the two methods showed good overall agreement. CONCLUSION: There was a good agreement for the size of the NVs in both methods. OCTA can be used as a simple and non-invasive method to visualize retinal neovascularizations.

Anatomic reconstruction of the medial patellofemoral ligament in children and adolescents using a pedicled quadriceps tendon graft shows favourable results at a minimum of 2-year follow-up.

PURPOSE: In adults, reconstruction of the medial patellofemoral ligament (MPFL) has shown good results. Treatment for recurrent patellar instability in children and adolescents with open growth plates, however, requires alternative MPFL reconstruction techniques. This study presents the outcomes of a minimally invasive technique for anatomic reconstruction of the MPFL in children using a pedicled superficial quadriceps tendon graft, hardware-free patellar graft attachment, and anatomic femoral fixation that spares the distal femoral physis. METHODS: Twenty-five consecutive patients with patellofemoral instability and open growth plates underwent anatomic reconstruction of the MPFL using a pedicled superficial quadriceps tendon graft. Preoperative radiographic examination included AP and lateral views to assess patella alta and limb alignment. Magnetic resonance imaging was performed to evaluate trochlear dysplasia and tibial tubercle-trochlear groove distance. Evaluation included pre- and post-operative physical examination, Kujala score, visual analog scale (VAS), and Tegner activity score. RESULTS: The average age at the time of operation was 12.8 years (9.5-14.7). The average follow-up after operation was 2.6 years (2.0-3.4). No recurrent dislocation occurred. Twenty patients were very satisfied (80%), four patients were satisfied (16%), and one patient was partially satisfied with the surgical procedure (4%). No patient was dissatisfied. The median Kujala score significantly improved from 63 (44-81) preoperatively to 89 (77-100) post-operatively (P < 0.01), and the median VAS score improved significantly from 4 (1-7) to 1 (0-4) (P < 0.01). The Tegner activity score increased, but not significantly, from 4 (3-8) preoperatively to 5 (3-8) post-operatively (non-significant). CONCLUSION: The described technique for MPFL reconstruction with a pedicled quadriceps tendon is a safe and effective technique with good clinical results and allows patients to return to sports without redislocation of the patella. It might therefore be a valuable alternative to more extensive procedures in paediatric and adolescent patients. LEVEL OF EVIDENCE: Prospective study, Level III.