Translation and Psychometric Testing of the Hägerbäumer Presenteeism Scale in English.

PURPOSE: Interest in presenteeism has increased in research. Presenteeism is a behaviour of going to work despite illness. It has been predominantly measured using single items, which introduce limitations to validity. To overcome these limitations, Hägerbäumer developed a German multi-item presenteeism scale. METHODS: The aim of the study was to provide an English translation and psychometric testing of the scale. This was conducted in two phases with native English-speaking employed adults. Phase 1 includes translation and cognitive debriefing, phase 2 testing construct validity and internal consistency reliability. RESULTS: Cognitive debriefing with 10 employees revealed no problems with understanding or answering the translated items. In total, 487 employed adults participated in the study, of which data from 287 were included in the analysis. For structural validity, the goodness-of-fit indicators all reached their thresholds (TLI = 0.98, CFI = 0.99, RMSEA = 0.07, SRMR = 0.02). The scale does not show differences between sexes and age groups but between sectors (F6,70.95 = 5.53, p < 0.001). The internal consistency reliability was satisfactory with α = 0.89 (CI 95%, 0.87-0.91). CONCLUSION: The translated multidimensional scale for measuring presenteeism at the behavioural level demonstrated good psychometric properties in an initial validation. Further psychometric testing is required before using this scale in cross-national comparison in research and international companies.

Threshold Photoelectron Spectrum of m-Benzyne.

Due to their unusual electronic structure, the biradical m-benzyne, C6H4, and its cation are of considerable interest in chemistry. Here, the photoion mass-selected threshold photoelectron spectrum of the m-benzyne biradical is presented. An adiabatic ionization energy of 8.65 ± 0.015 eV is derived, while a vibrational progression of 0.10 eV is assigned to the ν9+ ring breathing mode, in excellent agreement with computations. The experimental spectrum was reproduced well by Franck-Condon spectral modeling of the 2A1 ← X 1A1 transition, in which the cation retains a monocyclic C6 framework. The energetically close-lying bicyclic 2A2 cation state exhibits low Franck-Condon factors, due to the large change in geometry, and thus cannot be observed.

Therapeutic drug monitoring in children and adolescents with schizophrenia and other psychotic disorders using risperidone.

Risperidone is commonly used to treat different psychiatric disorders worldwide. Knowledge on dose-concentration relationships of risperidone treatment in children and adolescents with schizophrenia or other psychotic disorders is, however, scarce and no age-specific therapeutic ranges have been established yet. Multicenter data of a therapeutic drug monitoring service were analyzed to evaluate the relationship between risperidone dose and serum concentration of the active moiety (risperidone (RIS) plus its main metabolite 9-hydroxyrisperidone (9-OH-RIS)) in children and adolescents with psychotic disorders. Patient characteristics, doses, serum concentrations and therapeutic outcomes were assessed by standardized measures. The study also aimed to evaluate whether the therapeutic reference range for adults (20-60 ng/ml) is applicable for minors. In the 64 patients (aged 11-18 years) included, a positive correlation between daily dose and the active moiety (RISam) concentration was found (rs = 0.49, p = 0.001) with variation in dose explaining 24% (rs2 = 0.240) of the variability in serum concentrations. While the RISam concentration showed no difference, RIS as well 9-OH-RIS concentrations and the parent to metabolite ratio varied significantly in patients with co-medication of a CYP2D6 inhibitor. Patients with extrapyramidal symptoms (EPS) had on average higher RISam concentrations than patients without (p = 0.05). Considering EPS, the upper threshold of the therapeutic range of RISam was determined to be 33 ng/ml. A rough estimation method also indicated a possibly decreased lower limit of the preliminary therapeutic range in minors compared to adults. These preliminary data may contribute to the definition of a therapeutic window in children and adolescents with schizophrenic disorders treated with risperidone. TDM is recommended in this vulnerable population to prevent concentration-related adverse drug reactions.

Effectiveness of parathyroid hormone (PTH) analogues on fracture healing: a meta-analysis.

This meta-analysis evaluated the evidence for the use of parathyroid hormone (PTH) analogues to improve fracture healing. Eligible studies were prospective randomised controlled trials of adults with acute fractures treated with a PTH analogue. PTH improved functional outcomes but did not affect fracture healing rate or reduce pain. PURPOSE: This meta-analysis evaluated the evidence of parathyroid hormone (PTH) analogues in fracture healing. The use of PTH analogues to prevent osteoporotic fractures is well investigated, and studies are emerging on extended indications. One such indication receiving increasing attention is the effect of PTH in fracture healing; however, the overall degree of efficacy remains inconclusive. METHODS: A systematic electronic database search of MEDLINE, EMBASE and the Cochrane Library was conducted for relevant articles in August 2019 with no date restrictions. Randomised controlled trials of adults with acute fractures treated with a PTH analogue were included. PTH was compared with a comparator intervention, placebo or no treatment. RESULTS: PTH analogue treatment improved functional outcomes in a range of fracture types but did not affect the fracture healing rate or reduce pain. Most trials included in this review were in elderly patients with osteoporosis. There was no evidence that PTH treatment caused harm or impeded fracture healing. CONCLUSIONS: Meta-analysis of published data supports the use of PTH analogues to improve functional outcomes but not fracture healing rate or pain for different fracture types. The evidence for PTH analogue use in fracture healing is less clear in younger, non-osteoporotic patient populations. Trial design was heterogeneous and of limited quality, justifying further original trials.

Estimation of a preliminary therapeutic reference range for children and adolescents with tic disorders treated with tiapride.

PURPOSE: Tiapride is commonly used in Europe for the treatment of tics. The aim of this study was to examine the relationship between dose and serum concentrations of tiapride and potential influential pharmacokinetic factors in children and adolescents. In addition, a preliminary therapeutic reference range for children and adolescents with tics treated with tiapride was calculated. METHODS: Children and adolescents treated with tiapride at three university hospitals and two departments of child and adolescents psychiatry in Germany and Austria were included in the study. Patient characteristics, doses, serum concentrations, and therapeutic outcome were assessed during clinical routine care using standardised measures. RESULTS: In the 49 paediatric patients (83.7% male, mean age = 12.5 years), a positive correlation was found between tiapride dose (median 6.9 mg/kg, range 0.97-19.35) and serum concentration with marked inter-individual variability. The variation in dose explained 57% of the inter-patient variability in tiapride serum concentrations; age, gender, and concomitant medication did not contribute to the variability. The symptoms improved in 83.3% of the patients. 27.1% of the patients had mild or moderate ADRs. No patient suffered from severe ADRs. CONCLUSIONS: This study shows that tiapride treatment was effective and safe in most patients with tics. Compared with the therapeutic concentration range established for adults with Chorea Huntington, our data hinted at a lower lower limit (560 ng/ml) and similar upper limit (2000 ng/ml).

Consensus Guidelines for Therapeutic Drug Monitoring in Neuropsychopharmacology: Update 2017.

Therapeutic drug monitoring (TDM) is the quantification and interpretation of drug concentrations in blood to optimize pharmacotherapy. It considers the interindividual variability of pharmacokinetics and thus enables personalized pharmacotherapy. In psychiatry and neurology, patient populations that may particularly benefit from TDM are children and adolescents, pregnant women, elderly patients, individuals with intellectual disabilities, patients with substance abuse disorders, forensic psychiatric patients or patients with known or suspected pharmacokinetic abnormalities. Non-response at therapeutic doses, uncertain drug adherence, suboptimal tolerability, or pharmacokinetic drug-drug interactions are typical indications for TDM. However, the potential benefits of TDM to optimize pharmacotherapy can only be obtained if the method is adequately integrated in the clinical treatment process. To supply treating physicians and laboratories with valid information on TDM, the TDM task force of the Arbeitsgemeinschaft für Neuropsychopharmakologie und Pharmakopsychiatrie (AGNP) issued their first guidelines for TDM in psychiatry in 2004. After an update in 2011, it was time for the next update. Following the new guidelines holds the potential to improve neuropsychopharmacotherapy, accelerate the recovery of many patients, and reduce health care costs.

Prospective quality control study of a novel gravity-driven whole blood separation system suitable for humanitarian crises.

Centrifugation-based whole blood (WB) separation represents the worldwide standard but it depends on electricity and infrastructure. We have prospectively evaluated a novel hollow-fibre WB separation system that does not require manual priming or blood flow regulation (n = 29). RBC units contained sufficient Hb (50·4 g ± 4·3), low leucocytes (90 000 ± 0·008), exhibited low haemolysis (0·57% ± 0·49) and robust ATP content (51·47% ± 8·2) after 43 days storage. Plasma units contained low leucocytes and mean coagulation factor activities for FV, FVIII and FXI were 47%, 90% and 68%, respectively. RBC met quality specifications but plasma units exhibited reduced FV and FXI activity.

[Guidelines in Practice: The New S3 Guideline "Sleeping Disorders - Sleep-Related Abnormal Breathing"]. / Leitlinien in der Praxis: Die neue S3-Leitlinie "Nicht erholsamer Schlaf/Schlafstörungen" ­ Kapitel "Schlafbezogene Atmungsstörungen".

Sleep related breathing disorders include central sleep apnea (CSA), obstructive sleep apnea (OSA), sleep-related hypoventilation, and sleep-related hypoxia. These disorders are frequent and growing in clinical relevance. The related chapter of the S3 guideline "Non-restorative sleep/Sleep disorders", published by the German Sleep Society (DGSM), has recently been updated in November 2016. Epidemiology, diagnostics, therapeutic procedures, and classification of sleep related disorders have been revised. Concerning epidemiology, a considerably higher mortality rate among pregnant women with OSA has been emphasized. With regards to diagnostics, the authors point out that respiratory polygraphy may be sufficient in diagnosing OSA, if a typical clinical condition is given. For CSA, recommendations were changed to diagnose CSA with low apnea rates present. Significant changes for treating CSA in patients with left ventricular dysfunction have been introduced. In addition, there is now to be differentiated between sleep-related hypoventilation and sleep-related hypoxaemia. Obesity hypoventilation syndrome is discussed in more detail. This article sums up and comments on the published changes.

Efficacy of feline anti-parvovirus antibodies in the treatment of canine parvovirus infection.

OBJECTIVE: This prospective, randomised, placebo-controlled, double-blinded study aimed to evaluate efficacy of commercially available feline anti-parvovirus antibodies in dogs with canine parvovirus infection. METHODS: First, cross-protection of feline panleukopenia virus antibodies against canine parvovirus was evaluated in vitro. In the subsequent prospective clinical trial, 31 dogs with clinical signs of canine parvovirus infection and a positive faecal canine parvovirus polymerase chain reaction were randomly assigned to a group receiving feline panleukopenia virus antibodies (n=15) or placebo (n=16). All dogs received additional routine treatment. Clinical signs, blood parameters, time to clinical recovery and mortality were compared between the groups. Serum antibody titres and quantitative faecal polymerase chain reaction were compared on days 0, 3, 7, and 14. RESULTS: In vitro, canine parvovirus was fully neutralised by feline panleukopenia virus antibodies. There were no detected significant differences in clinical signs, time to clinical recovery, blood parameters, mortality, faecal virus load, or viral shedding between groups. Dogs in the placebo group showed a significant increase of serum antibody titres and a significant decrease of faecal virus load between day 14 and day 0, which was not detectable in dogs treated with feline panleukopenia virus antibodies. CLINICAL SIGNIFICANCE: No significant beneficial effect of passively transferred feline anti-parvovirus antibodies in the used dosage regimen on the treatment of canine parvovirus infection was demonstrated.

Is this scaling nonlinear?

One of the most celebrated findings in complex systems in the last decade is that different indexes y (e.g. patents) scale nonlinearly with the population x of the cities in which they appear, i.e. y∼x (ß) ,ß≠1. More recently, the generality of this finding has been questioned in studies that used new databases and different definitions of city boundaries. In this paper, we investigate the existence of nonlinear scaling, using a probabilistic framework in which fluctuations are accounted for explicitly. In particular, we show that this allows not only to (i) estimate ß and confidence intervals, but also to (ii) quantify the evidence in favour of ß≠1 and (iii) test the hypothesis that the observations are compatible with the nonlinear scaling. We employ this framework to compare five different models to 15 different datasets and we find that the answers to points (i)-(iii) crucially depend on the fluctuations contained in the data, on how they are modelled, and on the fact that the city sizes are heavy-tailed distributed.

Trust, but verify. The errors and misinterpretations in the Cochrane analysis by O. J. Storebo and colleagues on the efficacy and safety of methylphenidate for the treatment of children and adolescents with ADHD.

Objective: A recent Cochrane review published by O. J. Storebo and colleagues (2015) raised substantial doubts about the benefit from stimulant medication with methylphenidate in the treatment of childhood ADHD due to the overall poor quality of studies. The systematic review thus contradicts all previous reviews and meta-analyses. Method: We here detail various examples of errors, inconsistencies, and misinterpretations in the review which led to false results and inadequate conclusions. Results: We demonstrate that the study selection is flawed and undertaken without sufficient scientific justification resulting in an underestimation of effect sizes, which, furthermore, are inadmissibly clinically interpreted. The methodology of the assessment of bias and quality is not objective and cannot be substantiated by the data. Conclusions: Cochrane reviews lay claim to a high scientific quality and substantial relevance for evidence-based clinical decisions. The systematic review by Storebo and colleagues (2015) illustrates that, despite adhering to strict standards and high-quality protocols, even Cochrane works should be critically read and verified, sometimes with surprising results.

Slice cultures from head and neck squamous cell carcinoma: a novel test system for drug susceptibility and mechanisms of resistance.

BACKGROUND: Human head and neck squamous cell carcinoma (HNSCC) fundamentally vary in their susceptibility to different cytotoxic drugs and treatment modalities. There is at present no clinically accepted test system to predict the most effective therapy for an individual patient. METHODS: Therefore, we established tumour-derived slice cultures which can be kept in vitro for at least 6 days. Upon treatment with cisplatin, docetaxel and cetuximab, slices were fixed and paraffin sections were cut for histopathological analysis. RESULTS: Apoptotic fragmentation, activation of caspase 3, and cell loss were observed in treated tumour slices. Counts of nuclei per field in untreated compared with treated slices deriving from the same tumour allowed estimation of the anti-neoplastic activity of individual drugs on an individual tumour. CONCLUSION: HNSCC-derived slice cultures survive well in vitro and may serve not only to improve personalised therapies but also to detect mechanisms of tumour resistance by harvesting surviving tumour cells after treatment.

Combined enrichment of neuromelanin granules and synaptosomes from human substantia nigra pars compacta tissue for proteomic analysis.

This article gives a detailed description of a protocol using density gradient centrifugation for the enrichment of neuromelanin granules and synaptosomes from low amounts (≥0.15g) of human substantia nigra pars compacta tissue. This has a great advantage compared to already existing methods as it allows for the first time (i) a combined enrichment of neuromelanin granules and synaptosomes and (ii) just minimal amounts of tissue necessary to enable donor specific analysis. Individual specimens were classified as control or diseased according to clinical evaluation and neuropathological examination. For the enrichment of synaptosomes and neuromelanin granules from the same tissue sample density gradient centrifugations using Percoll® and Iodixanol were performed. The purity of resulting fractions was checked by transmission electron microscopy. We were able to establish a reproducible and easy to handle protocol combining two different density gradient centrifugations: using an Iodixanol gradient neuromelanin granules were enriched and in parallel, from the same sample, a fraction of synaptosomes with high purity using a Percoll® gradient was obtained. Our subfractionation strategy will enable a subsequent in depth proteomic characterization of neurodegenerative processes in the substantia nigra pars compacta in patients with Parkinson's disease and dementia with Lewy bodies compared to appropriate controls. BIOLOGICAL SIGNIFICANCE: Key features of Parkinson's disease are the degeneration of dopaminergic neurons in the substantia nigra pars compacta, an associated loss of the brain pigment neuromelanin and a resulting impairment of the neuronal network. The accumulation of iron binding neuromelanin granules is age- and disease-dependent and disease specific alterations could affect the neuronal iron homeostasis leading to oxidative stress induced cell death. The focus of the described method is the analysis of neuromelanin granules as well as axonal cell-endings of nerve cells (synaptosomes) of individual donors (control and diseased). It is the basis for the identification of disease-relevant changes in the iron homeostasis and the generation of new insight into altered protein compositions or regulations which might lead to disturbed communications between nerve cells resulting in pathogenic processes.

Measurement of the mass energy-absorption coefficient of air for x-rays in the range from 3 to 60 keV.

For the first time the absolute photon mass energy-absorption coefficient of air in the energy range of 10 to 60 keV has been measured with relative standard uncertainties below 1%, considerably smaller than those of up to 2% assumed for calculated data. For monochromatized synchrotron radiation from the electron storage ring BESSY II both the radiant power and the fraction of power deposited in dry air were measured using a cryogenic electrical substitution radiometer and a free air ionization chamber, respectively. The measured absorption coefficients were compared with state-of-the art calculations and showed an average deviation of 2% from calculations by Seltzer. However, they agree within 1% with data calculated earlier by Hubbell. In the course of this work, an improvement of the data analysis of a previous experimental determination of the mass energy-absorption coefficient of air in the range of 3 to 10 keV was found to be possible and corrected values of this preceding study are given.

Pre-hospital discharge testing after implantable cardioverter defibrillator implantation: a measure of safety or out of date? A retrospective analysis of 975 patients.

AIMS: The present study evaluates the relevance and additional safety value of pre-hospital discharge (PHD) testing in patients with implantable cardioverter defibrillator (ICD) therapy. METHODS: From June 1998 to May 2009, 975 patients (830 male, 145 female) with ICD were screened retrospectively for failed PHD and analysed for its consequences, risk factors, and patient characteristics after successful intra-operative testing in the implantation procedure. RESULTS: Pre-hospital discharge testing procedure was performed in 809 cases. No serious adverse events (e.g. death, persistant ventricular fibrillation or ventricular tachycardia, stroke) occurred. The overall incidence of failed PHD was 1.4% (n = 11). The underlying mechanisms were defibrillation threshold failure in 9/11 cases and sensing failure in 2/11 cases. CONCLUSIONS: In this study predictors for PHD-failure are: (i) cardiomyopathy other than ischaemic or dilative, (ii) young age, and (iii) small or very large left ventricular end-diastolic diameter ( < 40 or > 65 mm). Particularly, (i) manufacture of device or leads, (ii) lead design, (iii) medical treatment, or (iv) gender have no significant influence on PHD failure.

Therapeutic drug monitoring of children and adolescents treated with fluoxetine.

INTRODUCTION: Information about therapeutic serum levels of fluoxetine (FLX) and its major metabolite norfluoxetine (NORFLX) in children and adolescents is scarce. METHODS: Therapeutic drug monitoring (TDM) of FLX was routinely performed in 71 subjects treated for a major depressive disorder (MDD) (10-60 mg/d FLX, median: 20 mg/d). Correlations between serum concentration and dosage, age, gender, smoking habits and adverse events were analysed. RESULTS: Serum concentrations of the active moiety (FLX + NORFLX) ranged from 21 to 613 ng/mL (mean concentration of 213 ± 118 ng/mL, median: 185 ng/mL). High inter-individual variability in serum concentrations of the active moiety of FLX at each dosage level was observed and no relationship between serum concentration and clinical outcome was found. Apart from smoking, none of the factors tested had a significant eff ect on the serum concentration. DISCUSSION: It was shown that serum concentrations of the active moiety of FLX in children and adolescents seem to be similar to those in adults, with a high level of inter-individual variation. The proportion of patients who showed benefits from treatment with a dose of 20 mg/d FLX was high.