Pharmacotherapy for ADHD in children and adolescents: A summary and overview of different European guidelines.

Attention deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by a persistent pattern of inattention, hyperactivity, and impulsivity. It is the most common neurodevelopmental disorder presenting to pediatric services, and pediatricians are often involved in the early assessment, diagnosis, and treatment of children with ADHD. The treatment of ADHD typically involves a multimodal approach that encompasses a combination of psychoeducation, parent/teacher training, psychosocial/psychotherapeutic interventions, and pharmacotherapy. Concerning pharmacotherapy, guidelines vary in drug choice and sequencing, with psychostimulants, such as methylphenidate and (lis)dexamfetamine, generally being the favored initial treatment. Alternatives include atomoxetine and guanfacine. Pharmacotherapy has been proven effective, but close follow-up focusing on physical growth, cardiovascular monitoring, and the surveillance of potential side effects including tics, mood fluctuations, and psychotic symptoms, is essential. This paper presents an overview of current pharmacological treatment options for ADHD and explores disparities in treatment guidelines across different European countries.   Conclusion: Pharmacological treatment options for ADHD in children and adolescents are effective and generally well-tolerated. Pharmacotherapy for ADHD is always part of a multimodal approach. While there is a considerable consensus among European guidelines on pharmacotherapy for ADHD, notable differences exist, particularly concerning the selection and sequencing of various medications. What is Known: • There is a significant base of evidence for pharmacological treatment for ADHD in children and adolescents. • Pediatricians are often involved in assessment, diagnosis and management of children with ADHD. What is New: • Our overview of different European guidelines reveals significant agreement in the context of pharmacotherapy for ADHD in children and adolescents. • Discrepancies exist primarily in terms of selection and sequencing of different medications.

Nitrofurantoin for the treatment of uncomplicated urinary tract infection in female patients: the impact of dosing regimen, age, and renal function on drug exposure.

PURPOSE: The aim of this study is to determine nitrofurantoin exposure in female patients with different age and renal function with complaints of an uncomplicated UTI. Also the nitrofurantoin exposure in relation to the dosage regimen will be studied. METHODS: Eight general practitioners (GP) participated in the study and included 38 patients with symptoms of an uncomplicated UTI, treated either with a dose of 50 mg q6h or 100 mg q12h, upon the discretion of the GP. Nitrofurantoin exposure was quantified in the patient's 24-h urine samples by UHPLC-UV and the area under the curve was calculated. RESULTS: The 38 patients provided a range of 2-17 urine samples. The urine nitrofurantoin exposure was 1028 mg h/L for the patients receiving 50 mg q6h and 1036 mg h/L for those treated with 100 mg q12h (p = 0.97) and was not affected by age and eGFR (p = 0.64 and p = 0.34, respectively). CONCLUSION: The data obtained do not support the discouragement of nitrofurantoin use in the elderly and in patients with impaired renal function. Since only a small number of patients were included, a larger study with more patients is warranted to evaluate nitrofurantoin exposure and adverse effects.

The effect of combining therapeutic drug monitoring of antihypertensive drugs with personalised feedback on adherence and resistant hypertension: the (RHYME-RCT) trial protocol of a multi-centre randomised controlled trial.

BACKGROUND: Adherence to antihypertensive drugs (AHDs) is important for adequate blood pressure control. Not taking these drugs as prescribed is one of the main underlying causes for resistant hypertension (RH), which in turn leads to an increased risk of cardiovascular events, stroke and kidney damage. Therefore, correct identification of patients that are non-adherent to AHDs is crucial to improve clinical outcome. For this goal, therapeutic drug monitoring is the most reliable method. The primary objective of this trial is to investigate whether monitoring of drug concentrations with a dried blood spot (DBS) sampling method combined with personalised feedback leads to a decrease in prevalence of RH after 12 months due to an increase in adherence. Secondary objectives include the difference over time in the number of required AHDs as well as the defined daily dose (DDD). Lastly, the cost-utility of SoC versus the intervention in RH is determined. METHODS: This is a multi-centre single-blinded randomised controlled trial (RHYME-RCT). First, at an eligibility visit, DBS sampling, to monitor drug concentrations in blood, and a 24-h ambulatory blood pressure measurement (24-h ABPM) are performed simultaneously. Patients with a daytime systolic blood pressure (SBP) > 135 and/or diastolic blood pressure (DBP) > 85 mmHg are randomised to SoC or intervention + SoC. The intervention is performed by the treating physician and includes information on drug concentrations and a comprehensive personalised feedback conversation with the use of a communication tool. The follow-up period is one year with visits at 3, 6 and 12 months randomisation and includes 24-h ABPM and DBS sampling. DISCUSSION: This will be the first trial that focusses specifically on patients with RH without taking into account suspicion of non-adherence and it combines monitoring of AHD concentrations to identify non-adherence to AHDs with a comprehensive feedback to improve non-adherence. Furthermore, if this trial shows positive outcomes for the intervention it can be directly implemented in clinical practice, which would be a great improvement in the treatment of RH. TRIAL REGISTRATION: RHYME-RCT is registered in the Dutch Trial Register on 27/12/2017 (NTR6914) and can be found in the International Clinical Trials Registry Platform.

Lessons learned from conducting a randomized controlled trial to improve non-adherence to antihypertensive drug treatment.

PURPOSE: Hypertension significantly contributes to cardiovascular diseases and premature deaths. Effective treatment is crucial to reduce cardiovascular risks, but poor adherence to antihypertensive drugs is a major issue. Numerous studies attempted to investigate interventions for identifying non-adherence, but often failed to address the issue effectively. The RHYME-RCT trial sought to bridge this gap by measuring non-adherence by determining antihypertensive drug concentrations in blood through a dried blood spot (DBS) method in patients with resistant hypertension. This measurement was followed by personalized feedback to improve adherence. During the course of this trial several challenges emerged, including selection bias, the gatekeeper role of physicians, the Hawthorne effect and the role of randomization. AIM: This communication aims to inform fellow researchers and clinicians of challenges that can arise when conducting clinical trials to improve adherence and offer insights for refining study designs to avoid these issues in forthcoming adherence studies.

Purpose: High blood pressure is a serious problem that can lead to heart and kidney problems and early deaths. Treating high blood pressure is therefore crucial. Initially, lifestyle changes are recommended, but if they don't work, medications are needed. However, taking these drugs daily can be challenging, and many patients miss doses which is called non-adherence. Despite numerous studies, a perfect solution hasn't been found to solve non-adherence to blood pressure lowering drugs.In the RHYME-RCT study, researchers aimed to improve drug adherence in patients with resistant hypertension. They monitored drug intake by measuring drug concentrations in the blood alongside 24-hour blood pressure monitoring. These data allowed healthcare providers to offer personalized advice to patients. The study encountered some important challenges in its design, including selection bias, where some participants shouldn't have been included or excluded in the study, and the Hawthorne effect, where patients changed their behavior because they knew they were being observed.Aim: This message is to inform fellow scientists and doctors about issues that can arise when conducting clinical trials to improve adherence and to encourage the exchange of ideas between scientists to improve future studies on medication adherence, which is essential for managing conditions like high blood pressure.

Comparison of antipsychotic drug use among Dutch Youth before and after implementation of the Youth Act (2010-2019).

OBJECTIVE: The Dutch law on youth care (the Youth Act) was implemented from 2015 onwards. One of the government's aims by implementing this new policy was de-medicalization of youths by separating youth mental healthcare from the rest of the healthcare system. A previous study conducted by our research group showed that prevalence rates of antipsychotic drug prescriptions stabilized among Dutch youth in the period 2005-2015, just before the introduction of the Youth Act. In our study, we aimed to describe antipsychotic drug use among Dutch children aged 0-19 years old before and after implementation of the Youth Act (2010-2019). METHODS: We analyzed prescription data of 7405 youths aged 0-19 years using antipsychotic drugs between 2010 and 2019, derived from a large Dutch community pharmacy-based prescription database (IADB.nl). RESULTS: Prevalence rates of antipsychotic drug use per thousand youths decreased significantly in youths aged 7-12 years old in 2019 compared to 2015 (7.9 vs 9.0 p < 0.05). By contrast, prevalence rates increased in adolescent females in 2019 compared to 2015 (11.8 vs 9.5 p < 0.05). Incidence rates increased significantly in adolescent youths in 2019 compared to 2015 (3.9 vs 3.0 p < 0.05), specifically among adolescent girls (4.2 per thousand in 2019 compared to 3.0 per thousand in 2015). Dosages in milligram declined for the most commonly prescribed antipsychotic drugs during the study period. The mean duration of antipsychotic drug use in the study period was 5.7 (95% CI 5.2-6.2) months. CONCLUSION: Despite the aim of the Youth Act to achieve de-medicalization of youths, no clear reduction was observed in prevalence rates of antipsychotic drugs or treatment duration in all subgroups. Prevalence rates even increased in adolescent females.

[Improving the safety of antipsychotic drugs in children and adolescents by antipsychotic drug concentration measurements using a fingerprick]. / Naar veiliger antipsychoticagebruik bij jongeren: bloedspiegelbepalingen met vingerprik.

BACKGROUND: Antipsychotic drugs are associated with serious side effects in children and adolescents including weight gain. It is still unknown whether therapeutic drug monitoring (TDM) can improve patient outcomes. AIM: To test whether the dried blood spot method is a valid and feasible method to measure antipsychotic drug concentrations with a fingerprick; to assess the relationship between antipsychotic drug concentrations, side-effects and effectiveness in minors. METHOD: A dried blood spot (DBS) method was developed and tested for validity and feasibility. 89 children and adolescents with autism spectrum disorder (ASD) and behavioral problems were included in the multicenter, prospective, observational study SPACe (NTR6050). Antipsychotic drug concentrations, side-effects and effectiveness were measured during a 6-month follow-up. RESULTS: The DBS method showed a higher variability than venipuncture in measuring antipsychotic drug concentrations, but seemed feasible in minors with behavioral problems. Higher risperidon trough concentrations were associated with more weight gain and more effectiveness. A therapeutic window with optimal effectiveness and minimal side-effects was defined. CONCLUSION: The DBS method can be used to measure antipsychotic drug concentrations in children and adolescents with ASD and behavioral problems. As a relationship between antipsychotic drug concentrations and clinical outcomes was established, TDM might improve safety and effectiveness of antipsychotic drugs in this population.

Comprehensive assessments and related interventions to enhance the long-term outcomes of child, adolescent and young adult cancer survivors - presentation of the CARE for CAYA-Program study protocol and associated literature review.

BACKGROUND: Improved, multimodal treatment strategies have been shown to increase cure rates in cancer patients. Those who survive cancer as a child, adolescent or young adult (CAYA), are at a higher risk for therapy-, or disease-related, late or long-term effects. The CARE for CAYA-Program has been developed to comprehensively assess any potential future problems, to offer need-based preventative interventions and thus to improve long-term outcomes in this particularly vulnerable population. METHODS: The trial is designed as an adaptive trial with an annual comprehensive assessment followed by needs stratified, modular interventions, currently including physical activity, nutrition and psycho-oncology, all aimed at improving the lifestyle and/or the psychosocial situation of the patients. Patients, aged 15-39 years old, with a prior cancer diagnosis, who have completed tumour therapy and are in follow-up care, and who are tumour free, will be included. At baseline (and subsequently on an annual basis) the current medical and psychosocial situation and lifestyle of the participants will be assessed using a survey compiled of various validated questionnaires (e.g. EORTC QLQ C30, NCCN distress thermometer, PHQ-4, BSA, nutrition protocol) and objective parameters (e.g. BMI, WHR, co-morbidities like hyperlipidaemia, hypertension, diabetes), followed by basic care (psychological and lifestyle consultation). Depending on their needs, CAYAs will be allocated to preventative interventions in the above-mentioned modules over a 12-month period. After 1 year, the assessment will be repeated, and further interventions may be applied as needed. During the initial trial phase, the efficacy of this approach will be compared to standard care (waiting list with intervention in the following year) in a randomized study. During this phase, 530 CAYAs will be included and 320 eligible CAYAs who are willing to participate in the interventions will be randomly allocated to an intervention. Overall, 1500 CAYAs will be included and assessed. The programme is financed by the innovation fund of the German Federal Joint Committee and will be conducted at 14 German sites. Recruitment began in January 2018. DISCUSSION: CAYAs are at high risk for long-term sequelae. Providing structured interventions to improve lifestyle and psychological situation may counteract against these risk factors. The programme serves to establish uniform regular comprehensive assessments and need-based interventions to improve long-term outcome in CAYA survivors. TRIAL REGISTRATION: Registered at the German Clinical Trial Register (ID: DRKS00012504, registration date: 19th January 2018).

The effect of therapeutic drug monitoring of beta-lactam and fluoroquinolones on clinical outcome in critically ill patients: the DOLPHIN trial protocol of a multi-centre randomised controlled trial.

BACKGROUND: Critically ill patients undergo extensive physiological alterations that will have impact on antibiotic pharmacokinetics. Up to 60% of intensive care unit (ICU) patients meet the pharmacodynamic targets of beta-lactam antibiotics, with only 30% in fluoroquinolones. Not reaching these targets might increase the chance of therapeutic failure, resulting in increased mortality and morbidity, and antibiotic resistance. The DOLPHIN trial was designed to demonstrate the added value of therapeutic drug monitoring (TDM) of beta-lactam and fluoroquinolones in critically ill patients in the ICU. METHODS: A multi-centre, randomised controlled trial (RCT) was designed to assess the efficacy and cost-effectiveness of model-based TDM of beta-lactam and fluoroquinolones. Four hundred fifty patients will be included within 24 months after start of inclusion. Eligible patients will be randomly allocated to either study group: the intervention group (active TDM) or the control group (non-TDM). In the intervention group dose adjustment of the study antibiotics (cefotaxime, ceftazidime, ceftriaxone, cefuroxime, amoxicillin, amoxicillin with clavulanic acid, flucloxacillin, piperacillin with tazobactam, meropenem, and ciprofloxacin) on day 1, 3, and 5 is performed based upon TDM with a Bayesian model. The primary outcome will be ICU length of stay. Other outcomes amongst all survival, disease severity, safety, quality of life after ICU discharge, and cost effectiveness will be included. DISCUSSION: No trial has investigated the effect of early TDM of beta-lactam and fluoroquinolones on clinical outcome in critically ill patients. The findings from the DOLPHIN trial will possibly lead to new insights in clinical management of critically ill patients receiving antibiotics. In short, to TDM or not to TDM? TRIAL REGISTRATION: EudraCT number: 2017-004677-14. Sponsor protocol name: DOLPHIN. Registered 6 March 2018 . Protocol Version 6, Protocol date: 27 November 2019.

Population pharmacokinetic modelling of intravenous paracetamol in fit older people displays extensive unexplained variability.

AIMS: Paracetamol is the analgesic most used by older people. The physiological changes occurring with ageing influence the pharmacokinetics (PK) of paracetamol and its variability. We performed a population PK-analysis to describe the PK of intravenous (IV) paracetamol in fit older people. Simulations were performed to illustrate target attainment and variability of paracetamol exposure following current dosing regimens (1000 mg every 6 h, every 8 h) using steady-state concentration (Css-mean ) of 10 mg l-1 as target for effective analgesia. METHODS: A population PK-analysis, using NONMEM 7.2, was performed based on 601 concentrations of paracetamol from 30 fit older people (median age 77.3 years, range [61.8-88.5], body weight 79 kg [60-107]). All had received an IV paracetamol dose of 1000 mg (over 15 min) after elective knee surgery. RESULTS: A two-compartment PK-model best described the data. Volume of distribution of paracetamol increased exponentially with body weight. Clearance was not influenced by any covariate. Simulations of the standardized dosing regimens resulted in a Css of 9.2 mg l-1 and 7.2 mg l-1 , for every 6 h and every 8 h respectively. Variability in paracetamol PK resulted in Css above 5.4 and 4.1 mg l-1 , respectively, in 90% of the population and above 15.5 and 11.7, respectively, in 10% at these dosing regimens. CONCLUSIONS: The target concentration was achieved in the average patient with 1000 mg every 6 h, while every 8 h resulted in underdosing for the majority of the population. Furthermore, due to a large (unexplained) interindividual variability in paracetamol PK a relevant proportion of the fit older people remained either under- or over exposed.

Changes in fermentation and animal performance during recovery from classical diet-induced milk fat depression using corn with differing rates of starch degradability.

Diet-induced milk fat depression (MFD) is a multifactorial disorder that can be triggered by a variety of conditions. Feeding high amounts of starch and unsaturated fatty acids has been shown to reduce milk fat yield and composition, as well as alter ruminal biohydrogenation patterns. However, little is known about how starch degradability in the rumen influences recovery from diet-induced MFD and if production of milk fat-inhibiting isomers will persist following an episode of MFD. The objective of this study was to evaluate production performance and ruminal fermentation in cows recovering from MFD when corn with a low or high starch degradability is fed. Six ruminally fistulated Holstein cows were used in a crossover design with 2 periods. During each period, MFD was induced for 10 d by feeding a diet with low fiber, high starch, and high unsaturated fatty acid. The polyunsaturated fatty acid concentration of the diet during the induction phase was modified primarily through inclusion of soybean oil. Following induction, cows were switched to either a high degradable starch recovery diet (HDS) or a low degradable starch recovery diet (LDS) for 18 d. The 7-h starch degradability was 66.5% for LDS and 87.8% for HDS. Milk was collected every 3 d for component and fatty acid analysis. On d 0, 4, 7, 10, 16, 22, and 28 of each period, ruminal pH and rumen fluid were collected every 2 h. Milk fat yield and composition was reduced during MFD induction and progressively increased by day in both HDS and LDS during recovery. Dry matter intake was similar among treatments and increased steadily over time during recovery. Preformed fatty acids were greater for HDS-fed animals, and de novo fatty acid in milk fat was greater for LDS-fed animals. Milk trans-10 C18:1 tended to be greater for HDS, and trans-10,cis-12 conjugated linoleic acid was significantly greater for HDS. cis-9,trans-11 conjugated linoleic acid was not affected by starch degradability during recovery. Total volatile fatty acids, butyrate, and valerate tended to differ or differed with recovery treatment, but ruminal pH and ammonia concentration were unaffected. The HDS diet responded similarly to the LDS diet during recovery with regard to milk fat percentage, but milk and fat yield tended to consistently be lower in HDS. When considering approaches to ameliorate diet-induced MFD, the degradability of the starch within rations should be evaluated. Although animal performance was similar, some trans fatty acid isomers were persistent in the milk through the recovery phase with HDS-fed animals, suggesting that milk fat synthesis might be potentially inhibited and biohydrogenation pathways modified in the rumen following an episode of MFD.

Population pharmacokinetics of haloperidol in terminally ill adult patients.

PURPOSE: Over 80% of the terminally ill patients experience delirium in their final days. In the treatment of delirium, haloperidol is the drug of choice. Very little is known about the pharmacokinetics of haloperidol in this patient population. We therefore designed a population pharmacokinetic study to gain more insight into the pharmacokinetics of haloperidol in terminally ill patients and to find clinically relevant covariates that may be used in developing an individualised dosing regimen. METHODS: Using non-linear mixed effects modelling (NONMEM 7.2), a population pharmacokinetic analysis was conducted with 87 samples from 28 terminally ill patients who received haloperidol either orally or subcutaneously. The covariates analysed were patient and disease characteristics as well as co-medication. RESULTS: The data were accurately described by a one-compartment model. The population mean estimates for oral bioavailability, clearance and volume of distribution for an average patient were 0.86 (IIV 55%), 29.3 L/h (IIV 43%) and 1260 L (IIV 70%), respectively. This resulted in an average terminal half-life of haloperidol of around 30 h. CONCLUSION: Our study showed that the pharmacokinetics of haloperidol could be adequately described by a one-compartment model. The pharmacokinetics in terminally ill patients was comparable to other patients. We were not able to explain the wide variability using covariates.

Improved nutrition in adolescents and young adults after childhood cancer - INAYA study.

BACKGROUND: Multimodality treatment improves the chance of survival but increases the risk for long-term side effects in young cancer survivors, so-called" Adolescents and Young Adults"(AYAs). Compared to the general population AYAs have a 5 to 15-fold increased risk of cardiovascular morbidity. Thus, improving modifiable lifestyle risk factors is of particular importance. METHODS: The INAYA trial included AYAs between 18 and 39 years receiving an intensified individual nutrition counseling at four time points in a 3-month period based on a 3-day dietary record. At week 0 and 12 AYAs got a face-to-face counseling, at week 2 and 6 by telephone. Primary endpoint was change in nutritional behavior measured by Healthy Eating Index - European Prospective Investigation into Cancer and Nutrition (HEI-EPIC). RESULTS: Twenty-three AYAs (11 female, 12 male, median age 20 years (range 19-23 years), median BMI: 21.4 kg/m2 (range: 19.7-23.9 kg/m2) after completion of cancer treatment for sarcoma (n = 2), carcinoma (n = 2), blastoma (n = 1), hodgkin lymphoma (n = 12), or leukemia (n = 6) were included (median time between diagnosis and study inclusion was 44 month). The primary endpoint was met, with an improvement of 20 points in HEI-EPIC score in 52.2 % (n = 12) of AYAs. At baseline, median HEI-EPIC score was 47.0 points (range from 40.0 to 55.0 points) and a good, moderate and bad nutritional intake was seen in 4.3, 73.9 and 21.7 % of AYAs. At week 12, median HEI-EPIC improved significantly to 65.0 points (range from 55.0 to 76.0 points) (p ≤ 0.001) and a good, moderate and bad nutritional intake was seen in 47.8, 52.2 and 0 % of AYAs. No change was seen in quality of life, waist-hip ratio and blood pressure. CONCLUSION: Intensified nutrition counseling is feasible and seem to improve nutritional behavior of AYAs. Further studies will be required to demonstrate long-term sustainability and confirm the results in a randomized design in larger cohorts. TRIAL REGISTRATION: Clinical trial identifier DRKS00009883 on DRKS.

[Motor Skills of Extremely Obese Children and Adolescents Based on the Multicentre Longitudinal Obesity Database (APV)]. / Motorische Fitness extrem adipöser Kinder und Jugendlicher basierend auf der multizentrischen Adipositas-Patienten-Verlaufsdokumentation (APV).

BACKGROUND: Obese children and adolescents often exhibit progressively declining motor skills. To support young obese patients adequately, it is necessary to assess their individual physical and motor abilities, taking the degree of obesity into account. PATIENTS: A total of 5 924 children and adolescents (mean age: 12.7±2.5 years, range 6.0-18.0 years, 3 195 girls) were examined in a standardised multicentre evaluation survey (APV). Fitness parameters were correlated with age- and gender-specific BMI-SDS (Standard Deviation Score) Methods: Anthropometric data were collected and patients performed the modified Munich fitness test (mMFT: maximal power, coordination, trunk flexibility) and a 6-min walk-test (aerobic endurance capacity). RESULTS: 33% of patients were extremely obese (BMI>99.5th percentile). Mean BMI-SDS was + 2.32±0.53 (♀-Δ=+ 0.06; p<0.001). The data indicated significant negative correlations between BMI-SDS and selected components of motor performance, especially maximal power (r=- 0,134), and particularly aerobic endurance capacity (r=- 0,214; all p<0.001). Motor performance was significantly below average (n=27 473, 6-18 years), especially among extremely obese patients. Performance in all motor tasks was lower in girls compared to boys, except for trunk flexibility (p<0.001). CONCLUSION: Correlations were found between BMI-SDS and motor performance. Extremely obese patients and obese girls showed the most pronounced motor deficits. These results emphasize the importance of standardized evaluation of individual motor performance in children and adolescents with obesity.

[Development and implementation of a state-wide "train the trainer" model of the school-based prevention programme "Join the Healthy Boat - Primary School"]. / Entwicklung und Implementierung eines landesweiten Multiplikatorensystems zur flächendeckenden Umsetzung des schulbasierten Präventionsprogramms "Komm mit in das gesunde Boot - Grundschule"

STUDY AIM: This paper shows how a state-wide health-promotion intervention at primary schools can be implemented by considering the example of the programme "Join the Healthy Boat - Primary School". Additionally, it is illustrated how quality control throughout the whole process can be incorporated. METHODS: To operate long-term and target-group orientated in the whole state of Baden-Württemberg, the school-based prevention programme "Join the Healthy Boat" uses a "train the trainer" model. The trainers are teachers who were instructed by the project team. In the school year 2009/10, these trainers offered quadrinominal training courses for further teachers. Every urban and rural district is covered by 1 trainer. The trainers evaluated the 6 preparatory training courses they had been given using questionnaires. The following 4 training courses the trainers offered to the teachers were reviewed by the trainers as well as the teachers using questionnaires, too. Additionally, at the end of the school year 2009/10, the teachers completed a questionnaire about their satisfaction regarding the programme itself and the work with the trainer. RESULTS: During the school year 2009/10, 453 teachers were trained by 32 trainers. According to indications on the questionnaires about the preparatory training courses, all trainers felt themselves "very well" or "well" prepared for their task. The teachers evaluated the expertise of the respective trainer, the quality of the training courses and the satisfaction with the programme itself throughout highly. CONCLUSION: Based on the excellent results of the process evaluation and the programme's wide coverage, an adoption of a "train the trainer" model seems worthwhile for other school-based prevention programmes, as well.

[Physical performance of older patients training regularly: comparison with a normal population]. / Körperliche Leistungsfähigkeit regelmäßig trainierender, älterer Patienten im Vergleich zur Normalpopulation.

Previous studies indicate that physical performance, being a relevant prognostic parameter for cardiovascular events and mortality, decreases with age. Thus, the maintenance and restoration of physical performance as part of a rehabilitation program is of great interest. In the present study, 35 physically active participants, aged 58 - 78 years, were investigated by cardiopulmonary exercise testing. In comparison to matched participants drawn from an epidemiological study, there was no significant difference in performance g between the two groups. Additionally, oxygen kineticswere incrementally measured in order to evaluate a fairly simple procedure for determining fitness under activities of daily life. Surprisingly, this method did not reveal any clinically relevant association between oxygen kinetics and physical fitness.

[Reference values for arterial oxygen content]. / Referenzwerte für den arteriellen Sauerstoffgehalt.

BACKGROUND: In clinical practice, oxygen saturation as measured by photoplethysmography and arterial oxygen tension as determined by blood gas analysis are the parameters used frequently to estimate the oxygen status of a patient. Additionally, the cardiac output CO and the arterial oxygen content CaO2 are critical for the delivery of oxygen DO2 to organs and tissues. So far, CaO2 reference values published by Mertzlufft and Zander (1984) and Siggaard-Andersen (1990) are widely used. The aim of the present study was to reevaluate previously published results using the results of a population-based study. Furthermore, the impact of smoking on CaO2 will be assessed. PATIENTS AND METHODS: Data of 1018 volunteers from the Study of Health in Pomerania (SHIP) were analyzed. CaO2 was calculated from blood gas analysis of capillary blood obtained from a hyperemised ear lobe. Reference value equations controlled for sex, age and smoking were derived with quantile regression analysis and fractional polynomials. RESULTS: Lower limits of normal (LLN) decline with age. Current smoking has no significant influence on LLN for CaO2. CONCLUSION: Sex, age and smoking-specific normal values can be calculated using the current equations.

Quantification of cefuroxime and flucloxacillin in synovial tissue and bone using ultra-performance convergence chromatography-tandem mass spectrometry.

After a revision surgery, approximately 1-2 % of patients will develop a periprosthetic joint infection (PJI). During the revision surgery, the infected prosthesis is removed, a debridement is performed and a new or temporary spacer is placed. Additionally, patients are treated with antibiotics during and after the surgery. Adequate exposure of the administered antibiotic to the pathogen is of crucial importance during the treatment of any infection. Inadequately low concentrations are associated with an increase in antibiotic resistance, antibiotic related side effects, treatment failures and prolonged infections. While high concentrations may lead to serious adverse events and potential lasting damage. Despite the importance of optimal dosing, there is a lack of knowledge with respect to the correlation between the plasma concentrations and target site concentrations of the antibiotics. Two of the commonly administered antimicrobial agents during the arthroplasty exchange are cefuroxime and flucloxacillin. Therefore, an accurate, specific, and sensitive quantification method is required in order to assess pharmacokinetics of cefuroxime and flucloxacillin in synovial tissue and bone. The aim of this study is to develop and validate a quantification method for the measurement of cefuroxime and flucloxacillin in human synovial tissue and bone using the UPC2-MS/MS conform Food and Drug Administration guidelines. The method was found linear for both compounds in both matrices (r2 > 0.990) from 1 µg/g to 20 µg/g, except for cefuroxime in bone, which was validated from 1 µg/g to 15 µg/g. We developed and validated a quantification method for cefuroxime and flucloxacillin in synovial tissue and bone using a simple sample preparation and a short analysis run time of 5.0 min, which has been already successfully applied in a clinical study. To our knowledge, no methods have been described earlier for the simultaneous quantification of cefuroxime and flucloxacillin in synovial tissue and bone.

[The Study of Health in Pomerania (SHIP) reference values for cardiopulmonary exercise testing]. / Referenzwerte für die Spiroergometrie - Ergebnisse der Study of Health in Pomerania (SHIP).

The interpretation of gas exchange measured by cardiopulmonary exercise testing (CPET) depends on reliable reference values. Within the population based Study of Health in Pomerania (SHIP) CPET was assessed in 1706 volunteers. The assessment based on symptom limited exercise tests on a bicycle in a sitting position according to a modified Jones protocol. CPET was embedded in an extensive examination program. After the exclusion of active smokers and volunteers with evidence of cardiopulmonary and musculoskeletal disorders the reference population comprised 616 healthy subjects (333 women) aged 25 to 85 years. Reference equations including upper and/or lower limits based on quantile regression were assessed. All values were corrected for the most important influencing factors.This study provides reference equations for gas exchange and exercise capacity assessed within a population in Germany.