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.

Battling the obesity epidemic with a school-based intervention: Long-term effects of a quasi-experimental study.

BACKGROUND: School-based health-promoting interventions are increasingly seen as an effective population strategy to improve health and prevent obesity. Evidence on the long-term effectiveness of school-based interventions is scarce. This study investigates the four-year effectiveness of the school-based Healthy Primary School of the Future (HPSF) intervention on children's body mass index z-score (BMIz), and on the secondary outcomes waist circumference (WC), dietary and physical activity (PA) behaviours. METHODS AND FINDINGS: This study has a quasi-experimental design with four intervention schools, i.e., two full HPSFs (focus: diet and PA), two partial HPSFs (focus: PA), and four control schools. Primary school children (aged 4-12 years) attending the eight participating schools were invited to enrol in the study between 2015 and 2019. Annual measurements consisted of children's anthropometry (weight, height and waist circumference), dietary behaviours (child- and parent-reported questionnaires) and PA levels (accelerometers). Between 2015 and 2019, 2236 children enrolled. The average exposure to the school condition was 2·66 (SD 1·33) years, and 900 participants were exposed for the full four years (40·3%). After four years of intervention, both full (estimated intervention effect (B = -0·17 (95%CI -0·27 to -0·08) p = 0·000) and partial HPSF (B = -0·16 (95%CI-0·25 to -0·06) p = 0·001) resulted in significant changes in children's BMIz compared to control schools. Likewise, WC changed in favour of both full and partial HPSFs. In full HPSFs, almost all dietary behaviours changed significantly in the short term. In the long term, only consumption of water and dairy remained significant compared to control schools. In both partial and full HPSFs, changes in PA behaviours were mostly absent. INTERPRETATION: This school-based health-promoting intervention is effective in bringing unfavourable changes in body composition to a halt in both the short and long term. It provides policy makers with robust evidence to sustainably implement these interventions in school-based routine.

[Transcranial magnetic stimulation in obsessive compulsive disorder: a systematic review]. / Systematische review: transcraniële magnetische stimulatie voor obsessieve-compulsieve stoornis.

BACKGROUND: Ten per cent of patients with obsessive-compulsive disorder (ocd) are resistant to treatment. For these patients, repetitive transcranial magnetic stimulation (rtms) may be an alternative form of treatment.
AIM: To clarify the effect and clinical application of rtms for treatment-resistant ocd.
METHOD: We searched the literature systematically and we discuss the relevant articles critically.
RESULTS: We included 17 randomised controlled trials (rcts) with 502 patients. The reported trials were small and heterogeneous. A small but consistent treatment effect was found for rtms (mean decrease y-bocs score 6.6 points) compared to placebo stimulation (mean decrease y-bocs score 2.4 points). However, the differences between the effects of rtms and the effects of placebo were often not statistically or clinically significant. The effect frequently disappeared within several weeks after ending rtms and the follow-up period was never longer than three months.
CONCLUSION: rtms is still not entirely suitable for inclusion in the regular treatment of resistant ocd. More information is needed about follow-up requirements and about the advisable length and intensity of the applied stimulation. Future developments may involve increasing the number of stimulation sessions, combining these with cognitive behavioral therapy and delivering a more personalised form of rtms.

Clinical Pearls - how my patients taught me: The fainting lark symptom.

BACKGROUND: Compulsive movements, complex tics and stereotypies are frequent, especially among patients with autism or psychomotor retardation. These movements can be difficult to characterize and can mimic other conditions like epileptic seizures or paroxysmal dystonia, particularly when abnormal breathing and cerebral hypoxia are induced. CASE PRESENTATION: We describe an 18-year-old patient with Asperger syndrome who presented with attacks of tonic posturing of the trunk and neck. The attacks consisted of self-induced stereotypic stretching of the neck combined with a compulsive Valsalva-like maneuver. This induced cerebral hypoperfusion and subsequently dysautonomia and some involuntary movements of the arms. CONCLUSION: This patient suffered from a complex tic with compulsive respiratory stereotypies. His symptoms contain aspects of a phenomenon described in early literature as 'the fainting lark'.

The effects of school-based lifestyle interventions on body mass index and blood pressure: a multivariate multilevel meta-analysis of randomized controlled trials.

Primary prevention of childhood obesity and related hypertension is warrant given that both risk factors are intertwined and track into adulthood. This systematic review and meta-analysis assess the impact of school-based lifestyle interventions on children's body mass index (BMI) and blood pressure. We searched databases and prior reviews. Eligibility criteria were the following: randomized controlled trial design, evaluation of a school-based intervention, targeting children aged 4-12 years, reporting on BMI and/or related cardiovascular risk factors, reporting data on at least one follow-up moment. The effects on BMI, systolic blood pressure (SBP) and diastolic blood pressure (DBP) were evaluated by means of univariate and multivariate three-level random effects models. A total of 85 RCTs (91 papers) were included in the meta-analyses. In univariate models, the pooled effects were -0.072 (95%CI: -0.106; -0.038) for BMI, -0.183 (95%CI: -0.288; -0.078) for SBP and -0.071 (95%CI: -0.185; 0.044) for DBP. In multivariate analyses, the pooled effects of interventions were -0.054 (95%CI: -0.131; 0.022) for BMI, -0.182 (95%CI: -0.266; -0.098) for SBP and -0.144 (95%CI: -0.230; -0.057) for DBP. Parental involvement accentuated the beneficial effects of interventions. School-based lifestyle prevention interventions result in beneficial changes in children's BMI and blood pressure, and the effects on the latter may be stronger than and accrue independently from those in the former.

The Healthy Primary School of the Future: study protocol of a quasi-experimental study.

BACKGROUND: Unhealthy lifestyles in early childhood are a major global health challenge. These lifestyles often persist from generation to generation and contribute to a vicious cycle of health-related and social problems. This design article presents a study evaluating the effects of two novel healthy school interventions. The main outcome measure will be changes in children's body mass index (BMI). In addition, lifestyle behaviours, academic achievement, child well-being, socio-economic differences, and societal costs will be examined. METHODS: In close collaboration with various stakeholders, a quasi-experimental study was developed, for which children of four intervention schools (n = 1200) in the southern part of the Netherlands are compared with children of four control schools (n = 1200) in the same region. The interventions started in November 2015. In two of the four intervention schools, a whole-school approach named 'The Healthy Primary School of the Future', is implemented with the aim of improving physical activity and dietary behaviour. For this intervention, pupils are offered an extended curriculum, including a healthy lunch, more physical exercises, and social and educational activities, next to the regular school curriculum. In the two other intervention schools, a physical-activity school approach called 'The Physical Activity School', is implemented, which is essentially similar to the other intervention, except that no lunch is provided. The interventions proceed during a period of 4 years. Apart from the effectiveness of both interventions, the process, the cost-effectiveness, and the expected legal implications are studied. Data collection is conducted within the school system. The baseline measurements started in September 2015 and yearly follow-up measurements are taking place until 2019. DISCUSSION: A whole-school approach is a new concept in the Netherlands. Due to its innovative, multifaceted nature and sound scientific foundation, these integrated programmes have the potential to form a template for primary schools worldwide. The effects of this approach may extend further than the outcomes associated with well-being and academic achievement, potentially impacting legal and cultural aspects in our society. TRIAL REGISTRATION: The study protocol was registered in the database ClinicalTrials.gov on 14-06-2016 with the reference number NCT02800616 .

Elevated D8/17 expression on B lymphocytes, a marker of rheumatic fever, measured with flow cytometry in tic disorder patients.

OBJECTIVE: Elevated D8/17 expression on B lymphocytes is a known susceptibility marker of rheumatic fever. Previous studies have reported higher than usual D8/17 expression on B lymphocytes of patients with tic disorders. The purpose of this study was to assess D8/17 expression on B lymphocytes of tic disorder patients by using an objective method in which no operator variability was involved. METHOD: D8/17 expression on B lymphocytes was assessed with flow cytometry by using an immunoglobulin M (IgM) monoclonal D8/17-specific antibody in an unselected group of Dutch patients with tic disorders (N=33) and healthy volunteers (N=20). Binding of this monoclonal antibody was compared with binding of an irrelevant IgM monoclonal antibody, and the shift in mean fluorescence intensity of the D8/17-specific antibody compared to that of the irrelevant IgM monoclonal antibody was used as a measure of D8/17 overexpression. For the patients, Yale Global Tic Severity Scale scores were used to assess disease severity. RESULTS: D8/17 overexpression in the patient group (mean=16.8 arbitrary units, SD=30.5) was significantly higher than in the comparison group (mean=3.2, SD=3.0). A significant minority of the patients (N=13, 39.4%), however, had levels of D8/17 overexpression within the range of that of the healthy comparison subjects. Flow cytometric analysis did not indicate a separate subpopulation of D8/17-positive B cells. CONCLUSIONS: These data confirm the utility of D8/17 B cell overexpression as a peripheral blood marker in patients with tic disorders and are compatible with a streptococcus-related pathogenesis for at least a subgroup of patients with tic disorders.

Lack of effect of clonidine on stuttering in children.

OBJECTIVE: The authors studied the effects of the alpha 2-receptor agonist clonidine on stuttering in children. METHOD: Using a double-blind crossover study, they gave placebo or 4 micrograms/kg body weight per day to 25 stuttering children who were 6-13 years old. Stuttering was measured by counting the occurrences of four elementary speech difficulties and by asking parents and teachers to give an overall impression of the amount of stuttering, as well as their impression of how troublesome the stuttering was to the children. RESULTS: Clonidine did not improve stuttering. CONCLUSIONS: Clonidine cannot be recommended as a useful drug for treating children who stutter.