[Differences in injury patterns in motorcycle accidents involving children and adolescents]. / Unterschiede der Verletzungsmuster bei Motorradunfällen von Kindern und Jugendlichen.

BACKGROUND: Traffic accidents and the traumatic injury consequences are frequent causes of mortality and irreversible damage in children and young adults. In motorcycle accidents the injury patterns differ depending on the age of the patient. OBJECTIVE: The aim of this study was to describe the typical injury patterns after motorcycle accidents involving children and adolescents as these can have a decisive influence on the prevention and the adequate treatment in the respective patient groups. MATERIAL AND METHODS: The study included 22,923 patients from the years 2002-2018 which were extracted from the TraumaRegister DGU®. Injury patterns of 4 age categories were analyzed: group 1 (4-15 years), group 2 (16-17 years), group 3 (18-20 years) and group 4 (21-50 years). RESULTS: In both younger age groups, limb injuries mostly of the lower extremities, showed the highest incidence. Moreover, younger patients with traumatic brain injury showed better outcomes despite of initially poor conditions. Ribcage, abdominal, pelvic and spinal injuries are the least frequent in younger patients. In terms of diagnostics, children are less likely to undergo whole-body computed tomography (CT) diagnostics than adults. CONCLUSION: The study revealed age-specific differences with respect to injury patterns in patients involved in motorcycle accidents, either as drivers or co-drivers. Furthermore, the analysis of preclinical and in-hospital treatment elucidated the relevance of preventive and protective measures.

Comparing Diagnosis of Fetal Growth Restriction and the Potential Impact on Management and Outcomes Using Different Growth Curves.

OBJECTIVES: The diagnosis of fetal growth restriction (FGR) is managed with close fetal surveillance and often requires iatrogenic delivery, as there is an associated increased risk of fetal demise. However, there is no standard reference for fetal growth. We sought to compare the intrauterine growth curve of Hadlock et al (Radiology 1991; 181:129-133) to other known growth curves to determine which one best identifies fetuses at risk without overburdening the patient and health care system with unnecessary intervention. METHODS: We retrospectively reviewed charts of singleton euploid pregnancies with a diagnosis of FGR (per Hadlock) at a tertiary care center from June 2014 to May 2015. We applied the estimated fetal weights from ultrasound at diagnosis of FGR to 4 population-based growth curves by Brenner et al (Am J Obstet Gynecol 1976; 126:555-564), Williams et al (Obstet Gynecol 1982; 59:624-632), Alexander et al (Obstet Gynecol 1996; 87:163-168), and Duryea et al (Obstet Gynecol 2014; 124:16-22) and reassessed the incidence of FGR using each curve. We reviewed pregnancy demographics, risk factors, pregnancy management, and outcomes of FGR cohorts on each curve to evaluate whether poor outcomes may be missed or interventions may be avoided using the population-based curves. A sensitivity analysis was also done to see how well each curve predicted small-for-gestational-age birth weights. RESULTS: Applying any of the population-based growth curves decreased the number of FGR diagnoses, iatrogenic deliveries, and primary cesarean deliveries. Brenner's growth curve identified the least number of FGR diagnoses at 22 of the 107 identified by Hadlock. Williams' growth curve performed best in the sensitivity analysis with sensitivity of 99% and specificity of 97%. A small number of patients with absent/reversed end-diastolic flow would have been missed by applying the population curves. CONCLUSIONS: Applying the population-based growth curves instead of Hadlock's for diagnosis of FGR decreases its incidence, therefore decreasing the number of visits for ultrasound and fetal surveillance and the number of iatrogenic deliveries. However, using these curves could miss a few fetuses with increased risk of fetal demise.

Methylphenidate and the risk of psychotic disorders and hallucinations in children and adolescents in a large health system.

Previous studies have suggested that risk of psychotic events may be increased in children exposed to methylphenidate (MPH). However, this risk has not been fully examined, and the possibility of confounding factors has not been excluded. Patients aged 6-19 years who received at least one MPH prescription were identified using Hong Kong population-based electronic medical records on the Clinical Data Analysis and Reporting System (2001-2014). Using the self-controlled case series design, relative incidence of psychotic events was calculated comparing periods when patients were exposed to MPH with non-exposed periods. Of 20,586 patients prescribed MPH, 103 had an incident psychotic event; 72 (69.9%) were male and 31 (30.1%) female. The mean age at commencement of observation was 6.95 years and the mean follow-up per participant was 10.16 years. On average, each participant was exposed to MPH for 2.17 years. The overall incidence of psychotic events during the MPH exposure period was 6.14 per 10,000 patient-years. No increased risk was found during MPH-exposed compared with non-exposed periods (incidence rate ratio (IRR) 1.02 (0.53-1.97)). However, an increased risk was found during the pre-exposure period (IRR 4.64 (2.17-9.92)). Results were consistent across all sensitivity analyses. This study does not support the hypothesis that MPH increases risk of incident psychotic events. It does indicate an increased risk of psychotic events before the first prescription of MPH, which may be because of an association between psychotic events and the behavioural and attentional symptoms that led to psychiatric assessment and initiation of MPH treatment.

Automatic segmentation of the glenohumeral cartilages from magnetic resonance images.

PURPOSE: Magnetic resonance (MR) imaging plays a key role in investigating early degenerative disorders and traumatic injuries of the glenohumeral cartilages. Subtle morphometric and biochemical changes of potential relevance to clinical diagnosis, treatment planning, and evaluation can be assessed from measurements derived from in vivo MR segmentation of the cartilages. However, segmentation of the glenohumeral cartilages, using approaches spanning manual to automated methods, is technically challenging, due to their thin, curved structure and overlapping intensities of surrounding tissues. Automatic segmentation of the glenohumeral cartilages from MR imaging is not at the same level compared to the weight-bearing knee and hip joint cartilages despite the potential applications with respect to clinical investigation of shoulder disorders. In this work, the authors present a fully automated segmentation method for the glenohumeral cartilages using MR images of healthy shoulders. METHODS: The method involves automated segmentation of the humerus and scapula bones using 3D active shape models, the extraction of the expected bone-cartilage interface, and cartilage segmentation using a graph-based method. The cartilage segmentation uses localization, patient specific tissue estimation, and a model of the cartilage thickness variation. The accuracy of this method was experimentally validated using a leave-one-out scheme on a database of MR images acquired from 44 asymptomatic subjects with a true fast imaging with steady state precession sequence on a 3 T scanner (Siemens Trio) using a dedicated shoulder coil. The automated results were compared to manual segmentations from two experts (an experienced radiographer and an experienced musculoskeletal anatomist) using the Dice similarity coefficient (DSC) and mean absolute surface distance (MASD) metrics. RESULTS: Accurate and precise bone segmentations were achieved with mean DSC of 0.98 and 0.93 for the humeral head and glenoid fossa, respectively. Mean DSC scores of 0.74 and 0.72 were obtained for the humeral and glenoid cartilage volumes, respectively. The manual interobserver reliability evaluated by DSC was 0.80 ± 0.03 and 0.76 ± 0.04 for the two cartilages, implying that the automated results were within an acceptable 10% difference. The MASD between the automatic and the corresponding manual cartilage segmentations was less than 0.4 mm (previous studies reported mean cartilage thickness of 1.3 mm). CONCLUSIONS: This work shows the feasibility of volumetric segmentation and separation of the glenohumeral cartilages from MR images. To their knowledge, this is the first fully automated algorithm for volumetric segmentation of the individual glenohumeral cartilages from MR images. The approach was validated against manual segmentations from experienced analysts. In future work, the approach will be validated on imaging datasets acquired with various MR contrasts in patients.

Prospective observational study protocol to investigate long-term adverse effects of methylphenidate in children and adolescents with ADHD: the Attention Deficit Hyperactivity Disorder Drugs Use Chronic Effects (ADDUCE) study.

INTRODUCTION: Methylphenidate is the most frequently used medication for the treatment of attention-deficit/hyperactivity disorder (ADHD) in Europe. Following concerns about its safety, the European Commission called for research into the long-term effects of methylphenidate on children and adolescents with ADHD. The Attention Deficit Hyperactivity Disorder Drugs Use Chronic Effects (ADDUCE) research programme was designed to address this call. At the heart of this programme is a 2-year longitudinal naturalistic pharmacovigilance study being conducted in 27 European sites. METHODS AND ANALYSIS: 3 cohorts of children and adolescents (aged 6-17) living in the UK, Germany, Italy and Hungary are being recruited:Group 1 (Medicated ADHD): 800 ADHD medication-naive children and adolescents with a clinical diagnosis of ADHD about to start methylphenidate treatment for the first time.Group 2 (Unmedicated ADHD): 400 children and adolescents with a clinical diagnosis of ADHD who have never been treated with ADHD medication and have no intention of beginning medication.Group 3 (Non-ADHD): 400 children and adolescents without ADHD who are siblings of individuals in either group 1 or 2.All participants will be assessed 5 times during their 2-year follow-up period for growth and development, psychiatric, neurological and cardiovascular health. The primary outcome measure will be the height velocity SD score. ETHICS AND DISSEMINATION: Ethical approval for the study has been granted by the East of Scotland Research Ethics Service. Following this approval, patient information leaflets and consent forms were translated as necessary and submissions made by lead sites in each of the other 3 countries to their own ethics committees. Following ethical approval in each country, local ethical permissions at each site were sought and obtained as needed. The study's website (http://www.adhd-adduce.org/page/view/2/Home) provides information for researchers, participants and the general public. TRIAL REGISTRATION NUMBER: NCT01470261.

Successful private-public funding of paediatric medicines research: lessons from the EU programme to fund research into off-patent medicines.

UNLABELLED: The European Paediatric Regulation mandated the European Commission to fund research on off-patent medicines with demonstrated therapeutic interest for children. Responding to this mandate, five FP7 project calls were launched and 20 projects were granted. This paper aims to detail the funded projects and their preliminary results. Publicly available sources have been consulted and a descriptive analysis has been performed. Twenty Research Consortia including 246 partners in 29 European and non-European countries were created (involving 129 universities or public-funded research organisations, 51 private companies with 40 SMEs, 7 patient associations). The funded projects investigate 24 medicines, covering 10 therapeutic areas in all paediatric age groups. In response to the Paediatric Regulation and to apply for a Paediatric Use Marketing Authorisation, 15 Paediatric Investigation Plans have been granted by the EMA-Paediatric Committee, including 71 studies of whom 29 paediatric clinical trials, leading to a total of 7,300 children to be recruited in more than 380 investigational centres. CONCLUSION: Notwithstanding the EU contribution for each study is lower than similar publicly funded projects, and also considering the complexity of paediatric research, these projects are performing high-quality research and are progressing towards the increase of new paediatric medicines on the market. Private-public partnerships have been effectively implemented, providing a good example for future collaborative actions. Since these projects cover a limited number of off-patent drugs and many unmet therapeutic needs in paediatrics remain, it is crucial foreseeing new similar initiatives in forthcoming European funding programmes.

Automated segmentation and analysis of normal and osteoarthritic knee menisci from magnetic resonance images--data from the Osteoarthritis Initiative.

OBJECTIVE: To validate an automatic scheme for the segmentation and quantitative analysis of the medial meniscus (MM) and lateral meniscus (LM) in magnetic resonance (MR) images of the knee. METHOD: We analysed sagittal water-excited double-echo steady-state MR images of the knee from a subset of the Osteoarthritis Initiative (OAI) cohort. The MM and LM were automatically segmented in the MR images based on a deformable model approach. Quantitative parameters including volume, subluxation and tibial-coverage were automatically calculated for comparison (Wilcoxon tests) between knees with variable radiographic osteoarthritis (rOA), medial and lateral joint space narrowing (mJSN, lJSN) and pain. Automatic segmentations and estimated parameters were evaluated for accuracy using manual delineations of the menisci in 88 pathological knee MR examinations at baseline and 12 months time-points. RESULTS: The median (95% confidence-interval (CI)) Dice similarity index (DSI) (2 ∗|Auto ∩ Manual|/(|Auto|+|Manual|)∗ 100) between manual and automated segmentations for the MM and LM volumes were 78.3% (75.0-78.7), 83.9% (82.1-83.9) at baseline and 75.3% (72.8-76.9), 83.0% (81.6-83.5) at 12 months. Pearson coefficients between automatic and manual segmentation parameters ranged from r = 0.70 to r = 0.92. MM in rOA/mJSN knees had significantly greater subluxation and smaller tibial-coverage than no-rOA/no-mJSN knees. LM in rOA knees had significantly greater volumes and tibial-coverage than no-rOA knees. CONCLUSION: Our automated method successfully segmented the menisci in normal and osteoarthritic knee MR images and detected meaningful morphological differences with respect to rOA and joint space narrowing (JSN). Our approach will facilitate analyses of the menisci in prospective MR cohorts such as the OAI for investigations into pathophysiological changes occurring in early osteoarthritis (OA) development.

Memorandum on the use of information technology to improve medication safety.

BACKGROUND: Information technology in health care has a clear potential to improve the quality and efficiency of health care, especially in the area of medication processes. On the other hand, existing studies show possible adverse effects on patient safety when IT for medication-related processes is developed, introduced or used inappropriately. OBJECTIVES: To summarize definitions and observations on IT usage in pharmacotherapy and to derive recommendations and future research priorities for decision makers and domain experts. METHODS: This memorandum was developed in a consensus-based iterative process that included workshops and e-mail discussions among 21 experts coordinated by the Drug Information Systems Working Group of the German Society for Medical Informatics, Biometry and Epidemiology (GMDS). RESULTS: The recommendations address, among other things, a stepwise and comprehensive strategy for IT usage in medication processes, the integration of contextual information for alert generation, the involvement of patients, the semantic integration of information resources, usability and adaptability of IT solutions, and the need for their continuous evaluation. CONCLUSION: Information technology can help to improve medication safety. However, challenges remain regarding access to information, quality of information, and measurable benefits.

[Venous thromboembolism in adolescents associated with fourth-generation oral contraceptives]. / Venöse Thromboembolien bei Jugendlichen mit Kontrazeptiva der vierten Generation.

Venous thromboembolism (VTE) is a rare, but feared adverse drug reaction of combined oral contraceptives. Modern oral contraceptives contain novel progestins, which are suspected of causing thrombotic events more frequently than well-known progestins. Drospirenone is one of those new fourth-generation progestins with antiandrogenic and antimineralocorticoid effects. Especially girls and young women do not only wish for contraception, but also for positive effects on skin and body weight. In the last decade, however, the safety of this progestin was often under discussion.A detailed literature search was conducted to obtain an overview of currently available data on the risk of VTE among girls and young women using drospirenone-containing contraceptives. It appears that drospirenone-containing contraceptives have a similar increase in risk as third-generation oral contraceptives and antiandrogens. Compared to second-generation contraceptives containing the progestin levonorgestrel there is an approximate 2-fold risk increase (1.0 to 2.8-fold) in women aged 10-55 years. Accurate data regarding the risk in the age group under 18 years are lacking. Nevertheless, the risk of VTE appears to be higher in young -women during the first months of treatment. Until more data for nov-el progestins are available and the safety profile is well defined well-studied second-generation oral contraceptives with low dose estrogen and better risk-benefit ratio should be preferred in young women. In any case, all patients should be comprehensively informed regarding the benefits and risks of each contraceptive method.

Prevalence of antibodies against hepatitis A virus among children and adolescents in Germany.

Since hepatitis A virus (HAV) infection during childhood is mostly asymptomatic, only seroprevalence studies can provide reliable information on incidence of HAV infection in children. The prevalence of anti-HAV antibodies was determined in sera taken in 2008 to 2010 from 1,645 children aged 0-17 years and in sera taken in 2010-2011 from 400 adult blood donors in Germany. For examination of trend over time, 715 sera collected between 1999 and 2006 from children at the age of 0-17 years within the federal state Thuringia were included. Antibody testing was carried out using the test kits ETI-AB-HAVK PLUS and ETI-HA-IGMK PLUS from DiaSorin. In children, the overall prevalence of antibodies was 10.8 %. After the seroprevalence declined from 8.8 % among the 0-2 year-olds to 2.4 % among the 3-4 year-olds, there was a significant increase to 20.5 % in the group of the 15-17 year-olds. Boys had with 12.7 % a significantly higher seroprevalence of anti-HAV antibodies compared to 8.8 % among girls. In adult blood donors, there was a HAV seroprevalence of 19.3 %. The likelihood of past infection or immunization within the age groups of children from 0 to 12 years differed significantly from that of adults. In conclusion, in Germany, only a small number of HAV infections occur in children, especially up to the age of 12 years. The proportion of susceptible children is greater than the proportion of susceptible adults. Thus, during outbreaks, the rate of infection among children would usually be higher than the rate among adults.

Three-dimensional morphological and signal intensity features for detection of intervertebral disc degeneration from magnetic resonance images.

BACKGROUND AND OBJECTIVES: Advances in MRI hardware and sequences are continually increasing the amount and complexity of data such as those generated in high-resolution three-dimensional (3D) scanning of the spine. Efficient informatics tools offer considerable opportunities for research and clinically based analyses of magnetic resonance studies. In this work, we present and validate a suite of informatics tools for automated detection of degenerative changes in lumbar intervertebral discs (IVD) from both 3D isotropic and routine two-dimensional (2D) clinical T2-weighted MRI. MATERIALS AND METHODS: An automated segmentation approach was used to extract morphological (traditional 2D radiological measures and novel 3D shape descriptors) and signal appearance (extracted from signal intensity histograms) features. The features were validated against manual reference, compared between 2D and 3D MRI scans and used for quantification and classification of IVD degeneration across magnetic resonance datasets containing IVD with early and advanced stages of degeneration. RESULTS AND CONCLUSIONS: Combination of the novel 3D-based shape and signal intensity features on 3D (area under receiver operating curve (AUC) 0.984) and 2D (AUC 0.988) magnetic resonance data deliver a significant improvement in automated classification of IVD degeneration, compared to the combination of previously used 2D radiological measurement and signal intensity features (AUC 0.976 and 0.983, respectively). Further work is required regarding the usefulness of 2D and 3D shape data in relation to clinical scores of lower back pain. The results reveal the potential of the proposed informatics system for computer-aided IVD diagnosis from MRI in large-scale research studies and as a possible adjunct for clinical diagnosis.

Diagnosing rupture of membranes using combination monoclonal/polyclonal immunologic protein detection.

OBJECTIVE: To compare the accuracy of a new combination monoclonal/polyclonal immunoassay point-of-care test with that of current conventional clinical assessment for diagnosis of ruptured amniotic membranes. STUDY DESIGN: This was a multicenter prospective observational study performed in patients presenting with signs or symptoms of ruptured amniotic membranes. This clinical trial included 3 sites in the United States. Initial evaluation included both the standard clinical assessment for rupture of membranes (ROM) (speculum examination for fluid pooling, ferning, and nitrazine test), as well as the use of a new combination immunoassay test containing a combination monoclonal/polyclonal antibody approach to detect placental protein 12 (PP12) and alpha-fetoprotein (AFP). ROM was diagnosed if fluid was seen leaking from the cervical os, or if 2 of the 3 conditions were present: pooling of fluid, positive nitrazine test, or ferning. ROM was confirmed on review of the medical records following delivery. RESULTS: Of the 285 patients (15-42 weeks of gestation), the false positive rate for the new combination immunoassay test was 9% and the false negative rate was 0.5%, sensitivity 99%, specificity 91%, positive and negative predictive values of 95% and 99%, respectively. The conventional clinical evaluation's sensitivity was 85%, specificity 98%, with positive and negative predictive values of 99% and 77%. Ferning's sensitivity was 99%, specificity 72%, with positive and negative predictive values of 80% and 99%. Nitrazine testing's sensitivity was 93%, specificity 83%, with positive and negative predictive values of 90% and 88%. CONCLUSION: This combination monoclonal and polyclonal immunoassay test that detects PP12 and AFP has an efficacy comparable to conventional testing and better than the individual components of conventional testing (ferning, nitrazine), is a quick and easy-to-use test that can be performed by a wider variety of care providers, and can improve triage and management of patients suspected of ROM.

Automated detection, 3D segmentation and analysis of high resolution spine MR images using statistical shape models.

Recent advances in high resolution magnetic resonance (MR) imaging of the spine provide a basis for the automated assessment of intervertebral disc (IVD) and vertebral body (VB) anatomy. High resolution three-dimensional (3D) morphological information contained in these images may be useful for early detection and monitoring of common spine disorders, such as disc degeneration. This work proposes an automated approach to extract the 3D segmentations of lumbar and thoracic IVDs and VBs from MR images using statistical shape analysis and registration of grey level intensity profiles. The algorithm was validated on a dataset of volumetric scans of the thoracolumbar spine of asymptomatic volunteers obtained on a 3T scanner using the relatively new 3D T2-weighted SPACE pulse sequence. Manual segmentations and expert radiological findings of early signs of disc degeneration were used in the validation. There was good agreement between manual and automated segmentation of the IVD and VB volumes with the mean Dice scores of 0.89 ± 0.04 and 0.91 ± 0.02 and mean absolute surface distances of 0.55 ± 0.18 mm and 0.67 ± 0.17 mm respectively. The method compares favourably to existing 3D MR segmentation techniques for VBs. This is the first time IVDs have been automatically segmented from 3D volumetric scans and shape parameters obtained were used in preliminary analyses to accurately classify (100% sensitivity, 98.3% specificity) disc abnormalities associated with early degenerative changes.

Gender-based differences in drug prescription: relation to adverse drug reactions.

BACKGROUND/AIM: The female gender appears to suffer from more adverse drug reactions (ADRs) than the male gender. So far, there has been no epidemiologic study analyzing gender-based differences in drug prescribing and its ADR risks. The aim of the present study was to establish a drug risk stratification adjusted to age, number of prescriptions and drug classes with respect to gender differences based on intensive data acquisition methods. METHOD: A prospective multicenter study was conducted in several departments in Germany and Israel (pediatrics, medicine and geriatrics) enclosing 2,371 inpatients. RESULTS: A total of 25,532 drug prescriptions during hospitalization were evaluated. At least 1 ADR was found in 774 patients (32.6%). Drugs for the cardiovascular system, nervous system, alimentary tract and musculoskeletal system were prescribed most often in females. The following drug classes led significantly more often to ADRs in women as compared to men: alimentary tract (OR 0.5; p = 0.0002), cardiovascular system (OR 0.72; p = 0.0140), musculoskeletal system (OR 0.31; p = 0.0004) and nervous system (OR 0.62; p = 0.0023). After adjustment to age, total number of prescriptions and drug class, only anti-infectives (antibacterials) and musculoskeletal system (anti-inflammatory) drugs stand out as causing more ADRs in women. CONCLUSION: Antibacterials and anti-inflammatory agents cause more ADRs in females as compared to males.

Analysis of vaccine-virus-associated rabies cases in red foxes (Vulpes vulpes) after oral rabies vaccination campaigns in Germany and Austria.

To eradicate rabies in foxes, almost 97 million oral rabies vaccine baits have been distributed in Germany and Austria since 1983 and 1986, respectively. Since 2007, no terrestrial cases have been reported in either country. The most widely used oral rabies vaccine viruses in these countries were SAD (Street Alabama Dufferin) strains, e.g. SAD B19 (53.2%) and SAD P5/88 (44.5%). In this paper, we describe six possible vaccine-virus-associated rabies cases in red foxes (Vulpes vulpes) detected during post-vaccination surveillance from 2001 to 2006, involving two different vaccines and different batches. Compared to prototypic vaccine strains, full-genome sequencing revealed between 1 and 5 single nucleotide alterations in the L gene in 5 of 6 SAD isolates, resulting in up to two amino acid substitutions. However, experimental infection of juvenile foxes showed that those mutations had no influence on pathogenicity. The cases described here, coming from geographically widely separated regions, do not represent a spatial cluster. More importantly, enhanced surveillance showed that the vaccine viruses involved did not become established in the red fox population. It seems that the number of reported vaccine virus-associated rabies cases is determined predominantly by the intensity of surveillance after the oral rabies vaccination campaign and not by the selection of strains.

Women encounter ADRs more often than do men.

BACKGROUND: Several publications indicate that the female gender experiences a higher incidence of adverse drug reactions (ADRs) than does the male gender. The reasons, however, remain unclear. Gender-specific differences in the pharmacokinetic and pharmacodynamic behaviour of drugs could not be identified as an explanation. The aim of this study was to analyse ADR risk with respect to gender, age and number of prescribed drugs. METHODS: A prospective multicenter study based on intensive pharmacovigilance was conducted. Information on patient characteristics and evaluated ADRs was stored in a pharmacovigilance database--KLASSE. RESULTS: In 2,371 patients (1,012 female subjects), 25,532 drugs were prescribed. In 782 patients, at least one ADR was found. A multivariate regression analysis adjusting for age, body mass index (BMI) and number of prescribed drugs showed a significant influence of female gender on the risk of encountering ADRs [odds ratio (OR) 1.596, confidence interval (CI) 1.31-1.94; p < 0.0001). Dose-related ADRs (51.8%) were the dominant type in female subjects. Comparing system organ classes of the World Health Organisation (SOC-WHO), cardiovascular (CV) ADRs were particularly frequent in female subjects (OR 1.92, CI 1.15-3.19; p = 0.012). CONCLUSION: Our data confirm the higher risk of ADRs among female subjects compared with a male cohort. Several explanations were investigated. No single risk factor could be identified.

Medicines for children licensed by the European Medicines Agency (EMEA): the balance after 10 years.

OBJECTIVE: The 1995-2005 balance of EMEA activities in the field of paediatric medicines was evaluated, taking into account the number both of drugs authorised for children and paediatric studies supporting the Marketing Authorisation (MA). METHODS: Data on drugs authorised by EMEA were extracted from EPARs (European Public Assessment Reports). Active substance, year of approval, anatomical, therapeutic and chemical (ATC) code, indication, orphan status, ages, and registrative clinical studies characteristics were assessed. RESULTS: The percentage of authorised substances for paediatrics is 33.3%. This percentage decreased or increased when different subsets of medicines were considered [medicines for children under 2 years (23.4%), N-ATC code drugs (6%) and orphan drugs (46.4%)]. A total of 165 trials were included in the MA dossiers of 51 drugs at the time of approval, and additional 22 studies were added to the dossiers of 12 active substances submitted for paediatric variations. PK and Efficacy/Safety studies were performed for 32 (52%) active substances, while either one PK or one Efficacy/Safety study was carried out for 43 (69%) and 45 (73%) substances, respectively. CONCLUSIONS: This report demonstrates that the total number of paediatric medicines approved by EMEA is stable over the 10-year period, while an increase in drugs to treat serious or orphan diseases has been observed. In addition, under the Centralised Procedure, a valuable number of paediatric trials have been submitted to support drug approval.

Obesity and pregnancy.

UNLABELLED: Obesity is dramatically increasing throughout the world and is known to be a major cause of preventable morbidity and mortality. By screening women for obesity and obesity-related complications, the obstetrician/gynecologist can help improve health outcomes for women and their infants. Many pregnancy complications have been linked to obesity ranging from increased risk of gestational diabetes and hypertension to increased risk of cesarean delivery and postoperative wound infection. This article reviews antepartum, intrapartum, and postpartum complications associated with obesity in pregnancy and offers suggestions to optimize care and improve outcomes. TARGET AUDIENCE: Obstetricians & Gynecologists, Family Physicians LEARNING OBJECTIVES: After completion of this article, the reader should be able to define obesity in pregnancy, to list the various complications associated with obesity, and to describe the limitations of ultrasonography in obese gravidas.