Recommended data elements for health registries: a survey from a German funding initiative.

BACKGROUND: The selection of data elements is a decisive task within the development of a health registry. Having the right metadata is crucial for answering the particular research questions. Furthermore, the set of data elements determines the registries' readiness of interoperability and data reusability to a major extent. Six health registries shared and published their metadata within a German funding initiative. As one step in the direction of a common set of data elements, a selection of those metadata was evaluated with regard to their appropriateness for a broader usage. METHODS: Each registry was asked to contribute a 10%-selection of their data elements to an evaluation sample. The survey was set up with the online survey tool "LimeSurvey Cloud". The registries and an accompanying project participated in the survey with one vote for each project. The data elements were offered in content groups along with the question of whether the data element is appropriate for health registries on a broader scale. The question could be answered using a Likert scale with five options. Furthermore, "no answer" was allowed. The level of agreement was assessed using weighted Cohen's kappa and Kendall's coefficient of concordance. RESULTS: The evaluation sample consisted of 269 data elements. With a grade of "perhaps recommendable" or higher in the mean, 169 data elements were selected. These data elements belong preferably to groups' demography, education/occupation, medication, and nutrition. Half of the registries lost significance compared with their percentage of data elements in the evaluation sample, one remained stable. The level of concordance was adequate. CONCLUSIONS: The survey revealed a set of 169 data elements recommended for health registries. When developing a registry, this set could be valuable help in selecting the metadata appropriate to answer the registry's research questions. However, due to the high specificity of research questions, data elements beyond this set will be needed to cover the whole range of interests of a register. A broader discussion and subsequent surveys are needed to establish a common set of data elements on an international scale.

[Educating Parents about Fever in Childhood Evaluation of the Effect of an Information Leaflet]. / Aufklärung von Eltern zu Fieber im Kindesalter Evaluation der Wirkung einer Informationsbroschüre.

BACKGROUND: Fever is an important immune reaction of the body in infections and plays a major role in childhood. Fear and uncertainty in dealing with fever are still widespread among parents. Information leaflets on the knowledge and handling of fever in childhood can serve as an educational tool for parents. It has not yet been investigated whether this type of information transfer is a suitable tool for educating parents. METHODS: 16 kindergartens in Saarland were visited. 481 parents of at least one child between the ages of 1 and 7 years answered a questionnaire on knowledge, approach and handling of fever in infections. Subsequently, an information leaflet on fever was handed out. On the following day, the questionnaire was answered again by the 190 parents who had read the information leaflet. The change due to reading the information leaflet was analyzed. RESULTS: 40% of the participants read the information leaflet. 87% mothers and 13% fathers participated in the follow-up survey. 10% of the post-survey respondents had a secondary school diploma and 34% had a university degree. After reading, fever was considered useful significantly more often and febrile convulsions and consequential damage were mentioned significantly less often as a reason for fever reduction. CONCLUSION: Information leaflets on fever can be a complementary tool for education, the short-term effect is confirmed, the sustainability needs to be further evaluated. There is also a need to reach the majority.

Does Chronic Kidney Disease Have an Impact on the Use of Oral Anticoagulants after Stroke? An Observational Follow-Up Study.

INTRODUCTION: Chronic kidney disease is common in patients with acute ischemic stroke. We investigated whether chronic kidney disease has an impact on anticoagulation treatment recommendations after ischemic stroke or transient ischemic attack (TIA) related with atrial fibrillation (AF). MATERIALS AND METHODS: We extracted treatment-related data concerning stroke/TIA patients with AF and available estimated glomerular filtration rates (eGFR) from a monocentric prospective German stroke registry. Chronic kidney disease was defined as eGFR <60 mL/min/1.73 m2. Using uni- and multivariate logistic regression analyses, we investigated whether chronic kidney disease was associated with a lower probability to be treated with anticoagulation early after stroke. RESULTS: A total of 273 patients entered the analysis. In 242 AF patients (88.6%), oral anticoagulation was recommended after stroke. In multivariate logistic regression analysis, chronic kidney disease was not identified as an independent factor for the decision against anticoagulation (OR 1.63, 95% CI: 0.50-5.31, p = 0.421); only increasing age (OR 1.10, 95% CI: 1.00-1.21, p = 0.061) and a modified Rankin Scale >3 at discharge (OR 3.41, 95% CI: 0.88-13.24, p = 0.077) showed a nonsignificant trend for the decision to omit anticoagulation. A total of 155 of 167 patients (92.8%) were still anticoagulated at follow-up. A total of 44 patients with chronic kidney disease completed follow-up, and of those, 37 were still anticoagulated (84%). In patients without chronic kidney disease, 118/167 (70.7%) had continued anticoagulation (p = 0.310). CONCLUSION: Our results show that chronic kidney disease was not the main factor in the decision to withhold oral anticoagulation in patients with recent stroke/TIA and AF.

Parental risk factors for congenital diaphragmatic hernia - a large German case-control study.

BACKGROUND: Evidence for periconceptional or prenatal environmental risk factors for the development of congenital diaphragmatic hernia (CDH) is still scarce. Here, in a case-control study we investigated potential environmental risk factors in 199 CDH patients compared to 597 healthy control newborns. METHODS: The following data was collected: time of conception and birth, maternal BMI, parental risk factors such as smoking, alcohol or drug intake, use of hairspray, contact to animals and parental chronic diseases. CDH patients were born between 2001 and 2019, all healthy control newborns were born in 2011. Patients and control newborns were matched in the ratio of three to one. RESULTS: Presence of CDH was significantly associated with maternal periconceptional alcohol intake (odds ratio = 1.639, 95% confidence interval 1.101-2.440, p = 0.015) and maternal periconceptional use of hairspray (odds ratio = 2.072, 95% confidence interval 1.330-3.229, p = 0.001). CONCLUSION: Our study suggests an association between CDH and periconceptional maternal alcohol intake and periconceptional maternal use of hairspray. Besides the identification of novel and confirmation of previously described parental risk factors, our study underlines the multifactorial background of isolated CDH.

Age dependency of body mass index distribution in childhood and adolescent inpatients with anorexia nervosa with a focus on DSM-5 and ICD-11 weight criteria and severity specifiers.

Both DSM-5 and ICD-11 have provided weight cut-offs and severity specifiers for the diagnosis of anorexia nervosa (AN) in childhood, adolescence and adulthood. The aims of the current study focusing on inpatients aged < 19 years were to assess (1) the relationship between age and body mass index (BMI; kg/m2), BMI-centiles, BMI-standard deviation scores (BMI-SDS) and body height-SDS at referral, (2) the percentages of patients fulfilling the DSM-5 and ICD-11 weight criteria and severity categories for AN, and (3) the validity of the AN severity specifiers via analysis of both weight related data at discharge and inpatient treatment duration. The German Registry for Anorexia Nervosa encompassed complete data sets for 469 female patients (mean age = 15.2 years; range 8.9-18.9 years) with a diagnosis of AN (n = 404) or atypical AN (n = 65), who were ascertained at 16 German child and adolescent psychiatric hospitals. BMI at referral increased up to age 15 to subsequently plateau. Approximately one tenth of all patients with AN had a BMI above the fifth centile. The ICD-11 specifier based on a BMI-centile of 0.3 for childhood and adolescent AN entailed two equally sized groups of patients. Discharge data revealed limited validity of the specifiers. Height-SDS was not correlated with age thus stunting had no impact on our data. We corroborate the evidence to use the tenth instead of the fifth BMI-centile as the weight criterion in children and adolescents. Weight criteria should not entail major diagnostic shifts during the transition from adolescence to adulthood. The severity specifiers based on BMI or BMI-centiles do not seem to have substantial clinical validity.

[The FeverApp Registry - A Way to Empower Parents through their Own Documentation to a Graduated Decision]. / Das FieberApp Register ­ ein Weg, um Eltern durch eigene Dokumentation zu einer abgestuften Entscheidung zu führen.

AIM OF THE STUDY: To demonstrate the feasibility and exemplarity of an app-based parent registry. METHODS: The app as an elaborated interactive electronic case report form and the underlying data structure of the registry are presented. The initial recruitment efforts are illustrated and the temperature distribution, as well as the distribution of fever events in 2020, are analyzed. RESULTS: The FeverApp successfully collects data into a central registry. Like every study, it also provides information on the current knowledge. The ecological momentary assessment can represent the illness situation at several levels (measurement, fever episode, individual, family, practice, country). Methods for data collection needed to be developed in a flexible manner due to pandemic conditions. The initial recruitment goal of 2400 fever phases in the first two years was met, with nationwide dissemination pending. It is shown that body temperature does not rise indefinitely; fevers reach an average of 39 degrees without antipyretics, although in rare cases temperatures beyond 41 degrees are reached without harm. Furthermore, a comparison with a reference practice shows that fever episodes can be recorded more comprehensively in the app, including infections that do not come to the presentation in a pediatrician's office. Thus, the FeverApp fulfills in a model-like fashion the use of registers in persons basically healthy and maps a multi-level diagnostics. CONCLUSION: The FeverApp could basically establish itself as a supporting tool, the registry can reliably collect data with the method used and maps the current infection situation. In researching the question of how infections develop in the post-Covid period, the app could perform an important task.

Incontinence and constipation in adolescent patients with anorexia nervosa-Results of a multicenter study from a German web-based registry for children and adolescents with anorexia nervosa.

OBJECTIVE: Nocturnal enuresis (NE), daytime urinary incontinence (DUI), and fecal incontinence (FI) are common disorders in childhood and are frequently accompanied by comorbid psychiatric disorders. Despite a high association between urinary and fecal incontinence with psychiatric and neurodevelopmental disorders, research on comorbidity between incontinence and anorexia nervosa (AN) remains scarce. Yet, it is well known that somatic consequences of AN include metabolic and gastrointestinal disorders. The study sought to assess the prevalence of incontinence and constipation in children and adolescents with AN and to examine associations of these two symptoms with body weight at admission and with BMI changes during inpatient treatment. METHODS: Data collected between 2015 and 2017 by a multicenter German web-based registry for AN were analyzed. Three hundred and forty-eight patients with AN (96.3% female, mean age = 15.1 ± 1.8 years) were assessed regarding AN subtype, psychiatric comorbidity, body weight, incontinence, and constipation. RESULTS: Overall, 27.6% of patients had constipation, 1.8% had NE and 1.8% DUI. Prevalence of constipation did not significantly differ between AN subtypes. Constipation did not lead to any significant differences in weight/BMI changes during inpatient treatment. DISCUSSION: This is the largest study of incontinence and constipation in patients with AN, so far. Our results indicate that constipation is highly prevalent in adolescent patients with AN and reflects a clinically relevant condition. Despite, patients with AN do not have an increased prevalence of incontinence compared with the general population. Future studies should include medical examinations like ultrasound and physical examination of the lower abdomen to evaluate the severity of constipation.

The FeverApp registry - ecological momentary assessment (EMA) of fever management in families regarding conformity to up-to-date recommendations.

BACKGROUND: Fever is one of the most common symptoms of pediatric consultations and its mismanagement is a health care burden. Guidelines on fever management are incoherent and data on fever management are still missing. This study protocol describes an app-based registry to evaluate the fever management of parents. OBJECTIVE: The primary objectives are to assess guideline adherence (primary outcome) and parental confidence in managing fever, and thus to reduce overuse of antipyretics, antibiotics and healthcare providers. Secondary objectives include creating a "FeverApp" that will enable parents to handle fever safely and to use the FeverApp registry as symptom and fever management diary. Further objectives include developing and testing a symptom-led registry model by app-based acquisition of parental entries of febrile illness cycle data and developing and testing models of how an interactive app-based registry can enable nationwide EMA information to inform science, guideline and policy makers, and the public. METHODS: A FeverApp, guiding parents and carers in handling and documenting fever, will be developed with family pediatricians according to current guidelines and recommended for all parents in Germany. A registry will anonymously document features, management and outcomes of febrile episodes: basic sociodemographic and medical information, initial symptoms, course of fever, pharmacological and non-pharmacological interventions, consultations with doctors, outcomes, fever-associated fears, and app satisfaction. RESULTS: This app may improve communication quality and health, e.g. asthma and antimicrobial resistance. Results will be published via website www.feverapp.de . TRIAL REGISTRATION: This app-based registry protocol is registered in the German Clinical Trials Register (DRKS) with registration number: DRKS00016591 .

Renal Impairment Is Associated with Intracerebral Hemorrhage after Mechanical Thrombectomy in Vertebrobasilar Stroke.

BACKGROUND AND PURPOSE: Renal dysfunction (RD) is overall associated with unfavorable functional outcome and higher risk of mortality after acute ischemic stroke. Associations between RD and outcome in patients with acute vertebrobasilar stroke treated with thrombectomy have not been evaluated so far. MATERIALS AND METHODS: Consecutive patients with vertebrobasilar stroke treated with mechanical thrombectomy between October 2010 and July 2017 at our center were analyzed. RD was defined as glomerular filtration rate (GFR) < 60 mL/min/1.73 m2 at admission. Endpoints were (I) poor clinical outcome (modified Rankin Scale > 2) at 3 months, (II) 3-month mortality, and (III) intracerebral hemorrhage (ICH) after treatment. RESULTS: Overall, 106 patients were included. Median age was 73.0 years (interquartile range 62.0-80.0), and RD was present in 20.8%. Multivariate analysis revealed that RD was associated with a higher risk for any ICH (OR 3.54; 95% CI 1.09-11.49; p = 0.035). Stroke severity at onset predicted poor clinical outcome (OR 1.08; 95% CI 1.03-1.14; p = 0.003). Neither low GFR nor any ICH, but stroke severity (OR 1.08; 95% CI 1.03-1.14; p = 0.002) and poor recanalization results (OR 11.38; 95% CI 2.01-64.41; p = 0.006) were associated with a higher risk for mortality. CONCLUSIONS: Patients with RD and acute vertebrobasilar stroke should be thoroughly monitored to prevent ICH after thrombectomy. Our results support performing mechanical thrombectomy in acute stroke patients with large vessel occlusions of the posterior circulation, irrespective of their renal function.

What do pediatric surgeons think about sexual issues in dealing with patients with anorectal malformations? The ARM-Net consortium members' opinion.

PURPOSE: Since pediatric surgeons aim to follow their patients with anorectal malformations (ARM) into adulthood the aim of this study was to investigate how pediatric surgeons deal with sexual issues related to ARM. METHODS: In 2018, a questionnaire was developed by the working group "Follow-up and sexuality" of the ARM-Net consortium and sent to all consortium-linked pediatric surgeons from 31 European pediatric surgical centers. Obtained data were statistically analyzed. RESULTS: Twenty-eight of 37 pediatric surgeons (18 males/10 females) answered the questionnaire. The majority of pediatric surgeons (82%) think they should talk about sexual issues with their patient. More than 50% of pediatric surgeons do not feel at all or only moderately confident discussing the topic of sexuality. Most pediatric surgeons require more support (96%) and wish to be trained in sexuality and sexual issues (78%) to feel confident towards their ARM-patients/parents. For optimal care, sexual issues with ARM-patients should be managed by a multidisciplinary team. CONCLUSIONS: Pediatric surgeons feel that sexuality is an important issue for their ARM-patients, which they are primarily responsible of but should be managed in concert with a multidisciplinary team. A training in sexuality is wished to feel more confident about this specific issue.

Genome-wide association study and meta-analysis identify ISL1 as genome-wide significant susceptibility gene for bladder exstrophy.

The bladder exstrophy-epispadias complex (BEEC) represents the severe end of the uro-rectal malformation spectrum, and is thought to result from aberrant embryonic morphogenesis of the cloacal membrane and the urorectal septum. The most common form of BEEC is isolated classic bladder exstrophy (CBE). To identify susceptibility loci for CBE, we performed a genome-wide association study (GWAS) of 110 CBE patients and 1,177 controls of European origin. Here, an association was found with a region of approximately 220kb on chromosome 5q11.1. This region harbors the ISL1 (ISL LIM homeobox 1) gene. Multiple markers in this region showed evidence for association with CBE, including 84 markers with genome-wide significance. We then performed a meta-analysis using data from a previous GWAS by our group of 98 CBE patients and 526 controls of European origin. This meta-analysis also implicated the 5q11.1 locus in CBE risk. A total of 138 markers at this locus reached genome-wide significance in the meta-analysis, and the most significant marker (rs9291768) achieved a P value of 2.13 × 10-12. No other locus in the meta-analysis achieved genome-wide significance. We then performed murine expression analyses to follow up this finding. Here, Isl1 expression was detected in the genital region within the critical time frame for human CBE development. Genital regions with Isl1 expression included the peri-cloacal mesenchyme and the urorectal septum. The present study identified the first genome-wide significant locus for CBE at chromosomal region 5q11.1, and provides strong evidence for the hypothesis that ISL1 is the responsible candidate gene in this region.

Influence of Renal Function on Treatment Results after Stroke Thrombectomy.

BACKGROUND: Renal dysfunction (RD) may be associated with poor outcome in ischemic stroke patients treated with mechanical thrombectomy (MT), but data concerning this important and emerging comorbidity do not exist so far. Here, we investigated the influence of RD on postprocedural intracerebral hemorrhage (ICH), clinical outcome, and mortality in a large prospectively collected cohort of acute ischemic stroke patients treated with MT. METHODS: Consecutive patients with anterior-circulation stroke treated with MT between October 2010 and January 2016 were included. RD was defined as glomerular filtration rate (GFR) <60 mL/min/1.73 m2. In a prospective database, clinical characteristics were recorded and brain images were analyzed for the presence of ICH after treatment in all patients. Clinical outcome was assessed by the modified Rankin Scale (mRS) after 3 months. To evaluate associations between clinical factors and outcomes uni- and multivariate regression analyses were conducted. RESULTS: In total, 505 patients fulfilled all inclusion criteria (female: 49.7%, mean age: 71.0 years). RD at admission was present in 20.2%. RD patients were older and had cardiovascular risk factors more often. Multivariate regression analysis after adjustment for age, stroke severity, diabetes, hypertension, GFR, previous stroke, MT alone, or additional thrombolysis and recanalization results revealed that lower GFR was not independently associated with poor outcome (mRS 3-6; OR 1.13, 95% CI 0.99-1.28; p = 0.072) or ICH. However, lower GFR at admission was associated with a higher risk of mortality (OR 1.15, 95% CI 1.01-1.31; p = 0.038). Compared to admission, GFR values were higher at discharge (mean: 77.9 vs. 80.8 mL/min/1.73 m2; p = 0.046). CONCLUSIONS: We did not find evidence for an association of lower GFR with an increased risk of poor outcome and ICH, but lower GFR was a determinant of 90-day mortality after endovascular stroke treatment. Our findings encourage also performing MT in this relevant subgroup of acute ischemic stroke patients.

Preexisting Heart Disease Underlies Newly Diagnosed Atrial Fibrillation After Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: Whether newly diagnosed atrial fibrillation (nAF) after stroke reflects underlying heart disease and represents an increased risk of cardioembolic stroke, or whether it is triggered by neurogenic mechanisms remains uncertain. We investigated, whether cardiovascular risk factors and echocardiographic parameters in patients with nAF are similar to patients with known AF (kAF) and differ from patients without AF. METHODS: Consecutive acute ischemic stroke patients were enrolled into a prospective stroke database. All patients with echocardiography were included and univariable and multivariable testing was applied to compare clinical characteristics and echocardiographic findings among patients with nAF, kAF, and no AF. RESULTS: A total of 1397 patients were included (male, 62.3%; median age, 71 years). AF was present in 320 (22.9%) patients. Of those, nAF was present in 36.2% (116/320) and kAF in 63.8% (204/320). No clinical or echocardiographic factor was independently associated with detection of nAF compared with kAF but a trend toward larger left atrial diameters in patients with kAF was observed (P=0.070). In contrast, patients with nAF were more often female (P<0.001), older (P<0.001) and had a larger left atrial diameters (P<0.001) compared with patients without AF. While stroke severity in patients with nAF and kAF was similar, patients without AF had less severe strokes. CONCLUSIONS: Stroke patients with nAF and with kAF share common cardiovascular risk factors, have similar echocardiographic findings and suffer equally severe strokes. We conclude that preexisting heart disease is the major cause of AF that is first diagnosed after stroke.

Genome-wide association study and mouse expression data identify a highly conserved 32 kb intergenic region between WNT3 and WNT9b as possible susceptibility locus for isolated classic exstrophy of the bladder.

Bladder exstrophy-epispadias complex (BEEC), the severe end of the urorectal malformation spectrum, has a profound impact on continence as well as sexual and renal functions. It is widely accepted that for the majority of cases the genetic basis appears to be multifactorial. Here, we report the first study which utilizes genome-wide association methods to analyze a cohort comprising patients presenting the most common BEEC form, classic bladder exstrophy (CBE), to identify common variation associated with risk for isolated CBE. We employed discovery and follow-up samples comprising 218 cases/865 controls and 78 trios in total, all of European descent. Our discovery sample identified a marker near SALL1, showing genome-wide significant association with CBE. However, analyses performed on follow-up samples did not add further support to these findings. We were also able to identify an association with CBE across our study samples (discovery: P = 8.88 × 10(-5); follow-up: P = 0.0025; combined: 1.09 × 10(-6)) in a highly conserved 32 kb intergenic region containing regulatory elements between WNT3 and WNT9B. Subsequent analyses in mice revealed expression for both genes in the genital region during stages relevant to the development of CBE in humans. Unfortunately, we were not able to replicate the suggestive signal for WNT3 and WNT9B in a sample that was enriched for non-CBE BEEC cases (P = 0.51). Our suggestive findings support the hypothesis that larger samples are warranted to identify association of common variation with CBE.

Parental risk factors of anorectal malformations: Analysis with a regional population-based control group.

BACKGROUND: Adequate evidence on environmental risk factors for anorectal malformations (ARMs) is very limited. We assessed maternal body weight and several prenatal exposures of the parents to tobacco, pregestational diabetes, chronic cardiovascular and respiratory diseases, periconceptional folic acid and multivitamin intake. METHODS: Data from the German Network for Congenital Uro-REctal malformations (CURE-Net) were compared with data from the Malformation Monitoring Centre Saxony-Anhalt of the Otto-von-Guericke University in Magdeburg, Germany. Controls were matched to cases by gender and birth year of the child. Crude and adjusted odds ratios (95% confidence intervals) were calculated for potential risk factors using multivariable logistic regression. RESULTS: In total, 158 ARM patients and 474 healthy infants born between 1993 and 2008 in Germany were included. Maternal age at birth of ARM cases and birth plurality were significantly higher and gestational age and weight significantly lower compared with controls (p < 0.0001). We observed significantly increased risks for ARMs associated with maternal smoking before conception and the first trimester of pregnancy (odds ratio = 2.23, 95% confidence interval 1.04-4.79, p = 0.039) and maternal chronic respiratory diseases (odds ratio = 29.25, 95% confidence interval 8.22-104.14, p < 0.0001). No statistically significant increased risk or protective effect was found for the other investigated factors. CONCLUSION: This study suggests an association between the occurrence of ARMs in the offspring and periconceptional maternal smoking as well as maternal chronic respiratory diseases. In addition, there might be a sign of an association for maternal diabetes, although not statistically significant. It can be assumed that the power is far too low to provide reliable estimates.

Adverse Events Following International Normalized Ratio Reversal in Intracerebral Hemorrhage.

BACKGROUND: Prothrombin complex concentrates (PCCs) are frequently used to reverse the effect of vitamin K antagonists (VKAs) in patients with non-traumatic intracerebral hemorrhage (ICH). However, information on the rate of thromboembolic events (TEs) and allergic events after PCC therapy in VKA-ICH patients is limited. METHODS: Consecutive VKA-ICH patients treated with PCC at our institution between December 2004 and June 2014 were included into this retrospective observational study. We recorded international normalized ratio (INR) values before and after PCC treatment, baseline clinical characteristics including the premorbid modified Rankin Scale (pmRS) score, TE and allergic event that occurred during the hospital stay. All events were classified by 3 reviewers as being 'related', 'probably related', 'possibly related', 'unlikely related' or 'not related' to treatment with PCC. To identify factors associated with TEs, log-rank analyses were applied. RESULTS: Two hundred and five patients were included. Median INR was 2.8 (interquartile range (IQR) 2.2-3.8) before and 1.3 (IQR 1.2-1.4) after PCC treatment and a median of 1,500 IU PCC (IQR 1,000-2,500) was administered. Nineteen TEs were observed (9.3%); none were classified 'related' but 9 were classified as 'possibly' or 'probably related' to PCC infusion (4.4%). One allergic reaction (0.5%), 'unlikely related' to PCC, was observed. In the whole cohort, PCC doses >2,000-3,000 IU, ICH volumes >40 ml, National Institute of Health Stroke Scale values >10 and a pmRS >2 were associated with the development of TEs (p = 0.031, p = 0.034, p = 0.050 and p = 0.036, respectively). CONCLUSIONS: Overall, INR reversal with PCC appears safe. Though no clear relationship between higher PCC dosing and TEs was observed, PCC doses between >2,000 and 3,000 IU and higher morbidity at ICH onset were associated with TEs. Hence, individual titration of PCC to avoid exposure to unnecessarily high doses using point-of-care devices should be prospectively explored.

Aversive tension in female adolescents with Anorexia Nervosa: a controlled ecological momentary assessment using smartphones.

BACKGROUND: Current models of Anorexia Nervosa (AN) emphasize the role of emotion regulation. Aversive tension, described as a state of intense arousal and negative valence, is considered to be a link between emotional events and disordered eating. Recent research focused only on adult patients, and mainly general emotion regulation traits were studied. However, the momentary occurrence of aversive tension, particularly in adolescents with AN, has not been previously studied. METHOD: 20 female adolescents with AN in outpatient treatment and 20 healthy adolescents aged 12 to 19 years participated in an ecological momentary assessment using their smartphones. Current states of aversive tension and events were assessed hourly for two consecutive weekdays. Mean and maximum values of aversive tension were compared. Multilevel analyses were computed to test the influence of time and reported events on aversive tension. The effect of reported events on subsequent changes of aversive tension in patients with AN were additionally tested in a multilevel model. RESULTS: AN patients showed higher mean and maximum levels of aversive tension. In a multilevel model, reported food intake was associated with higher levels of aversive tension in the AN group, whereas reported school or sport-related events were not linked to specific states of aversive tension. After food intake, subsequent increases of aversive tension were diminished and decreases of aversive tension were induced in adolescents with AN. CONCLUSIONS: Aversive tension may play a substantial role in the psychopathology of AN, particular in relation with food intake. Therefore, treatment should consider aversive tension as a possible intervening variable during refeeding. Our findings encourage further research on aversive tension and its link to disordered eating. TRIAL REGISTRATION: German register of clinical trials (DRKS): DRKS00005228 (Date of registration: September 2, 2013).

More than fetal urine: enteral uptake of amniotic fluid as a major predictor for fetal growth during late gestation.

UNLABELLED: The purpose of our study was to investigate the importance of amniotic fluid (AF) for fetal growth during late gestation using esophageal atresia (EA) patients as a model. In this retrospective cohort study, we compared the z-scores adapted for birth weights (BW z-scores) for each of 517 European newborns with congenital pre-gastric intestinal atresia, i.e., EA, to a European reference population. To account for the influence of the intestinal atresia on fetal growth per se, we compared adapted birth weights for each of 504 European newborns with post colonic intestinal atresia (anorectal malformation (ARM) with atresia of the anus) to the same European reference population. Analysis of the complete cohort showed (i) a significantly higher rate of small for gestational age newborns among EA compared to ARM newborns (p < 0.001) and (ii) significantly lower BW z-scores among EA compared to ARM newborns (p < 0.001). BW z-scores of EA newborns were significantly lower in term compared to preterm newborns with an inverse correlation with gestational age (GA) (Spearman correlation coefficient, r = -0.185, p < 0.001). CONCLUSIONS: Enteral uptake of AF seems to play a pivotal role in fetal growth during late gestation. WHAT IS KNOWN: • Peak velocity of fetal weight gain occurs at 33 weeks of gestation and continues until birth. During this period, fetal growth is mainly characterized by cellular hypertrophy. • Amniotic fluid (AF) comprises large amounts of hormones and growth regulators. What is New: • A significantly higher rate of small for gestational age and lower birth weights and z-scores are observed among newborn infants with congenital pre-gastric intestinal atresia. • These findings suggest that enteral uptake of AF is a major predictor for fetal growth during late gestation.

Genome-wide mapping of copy number variations in patients with both anorectal malformations and central nervous system abnormalities.

BACKGROUND: Anorectal malformations (ARM) have a prevalence of around 1 in 2500 live births. In around 50% of patients, the malformation is isolated, while in the remainder it arises within the context of complex genetic abnormalities or a defined genetic syndrome. Recent studies have implicated rare copy number variations (CNVs) in both isolated and nonisolated ARM, and identified plausible candidate genes. METHODS: In the present study, array-based molecular karyotyping was performed to identify causative CNVs in 32 sporadic ARM patients with comorbid abnormalities of the central nervous system (CNS). This phenotype was selected to enrich for rare CNVs, since previous research has implicated rare CNVs in both CNS abnormalities and ARM. RESULTS: In five patients, a probable disease-causing CNV was identified (del6q14.3q16.3, del14q32.2, del17q12q21.2, and two patients with del22q11.21). In three of these patients, the CNVs were de novo. For the remaining two patients, no parental DNA was available. Deletions at 22q11.21 and 6q14.3 have been associated with both CNS abnormalities and ARM. In contrast, deletions at 14q32.2 have only been described in patients with CNS abnormalities, and the del17q12q21.2 is a novel CNV. Expression studies in mice suggest that NEUROD2 and RARA, which reside within the newly identified del17q12q21.2 region, are candidate genes for the formation of microcephaly and ARM. CONCLUSION: The present data suggest that CNVs are a frequent cause of the ARM with CNS abnormalities phenotype, and that array-analysis is indicated in such patients.