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The COVID-19 pandemic represents a major public health threat. Risk of death from the infection is associated with age and pre-existing comorbidities such as diabetes, dementia, cancer, and impairment of immunological, hepatic or renal function. It remains incompletely understood why some patients survive the disease, while others do not. As such, we sought to identify novel prognostic factors for COVID-19 mortality. We performed an unbiased, observational retrospective analysis of real world data. Our multivariable and univariable analyses make use of U.S. electronic health records from 122,250 COVID-19 patients in the early stages of the pandemic. Here we show that a priori diagnoses of fluid, pH and electrolyte imbalance during the year preceding the infection are associated with an increased risk of death independently of age and prior renal comorbidities. We propose that future interventional studies should investigate whether the risk of death can be alleviated by diligent and personalized management of the fluid and electrolyte balance of at-risk individuals during and before COVID-19. Nahkuri et al. evaluate potential prognostic factors for COVID-19 mortality in a large US database of electronic health records. They find that fluid, pH and electrolyte imbalances – diagnosed at least one month prior to COVID-19 diagnosis – are associated with mortality. The clinical course of patients with COVID-19 is highly variable, with some patients barely affected and others dying. We wanted to better understand why this is the case and identify markers of COVID-19-associated mortality. To this end, we looked into the entire available medical history of more than 100,000 COVID-19 patients from the United States. We found that patients who had experienced a disturbance of electrolyte or fluid levels in the year before they contracted SARS-CoV-2 were more likely to die than patients without such a history. This observation suggests that careful monitoring and balancing of the hydration and electrolyte status during and even before a SARS-CoV-2 infection may be beneficial and possibly reduce the risk of death with COVID-19.

Introduction: Prognostic scores are important tools in oncology to facilitate clinical decision-making based on patient characteristics. To date, classic survival analysis using Cox proportional hazards regression has been employed in the development of these prognostic scores. With the advance of analytical models, this study aimed to determine if more complex machine-learning algorithms could outperform classical survival analysis methods.Methods: In this benchmarking study, two datasets were used to develop and compare different prognostic models for overall survival in pan-cancer populations: a nationwide EHR-derived de-identified database for training and in-sample testing and the OAK (phase III clinical trial) dataset for out-of-sample testing. A real-world database comprised 136K first-line treated cancer patients across multiple cancer types and was split into a 90% training and 10% testing dataset, respectively. The OAK dataset comprised 1,187 patients diagnosed with non-small cell lung cancer. To assess the effect of the covariate number on prognostic performance, we formed three feature sets with 27, 44 and 88 covariates. In terms of methods, we benchmarked ROPRO, a prognostic score based on the Cox model, against eight complex machine-learning models: regularized Cox, Random Survival Forests (RSF), Gradient Boosting (GB), DeepSurv (DS), Autoencoder (AE) and Super Learner (SL). The C-index was used as the performance metric to compare different models.Results: For in-sample testing on the real-world database the resulting C-index [95% CI] values for RSF 0.720 [0.716, 0.725], GB 0.722 [0.718, 0.727], DS 0.721 [0.717, 0.726] and lastly, SL 0.723 [0.718, 0.728] showed significantly better performance as compared to ROPRO 0.701 [0.696, 0.706]. Similar results were derived across all feature sets. However, for the out-of-sample validation on OAK, the stronger performance of the more complex models was not apparent anymore. Consistently, the increase in the number of prognostic covariates did not lead to an increase in model performance.Discussion: The stronger performance of the more complex models did not generalize when applied to an out-of-sample dataset. We hypothesize that future research may benefit by adding multimodal data to exploit advantages of more complex models.

Background Cardiopulmonary bypass (CPB) is often associated with degrees of complex inflammatory response mediated by various cytokines. This response can, in severe cases, lead to systemic hypotension and organ dysfunction. Cytokine removal might therefore improve outcomes of patients undergoing cardiac surgery. CytoSorb® (Cytosorbents, NJ, USA) is a recent device designed to remove cytokine from the blood using haemoadsorption (HA). This trial aims to evaluate the potential of CytoSorb® to decrease peri-operative cytokine levels in cardiac surgery. Methods We have conducted a single-centre pilot randomized controlled trial in 30 patients undergoing elective cardiac surgery and deemed at risk of complications. Patients were randomly allocated to either standard of care (n = 15) or CytoSorb® HA (n = 15) during cardiopulmonary bypass (CPB). Our primary outcome was the difference between the two groups in cytokines levels (IL-1a, IL-1b, IL-2, IL-4, IL-5, IL-6, IL-10, TNF-α, IFN-γ, MCP-1) measured at anaesthesia induction, at the end of CPB, as well as 6 and 24 h post-CPB initiation. In a consecutive subgroup of patients (10 in HA group, 11 in control group), we performed cross-adsorber as well as serial measurements of coagulation factors’ activity (antithrombin, von Willebrand factor, factor II, V, VIII, IX, XI, and XII). Results Both groups were similar in terms of baseline and peri-operative characteristics. CytoSorb® HA during CPB was not associated with an increased incidence of adverse event. The procedure did not result in significant coagulation factors’ adsorption but only some signs of coagulation activation. However, the intervention was associated neither with a decrease in pro- or anti-inflammatory cytokine levels nor with any improvement in relevant clinical outcomes. Conclusions CytoSorb® HA during CPB was not associated with a decrease in pro- or anti-inflammatory cytokines nor with an improvement in relevant clinical outcomes. The procedure was feasible and safe. Further studies should evaluate the efficacy of CytoSorb® HA in other clinical contexts. Trial registration ClinicalTrials.gov NCT02775123. Registered 17 May 2016. Electronic supplementary material The online version of this article (10.1186/s13054-019-2399-4) contains supplementary material, which is available to authorized users.

Heart failure (HF) is usually defined by the dominantly affected heart chamber; therefore, termed right or left HF (RHF or LHF). Pulmonologists understand RHF as a complex syndrome characterized by insufficient delivery of blood from the right ventricle associated with elevated systemic venous pressure at rest or exercise. Cardiologists specify LHF by its clinical functional class and the relation to a reduced (HFrEF), preserved (HFpEF) or mid-range ejection fraction (HFmrEF). Pediatric cardiologist, dealing also with patients with a failing single ventricle, define HF as a condition of insufficient systemic oxygen delivery (DO(2)). Certainly, pediatricians do not think of the right and left heart, or even a single ventricle as an isolated, independently acting entity. Because of the importance of cardiac interactions, the creation of a restrictive atrial communication aims at a palliative approach with the goal to diminish the congestive consequences of a dysfunctional ventricle; further to serve as a pop-off valve in order to prevent syncope and cardiovascular collapse. This review covers the background, the particular indications, the techniques and preliminary results achieved following the creation of a restrictive atrial septum defect (rASD) in different pathophysiological settings. Based on the institutional experience, percutaneous trans-catheter perforation of the atrial septum, followed by gradual balloon dilatation can be performed at any age and location worldwide. Medical institutions in low resource countries can make use of such palliating procedures in the setting of right as well as LHF independent of their pharmacological facilities.

Objective The goal of the present study was to investigate lines of therapy with biological drugs in patients followed in dermatology, gastroenterology, and rheumatology practices in Germany. Materials and methods The study included patients aged 18 years or over who had received a biological therapy in dermatology, gastroenterology, or rheumatology practices in Germany in 2017 (index date). The primary outcome of the study was the prevalence of different lines of therapy (first-, second-, third-, and at least fourth-line therapies) by type of practice, age, and gender. The second outcome was the association between basic characteristics (type of practice, age, and gender) and lines of therapy with biological drugs. Results The present study included 27,816 individuals. The mean age (SD) at index date was 50.7 years (15.4 years). Biological drugs were prescribed as first-line therapies in 60% of patients (dermatology 73%, gastroenterology 61%, and rheumatology 56%). The prevalence of first-line therapies ranged from 57% in individuals aged 41 - 50 years to 65% in those aged 18 - 30 years. Furthermore, 56% of women and 61% of men were prescribed biological drugs as first-line therapies. Finally, the likelihood of being prescribed biological drugs as second-, third-, or at least fourth-line therapies was significantly associated with being followed in a rheumatology or gastroenterology practice, older age, and female gender. Conclusion Biological drugs were prescribed as first-line therapies in most cases. The type of practice as well as the patient's age and gender had a significant impact on lines of therapy with biological drugs. .

BackgroundLeft atrial congestion results from backward failure in dilated cardiomyopathy. We aimed to evaluate feasibility and efficacy of percutaneous atrioseptostomy to create a restrictive atrial septum defect in management of dilated cardiomyopathy.Methods and resultsFrom June 2009 to December 2016, 27 interventions comprised left atria decompressions in 22 dilated cardiomyopathy patients; 9 females; age: 24 days to 36.9 years; weight: 3–50 kg; NYHA-/Ross class IV (n=16). Mean left ventricular ejection fraction was 21.5±9.7% and brain natriuretic peptide was 2291±1992 pg/ml. Dilated cardiomyopathy was classified as chronic (n=9); acute (n=1) myocarditis; idiopathic (n=5); left ventricular non-compaction (n=4); mitochondriopathy, pacemaker induced, and arrhythmogenic (n=3). Atrioseptostomy was concomitantly performed with myocardial biopsies 6.5 days (±11.7) after admission (n=11). Trans-septal puncture was used in 18 patients; foramen ovale dilatation was done in four patients. Mean balloon size was 11 mm (range 7–14 mm); total procedure time was 133±38 minutes. No procedural complications were observed. Mean left atrial pressure decreased from 15.8±6.8 to 12.2±4.8 mmHg (p=0.005), left/right atrial pressure gradient from 9.6±5.6 to 5±3.5 mmHg; brain natriuretic peptide (n=18) decreased from 1968±1606 to 830±1083 pg/ml (p=0.01). One patient unsuitable for heart transplantation died at home despite additionally performed pulmonary artery banding and three further left atrial decompressions; five patients were bridged to transplantation, two died afterwards. Functional recovery occurred in the remaining 14 patients and in six after additional pulmonary artery banding. No patient required assist device.ConclusionsPercutaneous left atrial decompression is an age-independent, effective palliation treating patients with dilated cardiomyopathy.

Vitamin B 12 deficiency is rare in the paediatric population. The most common cause is a diet low in animal products. Particularly at risk are infants exclusively breast-fed by mothers with hypovitaminosis B 12 . Much rarer causes include disorders of cobalamin absorption, transport or metabolism. There are mainly haematological, neurological and gastrointestinal symptoms. Diagnostic tests should include complete blood count with differential, including the MCV and RDW, the concentration of ferritin, folic acid and cobalamin in the serum and plasma homocysteine, and methylmalonic acid excretion in urine. We present the case of 10-month-old girl breast fed, admitted to the Paediatric Department due to inhibition of weight gain and developmental delay. Among the first symptoms of vitamin B 12 deficiency, which occurred in the child 6 months of age, was refusal to solid food. Increased MCV and RDW with normal haemoglobin values were observed in blood counts performed in 7 months of age. During hospitalization we noticed significantly elevated plasma homocysteine levels and a very large excretion of methylmalonic acid in the urine, which quickly normalized after the start of treatment with cyanocobalamin. At the beginning of therapy the benign myoclonic jerks occurred, which resolved spontaneously after a few days. Regression of neurological symptoms was not fully satisfactory. Lack of acceptance of foods other than breast milk can be one of the first signs of vitamin B 12 deficiency in infants and contribute to the severity of the deficit.

Atrial septostomy (AS) is recommended for pulmonary arterial hypertension (PAH)-associated right ventricular (RV) failure, recurrent syncope, or pulmonary hypertensive crisis (PHC). We aimed to evaluate the feasibility and efficacy of AS to manage PAH from infancy to adulthood. From June 2009 to December 2016, transcatheter atrial communications were created in 11 PAH patients (4 girls/women; median age = 4.3 years; range = 33 days–26 years; median body weight = 14 kg; range = 3–71 kg; NYHA-/Ross class IV; n = 11). PAH was classified as idiopathic (n = 6) or secondary (n = 5). History of syncope was dominant (n = 6); two with patent foramen ovale (PFO) admitted with recurrent PHC, three patients required resuscitation before AS. Three patients had PAH-associated low cardiac output. The average pulmonary arterial pressures (PAP systolic/diastolic) were 101/50 (±34/23); the corresponding systemic arterial pressures (SAP) were 99/54 (±23/11); and the mean ratio of PAPd / SAPd was 0.97 (±0.4). Percutaneous trans-septal puncture was uneventfully performed in nine patients; a PFO was dilated in two patients. There was no procedure-related mortality. The median balloon size was 10 mm (range = 6–14 mm); the mean catheter time was 174.6 ± 48 min; fluoroscopy time was 19.8 (±11) min. Syncope and PHC were successfully treated in all patients. The mean arterial oxygen saturation decreased from 97 ± 2 to 89 ± 11.7. One patient died awaiting lung transplantation, one continues to be listed; two patients received a reverse Potts-shunt, one patient died during follow-up; seven patients are stable with PAH-specific treatment. Percutaneous AS is an effective method palliating PAH-associated syncope, PHCs or right (bi-) ventricular heart failure.

Presented is a retrospective outcome study of a 15-year single institutional experience with a contemporary cohort of patients with hypoplastic left heart syndrome and complex that underwent a “Giessen Hybrid” stage I as initial palliation. Hybrid approach consisting of surgical bilateral pulmonary artery banding and percutaneous duct stenting with or without atrial septum manipulation was developed from a rescue approach to a first-line procedure. Comprehensive Aristotle score defined pre-operative condition. Fifteen-year follow-up mortality is reported as occurring within the staged univentricular palliation or before and after biventricular repair. Hybrid stage I was performed in 154 patients; 107 should be treated by single ventricle palliation, 33 by biventricular repair (BVR), 7 received heart transplantation, and 7 were treated by comfort care, respectively. Overall 34 children died. The Aristotle score (mean value 18.2 ± 3) classified for univentricular circulations in newborns did not have statistical impact on the outcome. Two patients died during stage I (1.2 %), and the interstage I mortality was 6.7 %, and stage II mortality 9 %, respectively. Stage III was up to now performed in 57 patients without mortality. At 1 year, the overall unadjusted survival of HLHS and variants was 84 % and following BVR 89 %, respectively. The Fifteen-year survival rate for HLHS and variants was 77 %, with no significant impact of birth weight of less than 2.5 kg. In conclusion, Hybrid stage I fulfilled the criteria of life-saving approach. In our institution, Hybrid procedure replaced Norwood-staged palliation with a considerable mid- and long-term survival rate. Considering interstage mortality close surveillance is mandatory.

Background and objective Electronic health records (EHRs) are increasingly being used to complement the FDA Adverse Event Reporting System (FAERS) and to enable active pharmacovigilance. Over 30% of all adverse drug reactions are caused by drug–drug interactions (DDIs) and result in significant morbidity every year, making their early identification vital. We present an approach for identifying DDI signals directly from the textual portion of EHRs. Methods We recognize mentions of drug and event concepts from over 50 million clinical notes from two sites to create a timeline of concept mentions for each patient. We then use adjusted disproportionality ratios to identify significant drug–drug–event associations among 1165 drugs and 14 adverse events. To validate our results, we evaluate our performance on a gold standard of 1698 DDIs curated from existing knowledge bases, as well as with signaling DDI associations directly from FAERS using established methods. Results Our method achieves good performance, as measured by our gold standard (area under the receiver operator characteristic (ROC) curve >80%), on two independent EHR datasets and the performance is comparable to that of signaling DDIs from FAERS. We demonstrate the utility of our method for early detection of DDIs and for identifying alternatives for risky drug combinations. Finally, we publish a first of its kind database of population event rates among patients on drug combinations based on an EHR corpus. Conclusions It is feasible to identify DDI signals and estimate the rate of adverse events among patients on drug combinations, directly from clinical text; this could have utility in prioritizing drug interaction surveillance as well as in clinical decision support.

Background: Sickle cell disease (SCD) is a genetic hematologic condition affecting more than 300,000 individuals worldwide. Most of the 100,000 individuals with SCD in the United States are African-American. An estimated 50% of those with the most severe genotype of SCD (HbSS) will have an overt or silent cerebral infarct (SCI) by age 30. While a significant number of studies have addressed the cognitive function and brain imaging of children with SCD, very few have included adults. As disease modification has increased over the last decade, a modern assessment of adults with SCD is needed. The aims of this study are to: 1. Determine the prevalence of cognitive impairment in adults with SCD 2. Determine if adults with SCD have deficits in functional task performance skills 3. Assess if and how cognitive function and task performance change over time Methods: This is a cross-sectional analysis of a prospective, observational cohort study. Adults, 18 years of age or older, with any form of SCD were recruited from the SCD clinics at Washington University in St. Louis. During baseline testing, participants completed the Wechsler Abbreviated Scale of Intelligence (WASI-II), National Institutes of Health Toolbox Cognition Battery (NIHTB-CB), and the Medication subtest of the Executive Function Performance Test (EFPT-M). The WASI-II and NIHTB-CB were repeated annually. Mean participant data from the baseline WASI-II and NIHTB-CB were compared with normative individual measure and composite scores using a one-sample t-test. The NIHTB-CB normative mean is a t-score of 50 with a SD of 10. Baseline results on Medication subtest of the EFPT were compared to previously tested control and stroke groups. Higher scores on the EFPT are indicative of greater executive dysfunction. Differences between Time 1 and Time 2 scores were evaluated using a paired-samples t-test. Univariate analyses were used to describe relationships between cognition and patient factors. Annual magnetic resonance imaging (MRI) was also conducted to assess infarct classification, with completion limited to 12-18 months from consent. Radiographical analyses were reviewed and recorded by the study neuroradiologists. Results: Forty participants were assessed at baseline; 9 completed Time 2 testing. Participant demographic information is presented in Table 1. Compared to the normative population, no significant differences were found on the WASI-II. On the NIHTB-CB, participants scored significantly lower on subtests measuring processing speed (Mean difference -13.8, p Of the 59 participants consented to yearly MRI evaluation, 45 have completed baseline imaging and 1 completed Time 2 imaging. Radiographical impressions reported: 1) overt strokes in 2 participants on transfusions (TF), 1 on hydroxyurea (HU), and 1 on no disease-modifying regimen (ND); 2) SCIs in 6 participants on TF, 6 on HU, and 4 on ND; 3) no infarct in 1 participant on TF, 18 on HU, and 9 on ND. Conclusion: Adults with SCD in this relatively highly educated cohort have marked deficits in executive function, attention, working memory, processing speed, and self-awareness. Cognitive deficits lead to difficulty completing everyday functional and disease-related activities, ranging from medication adherence to productivity in education and employment. Healthcare providers who treat individuals with SCD should be aware of the cognitive impairments in this population. Routine cognitive screening is needed to initiate referrals for cognitive rehabilitation. Disclosures King: Magenta Therapeutics: Membership on an entity's Board of Directors or advisory committees; Novimmune: Research Funding; RiverVest: Consultancy; Tioma Therapeutics (formerly Vasculox, Inc.):: Consultancy; WUGEN: Equity Ownership; Incyte: Consultancy; Amphivena Therapeutics: Research Funding; Cell Works: Consultancy; Bioline: Consultancy; Celgene: Consultancy.

Feeding disorders are common pediatric problems with diverse etiology. They are associated with organic diseases, especially digestive, circulatory and neurological conditions. Psychological factors may also play an important role. We present a case of infant admitted to hospital because of feeding disturbances and poor weight gain. Based on differential diagnostics we excluded organic causes of feeding disturbances in the presented case. Clinical observations and further events let us diagnose an incorrect mother–child relationship as possible reason of feeding disorder in our patient.

Background Dilated cardiomyopathy (DCM) in childhood has a considerable morbidity and mortality and high incidence of heart transplantation. Pulmonary artery banding (PAB) has been proposed in patients with corrected transposition of the great arteries to retrain the sub-pulmonic left ventricle (LV) and to improve a failing sub-aortic right ventricle. We evaluated the short-term and medium-term effects of PAB in young patients with LVDCM. Methods A retrospective single-center observational study was performed to evaluate the possible benefits of a dilatable surgical PAB in infants and young children with LVDCM. Results Reported are 12 patients (10 infants, 2 toddlers) with LVDCM referred for heart transplant who received a surgical PAB. There were no hospital deaths. Clinical functional status improved in all patients. The pressure gradient across the PAB increased within 20 days from 28 ± 7 to 43 ± 15 mm Hg. The LV ejection fraction increased from 14.5% ± 5% pre-PAB to 27% ± 13% at hospital discharge and to 47% ± 10% at 3 to 6 months. The LV end-diastolic diameter (z-score) decreased ( p > 0.001) from 46 ± 6.1 (+7.0 ± 1.3) to 35 ± 15 mm (+3.0 ± 1.3) after 3 to 6 months and to 34 ± 15 mm (+1.3 ± 1.14) after a median age of 2 years (maximum 6.6 years), respectively. Plasma B-type natriuretic peptide levels decreased from 3431 ± 2610 to 288 ± 321 pg/ml at discharge and to 102 ± 96 pg/ml 22 months later. Eight children were subsequently de-banded by transcatheter technique and 6 of them are currently at Ross Heart Failure Classification for Children class I. Two patients, both with non-compaction DCM, deteriorated at 5 and 6 months after PAB debanding and finally died. Conclusion In young children with LVDCM and still-preserved right ventricular function, PAB led to an improvement of LV and mitral valve function by ventricular interaction.

Lesch-Nyhan syndrome is a rare inborn error of metabolism with very poor prognosis. Patients vary in many ways but all seem to have impairments to some degree in uric acid metabolism, motor development, and behavior. A careful evaluation is essential toward making the appropriate diagnosis. A case of infant with motor delay, spasticity, dystonia, and crystalluria is reported. Treatment based on allopurinal (12 mg/kg of body weight/24 h) reduced serum hyperuricemia to values

Renal impairment because of CNI contributes to long-term morbidity. Therefore, CNI avoiding or sparing treatment strategies are important. In this article, we describe the results of a CNI-free treatment protocol with regard to recovery of renal function. Twenty-eight patients with heart transplantation were switched from CNI regimen to everolimus and mycophenolate, when cGFR was

Streszczenie Autorzy przedstawiają opis przebiegu klinicznego rozyczki wrodzonej u 5-tygodniowego niemowlecia hospitalizowanego na roznych oddzialach z powodu wielonarządowych objawow klinicznych wymagających wielospecjalistycznych interwencji, w tym zabiegowych.

Background Juvenile idiopathic arthritis is the most common rheumatic disease in children. Chronic uveitis is a common and serious comorbid condition of juvenile idiopathic arthritis, with insidious presentation and potential to cause blindness. Knowledge of clinical associations will improve risk stratification. Based on clinical observation, we hypothesized that allergic conditions are associated with chronic uveitis in juvenile idiopathic arthritis patients. Methods This study is a retrospective cohort study using Stanford’s clinical data warehouse containing data from Lucile Packard Children’s Hospital from 2000–2011 to analyze patient characteristics associated with chronic uveitis in a large juvenile idiopathic arthritis cohort. Clinical notes in patients under 16 years of age were processed via a validated text analytics pipeline. Bivariate-associated variables were used in a multivariate logistic regression adjusted for age, gender, and race. Previously reported associations were evaluated to validate our methods. The main outcome measure was presence of terms indicating allergy or allergy medications use overrepresented in juvenile idiopathic arthritis patients with chronic uveitis. Residual text features were then used in unsupervised hierarchical clustering to compare clinical text similarity between patients with and without uveitis. Results Previously reported associations with uveitis in juvenile idiopathic arthritis patients (earlier age at arthritis diagnosis, oligoarticular-onset disease, antinuclear antibody status, history of psoriasis) were reproduced in our study. Use of allergy medications and terms describing allergic conditions were independently associated with chronic uveitis. The association with allergy drugs when adjusted for known associations remained significant (OR 2.54, 95% CI 1.22–5.4). Conclusions This study shows the potential of using a validated text analytics pipeline on clinical data warehouses to examine practice-based evidence for evaluating hypotheses formed during patient care. Our study reproduces four known associations with uveitis development in juvenile idiopathic arthritis patients, and reports a new association between allergic conditions and chronic uveitis in juvenile idiopathic arthritis patients.

Background: Drug-related adverse events remain an important cause of morbidity and mortality and impose huge burden on healthcare costs. Routinely collected electronic healthcare data give a good snapshot of how drugs are being used in ‘real-world’ settings. Objective: To describe a strategy that identifies potentially drug-induced acute myocardial infarction (AMI) from a large international healthcare data network. Methods: Post-marketing safety surveillance was conducted in seven population-based healthcare databases in three countries (Denmark, Italy, and the Netherlands) using anonymised demographic, clinical, and prescription/dispensing data representing 21,171,291 individuals with 154,474,063 person-years of follow-up in the period 1996–2010. Primary care physicians’ medical records and administrative claims containing reimbursements for filled prescriptions, laboratory tests, and hospitalisations were evaluated using a three-tier triage system of detection, filtering, and substantiation that generated a list of drugs potentially associated with AMI. Outcome of interest was statistically significant increased risk of AMI during drug exposure that has not been previously described in current literature and is biologically plausible. Results: Overall, 163 drugs were identified to be associated with increased risk of AMI during preliminary screening. Of these, 124 drugs were eliminated after adjustment for possible bias and confounding. With subsequent application of criteria for novelty and biological plausibility, association with AMI remained for nine drugs (‘prime suspects’): azithromycin; erythromycin; roxithromycin; metoclopramide; cisapride; domperidone; betamethasone; fluconazole; and megestrol acetate. Limitations: Although global health status, co-morbidities, and time-invariant factors were adjusted for, residual confounding cannot be ruled out. Conclusion: A strategy to identify potentially drug-induced AMI from electronic healthcare data has been proposed that takes into account not only statistical association, but also public health relevance, novelty, and biological plausibility. Although this strategy needs to be further evaluated using other healthcare data sources, the list of ‘prime suspects’ makes a good starting point for further clinical, laboratory, and epidemiologic investigation. This research has been funded by the European Commission’s Seventh Framework Programme (FP7/2007–2013) under grant no. 215847–The EU-ADR Project.

BACKGROUND: Aortopulmonary collaterals (APCs) are frequently found in patients with a single-ventricle (SV) circulation. However, knowledge about the clinical significance of the systemic-to-pulmonary shunt flow in patients after the modified Fontan procedure and its potential causes is limited. Accordingly, the aim of our study was to detect and quantify APC flow using cardiovascular magnetic resonance (CMR) and assess its impact on SV volume and function as well as to evaluate the role of the size of the pulmonary arteries in regard to the development of APCs. METHODS: 60 patients (mean age 13.3 ± 6.8 years) after the Fontan procedure without patent tunnel fenestration underwent CMR as part of their routine clinical assessment that included ventricular functional analysis and flow measurements in the inferior vena cava (IVC), superior vena cava (SVC) and ascending aorta (Ao). APC flow was quantified using the systemic flow estimator: (Ao) - (IVC + SVC). Pulmonary artery index (Nakata index) was calculated as RPA + LPA area/body surface area using contrast enhanced MR angiography. The patient cohort was divided into two groups according to the median APC flow: group 1 < 0.495 l/min/m(2) and group 2 > 0.495 l/min/m(2). RESULTS: Group 1 patients had significant smaller SV enddiastolic (71 ± 16 vs 87 ± 25 ml/m(2); p=0.004) and endsystolic volumes (29 ± 11 vs 40 ± 21 ml/m(2); p=0.02) whereas ejection fraction (59 ± 9 vs 56 ± 13%; p=0.38) differed not significantly. Interestingly, pulmonary artery size showed a significant inverse correlation with APC flow (r=-0.50, p=0.002). CONCLUSIONS: Volume load due to APC flow in Fontan patients affected SV dimensions, but did not result in an impairment of SV function. APC flow was related to small pulmonary artery size, suggesting that small pulmonary arteries represent a potential stimulus for the development of APCs.

International audience; Aneurysmal subarachnoid haemorrhage (aSAH) is a devastating event with substantial case-fatality. Our purpose was to examine which clinical and neuro-imaging characteristics, available on admission, predict 60 day case-fatality in aSAH and to evaluate performance of our prediction model. We performed a secondary analysis of patients enrolled in the International Subarachnoid Aneurysm Trial (ISAT), a randomised multicentre trial to compare coiling with clipping in aSAH patients. Multivariable logistic regression analysis was used to develop a prognostic model to estimate the risk of dying within 60 days from aSAH based on clinical and neuro-imaging characteristics. The model was internally validated with bootstrapping techniques. The study population comprised of 2,128 patients who had been randomised to either endovascular coiling or neurosurgical clipping. In this population 153 patients (7.2%) died within 60 days. World Federation of Neurosurgical Societies (WFNS) grade was the most important predictor of case-fatality, followed by age, lumen size of the aneurysm and Fisher grade. The model discriminated reasonably between those who died within 60 days and those who survived ( statistic = 0.73), with minor optimism according to bootstrap re-sampling (optimism corrected statistic = 0.70). Several strong predictors are available to predict 60 day case-fatality in aSAH patients who survived the early stage up till a treatment decision; after external validation these predictors could eventually be used in clinical decision making.

Long-term antibiotic therapy is one of the main risk factors for mycosis. The urinary d -arabinitol/ l -arabinitol ( d -/ l -ARA) ratio (a biomarker of several Candida species) was determined by gas chromatography with an electron capture detector in samples from 51 infants undergoing long-term antibiotic therapy. Although 47 of these children had higher d -/ l -ARA ratios than healthy controls ( P < 0.0003), their values nonetheless remained within upper-normal limits ( d -/ l -ARA ratio of

Renal tubular citrate transport is accomplished by electrogenic Na(+) coupled dicarboxylate transporter NaDC-1, a carrier subjected to regulation by acidosis. Trafficking of the Na(+)/H(+) exchanger NHE3 is controlled by NHE regulating factors NHERF-1 and NHERF-2 and the serum and glucocorticoid inducible kinase SGK1. To test for a possible involvement in NaDC-1 regulation, mRNA encoding NaDC-1 was injected into Xenopus oocytes with or without cRNA encoding NHERF-1, NHERF-2, SGK1, SGK2, SGK3, and/or the constitutively active form of the related protein kinase B ((T308,S473D)PKB). Succinate induced inward currents (I(succ)) were taken as a measure of transport rate. Coexpression of neither NHERF-1 nor NHERF-2 in NaDC-1 expressing oocytes significantly altered I(succ). On the other hand, coexpression of SGK1, SGK3, and (T308,S473D)PKB stimulated I(succ), an effect further stimulated by additional coexpression of NHERF-2 but not of NHERF-1. The action of the kinases and NHERF-2 may link urinary citrate excretion to proximal tubular H(+) secretion.

One-hundred twenty-nine very low-birthweight infants were treated in Newborn and Infant Care Department of Children's Memorial Health Institute between 1985 and 1994; 89 were taken to prospective neurodevelopmental care. The newborns were divided into two groups. Group I had 38 preterm infants born from 1985 to 1989 and followed up at 7 to 11 years of age. Group II had 51 very low-birthweight infants treated from 1990 to 1994 and followed up at 2 to 5 years of age. Complicated, multiple pregnancy, normal delivery, and extremely low birthweight were significantly more frequent in group II. Very low-birthweight infants were frequently born by cesarean section in severe asphyxia. Only four (7.8%) newborns received surfactant therapy. From 1990 to 1994, respiratory distress syndrome III and IV, and a longer respiratotherapy period were significantly more frequent. From 1985 to 1994, the frequency of sepsis, periventricular leukomalacia, and normal ultrasonography was constant. Intraventricular hemorrhage I, II, and IV were frequently present in the 1990s, and intraventricular hemorrhage III was frequent in the 1980s. Cerebral palsy was diagnosed in 11 (28.9%) children in group I and 18 (35.2%) in group II (not statistically different). Multiple and complicated pregnancy, cesarean section, severe asphyxia, and respiratory distress syndrome did not increase the risk of cerebral palsy in very low-birthweight infants. Periventricular leukomalacia has a more predictive value for cerebral palsy in these infants than did intraventricular hemorrhage. ( J Child Neurol 2000;15:417-420).

BackgroundPeripheral arterial disease (PAD) is a growing problem with few available therapies. Cilostazol is the only FDA-approved medication with a class I indication for intermittent claudication, but carries a black box warning due to concerns for increased cardiovascular mortality. To assess the validity of this black box warning, we employed a novel text-analytics pipeline to quantify the adverse events associated with Cilostazol use in a clinical setting, including patients with congestive heart failure (CHF).Methods and resultsWe analyzed the electronic medical records of 1.8 million subjects from the Stanford clinical data warehouse spanning 18 years using a novel text-mining/statistical analytics pipeline. We identified 232 PAD patients taking Cilostazol and created a control group of 1,160 PAD patients not taking this drug using 1:5 propensity-score matching. Over a mean follow up of 4.2 years, we observed no association between Cilostazol use and any major adverse cardiovascular event including stroke (OR = 1.13, CI [0.82, 1.55]), myocardial infarction (OR = 1.00, CI [0.71, 1.39]), or death (OR = 0.86, CI [0.63, 1.18]). Cilostazol was not associated with an increase in any arrhythmic complication. We also identified a subset of CHF patients who were prescribed Cilostazol despite its black box warning, and found that it did not increase mortality in this high-risk group of patients.ConclusionsThis proof of principle study shows the potential of text-analytics to mine clinical data warehouses to uncover 'natural experiments' such as the use of Cilostazol in CHF patients. We envision this method will have broad applications for examining difficult to test clinical hypotheses and to aid in post-marketing drug safety surveillance. Moreover, our observations argue for a prospective study to examine the validity of a drug safety warning that may be unnecessarily limiting the use of an efficacious therapy.