bluuebunny/crossref_metadata_2025_split huggingface dataset:
P38 Identification of Nifurtimox metabolites in urine of pediatric Chagas disease patients by UHPLC-MS/MS
Authors: Pérez Montilla CA , Moroni S , González N , Moscatelli G , Altcheh JM , García Bournissen F 
Published: May 2019

BackgroundNifurtimox (NFX) is one of the only 2 available drugs for the treatment of Chagas disease, a parasitic disease endemic to Latin America. In spite of widespread use of this medication, little is known regarding its metabolism, particularly in children.The objective of this study was to develop a method to identify NFX metabolites in human samples, and apply it to the discovery of NFX metabolites in urine from pediatric patients undergoing treatment for Chagas disease.MethodsUrine was collected from 12 pediatric patients and 8 healthy volunteers (controls), and anonymized before analysis. Informed consent was obtained from all participants. Samples were aliquoted, deproteinized with ACN (BNZ as internal standard) and centrifuged in cold. 10% of supernatant in water was injected into a 1.8 µm C18 column and chromatographed in 3.5 min under a water/ACN gradient at 0.4 mL/min in a Shimadzu Nexera X2 UHPLC equipment. Species were positively ionized by a Turbo IonSpray source. Metabolites were identified and characterized by an ABSciex 6500 QTRAP spectrometer through Enhanced-Mass-Screening (EMS), Neutral-Loss (NL), Precursor-Ion (PREC), Enhanced-Product-Ion (EPI) and MS3 experiments. For chromatographic monitoring, parameters were optimized and the three most intense Multiple-Reaction-Monitoring (MRM) transitions were selected.ResultsDenitrated NFX conjugated with cysteine (M1) and N-acetyl-cysteine (M2), as well as other phase I metabolites like saturated nitrile (M3), hydroxyamide (M4), carboxylic acid (M5) or aldehyde (M6) were identified in most samples. The final MS/MS detection method was high reproducible and sensitive for all metabolites.ConclusionsWe found the main NFX metabolites in pediatric urine using a fast MS/MS method that can allow us to efficiently study the role of NFX and its metabolites in pediatric treatment response and the adverse drug reactions, and in combination with PK/PD experiments will facilitate future clinical trials, and possibly develop new therapeutic drug monitoring strategies.ReferenceThe research was carried out in the Translational Research Unit (IMIPP-CONICET), located in the Buenos Aires Children´s Hospital ‘Dr. Ricardo Gutiérrez’, and financed by the Fund for Scientific and Technological Research (FONCyT, Project BID-PICT 2015–0168).Disclosure(s)Nothing to disclose
P43 Pharmacokinetics and target attainment of antibiotics in critically ill children – a systematic review of current literature
Authors: Hartman S , Brüggemann R , Orriëns L , Dia N , Schreuder M , de Wildt S 
Published: May 2019

BackgroundPharmacokinetics (PK) are severely altered in critically ill patients due to changes in volume of distribution (Vd) and/or drug clearance (Cl). To what extent this affects the PK of antibiotics in critically children is largely unknown. We aimed to identify gaps in current knowledge and to compare published PK parameters and target attainment of antibiotics in critically ill children to healthy children and critically ill adults.MethodsSystematic literature search in PubMed, EMBASE and Web of Science. Articles were labelled as relevant when they included information on PK of antibiotics in critically ill, non-neonatal, pediatric patients. Extracted PK-parameters included Vd, Cl, trough concentrations, AUC, probability of target attainment, and elimination half-life.Results45 relevant articles were identified. Studies focusing on vancomycin were most prevalent (15/45). Other studies included data on penicillins, cephalosporins, carbapenems and aminoglycosides, but data on ceftriaxone, ceftazidime, penicillin and metronidazole could not be found. Critically ill children generally show a larger Vd and higher Cl than healthy children and critically ill adults. Reduced target attainment was described in critically ill children for multiple antibiotics, including amoxicillin, piperacillin, cefotaxime, vancomycin, gentamicin, teicoplanin, amikacin and daptomycin. 32/45 articles included information on both Vd and Cl, but a dosing advice was given in only 18 articles.ConclusionThe majority of studies focus on agents where therapeutic drug monitoring is applied, while other antibiotics lack data altogether. The larger Vd and higher Cl that is observed in critically ill children might warrant a higher dose or extended infusions of antibiotics in this patient population to increase target attainment. Studies frequently fail to provide a dosing advice for this patient population, even if the necessary information is available. Our study shows gaps in current knowledge and encourages future researchers to provide dosing advice for special populations whenever possible.Disclosure(s)Nothing to disclose
P46 Spontaneous reporting of suspected adverse drug reactions by children and young people: past, present and future
Authors: King C , Bhoombla N , Clarke J , Morgan V , Preston J , Ainsworth J , Hanson A , Hawcutt D 
Published: May 2019

BackgroundUK patients of all ages can contribute to the Medicines and Healthcare Regulatory Agency (MHRA) Yellow Card scheme (YCS), reporting suspected adverse drug reactions (ADRs). Children’s and young people’s (CYPs) contribution to, and awareness of, the YCS is not known.MethodsSuspected ADR reports received by the MHRA from 01/01/2008 to 29/11/2018 were examined. Prospective data from CYP and parents in paediatric outpatients were collected as part of the QUestionnaire study about Adverse Drug ReAcTions In Children (QUADRATIC) study (IRAS 242352).ResultsCYP contributed 2.3% of YCS reports for patients < 19 years. Patients from age 10 years old have contributed YCS reports, and CYP reports are increasing annually. Reports from CYP contain different suspected medications and reactions compared to YCS for all patients age < 19 years. Common CYP generated reports prioritiseadolescent vaccinations (Human papilloma virus most reported, n=69), oral contraceptives, acne medication, anti-infectives, and antidepressants.Common CYP generated reports identified depression, anxiety and suicidal ideation, which were not amongst common reports about CYP. Amongst CYP (n=50) attending outpatients, the YCS was not known to any CYP. The YCS was known to 16.3% of parents (8/49) interviewed. From this population of patients with a chronic illness, with high rates of drug therapy, 68 suspected ADRs were identified overall.ConclusionCYP contribute to YCS, with distinct patterns of suspected medications and reactions. Awareness of the YCS appears poor, particularly in populations you would expect to have a greater level of knowledge and understanding about medicines.Disclosure(s)Nothing to disclose
P58 Development of JUNIORMED – the Austrian paediatric pharmacopoeia
Authors: Lagler F , Hofbauer P , Danninger L , Hattinger B , Aichberger M , Mursch-Edlmayr U , Sperl W 
Published: May 2019

BackgroundDespite the regulatory measures to improve the availability of medicines for new-borns, infants and children, extemporaneous preparations are often necessary to cover the needs of these patients. In Austria the prescription of magistral medicines is more common (approx. 3,4% of all prescriptions) than in the European average (1,9%)1, yet a paediatric pharmacopoeia which sets standards for the preparation and use of extemporaneous preparations was missing so far.MethodsThe project was mutually conducted by the Austrian Chamber of Pharmacists, Austrian Society for Pediatric and Adolescent Medicine and the Austrian Society of General Practice/Family Medicine and funded by the Austrian Federal Ministry of Education, Science and Research (BMWFW-97.160/0001-C1/9/2015). 9.000 community and hospital pharmacists, paediatricians, dermatologists and general practitioners have been invited to submit commonly prescribed paediatric preparations. In a five step approach all submissions were assessed for completeness, pharmaceutical and medical correctness as well as level of evidence by the involved expert board (1 paediatric pharmacologist, 1 paediatrician, 4 pharmacists) and additional 10 external consultants covering 7 organ systems. Only preparations fulfilling the quality criteria for recommendation have been included in the compendium.Results1500 preparations have been submitted by 780 pharmacists, 227 general practitioners, 165 paediatricians and 3 dermatologists. 1175 were applicable for further assessment and 177 were recommended and included in the monograph compendium after assessment of correctness and level of evidence. These fell into 7 organ systems, namely 60 medicines for skin, 34 for the gastro intestinal tract, 20 for the respiratory system, 19 for CNS, 18 for ENT, 16 for circulation and kidneys, 10 for eyes.ConclusionThis project is an example of successful inter-professional cooperation with the aim to improve the quality of magistral formulations for children. The high number of excluded preparations underlines the need for quality control and standardisation.ReferenceHofbauer P. 19. GD Jahrestagung, 18. März 2015 in Berlin.Disclosure(s)Nothing to disclose
Determinants of anxiety in elite athletes: a systematic review and meta-analysis
Authors: Rice Simon M , Gwyther Kate , Santesteban-Echarri Olga , Baron David , Gorczynski Paul , Gouttebarge Vincent , Reardon Claudia L , Hitchcock Mary E , Hainline Brian , Purcell Rosemary 
Published: May 2019

ObjectiveTo identify and quantify determinants of anxiety symptoms and disorders experienced by elite athletes.DesignSystematic review and meta-analysis.Data sourcesFive online databases (PubMed, SportDiscus, PsycINFO, Scopus and Cochrane) were searched up to November 2018 to identify eligible citations.Eligibility criteria for selecting studiesArticles were included if they were published in English, were quantitative studies and measured a symptom-level anxiety outcome in competing or retired athletes at the professional (including professional youth), Olympic or collegiate/university levels.Results and summaryWe screened 1163 articles; 61 studies were included in the systematic review and 27 of them were suitable for meta-analysis. Overall risk of bias for included studies was low. Athletes and non-athletes had no differences in anxiety profiles (d=−0.11, p=0.28). Pooled effect sizes, demonstrating moderate effects, were identified for (1) career dissatisfaction (d=0.45; higher anxiety in dissatisfied athletes), (2) gender (d=0.38; higher anxiety in female athletes), (3) age (d=−0.34; higher anxiety for younger athletes) and (4) musculoskeletal injury (d=0.31; higher anxiety for injured athletes). A small pooled effect was found for recent adverse life events (d=0.26)—higher anxiety in athletes who had experienced one or more recent adverse life events.ConclusionDeterminants of anxiety in elite populations broadly reflect those experienced by the general population. Clinicians should be aware of these general and athlete-specific determinants of anxiety among elite athletes.
Mental health in elite athletes: International Olympic Committee consensus statement (2019)
Authors: Reardon Claudia L , Hainline Brian , Aron Cindy Miller , Baron David , Baum Antonia L , Bindra Abhinav , Budgett Richard , Campriani Niccolo , Castaldelli-Maia João Mauricio , Currie Alan , Derevensky Jeffrey Lee , Glick Ira D , Gorczynski Paul , Gouttebarge Vincent , Grandner Michael A , Han Doug Hyun , McDuff David , Mountjoy Margo , Polat Aslihan , Purcell Rosemary , Putukian Margot , Rice Simon , Sills Allen , Stull Todd , Swartz Leslie , Zhu Li Jing , Engebretsen Lars 
Published: May 2019

Mental health symptoms and disorders are common among elite athletes, may have sport related manifestations within this population and impair performance. Mental health cannot be separated from physical health, as evidenced by mental health symptoms and disorders increasing the risk of physical injury and delaying subsequent recovery. There are no evidence or consensus based guidelines for diagnosis and management of mental health symptoms and disorders in elite athletes. Diagnosis must differentiate character traits particular to elite athletes from psychosocial maladaptations.Management strategies should address all contributors to mental health symptoms and consider biopsychosocial factors relevant to athletes to maximise benefit and minimise harm. Management must involve both treatment of affected individual athletes and optimising environments in which all elite athletes train and compete. To advance a more standardised, evidence based approach to mental health symptoms and disorders in elite athletes, an International Olympic Committee Consensus Work Group critically evaluated the current state of science and provided recommendations.
Individual free fatty acids have unique associations with inflammatory biomarkers, insulin resistance and insulin secretion in healthy and gestational diabetic pregnant women
Authors: Chen Xinhua , Stein T Peter , Steer Robert A , Scholl Theresa O 
Published: May 2019

ObjectiveWe investigated the relationships of maternal circulating individual free fatty acids (FFA) with insulin resistance, insulin secretion and inflammatory biomarkers during mid-pregnancy.Research design and methodsThe data were drawn from a prospective cohort of generally healthy pregnant women (n=1368, African-American 36%, Hispanic 48%, Caucasian 16%) in Camden, NJ. We quantitatively determined 11 FFAs, seven cytokine/adipokine, homeostatic model assessment of insulin resistance (HOMA-IR) and C-peptide levels from the fasting blood samples that were collected at 16 weeks of gestation. Multivariate analyses were performed along with separate analyses for each individual FFA.ResultsHigh HOMA-IR (p<0.001) and C-peptide (p<0.0001) levels were positively associated with a twofold to fourfold increased risk for developing gestational diabetes mellitus (GDM). Negative relationships were found with specific FFAs (molecular percentage, palmitoleic, oleic, linolenic, myristic acids) and HOMA-IR and C-peptide levels (p<0.01 to p<0.0001). In contrast, palmitic, stearic, arachidonic, dihomo-γ-linolenic (DGLA) and docosahexaenoic acids were positively associated with HOMA-IR and C-peptide (p<0.01 to p<0.0001). The individual FFAs also predicted cytokine/adipokine levels. For example, women who had elevated DGLA (highest quartile) were twice as (adjusted OR 2.06, 95% CI 1.42 to 2.98) likely to have higher interleukin (IL)-8 (p<0.0001) levels. Conversely, women with high palmitoleic, oleic, and linolenic acid levels had reduced odds (≥2-fold, p<0.01 to p<0.001) for having higher IL-8, IL-6 or tumor necrosis factor-alpha levels.ConclusionOur results suggest that maternal individual FFAs uniquely affect insulin resistance and secretion. The effects are either direct or indirect via modulation of the inflammatory response. Modifying the composition of FFAs may help in reducing the risk of GDM.
Vaginal herb use andChlamydia trachomatisinfection: cross-sectional study among women of various ethnic groups in Suriname
Authors: Van der Helm Jannie J , Schim van der Loeff Maarten Franciscus , de Vries Esther , van der Veer Charlotte , Grünberg Antoon W , Mans Dennis , de Vries Henry J C 
Published: May 2019

ObjectiveVaginal steam baths with herb leaves (herb use) is practised by some Surinamese women. We assessed herb use among women from the five most prevalent ethnic groups, and if herb use is associated withChlamydia trachomatisinfection.SettingParticipants were recruited at a sexually transmitted infection (STI) clinic and a family planning clinic (FP) in Paramaribo, Suriname.Participants1040 women were included subsequently, comprising the following ethnic groups: Creole (26.7%), Hindustani (24.6%), Javanese (15.7%), Maroon (13.3%) and mixed descent (19.7%).MethodsNurses collected a questionnaire and vaginal swabs for nucleic acid amplificationC. trachomatistesting.Primary outcomesDeterminants of vaginal herb use andC. trachomatisinfection via univariable and multivariable logistic regression.ResultsHerb use was most common among Maroon (68.8%) and Creole women (25.2%). In multivariable analysis including only Maroon and Creole women, determinants significantly associated with vaginal herb use were (OR; 95% CI): Maroon ethnic descent (5.33; 3.26 to 8.71 vs Creole), recruitment at the STI clinic (2.04; 1.24 to 3.36 vs FP), lower education levels (3.80; 1.68 to 8.57 lower vs higher, and 2.02; 0.90 to 4.51 middle vs higher). Lower age and recruitment at the STI clinic were associated withC. trachomatisinfection, but not vaginal herb use.ConclusionIn Suriname, vaginal herb use is common among Maroon and Creole women. Education, ethnic group and recruitment site were determinants for herb use. Vaginal herb use was not a determinant ofC. trachomatisinfection. Future research should focus on the effect of herb use on the vaginal microbiome and mucosal barrier.
Physical heaviness of work and sitting at work as predictors of mortality: a 26-year follow-up of the Helsinki Birth Cohort Study
Authors: Mikkola Tuija M , von Bonsdorff Mikaela B , Salonen Minna K , Kautiainen Hannu , Ala-Mursula Leena , Solovieva Svetlana , Viikari-Juntura Eira , Eriksson Johan G 
Published: May 2019

ObjectivesTo examine the relationships of late-career physical heaviness of work and sitting at work with mortality. A national-level job exposure matrix was used to determine the occupation-specific level of physical heaviness and sitting.DesignProspective cohort study between years 1990 and 2015.SettingCommunity.Participants5210 men and 4725 women from the Helsinki Birth Cohort Study with an occupational code at baseline (ages 45–57 years).Primary and secondary outcome measuresTotal, cardiovascular (International Classification of Diseases 10th Revision I00–I99), cancer (C00–C97) and external (S00–Y84) mortality.ResultsThe exposures, physical heaviness and sitting had a non-linear, inverse relationship. During the 26-year follow-up, 1536 men and 759 women died. Among men, physical heaviness of work was positively associated and sitting at work was negatively associated with all-cause, cardiovascular and external cause mortality but they were not associated with cancer mortality. The HRs for men in the highest quartile of physical heaviness of work compared with men in the lowest quartile were 1.54 (1.31–1.80) for all-cause mortality, 1.70 (1.30–2.23) for cardiovascular mortality and 3.18 (1.75–5.78) for external cause mortality (adjusted for age and years of education). Compared with the lowest quartile, the HRs for the highest quartile of sitting at work among men were 0.71 (0.61–0.82) for all-cause mortality, 0.59 (0.45–0.77) for cardiovascular mortality and 0.38 (0.22–0.66) for external cause mortality. In women, neither physical heaviness of work nor sitting at work was associated with mortality.ConclusionsMen in physically heavy work at their late-work career are at higher risk of death than men in physically light work.
Patient-reported outcomes after surgical and non-surgical treatment of proximal hamstring avulsions in middle-aged patients
Authors: Pihl Elsa , Skoldenberg Olof , Nasell Hans , Jonhagen Sven , Kelly Pettersson Paula , Hedbeck Carl Johan 
Published: May 2019

ObjectivesIn the literature on proximal hamstring avulsions, only two studies report the outcomes of non-surgically treated patients. Our objective was to compare subjective recovery after surgical and non-surgical treatment of proximal hamstring avulsions in a middle-aged cohort.MethodsWe included 47 patients (33 surgically and 14 non-surgically treated) with a mean (SD) age of 51 (±9) years in a retrospective cohort study. Follow-up time mean (SD) of 3.9 (±1.4) years. The outcome variables were the Lower Extremity Functional Scale (LEFS) and questions from the Proximal Hamstring Injury Questionnaire. Outcome variables were adjusted in regression models for gender, age, American Society of Anestesiologits (ASA) classification and MRI findings at diagnosis.ResultsThe baseline characteristics showed no differences except for the MRI result, in which the surgically treated group had a larger proportion of tendons retracted ≥ 2 cm. The mean LEFS score was 74 (SD±12) in the surgically treated cohort and 72 (SD±16) in the non-surgically treated cohort. This was also true after adjusting for confounders. The only difference in outcome at follow-up was the total hours performing physical activity per week, p=0.02; surgically treated patients reported 2.5 hours or more (5.2 vs 2.7).ConclusionThis study on middle-aged patients with proximal hamstring avulsions was unable to identify any difference in patient-reported outcome measures between surgically and non-surgically treated patients. The vast majority of patients treated surgically had complete proximal hamstring avulsions with ≥ 2 cm of retraction. We conclude that to obtain an evidence-based treatment algorithm for proximal hamstring avulsions studies of higher scientific level are needed.
Study of structural, electrical, optical and magnetic properties of Hexaferrite–Polyaniline nanocomposites
Authors: Ajmal Muhammad , Islam M. U. 
Published: May 2019

Y-type hexagonal ferrite (CaBaCo2Ga[Formula: see text]Fe[Formula: see text]O[Formula: see text]) was synthesized by sol–gel technique. The ferrite–polymer composites (1−x)CaBaCo2Ga[Formula: see text]Fe[Formula: see text]O[Formula: see text]+(x)polyaniline (x=0.25, 0.50, 0.75, 1) namely PF1, PF2, PF3 and polyaniline (PANI) were synthesized by in situ polymerization. The synthesized samples were characterized by XRD, SEM, electrical and dielectric measurements, optical and magnetic studies. XRD pattern reveals a broad peak of polyaniline which is an indication of amorphous nature of PANI. Room-temperature resistivity increases from 2.14 × 101 [Formula: see text]cm to 2.78 × 10[Formula: see text]cm as ferrite content increases due to resistive behavior of the ferrite particles dispersed in the PANI matrix. The value of dielectric constant decreases at fixed frequency with increasing concentration of ferrite filler which is predominantly due to exchange of electrons between Fe[Formula: see text] and Fe[Formula: see text] ions that ultimately results in enhancement of electric polarization and conductivity. The optical bandgap increases with increasing amount of ferrite in the composites. The saturation magnetization and remanence increase with the increase of ferrite filler amount in PANI matrix whereas coercivity decreases. The decrease in coercivity and increase in saturation magnetization are related to Brown’s relation. The present nanocomposite samples may be the best candidates for electromagnetic shielding.