bluuebunny/crossref_metadata_2025 huggingface dataset:
P28 Pharmacokinetics and implications for drug dosing in children with sickle cell disease: a systematic review
Authors: Dia N , Autmizguine J , Pastore Y , Litalien C , Rémy A , Amélie M , Théorêt Y , Kleiber N
Published: May 2019

Background

Children with sickle cell disease (SCD) are at high risk of intractable pain and severe infections despite early and aggressive drug treatment. SCD is a multisystemic disease potentially leading to liver and renal dysfunction. Altogether, those may lead to pharmacokinetic (PK) alterations, which may contribute to therapeutic failure or drug toxicity. We performed a systematic literature review to describe the current evidence on the effect of SCD on drug disposition in children.

Methods

A systematic literature search was conducted by a librarian on 5 databases until 08.2018 and independently assessed by two reviewers. All full-text articles, containing PK data in children, were included. The reported differences in PK parameters between SCD and non-SCD children were examined.

Results

Among 4213 retrieved abstracts, 50 full-text articles were assessed and 27 studies were included (13 exclusively children). Data on 15 drugs was available from which 5 were exclusively developed for SCD (impeding any comparison). From the remaining 10 drugs, a comparison of PK parameters was available in 8. Six were investigated in adults and children. Three (37.5%) showed significant PK alterations (morphine, cefotaxime,lidocaine) while 5 did not (hydroxyurea, sulfadoxine-pyrimethamine, methadone, rofecoxib,arginine butyrate). In children with SCD, clearance was higher by 42–61% for IV morphine, and by 24–62% for cefotaxime, compared with non-SCD controls. This difference led to a new dosing recommendation only for cefotaxime (400 mg/kg/day). Hepatic drug metabolism assessed by lidocaine was impaired in children with SCD compared to healthy controls.

Conclusion

SCD alters drug disposition of commonly used drugs but data is scarce. A significant increase in clearance of morphine and cefotaxime, two commonly used drugs in patients with SCD, suggests that recommended doses may not be sufficient to provide adequate analgesia and antimicrobial control. PK data is urgently needed to ensure adequate drug efficacy and safety in this high-risk population.

References

Dong M, McGann PT, Mizuno T, et al. Development of a pharmacokinetic-guided dose individualization strategy for hydroxyurea treatment in children with sickle cell anaemia. Brit J Clin Pharmacol. 2016;81:742–52.

Gremse DA, et al. Hepatic function as assessed by lidocaine metabolism in sickle cell disease. J Pediatr 1998;132:989–93.

Dampier CD, et al. Intravenous morphine pharmacokinetics in pediatric patients with sickle cell disease. J Pediatr 1995;126:461–7.

Kopecky EA, et al. Systemic exposure to morphine and the risk of acute chest syndrome in sickle cell disease. Clin Pharmacol Ther 2004;75:140–6.

Maksoud E, et al. Population Pharmacokinetics of Cefotaxime and Dosage Recommendations in Children with Sickle Cell Disease. Antimicrob Agents Chemother. 2018;62: e00637–1.

Disclosure(s)

Nothing to disclose
P36 What can be learnt from serious drug related medical errors in pediatric patients in Gothenburg 2015–2017?
Authors: Fjeldseth S
Published: May 2019

Background

2017 a rise in serious drug related medical errors in pediatric care at Sahlgrenska University hospital was discovered. 2018 a pediatric Clinical Decision Support System (CDSS) called ePed with weight based dose calculation, dosage control and easy access to pediatric drug information was integrated with the Electronic Medical Record.

Aim

Analyze causes and underlying factors to serious drug related medical errors, labeled Lex Maria, in children and further evaluate if these errors could be prevented within the framework of ePed.

Method

28 Lex Maria cases in children ≤16 years were registered during 2015–2017 at Sahlgrenska University hospital, Gothenburg. These were analyzed and summarized according to type of error, underlying cause and when during the drug managing process the error occurred. Finally, comparison between years was made.

Results

2015 and 2016 five Lex Maria cases occurred respectively. 2017 the number increased to 18 cases. Most commonly the patients received an incorrect dose. Errors divide equally between prescription, preparation and administration. Drugs requiring dilution were of certain risk especially when diluted in several steps. Midazolam was the most frequently involved drug. In 2017 especially one ward stands out in numbers and was responsible for 10 of the 18 cases.

Conclusions

ePed will help to avoid human calculation errors in prescription and provides easy access to pediatric drug information facilitating drug preparation and administration. Nurses are particularly exposed to medication incidents since they usually are the last link to the patient and need to be their own control. High-risk medicines need to be identified and made safe. A complex interplay between individual/human and systemic factors contribute to errors. However, to reduce serious drug related errors a CDSS is of great value but adequate education for medical staff, both pharmacologically and about the system is vital. Future follow up will be needed.

Disclosure(s)

Nothing to disclose
P40 Comparison of antibiotic consumption between pediatric hospitals
Authors: Gober H-J
Published: May 2019

Background

Antibiotic exposure and reduced microbiome diversity in early childhood are associated with the incidence of inflammatory bowel disease,1 asthma2 and type-1 diabetes3 later in life. Together with the emergence of microbial resistance, those adverse effects of antibiotics impacting on the individual and population levels.

Periodic monitoring of therapeutically used antibiotics in the framework of antimicrobial stewardship is required for their effective and restricted use in hospitals.

Children´s hospitals face two challenges for a meaningful quantification of antibiotic consumption:

§ Firstly, the algorithm DDD/inpatient days used in adult patients do not take into account the heterogeneity of the pediatric population. Up to date there is no global consensus on how to calculate and interpret the antibiotic consumption of wards and hospitals for children.

§ Second challenge is the relative scarcity of suitable pediatric hospitals as basis for comparison.

This study deals with the comparison and interpretation of antibiotic consumption between two similarly structured children´s hospitals in Austria.

Methodology

The annual use of antibiotics was assessed in two large pediatric clinical settings at geographically distinct locations in Austria, encompassing all relevant wards, such as neonatology, internal medicine, surgery, pediatric oncology and PICU´s. The analysis discriminates among the wards and classes of antibiotics.

In addition to DDD and inpatient days, alternative parameters such as number of patient-admittances and number of used vials were included in the calculation.

Result

Pediatric-specific pitfalls affecting the quantification and comparability were identified:

Hospital guidelines concerning the multiple usage of dissolved and diluted antibiotics.

Regional composition of the pediatric patient population in terms of pathology.

Intramural allocations of wards sharing the drug deposit.

Conclusion

Unexpected factors have severe impact on the reliability of annual antibiotic quantification and interpretation. Those factors need to be taken into account when comparing pediatric hospitals.

References

Am J Gastroenterol 2010 Dec;105(12):2687–92.

Nat Commun 2018 Jan;9(1):141.

Cell 2016 May;165(4):842–53.

Disclosure(s)

Nothing to disclose
P41 Prenatal exposure to antibiotics and development of epilepsy in children
Authors: Gorodischer R , Sassonker- Joseph N , Atar-Vardi M , Noyman I , Novak L
Published: May 2019

Background

Studies reported that prenatal exposure to antibiotics in general represents a risk factor for development of epilepsy and/or cerebral palsy in children. A pathophysiological relationship seemed improbable and required adjustment to possible confounders.

Methods

In a retrospective cohort investigation, we enrolled children aged 3 to 18 years born between 1998 and 2012 at the single regional hospital, and their mothers, members of ‘Clalit’ (the largest Health Service Organization in the region). Computerized medications database was linked with hospital records of mothers and their children. The exposed group included all children whose mothers purchased one or more antibiotic medications during their pregnancy. Epilepsy was defined by Epilepsy diagnosis and/or by chronic dispensing of antiepileptic drugs. After applying inclusion and exclusion criteria for mothers and children, 88,899 children and their 74,416 mothers were selected for the study.

Results

The group exposed prenatally to antibiotics comprised 36,622 (or 41.2%) children. Of them, 326 (0.9%) developed epilepsy compared to 370 (0.7%) in the unexposed group (p=0.002); Number Needed to Harm 500. Exposure during the first, second and third trimester was characterized by incidence of epilepsy in 0.8% (p= 0.928), 0.9% (p= 0.270) and 0.9% (p=0.094) of exposed children, respectively, compared to unexposed group Based on Poisson regression analysis, epilepsy was associated with male sex, maternal smoking and delivery by cesarean section. The possibility of confounding by indication was refuted by sensitivity analysis.

Conclusion

We found an association of intrauterine exposure to antibiotics (particularly in late pregnancy) and development of epilepsy in children. Possible pathophysiological mechanisms are discussed. The effect of some undetermined confounder(s) cannot be ruled out.

Disclosure(s)

Nothing to disclose
O08 Pharmacokinetics of prophylactic and therapeutic fluconazole in preterm neonates
Authors: Engbers A , Flint RB , Völler S , Reiss IKM , Liem KD , Degraeuwe PLJ , Andriessen P , Alffenaar JWC , Koch BCP , Simons SHP , Knibbe CAJ , Brüggemann R
Published: May 2019

Introduction

Fluconazole is a first choice drug for neonatal cerebral candidiasis and for prevention of candidemia/invasive candidiasis in neonates. Selection of the optimal neonatal dose is difficult and requires solid multiple dose pharmacokinetic (PK) research to guide dosing decisions. We performed a pharmacokinetic study in preterm neonates who received fluconazole prophylactically or as treatment.

Methods

Preterm neonates received fluconazole according to local protocol for either prophylaxis or treatment in 5 different hospitals. Samples were collected on multiple occasions with an opportunistic sampling scheme. Patient characteristics were bodyweight, birthweight, postnatal age (PNA), gestational age (GA), postmenstrual age, gender and weight for age. Population PK modelling was performed using NONMEM V.7.3.

Results

In 44 preterm neonates (median (range) GA 25.3 (24.0–31.3) weeks), 153 plasma samples were collected. Median PNA at treatment initiation was 1 (0–59) day, treatment duration 11 (2–67) days and median PNA during treatment 15 (4–60) days. A one-compartment model described the data best, with an estimated clearance (CL) for a neonate of 0.84 kg and PNA of 15 days of 0.0147 L/h (RSE 4.3%, interindividual variability 21.4%) and volume of distribution (Vd) of 0.815 L (RSE 5.9%). Bodyweight was found to influence both CL and V­d, with exponents of 1.05 (RSE 13.4%) and 1.19 (RSE 22.4%), respectively. Maturation of CL was best described by an exponent of 0.184 on PNA (RSE 34.3%).

Conclusion

In this pharmacokinetic study on fluconazole in preterm neonates, CL was influenced by both bodyweight and PNA while Vd was influenced by bodyweight only. These findings imply that initial dosing of fluconazole in preterm neonates should be based on bodyweight and that an increase of the dose with 32% during the first week and with 47% during the first month of life could be necessary because of increasing clearance with PNA.

Disclosure(s)

Nothing to disclose
P44 Type 2 diabetes mellitus in children: non-insulin medication, where are we up to?
Authors: Austin R , Paul P , Hawcutt D
Published: May 2019

Background

Childhood type 2 diabetes mellitus (T2DM) is a relatively rare condition but is an important health concern as its prevalence continues to rise. Current management consists of lifestyle modification, metformin and insulin. Several new pharmacological classes are currently used in adult medicine but are not yet available in paediatric care.

In this review we will look at the current evidence for use of these newer medications in the paediatric population.

Methods

A literature search (EMBASE, Medline, Pubmed, CINHAL) was performed for papers studying the use of non-insulin medications in children; including a separate search of ´clinicaltrials.gov´ to identify any ongoing trials in paediatric T2DM.

Results

Newer classes of medications include incretin mimetics, dipeptidyl peptidase-4-inhibitors, sodium/glucose-cotransporter-2-inhibitors, and thiazolidinediones. There have been a small number of pharmacokinetic/pharmacodynamic studies carried out in small cohorts of paediatric participants, but larger long-term efficacy and safety trials are lacking. These studies and individual case-reports have shown good tolerability but are unable to identify any long-term effects associated with these medications.

Randomised controlled trials studying rosiglitazone and glimepiride use in children have been performed. However, safety concerns in adults and notable side-effects including weight gain, mean their future use is uncertain.

Currently many relevant trials involving paediatric patients listed on ´clinicaltrials.gov´ are awaiting completion.

Conclusion

Medical management for T2DM in children remains limited. Ongoing studies are aiming to equip practitioners with wider treatment options in the future. However, there are concerns regarding the long-term safety of these medications due to the increased risk of pancreatitis, gallbladder conditions and bladder malignancy in adult patients.

Paediatric T2DM patients suffer from complications earlier and more severely compared with adults, making this is a pressing issue. Long-term surveillance studies to identify adverse effects and a framework for highlighting research gaps are required to enable improvements in paediatric T2DM management.

Disclosure(s)

Nothing to disclose
P45 The acceptability of using genetic information to guide treatment of asthma to children, young people, and parents (pilot study)
Authors: King C , Bracken L , McDonough E , Pirmohamed M , Peak M , Hawcutt D
Published: May 2019

Background

There are multiple pharmacogenomic studies in children’s asthma. It has not been established how (or if) children, young people or their parents/legal guardians would accept use of their genetic information to guide their treatment.

Aim

To determine the views of CYP, and parents/legal guardians, on aspects of using genetic testing to guide management of childhood asthma.

Methods

Focus group session with both the Liverpool’s young people advisory group (YPAG), and Parents’ group, at Alder Hey Children’s Hospital. Group members completed anonymous questionnaires determining the importance and privacy associated with different themes of data, with a special focus on health data.

Results

There were 11 responders, five parents/guardians and six CYP. Both the parents and the CYP considered personal data, such as date of birth, NI number and name, both the most important and the most private. Health data was considered the second most important, and private, although parents rated data from social media data an equal second in terms of privacy. Within healthcare data, CYP considered data regarding their mental health, followed by medical conditions and genomic data, as the sources to be of highest importance. Parents considered their child’s illnesses most important, followed by genomic data. In relation to privacy, CYP considered genomic data first followed by information concerning their mental health. The parents considered genomic data highest for data privacy.

Conclusion

From this session it is clear that health data in general, and genetic data in particular, has a high value of importance to CYP and parents, but there are variations in how data is prioritised. These pilot data will inform a large scale patient and parent acceptability study in personalised medicine and childhood asthma (CHANGE study).

Disclosure(s)

Nothing to disclose
P47 Prevalence, incidence and patterns of antiasthma medication use in children: a nationwide prescription study in France
Authors: Naim I , Tubach F , Guillo S , Ajrouche A , De Rycke Y , Kaguelidou F
Published: May 2019

Background

Use of antiasthmatic medications has increased over the years worldwide. The aim of this study was to describe the use of antiasthmatic drugs in children in France.

Methods

Data were retrieved from the permanent sample (1/97th) of the French national healthcare database - the Système National des Données de Santé (SNDS) for all individuals aged from 5 to 18 years old (n=143,909) from 1 January 2011 to 31 December 2017. Prevalence and incidence rate of antiasthmatic dispensing were calculated. All analyses were stratified by calendar year, age (5–11, 12–18 years) and gender. Users were classified as occasional if they had only one dispensing of antiasthmatic drugs over the year, moderate and high if they had antiasthmatic drug dispensing at two distinct occasions or at three or more occasions, respectively.

Results

The annual prevalence of antiasthmatic drug use varied between 12 (2011) and 11 (2017) per 100 persons and incidence varied between 4.3 (2013) and 3.8 (2017) per 100 PYs. Prevalence and incidence of use were higher in children aged between 5–11 years compared to adolescents and in boys compared to girls. Most users were occasional (52%) and only one third redeemed prescriptions on a regular basis (high users: 30%). No trend was observed regarding these percentages over time or with gender and age group.

Conclusions

Use of antiasthmatic drugs in France is higher than previously described in other European countries. Prevalence of use is also higher than the prevalence of asthma as assessed in epidemiological national studies suggesting that these drugs are over-prescribed.

Disclosure(s)

Nothing to disclose
O09 Drug delivery kinetics of intravenous gentamicin in a population of neonates
Authors: Salis G , Medlicott N , Reith D
Published: May 2019

Background

Gentamicin is commonly used in the NICU setting and is often administered via long lines, which increases variability in the rate of administration. We aimed to model drug delivery pharmacokinetic parameters for intravenous gentamicin administered via umbilical venous catheters (UVCs).

Methods

Data was modelled from infusion simulations of gentamicin delivery using UVCs with a background flow rate of 0.5 ml/h.1 Different combinations of dose (2 mg, 5 mg) were given by bolus injection over 3–5 minutes, followed by a normal saline flush (1 ml, 2 ml). Gentamicin levels were measured at 5 minute intervals over an hour via high pressure liquid chromatography.

Phoenix Certara (version 8.1) was used for modelling. An extravascular model with clearance removed was used to predict parameters: absorption constant (Ka), time lag (Tlag), and bioavailability (F). F was used to enable an estimate of the variability in dose administered. Different error models were tested to ascertain which best described the data.

Results

An extravascular one compartment model with first order absorption and additive error best described the data. Estimates for the model with a 2 mg dose and 1 ml flush were Ka 0.34L/min, Tlag 1.28min, F 0.97, standard deviation (stdev) 0.14. For 2 mg, 2 ml flush, estimates were Ka 0.86L/min, Tlag 3.01min, F 0.87, stdev 0.01. For 5 mg, 1 ml flush, estimates were Ka 0.48L/min, Tlag 3.13min, F 1.03, stdev 0.12. For 5 mg, 2 ml flush, estimates were Ka 0.83L/min, Tlag 3.29min, F 1.09, stdev 0.02. For each model epsshrinkage and nshrinkage for Tlag and F were low, however nshrinkage for ka was 0.9999.

Conclusion

This is the first known modelling of gentamicin delivery kinetics. The studies all had high nshrinkage for Ka, therefore the individual estimates of ka may be unreliable. Further studies with a higher number of replicates would provide more favourable data for estimating Ka.

Reference

Lala AC ( 2016). Variability in neonatal gentamicin administration influencing drug delivery kinetics (Thesis, Master of Medical Science). University of Otago.

Disclosure(s)

No conflict of interest declared. Funding for research via the Freemasons Society of New Zealand.
P55 Preventing inappropriate hydroxyurea dosing in children by introducing a child-appropriate preparation
Authors: Koren G
Published: May 2019

Background

Hydroxyurea (HU) is the only FDA- approved disease- modifying drug for sickle cell disease, by inducing the production of fetal hemoglobin and thus decreasing the sickling of red blood cells. Till recently HU was available only in adult doses of 1000 mg. This meant that to aim at the standard dose of 20 mg/kg/d, most young children had to be overdosed, or the dose had to be fluctuated daily to achieve the aimed mean dose. Because adherence improves with unchanged daily dose, and due to the more than 10 fold variability in HU pharmacokinetics in children, there was an urgent need for a pediatric formulation of HU.

Methods and results

This issue has been solved with the FDA approval of the French-originated orphan HU, Siklos, a preparation of 50 and 100 mg, which prevents the risk of inappropriate dosing in children.

Studies show that the child appropriate dose preparation much more closely allow young children to receive appropriate dose of Hydroxyurea, and increase adherence with this critical drug.

Conclusions

In summary, FDA approval of the French-originated orphan HU, Siklos in preparations of 50, 100 mg, prevents the risk of inappropriate dosing of the drug in children. This should encourage all involved in pediatric medicine, from health care physicians and pharmacists, to the pharmaceutical industry and regulators to act similarly in other therapeutic areas where inappropriate pediatric dose schedules are endangering the health and wellbeing of children.

Disclosure(s)

G Koren has been a consultant for Medunik USA.
P56 Breakthrough in the treatment of nausea and vomiting of pregnancy; the first dual release combination of doxylamine-pyridoxine
Authors: Koren G
Published: May 2019

Background

Nausea and vomiting of pregnancy (NVP) affect almost pregnancies. The only agent approved by the FDA and other countries for the management of NVP symptoms has been the delayed release combination of doxylamine and pyridoxine. This combination, formulated as a 10 mg/10 mg delayed release tablet, was approved by the FDA for the treatment of NVP in 2013 (Diclegis®).

Due to its delayed release properties, Diclegis® begins to exert its antiemetic properties 6–8 hours after ingestion, and hence symptom relief may be delayed and necessitate the use of an immediate release medication.

Methods

In 2016 the FDA approved Bonjesta®, a novel, dual- release combination of doxylamine and pyridoxine, whereby a rapid release phase is followed by a delayed release phase, thus overcoming the time delay in action of Diclegis®. Bonjesta®, is a multilayer, extended-release tablet consisting of an enteric-coated core containing 10 mg doxylamine succinate and 10 mg pyridoxine hydrochloride, and an immediate-release coating of 10 mg doxylamine succinate and 10 mg pyridoxine hydrochloride, delivering a total of 20 mg doxylamine succinate and 20 mg pyridoxine hydrochloride

Results

In a single-and multiple dose study in 48 healthy, premenopausal women, one Bonjesta® (20 mg doxylamine succinate and 20 mg pyridoxine) was bioequivalent to two combination tablets of 10 mg doxylamine succinate and 10 mg pyridoxine hydrochloride

Bonjesta has shown an immediate peak concentrations, followed by a delayed release phase.

Conclusions

The combination of the immediate release with a delayed action is unique to Bonjesta® as it allows for the bedtime dose to be effective immediately and also provide with sustained control of NVP symptoms throughout the day.

Disclosure(s)

G Koren has been a consuntant for Duchesnay Inc.
Bipolar and psychotic disorders in elite athletes: a narrative review
Authors: Currie Alan , Gorczynski Paul , Rice Simon M , Purcell Rosemary , McAllister-Williams R Hamish , Hitchcock Mary E , Hainline Brian , Reardon Claudia L
Published: May 2019

Bipolar and psychotic disorders are relatively common and likely to have a significant impact on quality of life and functioning which, in the context of elite sport, includes a potential negative impact on sporting performance. For this narrative review article, the literature on bipolar and psychotic disorders in elite athletes was comprehensively searched, and little empirical research was found. A diagnosis of bipolar or psychotic disorders may be challenging in elite athletes because of complicating factors related to the modifying role of exercise and potential precipitating impact of substance use. Medications used to treat bipolar and psychotic disorders may have side effects particularly problematic for elite athletes. Future research should be tailored to the specific characteristics and needs of elite athletes and to the sporting context in which the disorders may arise. Specifically, further research is needed on the prevalence and incidence of these conditions in elite athletes and the impact of both the disorders and their treatments on sporting performance.
Do informed consumers in Taiwan favour larger hospitals? A 10-year population-based study on differences in the selection of healthcare providers among medical professionals, their relatives and the general population
Authors: Kuo Raymond N , Chen Wanchi , Lin Yuting
Published: May 2019

Objectives

Exploring whether medical professionals, who are considered to be ‘informed consumers’ in the healthcare system, favour large providers for elective treatments. In this study, we compare the inclination of medical professionals and their relatives undergoing treatment for childbirth and cataract surgery at medical centres, against those of the general population.

Design

Retrospective study using a population-based matched cohort data.

Participants

Patients who underwent childbirth or cataract surgery between 1 January 2004 and 31 December 2013.

Primary and secondary outcomes measures

We used multiple logistic regression to compare the ORs of medical professionals and their relatives undergoing treatment at medical centres, against those of the general population. We also compared the rate of 14-day re-admission (childbirth) and 14-day reoperation (cataract surgery) after discharge between these groups.

Results

Multivariate analysis showed that physicians were more likely than patients with no familial connection to the medical profession to undergo childbirth at medical centres (OR 5.26, 95% CI 3.96 to 6.97, p<0.001), followed by physicians’ relatives (OR 2.68, 95% CI 2.20 to 3.25, p<0.001). Similarly, physicians (OR 1.63, 95% CI 1.21 to 2.19, p<0.01) and their relatives (OR 1.43, 95% CI 1.13 to 1.81, p<0.01) were also more likely to undergo cataract surgery at medical centres. Physicians also tended to select healthcare providers who were at the same level or above the institution at which they worked. We observed no significant difference in 14-day re-admission rates after childbirth and no significant difference in 14-day reoperation rates after cataract surgery across patient groups.

Conclusions

Medical professionals and their relatives are more likely than the general population to opt for service at medical centres. Understanding the reasons that medical professionals and general populations both have a preferential bias for larger medical institutions could help improve the efficiency of healthcare delivery.
Perioperative and early rehabilitation outcomes following osseointegration in UK military amputees
Authors: Wood Paul , Small C , Mahoney P
Published: May 2019

Introduction

This paper examines the pain management, from surgery to specialist rehabilitation, of the first seven military transfemoral amputee patients treated in the UK with femoral osseointegration. All the patients had sustained complex ballistic injuries on the battlefield. The patients were characterised by long-standing problems with functional rehabilitation due to limitations with conventional prostheses, including stump soft tissue issues and impaired biomechanics.

Methods

A prospective service investigation was undertaken to evaluate the effectiveness of the pain management of patients undergoing osseointegration. Data were collected by daily direct patient contact, supplemented by a focused review of perioperative and rehabilitation case notes. Physiological and medication details were recorded with specific reference to systemic and regional analgesia and the impact of postoperative complications, including infection and accidental injury.

Results

Seven patients underwent femoral osseointegration and were followed up for a period of up to 3 years following surgery. The perioperative recovery was associated with significant escalation of analgesic requirements. Postoperative systemic inflammatory response syndrome was identified in six patients, with wound infection persisting in some cases into the rehabilitation phase. Three patients suffered femoral fractures following accidental injuries secondary to increased mobilisation following surgery.

Conclusions

Successful surgical outcomes were achieved in a difficult patient cohort disadvantaged by previously restricted functional recovery from complex injuries. The importance of supporting the operative and recovery phases with a multidisciplinary pain service is emphasised. We offer this data and the lessons learnt to assist clinicians contemplating the establishment and service development of osseointegration services.
Recreational drugs and STI diagnoses among patients attending an STI/HIV reference clinic in Rome, Italy
Authors: Latini Alessandra , Dona' Maria Gabriella , Alei Lavinia , Colafigli Manuela , Frasca Mirko , Orsini Diego , Giuliani Massimo , Morrone Aldo , Cristaudo Antonio , Zaccarelli Mauro
Published: May 2019

Background

An observational study was conducted to assess recreational drug use in association with recent STIs among clients of an STI/HIV reference centre in Rome, Italy.

Methods

Attendees self-compiled a questionnaire concerning sexual behaviours and drug use, including the nine drugs used for sex (amphetamines, poppers, cocaine, ketamine, erectile dysfunction agent (EDA), steroids and the three chemsex drugs, ie, chems: γ-hydroxybutyric acid/γ-butyrolactone, crystal and Mcat).

Results

Overall, 703 patients participated, with men who have sex with men (MSM) accounting for 50.4% of the total and 73.2% of HIV-positive patients. Apart from condylomatosis, whose prevalence was higher among females (38.8%) and non-MSM (45.8%) than MSM (14.4%), STIs were more frequent among MSM, particularly syphilis (14.1%), gonorrhoea (4.8%), urethritis (3.4%) and hepatitis A (6.5%). Recreational drug use was significantly more frequent among MSM (39.8% vs 17.6% in females and 22.7% in non-MSM). A total of 26.3% of MSM used at least one of the nine drugs and 5.1% at least one of the three chems. Cocaine (13.3%) and poppers (13.0%) were the most used sex drugs in MSM.

The use of any of the nine drugs was associated with being MSM (adjusted OR (AOR): 1.94, 95% CI 1.05 to 3.58), sex with partner contacted online (1.99, 95% CI 1.14 to 3.45), group sex (4.08, 95% CI 2.40 to 6.93) and STI in the last year (1.65, 95% CI 1.05 to 2.61). Use of any of the nine chems among MSM was associated with condomless sex (2.24, 95% CI 1.21 to 4.14), group sex (2.08, 95% CI 1.01 to 4.31) and STI diagnosis in the last year (4.08, 95% CI 2.32 to 7.19).

Conclusions

Our data suggest that recreational drug use is quite common among MSM in Italy. No evidence of association with STI was found among non-MSM and females, where only cannabis and cocaine use was reported. The use of chems is still limited, but cocaine, poppers and EDA are widely used among MSM. Recreational drug use appears associated with high-risk sexual behaviours and a higher risk of STI.
Circulating messenger for neuroprotection induced by molecular hydrogen
Authors: Noda Mami , Uemura Yuya , Yoshii Yusuke , Horita Taichi , Takemi Shota , Sakata Ichiro , Sakai Takafumi
Published: May 2019

Molecular hydrogen (H2) showed protection against various kinds of oxidative-stress-related diseases. First, it was reported that the mechanism of therapeutic effects of H2was antioxidative effect due to inhibition of the most cytotoxic reactive oxygen species, hydroxy radical (•OH). However, after chronic administration of H2in drinking water, oxidative-stress-induced nerve injury is significantly attenuated even in the absence of H2. It suggests indirect signaling of H2and gastrointestinal tract is involved. Indirect effects of H2could be tested by giving H2water only before nerve injury, as preconditioning. For example, preconditioning of H2for certain a period (∼7 days) in Parkinson’s disease model mice shows significant neuroprotection. As the mechanism of indirect effect, H2in drinking water induces ghrelin production and release from the stomach via β1-adrenergic receptor stimulation. Released ghrelin circulates in the body, being transported across the blood–brain barrier, activates its receptor, growth-hormone secretagogue receptor. H2-induced upregulation of ghrelin mRNA is also shown in ghrelin-producing cell line, SG-1. These observations help with understanding the chronic effects of H2and raise intriguing preventive and therapeutic options using H2.
Quantifying the noise in bursty gene expression under regulation by small RNAs
Authors: Qiu Shigang , Jia Tao
Published: May 2019

Gene expression is a fundamental process in a living system. The small RNAs (sRNAs) is widely observed as a global regulator in gene expression. The inherent nonlinearity in this regulatory process together with the bursty production of messenger RNA (mRNA), sRNA and protein make the exact solution for this stochastic process intractable. This is particularly the case when quantifying the protein noise level, which has great impact on multiple cellular processes. Here, we propose an approximate yet reasonably accurate solution for the gene expression noise with infrequent burst and strong regulation by sRNAs. This analytical solution allows us to better analyze the noise and stochastic deviation of protein level. We find that the regulation amplifies the noise, reduces the protein level. The stochasticity in the regulation generates more proteins than what if the stochasticity is removed from the system. The sRNA level is most important to the relationship between the noise and stochastic deviation. The results provide analytical tools for more general studies of gene expression and strengthen our quantitative understandings of post-transcriptional regulation in controlling gene expression processes.
The economic restructuring under new industry: A model for leapfrogging development and the shift of leadership
Authors: Cui Jun-Ying , Han Xiao-Pu , Lü Linyuan
Published: May 2019

In this paper, a lattice-based minimum modeling framework is proposed to explain the leapfrogging development of lagging economy and the shift of economic leadership. In this modeling framework, the economic restructuring driven by new industries, which is occurring in some rapidly-growing countries, is considered to be the major factor, as well as the industrial transfer across countries. Using numerical simulations, we run the modeling framework under the simplest case with only two countries, and find that the economic restructuring can efficiently promote the overtaking of the relative lagging country. We further observe that country’s independence in economic interactions is the other key: the lack of it will seriously hamper the economy development of the lagging country and thus delay its overtaking process. This modeling framework provides a novel perspective to understand the rapid economic growth in some countries.
The cross-networks impact analysis and assessment in multilayer interdependent networks: A case study of critical infrastructures
Authors: Zhou Fang , Du Yanchao , Yuan Yongbo , Zhang Mingyuan
Published: May 2019

Critical infrastructures are tightly connected and extremely fragile multilayer coupled networks. This paper discusses the cross-networks impact of subnetworks and global network of networks on robustness by taking a critical infrastructures with three-layer interdependent networks as an example. The percolation theory is applied to capture the flow characteristics of cascading failures and evaluate the robustness of multilayer networks. And further discuss and compare the situation of each subnetwork affecting or being affected. The quantitative evaluation model of the interaction of multilayer networks is proposed based on cascading failures, where the influence expansion matrix and the dependency matrix are obtained. The results show that the power network has a high influence on other networks, and it is difficult to be affected. Meanwhile the influence ability of water network and gas network is limited.
An extended clustering method using H-index and minimum distance for searching multiple key spreaders
Authors: Yang Pingle , Liu Xin , Xu Guiqiong
Published: May 2019

Identifying multiple key spreaders in a network can effectively control the diffusion of information and optimize the use of available resources, which can be also called the influence maximization problem in sociology domains. In order to maximize collective influence in complex networks, multiple spreaders must have both large single influence and small overlapping influence, but it is rather difficult to satisfy these two conditions simultaneously. In this paper, we try to achieve the best compromise between importance and dispersibility for multiple spreaders through clustering. The cluster centers are surrounded by nodes with lower influence, and the distance among different cluster centers is relatively far. In addition, the initial centers selection directly affects the efficiency of clustering and the realization of global optimization. Consequently, we present an initial centers selection algorithm combining H-index and minimum distance. The experimental results on four actual datasets show that the proposed method has better performance than the traditional benchmark methods in terms of transmission speed, diffusion scale and structural characteristics.
Multi-priority routing algorithm based on source node importance in complex networks
Authors: Bai Yu , Han Ding-Ding , Tang Ming
Published: May 2019

Network transmission capacity is an important guarantee for the normal operation of the network. The effective routing strategy avoids the use of nodes with large degree value, which leads to low utilization of nodes and failure to consider the priorities of different packets. On this basis, a routing algorithm based on packet source node classification is proposed. This strategy introduces an adjustable parameter. By adjusting this parameter, the data packets generated at the important nodes are transferred to the nodes with higher degree, which is to say they can reach the destination faster. The data packets generated at the sub-important nodes are transmitted by nodes with smaller degrees, thus reaching the destination relatively slowly. The routing strategy is evaluated in terms of order parameters, average routing time and node utilization. Compared with nonclassified routing and randomly classified routing strategy, the network transmission capacity was increased by 19% and 38%, respectively. Each node in the network was used more evenly. At the same time, the network transmission capacity under different parameters is analyzed theoretically through a series of derivations. In order to explore the performance of routing strategy in actual networks, this paper selects the actual network of web-EPA for simulation. The experimental results show that the proposed routing strategy is 7% and 17% higher than the nonclassified routing and random classified routing, respectively.
Projective synchronization via adaptive pinning control for fractional-order complex network with time-varying coupling strength
Authors: Zhu Darui , Wang Rui , Liu Chongxin , Duan Jiandong
Published: May 2019

This paper presents an adaptive projective pinning control method for fractional-order complex network. First, based on theories of complex network and fractional calculus, some preliminaries of mathematics are given. Then, an analysis is conducted on the adaptive projective pinning control theory for fractional-order complex network. Based on the projective synchronization control method and the combined adaptive pinning feedback control method, suitable projection synchronization scale factor, adaptive feedback controller and the node selection algorithm are designed to illustrate the synchronization for fractional-order hyperchaotic complex network. Simulation results show that all nodes are stabilized to equilibrium point. Theoretical analysis and simulation results demonstrate that the designed adaptive projective pinning controllers are efficient.
Predicting human contacts through alternating direction method of multipliers
Authors: Huang Chunlin , Bu Dongbo
Published: May 2019

Transmission of respiratory infectious diseases depends greatly on human close-proximity contacts, making thorough understanding of current and upcoming contacts essential for epidemic containment. Although different devices and software have been developed for contact data collection, there are few effective methods for contact prediction available in the near future as far as the authors know. In this study, we propose an approach to predict human contacts. We first extract human features together with their significances from the human contacts through alternating direction method of multipliers (ADMM), then predict future significances based on periodicity of contacts, and finally construct future contacts from human features and future significances. With the help of contact data collected in a Chinese University, we compare this approach with a trivial method of directly averaging known contacts. The comparison shows that our approach generates contacts deviating less from the true ones.
A novel node gravitation-based label propagation algorithm for community detection
Authors: Shen Mengjia , Ma Zhixin
Published: May 2019

Community detection in networks is a very important area of research for revealing the structure and function of networks. Label propagation algorithm (LPA) has been widely used to detect communities in networks because it has the advantages of linear time complexity and is unnecessary to get prior information, such as objective function and the number of communities. However, LPA has the shortcomings of uncertainty and randomness in the label propagation process, which affects the accuracy and stability of the algorithm. In this paper, we propose a novel community detection algorithm, named NGLPA, in which labels are propagated by node gravitation defined by node importance and similarity between nodes. To select the label according to the gravitation between nodes can reduce the randomness of LPA and is consistent with reality. The proposed method is tested on several synthetic and real-world networks with comparative algorithms. The results show that NGLPA can significantly improve the quality of community detection and obtain accurate community structure.
Performance Analysis of Joining the Shortest Queue Model Among a Large Number of Queues
Authors: Dawson Donald A. , Tang Jiashan , Zhao Yiqiang Q.
Published: May 2019

Consider a queueing network with a large number [Formula: see text] nodes, in which each queue has a dedicated input stream, and, in addition, there is an extra input stream, balancing the network load by directing its arrivals to the shortest queue(s). A mean field interaction model is set up to study the performance of this network in terms of limiting results. One of our results shows that the stationary behavior of any of the queues is approximated by that of the [Formula: see text] queue with a modified arrival rate when the queue length is around zero.
Boundedness and absoluteness of some dynamical invariants in model theory
Authors: Krupiński Krzysztof , Newelski Ludomir , Simon Pierre
Published: May 2019

Let [Formula: see text] be a monster model of an arbitrary theory [Formula: see text], let [Formula: see text] be any (possibly infinite) tuple of bounded length of elements of [Formula: see text], and let [Formula: see text] be an enumeration of all elements of [Formula: see text] (so a tuple of unbounded length). By [Formula: see text] we denote the compact space of all complete types over [Formula: see text] extending [Formula: see text], and [Formula: see text] is defined analogously. Then [Formula: see text] and [Formula: see text] are naturally [Formula: see text]-flows (even [Formula: see text]-ambits). We show that the Ellis groups of both these flows are of bounded size (i.e. smaller than the degree of saturation of [Formula: see text]), providing an explicit bound on this size. Next, we prove that these Ellis groups do not depend (as groups equipped with the so-called [Formula: see text]-topology) on the choice of the monster model [Formula: see text]; thus, we say that these Ellis groups are absolute. We also study minimal left ideals (equivalently subflows) of the Ellis semigroups of the flows [Formula: see text] and [Formula: see text]. We give an example of a NIP theory in which the minimal left ideals are of unbounded size. Then we show that in each of these two cases, boundedness of a minimal left ideal (equivalently, of all the minimal left ideals) is an absolute property (i.e. it does not depend on the choice of [Formula: see text]) and that whenever such an ideal is bounded, then in some sense its isomorphism type is also absolute. Under the assumption that [Formula: see text] has NIP, we give characterizations (in various terms) of when a minimal left ideal of the Ellis semigroup of [Formula: see text] is bounded. Then we adapt the proof of Theorem 5.7 in Definably amenable NIP groups, J. Amer. Math. Soc. 31 (2018) 609–641 to show that whenever such an ideal is bounded, a certain natural epimorphism (described in [K. Krupiński, A. Pillay and T. Rzepecki, Topological dynamics and the complexity of strong types, Israel J. Math. 228 (2018) 863–932]) from the Ellis group of the flow [Formula: see text] to the Kim–Pillay Galois group [Formula: see text] is an isomorphism (in particular, [Formula: see text] is G-compact). We also obtain some variants of these results, formulate some questions, and explain differences (providing a few counterexamples) which occur when the flow [Formula: see text] is replaced by [Formula: see text].
Fabrication of oriented carbon nanotube–alginate microfibers using a microfluidic device
Authors: Zhao Junyi , Zhu Junwen , Yu Ning , Xiong Wei , Yang Xing
Published: May 2019

With the progress of microelectronic devices, more attention has been paid to carbon nanotube (CNTs) because of their excellent mechanical and electrical properties. A microfluidic-based method for fabricating oriented CNT strain-sensitive fibers is proposed in this work. By manipulating CNTs, NaAlg and CaCl2 solutions in a three-coaxial laminar flow glass capillary device, CNTs can be arranged in an oriented manner and solidified into microfibers with a hydrogel shell through a chemical polymerization reaction. The diameter of the fiber could be controlled by the microfluidic device. Scanning electron microscopy and Raman spectroscopy show that the CNTs are perfectly aligned along the fiber axis under the influence of the viscous drag force of the fluid, and the electrical and mechanical properties of the CNT fibers are obviously strengthened. Experiments suggest that the devices based on the oriented CNT–alginate microfibers are able to achieve simple motion monitoring function. The proposed microfluidic method is simple, cost effective and can be applied to produce functional nanomaterial fibers for application in flexible devices.