bluuebunny/crossref_metadata_2025 huggingface dataset:
There’s More to Science than Research: A Team-Based Role Game to Develop School Students’ Understanding of Science Careers in Pharmaceutical Quality Control
Authors: Collins Rachael , Krachler Anne Marie
Published: December 2015

School students lack information about STEM based careers, a subject that is not sufficiently embedded in the national science curriculum. As a result, students feel they receive insufficient advice to support their choice of subjects at GCSE level and beyond. Students struggle to envisage potential career pathways leading on from studying science at school, and especially for younger students it is difficult to convey typical science-based career pictures in a way that is easily accessible to them. To address this need, we developed an interactive team-based activity which uses role play to help students envisage typical work processes within a science-based career—microbial quality control in a pharmaceutical industrial environment. This activity addresses children’s curiosity about science-based careers, by enabling them to experience typical every day work processes in an industrial environment in a hands-on fashion. Additionally, the activity helps to convey abstract concepts, such as the abundance of microbes in the natural environment, microbial contamination and the importance of hygiene, which link to the science curriculum.
The Climate Experiences of Students in Introductory Biology
Authors: Barthelemy Ramón S. , Hedberg Gina , Greenberg Anne , McKay Timothy
Published: December 2015

Understanding course climate is important for improving students’ experiences and increasing the likelihood of their persistence in STEM fields. This study presents climate survey results from 523 students taking introductory biology at the University of Michigan. Principal component analysis revealed that a student’s climate experience is comprised of five main elements: comfort, school avoidance, relationship to course, academic stress, and discomfort. Of these climate factors, comfort, school avoidance, and relationship to course were significant predictors of course satisfaction, and academic stress was a significant predictor of persistence. The results indicated the importance of a positive climate that is facilitated by the instructor in order to promote a positive student experience. Climate may be an important metric for institutions to track across time and course.
The Use of Stuffed Microbes in an Undergraduate Microbiology Course Increases Engagement and Student Learning
Authors: Webb Ginny
Published: December 2015

Student engagement, attention, and attendance during a microbiology lecture are crucial for student learning. In addition, it is challenging to cover a large number of infectious diseases during a one-semester introductory microbiology course. The use of visual aids helps students retain the information presented during a lecture. Here, I discuss the use of stuffed, plush microbes as visual aids during an introductory microbiology course. The incorporation of these stuffed microbes during a microbiology lecture results in an increase in engagement, interest, attendance, and retention of material.
Powerful Soil: Utilizing Microbial Fuel Cell Construction and Design in an Introductory Biology Course
Authors: Jude Craig D. , Jude Brooke A.
Published: December 2015

This tool utilizes the construction of a microbial fuel cell (MFC) as the long-term laboratory experience for an introductory biology course. Students build multiple versions of MFCs during the semester, altering a number of variables to produce a more powerful battery. Through this iterative laboratory experience, students learn experimental design strategies, microbial culturing and identification techniques, and how to construct scientific figures, legends and tables. This laboratory can also be adapted to a one-hour workshop for middle school students, facilitated by college faculty and college students.

Editor's Note:

The ASM advocates that students must successfully demonstrate the ability to explain and practice safe laboratory techniques. For more information, read the laboratory safety section of the ASM Curriculum Recommendations: Introductory Course in Microbiology and the Guidelines for Biosafety in Teaching Laboratories, available at www.asm.org. The Editors of JMBE recommend that adopters of the protocols included in this article follow a minimum of Biosafety Level 2 practices. Adopters of the 8th grade outreach activity discussed in this article should follow Biosafety Level 1 practices.
An Alternative Approach to “Identification of Unknowns”: Designing a Protocol to Verify the Identities of Nitrogen Fixing Bacteria
Authors: Martinez-Vaz Betsy M. , Denny Roxanne , Young Nevin D. , Sadowsky Michael J.
Published: December 2015

Microbiology courses often include a laboratory activity on the identification of unknown microbes. This activity consists of providing students with microbial cultures and running biochemical assays to identify the organisms. This approach lacks molecular techniques such as sequencing of genes encoding 16S rRNA, which is currently the method of choice for identification of unknown bacteria. A laboratory activity was developed to teach students how to identify microorganisms using 16S rRNA polymerase chain reaction (PCR) and validate microbial identities using biochemical techniques. We hypothesized that designing an experimental protocol to confirm the identity of a bacterium would improve students’ knowledge of microbial identification techniques and the physiological characteristics of bacterial species. Nitrogen-fixing bacteria were isolated from the root nodules of
Medicago truncatula
and prepared for 16S rRNA PCR analysis. Once DNA sequencing revealed the identity of the organisms, the students designed experimental protocols to verify the identity of rhizobia. An assessment was conducted by analyzing pre- and posttest scores and by grading students’ verification protocols and presentations. Posttest scores were higher than pretest scores at or below p = 0.001. Normalized learning gains (G) showed an improvement of students’ knowledge of microbial identification methods (LO4, G = 0.46), biochemical properties of nitrogen-fixing bacteria (LO3, G = 0.45), and the events leading to the establishment of nitrogen-fixing symbioses (LO1&2, G = 0.51, G = 0.37). An evaluation of verification protocols also showed significant improvement with a p value of less than 0.001.
Updated Cases for Medical MicrobiologyReview of:
Cases in Medical Microbiology and Infectious Diseases
, 4
th
ed.; Peter H. Gilligan, Daniel S. Shapiro, and Melissa B. Miller; (2014). ASM Press, Washington, DC. 589 pages.
Authors: Govindan Brinda
Published: December 2015

Review of: Cases in Medical Microbiology and Infectious Diseases, 4th ed.; Peter H. Gilligan, Daniel S. Shapiro, and Melissa B. Miller; (2014). ASM Press, Washington, DC. 589 pages.
Effectiveness of a 5-year school-based intervention programme to reduce adiposity and improve fitness and lifestyle in Indian children; the SYM-KEM study
Authors: Bhave Sheila , Pandit Anand , Yeravdekar Rajiv , Madkaikar Vaishali , Chinchwade Trushna , Shaikh Nasreen , Shaikh Tasneem , Naik Shraddha , Marley-Zagar Ella , Fall Caroline H D
Published: December 2015

Design

Non-randomised non-blinded school-based intervention study.

Setting

Two schools in the cities of Pune and Nasik, India.

Participants

The intervention group comprised children attending a Pune school from 7–10 years until 12–15 years of age. Two control groups comprised children of the same age attending a similar school in Nasik, and children in the Pune intervention school but aged 12–15 years at the start of the study.

Intervention

A 5-year multi-intervention programme, covering three domains: physical activity, diet and general health, and including increased extracurricular and intracurricular physical activity sessions; daily yoga-based breathing exercises; making physical activity a ‘scoring’ subject; nutrition education; healthier school meals; removal of fast-food hawkers from the school environs; and health and nutrition education for teachers, pupils and families.

Main outcome measures

Body mass index (BMI), waist circumference, physical fitness according to simple tests of strength, flexibility and endurance; diet; and lifestyle indicators (time watching TV, studying and actively playing).

Results

After 5 years the intervention children were fitter than controls in running, long jump, sit-up and push-up tests (p<0.05 for all). They reported spending less time sedentary (watching TV and studying), more time actively playing and eating fruit more often (p<0.05). The intervention did not reduce BMI or the prevalence of overweight/obesity, but waist circumference was lower than in the Pune controls (p=0.004).

Conclusions

It was possible to achieve multiple health-promoting changes in an academically competitive Indian school. These changes resulted in improved physical fitness, but had no impact on the children's BMI or on the prevalence of overweight/obesity.
ORGAN FAILURE AND C-REACTIVE PROTEIN BOTH AFFECT MIDAZOLAM CLEARANCE IN CRITICALLY ILL CHILDREN: A POPULATION PK MODEL
Authors: Vet Nienke J , Brussee Janneke M , de Hoog Matthijs , Mooij Miriam G , Verlaat Carin WM , Tibboel Dick , AJ Knibbe Catherijne , de Wildt Saskia N
Published: December 2015

Objectives

To study the effect of organ failure and inflammation on midazolam clearance in critically ill children, using population pharmacokinetic modeling.

Methods

A total of 83 critically ill children (median age 5 months (range 1 day-17 years), n=523 samples) receiving intravenous midazolam for continuous sedation during mechanical ventilation were included. Disease severity was described using the validated and clinically used scores PELOD, PIM2 and PRISM II. Cytokines (IL-1, IL-2, IL-6, TNF-a) and C-reactive protein (CRP) were used as markers for inflammation. A population pharmacokinetic model for midazolam was developed using NONMEM 7.3. Body weight, age, severity of organ failure and inflammatory markers were considered as potential covariates.

Results

In a two-compartmental PK model, body weight was found as most significant covariate for clearance and volume of distribution. Moreover, both severity of organ failure (PELOD) and inflammation (IL6 and CRP) were significant determinants of clearance (p<0.01), and either of these factors improved the model significantly. With increasing number of organ failures, midazolam clearance significantly reduced. CRP was linearly correlated with clearance (slope −0.095), with higher CRP levels resulting in lower clearances. Either one of the covariates could explain part of the variability in clearance.

Conclusion

For midazolam clearance, apart from body weight, we found organ failure reflected by the PELOD score, and inflammation reflected by IL6 and CRP, as significant covariates. Most likely this effect is due to reduced activity of CYP3A in critically ill mechanically ventilated children. Both CRP concentration and organ failure should be considered when dosing midazolam and potentially other CYP3A substrates in critically ill children.
DOSE-FINDING STUDY AND PHARMACODYNAMIC ASSESSMENT OF PROPOFOL FOR (SEMI-)ELECTIVE INTUBATION IN NEONATES
Authors: Smits Anne , Thewissen Liesbeth , Caicedo Alexander , Nicolaï Johan , Annaert Pieter , Naulaers Gunnar , Allegaert Karel
Published: December 2015

Introduction

The optimal propofol dose and its safety for procedural sedation in neonates is controversial. The aim of this study was to perform a prospective propofol dose-finding study with pharmacodynamic (PD) assessment during (semi-)elective intubation in neonates.

Methods

Patients were stratified in 4 groups by postmenstrual and postnatal age. The first patient in each group received 1 mg/kg intravenous propofol bolus. Dosing for the next patient was determined using the up-and-down method. Propofol ED50 doses [effective dose for successful intubation (as well as extubation in INSURE -intubation, surfactant, extubation-cases) in 50% of patients] were calculated, with simultaneous assessment of clinical scores, continuous vital sign monitoring and propofol blood concentrations (3 and 12h after dosing).

Results

Thirty-five neonates (weight 540–3290 g) were included. Using initial and total propofol dose ranges of 0.5–2 and 0.5–4.5 mg/kg respectively, median propofol ED50 range for preterm neonates <10 days was 0.480–1.287 mg/kg. Clinical recovery was not attained at the end of the scoring period (21 minutes). A median decrease in mean arterial blood pressure (MABP) between −29.41% and −39.09% from baseline, and a short-lasting decrease in peripheral (SaO2) and regional cerebral (rScO2) oxygen saturation was documented. Variability in MABP, SaO2 and rScO2 was not explained by weight, age or propofol concentrations.

Conclusions

Low propofol doses sufficiently sedate neonates for intubation, but clinical recovery takes time and is accompanied by permissive hypotension. Propofol ED50 doses are provided and need integration in a prospective validation approach. Finally, feasibility of continuous monitoring for neonatal pharmacodynamic research was demonstrated.
PEDIATRIC DRUG TRIALS IN CHINA
Authors: Hao Guo-Xiang , Wang Xiao-Ling , Shen A-Dong , Jacqz-Aigrain Evelyne , Zhao Wei
Published: December 2015

Background and objective

The introduction of the Pediatric Regulation by the European Union, together with the renewal of the Pediatric Rule by the US Food and Drug Administration on the requirements for pediatric labeling made it mandatory for sponsors to develop drugs for the pediatric population and promotes the pediatric drug trials in Europe and US. However, very little is known about the situation of pediatric drug trials in other countries, particularly in China, home to nearly 300 millions children. In order to support the global research in pediatric drug development and clarify the specific characteristics of pediatric drugs trials in China, we analyzed the drug trials registered in the Chinese Clincial Trial Registry database.

Methods

The pediatric drug trials registered in Chinese Clincial Trial Registry database between 2007 and 2014 were analyzed. The following information was extracted from the database by two authors: type of the trial, registered time, drug name, inclusion and exclusion criteria, population, number of patients, and sponsor.

Results

Among all (4786) trials registered, 729 trials (15.2%) involved the pediatric population, and only 308 trials (6.4%) were pediatric drug trials. From 2007 to 2013 pediatric drug trials increased from 3 to 121. There were 66 pediatric drug trials including Chinese traditional medicine.

Conclusion

Our results demonstrated for the first time the situation of pediatric drug trials in China. Consistent with the initiatives of promoting pediatric drug development in Europe and US, the pediatric drug trial in China made a significant progress after 2012. The pediatric drug legislation is urgently needed in China.
POPULATION PHARMACOKINETICS OF INTRAVENOUS ALBUTEROL IN CHILDREN WITH STATUS ASTHMATICUS
Authors: Vet Nienke J , de Winter Brenda CM , de Wildt Saskia N , der Nagel Bart CH van , AJ Knibbe Catherijne , Koninckx Muriel , de Hoog Matthijs , Koch Birgit CP
Published: December 2015

Objectives

To develop a population pharmacokinetic model of R-albuterol and S-albuterol for children suffering from status asthmaticus following continuous intravenous administration.

Methods

At the pediatric ICU 19 children suffering from severe status asthmaticus were treated using continuous intravenous albuterol in doses based on clinical symptoms (range 0.1–10 µg/kg/min). During therapy 111 blood samples were collected and analysed for R- and S-albuterol using a validated LC/MS-MS method. A population pharmacokinetic analysis was conducted using non-linear mixed effects modelling (NONMEM 7.2). Data was logarithmically transformed. Model selection criteria were decrease in objective function, diagnostic plots and NPDE. The covariates (range) analysed were bodyweight (7.8–70 kg), age (0.8–15.3 years), creatinine concentration (17–70 µmol/L), alanine transaminase (5–29 IU/L), and urea (1.6–4.8 mmol/L).

Results

A two-compartment model with separated clearance for R- (16.3 L/h) and S-albuterol (8.8 L/h) best described the data. Separated values for central volume of distribution (12.9 L), peripheral volume of distribution (45.2 L) and intercompartmental clearance (20.0 L/h) did not improve the model. Between-subject variability was described for clearance of R-albuterol (42%), clearance of S-albuterol (37%) and central volume of distribution (280%). Weight is a significant covariate using a power function. The exponent of the powerfunction was fixed at 0.75 for clearance and intercompartmental and at 1 for central and peripheral volume of distribution. Estimation of the exponent resulted in similar values and did not improve the model. No other covariates were identified.

Conclusion

The population pharmacokinetics of R- and S-albuterol are described. This model can be used to evaluate the correlation between albuterol pharmacokinetics and effect in a population pharmacokinetic-pharmacodynamic analysis.
MAPPING IN VITRO AND IN VIVO DERIVED CYP2C9 AND CYP2C19 ONTOGENY FUNCTIONS: A CRITICAL COMPARISON BETWEEN VARIOUS ONTOGENY MODELS
Authors: Salem Farzaneh , Johnson Trevor , Rostami-Hodjegan Amin
Published: December 2015

In vivo derived ontogeny profiles for CYP1A2 and CYP3A4, show improved clearance (CL) predictions within a paediatric physiologically based pharmacokinetic (p-PBPK) model1. The aim of this study is to derive ontogeny functions (OF) for CYP2C9 and CYP2C19 based on age related CL data on ibuprofen and pantoprazole & lansoprazole, respectively.

A literature review was undertaken to collect age related CL data for these probes, the values were deconvoluted back to intrinsic CL values (per mg of liver microsomal protein) as described previously. The 'best-fit' algorithm for ratio of paediatric to mean adult intrinsic CL with age was determined in Graphpad Prism5 to obtain in vivo OF for CYP2C9 and CYP2C19. These were compared for performance with previously established ‘in vitro' OF in Simcyp Paediatric simulator (v14) using validation datasets.

CYP2C9 and CYP2C19 enzyme activities showed an increase with age to values higher than adults by ages 2 and 1 month respectively, maximum values were reached at 1.5 years and 6 months, respectively before declining to typical adult levels by around 25 years.

The CYP2C9 in vivo derived OF led to improved predictions of diclofenac and S-Warfarin CL compared to in vitro derived OF across the age range. For CYP2C19 there is a dearth of suitable validation compounds due to lack of clinical data with a possibility of using omeprazole or voriconazole. The reasons for discrepancy between in vitro and in vivo derived OF require further investigation.
IMPLEMENTATION OF CLONIDINE AS A NEW SEDATIVE AND ANALGESIC DRUG IN THE NICU–A RETROSPECTIVE REPORT ON MEDICAL RECORDS
Authors: Ragnarsson Charlotte , Norman Elisabeth
Published: December 2015

Background

Adequate pain relief is crucial for neonatal intensive care. Opioids are used despite their side effects. Clonidine has been introduced to reduce the opioid doses. Clonidine has never been studied in newborn infants.

This study describes the strategy and the clinical response during a three year implementation period in a Swedish level-III NICU.

Methods

This is a retrospective study based on medical records, monitoring charts of physiological parameters and pain assessment, and Swedish national perinatal quality register data.

Clonidine was administered to 97 patients and analyzed according to modes of intravenous administration (boluses and/or infusions). The indication, gestational and postnatal age at administration, doses, treatment duration, pain scoring, effects and concurrent medication were analyzed. Non-parametric statistics was performed (medians, IQR).

Results

The infants were born at 28.6 (24.9–36.3) gestational weeks, birth weight 1058 (727–2660) g. The medication was introduced at postnatal age of 9 ((1–27) days. The maximum dosing was 1.4 microg/kg and 0.2 microg/kg/h for bolus doses and infusions, respectively, and the duration of exposure for the most common administration way (boluses followed by start of infusion) was 6 (3.8–11.5) days. The indication was sedation in 71%. Concurrent analgesics or sedatives, most commonly morphine, were given in 39% at start and 42% during the treatment period. The subjective effects were positive, and the side effects were few.

Conclusions

Our study data support the benefits of clonidine with positive effects and few side effects. Pharmacokinetic and pharmacodynamics studies are needed in accordance with the FDA and EMA directives.
ACUTE POISONINGS IN A CHILDREN'S EMERGENCY DEPARTMENT
Authors: Starkey Elizabeth , Sammons Helen
Published: December 2015

Objective

To determine the incidence of children presenting to a children's emergency department with acute ingestion or poisoning. To identify common substances involved and those requiring admission and/or treatment.

Method

A retrospective notes survey was performed in children <16 years with a diagnosis of overdose or poisoning attending the local emergency department in 2013.

Results

A total of 441 events occurred with a potential diagnosis of overdose or poisoning in 428 children. This was 1.46% of all emergency attendances. 223 events (50%) were under 5 years with medicines or soaps and detergents being the commonest causes of accidental ingestion in 40% and 21% respectively. 182 events were over 12 years; 137 due to self-harm, 25 from alcohol and 9 from illicit drugs. 40% of all events required admission; 77% and 97% staying less than 24 and 48 hours respectively. In those staying over 2 days, only 1 patient remained for medical reasons requiring PICU care for a significant alcohol overdose. 10 patients received HDU care, 9 for close observation and 1 for treatment of recurrent seizures post mixed overdose. Only 2 patients had severe symptoms defined by the poisoning severity score.

Conclusion

Acute poisoning is a common reason to attend paediatric emergency departments. Most under 5 years don't require admission or treatment whereas over 12 years poisonings and overdoses are more problematic. Severe symptoms in children are rare suggesting further studies are required for determining the incidence of severe paediatric poisonings within the UK and Europe.
SEASONAL VARIATIONS IN ANTIBIOTIC CONSUMPTION IN PAEDIATRIC PRIMARY CARE SETTINGS IN SERBIA
Authors: Božić Bojana , Bajčetić Milica
Published: December 2015

Background/Objective

Antibiotics are the most irrational prescribed drugs among the paediatric population. The aim of this study was to evaluate the seasonal variations in antibiotic prescribing profile among children in primary care settings in Serbia.

Methods

Prescriptions of systemic antibiotics to the paediatric population (<18 years) for the period between 2011 and 2013 were analyzed by using the National Health Insurance Fund's outpatient reimbursement database.

Results

The average number of antibiotic prescriptions was 1.887.615, while the average number of children receiving antibiotics was 728.285. The average annual rate was 1.394 antibiotic prescriptions per 1000 children. Significant differences in prescription rates in winter months compared to summer months were observed (t=5.51 p<0.001; t=2.29 p=0.045; t=3.65 p=0.004 for 95% confidence interval) during the followed up period. The average annual prevalence of antibiotic prescriptions was 54%. The most commonly prescribed antibiotics in paediatric population were amoxicillin, amoxicillin/clavulanic acid, cephalexin, azithromycin and erythromycin (90% of all prescribed antibiotics). The highest percentage of prescribed antibiotics was observed in the group of 2- to- 23- months-old children. Broad spectrum penicillins were the most prescribed antibiotics in all age groups, especially for children from 2–11 years of age, 51.92% (44.90%–57.13%), while the rate for cephalosporins was highest for children from 2–23 months, 30.91% (26.38%–36.44%), macrolides from 12 to 18 years, 22.67% (19.79%–26.05%) and quinolones from 0–1 month of age, 6.64% (5.09%–9.52%).

Conclusions

Significant seasonal variations in prescription practice and frequently used broad-spectrum antibiotics indicate that antibiotic prescribing is inappropriate.
LEGAL RESPONSIBILITY PRESCRIBING OFF-LABEL DRUGS: IS SPAIN DIFFERENT?
Authors: Peire Maria A.
Published: December 2015

– In Spain the compassionate use and off-label prescription, are both regulated in the same law: the Royal Decree 1015/2009. This norm facilitates the access to drugs in specific clinical situations, similar to US regulation and in a different way to the UE regulation.

– It is a legal practice to prescribe in an off-label manner if the following requirements are followed: there are no authorized therapeutic alternatives, prescribed in health centers, when access to these drugs is provided through a protocol of use after justifying (written) and properly informing (verbal) and obtaining the patient's consent.

– When prescribing off-label the doctor's decision is based on contrasted scientific evidence (not merely on personal intuition nor personal experience). In fact, this anticipates an eventual update of the data sheet for new indications or populations, unlike the French situation where they have the ATU (Temporary Utilization Authorization).

– In Spain the holder of the Marketing Authorization is obliged not to promote or advertise the use of the drug in different conditions to those approved (unlike the USA regulation).

– The jurisprudential analysis from the Spanish Courts states that the doctor's responsibility is equal than that concerning on-label prescription, that is, only in the case of bad medical praxis (as in the USA). The most important cause of sentencing were: the lack of informed consent, lack of control of the medication and lack of correct follow-up of the illness, whereas this does not include the drug, dose, duration or even the patient's age.

– In European Union the general rule dictated by the Courts is to permit off-label use if this is according to the best medical practice (lex artis ad hoc). Even more, there are some specific cases (in Germany, like in the USA) where it is possible to generate doctor's responsibility for no prescribing in a off-label manner.
A BLUE-PRINT FOR PERFORMING PAEDIATRIC PHARMACOLOGICAL RESEARCH
Authors: Vermeulen Eric , Nuytemans Debbie , de Haan Timo , Flint Robert , der Lee Johanna van
Published: December 2015

Introduction

In order to develop rational, patient tailored dosing schemes, population PK/PD studies in children and infants are needed. The emergence of new laboratory techniques (LC-MS/MS) and statistical tools (population PK/PD modeling) allows for the analysis of sparse and unbalanced data and has increased the possibilities to perform (observational) PK/PD studies in the paediatric clinic.

To improve the quality of future pediatric PK/PD investigations the experience and knowledge about these tools should be shared and a basic study template agreed upon.

Objective

We aim to present a possible blue-print to assist paediatricians in the design and conduct of multicentre PK/PD studies in children and infants.

Methods

Based on a review of the existing literature and multiple interviews with paediatricians and pharmacologists involved in multicenter paediatric PK/PD research a blue-print is drafted containing recommendations and examples for the design and implementation of PK/PD studies in children. The draft blue-print will be available at the conference and participants are asked for feed-back.

Results

PK/PD research to determine dosing in children and infants is preferably performed in a multi-center infrastructure in order to include a sufficient number of subjects within a reasonable time, covering all covariates relevant for dosage. The multi-center collaboration may also enable the analysis of multiple drugs in one cohort increasing cost-efficiency. Formal monitoring is needed to guarantee the quality of collected data.

Discussion

If performed well, the results of these studies will contribute to the evidence base underlying clinical guidelines and regulatory decisions concerning labeling adjustments.
NEW QUALITY INDICATORS FOR PAEDIATRIC ANTIBIOTIC PRESCRIBING IN PRIMARY CARE: A POPULATION BASED COHORT STUDY IN THE UNITED KINGDOM, ITALY AND THE NETHERLANDS FROM 1995–2010
Authors: Kaguelidou Florentia , de Bie Sandra , Verhamme Katia , de Ridder Maria , Picelli Gino , Strauś Sabine , Giaquinto Carlo , Stricker Bruno , Bielicki Julia , Sharland Mike , Sturkenboom Miriam
Published: December 2015

Background

Suboptimal use of antibiotics may lead to antimicrobial resistance. The aim of this study was to develop and assess two new quality indicators (QIs) of optimal community-based prescribing applied to childhood community antibiotic (AB) prescribing in three European countries.

Methods

A cohort study was conducted using electronic primary care medical records of 2,195,312 children up to 14 (Italy, Pedianet database, 2001–2010) or 18 years of age (UK, THIN database, 1995–2010; the Netherlands, IPCI database, 1996–2010) contributing for a total of 12,079,620 person-years (PYs). Prevalence rates of antibiotic prescribing were defined as the number of children with at least one antibiotic prescription per year and were expressed as the number of users per 100 PYs (%). Quality of prescribing was determined using four QIs: the drug utilisation 90% method, the ratio between users of broad and narrow spectrum penicillins, cephalosporins and macrolides (B/N ratio) and two new QMs: (i) the overall proportion of amoxicillin users (amoxicillin index, AI); (ii) the ratio between users of amoxicillin and those of broad spectrum antibiotics (the A/B ratio).

Results

The overall annual prevalence of antibiotic prescriptions was 18% in the Netherlands, 36.2% in the UK and 52% in Italy. Prevalence was highest in the youngest children. Almost half of all prescriptions included amoxicillin with or without clavulanic acid. Cephalosporins were frequently prescribed in Italy. The AI provided trends for the utilization of a relatively narrow spectrum option targeting acute respiratory infections, and was highest in the Netherlands and in the UK (50–60%) and lower in Italy (30%), with a slight decrease over time in the UK and Italy. The overall B/N ratio varied between countries from 0.3 to 74.7, whereas the overall A/B ratio varied less from 0.5 in Italy to 6 in the UK, indicating a substantial proportion of narrower-spectrum prescribing in the UK.

Conclusions

The prevalence of antibiotic prescribing varied highly with age and country. A combination of total antibiotic prevalence and quality of prescribing based on amoxicillin use provide a clear picture of community childhood antibiotic prescribing. These measures could be used to evaluate the impact of programs aiming at reduction of AB use and appropriate antibiotic prescribing.
The woman with unexplained anaemia
Authors: Al-Hadithy Nada , Coelho James , Gorman Mark , Stone Christopher
Published: December 2015

A 77-year-old woman was admitted to hospital for 3 weeks to treat cellulitis and investigate unexplained anaemia. Earlier, when her neck had been examined on outpatient review of her lymphoedema, a large fungating tumour had been noted. This was biopsied and found to be a mixed basaloid adenocarcinoma. She was subsequently admitted under the plastic surgeons and treated with wide local excision on postero-lateral neck dissection. The defect was reconstructed with a deltopectoral flap.
Leukemoid reaction as a paraneoplastic syndrome in hypopharyngeal squamous cell carcinoma with cutaneous metastasis: an exceedingly rare occurrence
Authors: Subramaniam Narayana , Hiremath Bharati
Published: December 2015

Head and neck squamous cell carcinoma is considered a locoregional disease, with a distinct chance of metastasis, however, skin is an unusual site. Haematological paraneoplastic syndromes are even rarer, and may be the only presenting feature in these malignancies, producing diagnostic confusion. Cutaneous metastasis, in addition to signifying poor response to treatment and prognosis, can cause diagnostic difficulty if the metastasis is located with an occult primary, and is associated with a higher incidence of multiple synchronous primaries. This article describes a 52-year-old patient with multiple swellings on the left side of the neck and hoarseness of voice. On evaluation, the multiple swellings were found to be cutaneous metastasis from a hypopharyngeal squamous cell carcinoma, with a leukemoid reaction. He opted for palliative radiotherapy and succumbed to his illness within 3 months of presentation. This article discusses the importance of this unusual presentation and diagnostic difficulties associated with it.
Postpartum acute abdomen and its diagnostic challenges
Authors: Sheppeard Rhian , Wilson Catherine
Published: December 2015

This is the case of a 25-year-old primigravida with gradual onset abdominal pain and vomiting, 1 day postvaginal delivery. After three hospital admissions over the following 3 weeks, a diagnosis of small bowel obstruction secondary to adhesions was made; the patient had undergone a previous appendicectomy. The patient was taken to theatre for laparotomy and adhesiolysis, where the bowel was found to be viable but with two small serosal tears. Postoperative recovery was uncomplicated. This case highlights the importance of assessing abdominal pain in the puerperium in a similar manner to that done in a non-pregnant state, to avoid delay in diagnosis.
Abacavir-induced fulminant hepatic failure in a HIV/HCV co-infected patient
Authors: Haas Christopher , Ziccardi Mary Rodriguez , Borgman Jody
Published: December 2015

Abacavir hypersensitivity is a rare, yet significant adverse reaction that results in a spectrum of physical and laboratory abnormalities, and has been postulated to stem from a variety of aetiological factors. The major histocompatibility complex haplotype human leucocyte antigen (HLA)-B5701 is a significant risk factor in development of hypersensitivity reactions, yet only 55% of HLA-B5701+ individuals develop such reactions, suggesting a multifactorial aetiology. Nevertheless, prospective screening and avoidance of abacavir in these patients has limited adverse events. Within this spectrum of adverse events, abacavir-induced liver toxicity is exceedingly rare and reported events have ranged from mild elevations of aminotransferases to fulminant hepatic failure. We report the case of a 50-year-old Caucasian woman with a history significant for HIV, hepatitis C virus and a HLA-B5701+ status, transferred to our emergency department in a hypotensive state and found to have acute liver failure, acute renal failure and significant rhabdomyolysis following a change of highly active antiretroviral therapy regimen.
Thyroid storm in a patient with Wolff-Parkinson-White syndrome
Authors: Naqvi Syed Yaseen , Luebbert Jeffrey J , Rosen Stephen G
Published: December 2015

A 44-year-old woman with no medical history presented to the emergency department with a 2 h history of sudden onset chest pressure, palpitations, diaphoresis and shortness of breath. She reported a 90-pound unintentional weight loss, increased appetite, irritability, night sweats and palpitations for 2 months. Physical examination revealed a heart rate (HR) of 269 bpm and a blood pressure of 116/94 mm Hg. Her ECG revealed a wide-complex tachycardia with right bundle branch morphology and an HR of 265 bpm. Intravenous adenosine was administered with resolution of the arrhythmia and symptoms. Her subsequent ECG revealed sinus tachycardia with δ waves, which was consistent with Wolff-Parkinson-White (WPW) syndrome. Laboratory findings confirmed thyroid storm and treatment began with intravenous hydrocortisone, methimazole, metoprolol, amiodarone and iodine drops. Graves’ disease was confirmed based on the presence of serum thyroid-stimulating hormone receptor antibody. The patient underwent successful WPW accessory tract ablation 6 weeks after initial presentation.
Insulinoma with focal hepatic lesions: malignant insulinoma?
Authors: Jerraya Hichem , Zidi-Mouaffek Yossra , Dokmak Safi , Dziri Chadli
Published: December 2015

Insulinoma is a rare tumour that is malignant in only 10% of cases. We report a case of insulinoma in a 59-year-old woman, associated with focal liver lesions, which raised the suspicion of malignancy of a pancreatic tumour. Enucleation of the insulinoma was performed with wedge resection of one hepatic nodule. Pathological examination indicated that the pancreatic tumour was compatible with insulinoma whereas the hepatic lesion was related to focal nodular hyperplasia. This clinical case highlights the need for histopathological proof of malignancy before selecting therapeutic strategies for insulinomas.
Feeling blue, going green and finding other attractive alternatives: a case of biphasic anaphylaxis to patent blue and a literature review of alternative sentinel node localisation methods
Authors: Iqbal Fahad Mujtaba , Basit Abdul , Salem Fathi , Vidya Raghavan
Published: December 2015

Patent blue dye is used for sentinel lymph node localisation in order to stage the axilla in patients with breast cancer. Patent blue is one of the most common dyes used across the UK, however, the incidence of adverse effects seems to be increasing. This case highlights our experience of a biphasic anaphylactic reaction to patent blue dye, and we conduct a brief literature review of alternative and more novel methods to adequately visualise the lymphatics for sentinel lymph node biopsy.
Comparison of clinical outcomes in patients with acute ischemic strokes treated with mechanical thrombectomy using either Solumbra or ADAPT techniques
Authors: Delgado Almandoz Josser E , Kayan Yasha , Young Mark L , Fease Jennifer L , Scholz Jill M , Milner Anna M , Hehr Timothy H , Roohani Pezhman , Mulder Maximilian , Tarrel Ronald M
Published: December 2015

Purpose

To compare rates of symptomatic intracranial hemorrhage (SICH) and good clinical outcome at 90 days in patients with ischemic strokes from anterior circulation emergent large vessel occlusions (ELVO) treated with mechanical thrombectomy using either Solumbra or A Direct Aspiration first-Pass Thrombectomy (ADAPT) techniques.

Methods

We compared clinical characteristics, procedural variables, and clinical outcomes in patients with anterior circulation ELVOs treated with mechanical thrombectomy using either a Solumbra or ADAPT technique at our institution over a 38-month period. SICH was defined using the SITS-MOST criteria. A good clinical outcome was defined as a modified Rankin Scale score of 0–2 at 90 days.

Results

One hundred patients were included, 55 in the Solumbra group and 45 in the ADAPT group. Patients in the ADAPT group had higher National Institutes of Health Stroke Scale (NIHSS) (19.2 vs 16.8, p=0.02) and a higher proportion of internal carotid artery terminus thrombi (42.2% vs 20%, p=0.03) than patients in the Solumbra group. Patients in the ADAPT group had a trend toward a lower rate of SICH than patients in the Solumbra group (2.2% vs 12.7%, p=0.07). Patients in the ADAPT group had a significantly higher rate of good clinical outcome at 90 days than patients in the Solumbra group (55.6% vs 30.9%, p=0.015). Use of the ADAPT technique (OR 6 (95% CI 1.0 to 31.2), p=0.049) was an independent predictor of a good clinical outcome at 90 days in our cohort.

Conclusions

In our cohort, the ADAPT technique was associated with significantly higher good clinical outcomes at 90 days in patients with acute ischemic stroke due to anterior circulation ELVOs treated with mechanical thrombectomy.
Fourier–Mukai transforms and Bridgeland stability conditions on abelian threefolds II
Authors: Maciocia Antony , Piyaratne Dulip
Published: December 2015

We show that the conjectural construction proposed by Bayer, Bertram, Macrí and Toda gives rise to Bridgeland stability conditions for a principally polarized abelian threefold with Picard rank one by proving that tilt stable objects satisfy the strong Bogomolov–Gieseker (BG) type inequality. This is done by showing certain Fourier–Mukai transforms (FMTs) give equivalences of abelian categories which are double tilts of coherent sheaves.
Dynamics of public opinion under the influence of epidemic spreading
Authors: Wu Junhui , Ni Shunjiang , Shen Shifei
Published: December 2015

In this paper, we propose a novel model with dynamically adjusted confidence level of others to investigate the propagation of public opinion on whether to buy chicken in the case of avian influenza infection in humans. We study how people adjust their confidence level in other people’s opinions according to their perceived infection risk and how the opinion evolution and epidemic spreading affect each other on different complex networks by taking into account the spreading feature of avian influenza, that is, only people who buy chicken are possible to be infected. The simulation results show that in a closed system, people who support buying chicken and people who are infected can achieve a dynamic balance after a few time-steps, and the final stable state is mainly dependent on the level of people’s risk perception, rather than the initial distribution of the different opinions. Our results imply that in the course of the epidemic spread, transparent and timely announcement of the number of infections and the risk of infection can help people take the right self-protection actions, and thus help control the spread of avian influenza.
On indecomposable solvable Lie superalgebras having a Heisenberg nilradical
Authors: Rodríguez-Vallarte M. C. , Salgado G. , Sánchez-Valenzuela O. A.
Published: December 2015

All solvable, indecomposable, finite-dimensional, complex Lie superalgebras [Formula: see text] whose first derived ideal lies in its nilradical, and whose nilradical is a Heisenberg Lie superalgebra [Formula: see text] associated to a [Formula: see text]-homogeneous supersymplectic complex vector superspace [Formula: see text], are here classified up to isomorphism. It is shown that they are all of the form [Formula: see text], where [Formula: see text] is even and consists of non-[Formula: see text]-nilpotent elements. All these Lie superalgebras depend on an element [Formula: see text] in the dual space [Formula: see text] and on a pair of linear maps defined on [Formula: see text], and taking values in the Lie algebras naturally associated to the even and odd subspaces of [Formula: see text]; namely, if the supersymplectic form is even, the pair of linear maps defined on [Formula: see text] take values in [Formula: see text], and [Formula: see text], respectively, whereas if the supersymplectic form is odd these linear maps take values on [Formula: see text]. When the supersymplectic form is even, a bilinear, skew-symmetric form defined on [Formula: see text] is further needed. Conditions on these building data are given and the isomorphism classes of the resulting Lie superalgebras are described in terms of appropriate group actions.
Transform margins of the Arctic: a synthesis and re-evaluation
Authors: Doré A. G. , Lundin E. R. , Gibbons A. , Sømme T. O. , Tørudbakken B. O.
Published: December 2015

Transform-margin development around the Arctic Ocean is a predictable geometric outcome of multi-stage spreading of a small, confined ocean under radically changing plate vectors. Recognition of several transform-margin stages in the development of the Arctic Ocean enables predictions to be made regarding tectonic styles and petroleum systems. The De Geer margin, connecting the Eurasia Basin (the younger Arctic Ocean) and the NE Atlantic during the Cenozoic, is the best known example. It is dextral, multi-component, features transtension and transpression, is implicated in microcontinent release, and thus bears close comparison with the Equatorial Shear Zone. In the older Arctic Ocean, the Amerasia Basin, Early Cretaceous counterclockwise rotation around a pole in the Canadian Mackenzie Delta was accommodated by a terminal transform. We argue on geometric grounds that this dislocation may have occurred at the Canada Basin margin rather than along the more distal Lomonosov Ridge, and review evidence that elements of the old transform margin were detached by the Makarov–Podvodnikov opening and accommodated within the Alpha–Mendeleev Ridge. More controversial is the proposal of transform along the Laptev–East Siberian margin. We regard an element of transform motion as the best solution to accommodating Eurasia and Makarov–Podvodnikov Basin opening, and have incorporated it into a three-stage plate kinematic model for Cretaceous–Cenozoic Arctic Ocean opening, involving the Canada Basin rotational opening at 125–80 Ma, the Makarov–Povodnikov Basin opening at 80–60 Ma normal to the previous motion and a Eurasia Basin stage from 55 Ma to present. We suggest that all three opening phases were accompanied by transform motion, with the right-lateral sense being dominant. The limited data along the Laptev–East Siberian margin are consistent with transform-margin geometry and kinematic indicators, and these ideas will be tested as more data become available over less explored parts of the Arctic, such as the Laptev–East Siberia–Chukchi margin.
Ecology of Varroa destructor, the Major Ectoparasite of the Western Honey Bee, Apis mellifera
Authors: Nazzi Francesco , Le Conte Yves
Published: December 2015

Varroa destructor is the most important ectoparasite of Apis mellifera. This review addresses the interactions between the varroa mite, its environment, and the honey bee host, mediated by an impressive number of cues and signals, including semiochemicals regulating crucial steps of the mite's life cycle. Although mechanical stimuli, temperature, and humidity play an important role, chemical communication is the most important channel. Kairomones are used at all stages of the mite's life cycle, and the exploitation of bees' brood pheromones is particularly significant given these compounds function as primer and releaser signals that regulate the social organization of the honey bee colony. V. destructor is a major problem for apiculture, and the search for novel control methods is an essential task for researchers. A detailed study of the ecological interactions of V. destructor is a prerequisite for creating strategies to sustainably manage the parasite.
Leptin acts in the brain to influence hypoglycemic counterregulation: disparate effects of acute and recurrent hypoglycemia on glucagon release
Authors: Reno Candace M. , Ding Yuyan , Sherwin Robert
Published: December 2015

Leptin has been shown to diminish hyperglycemia via reduced glucagon secretion, although it can also enhance sympathoadrenal responses. However, whether leptin can also inhibit glucagon secretion during insulin-induced hypoglycemia or increase epinephrine during acute or recurrent hypoglycemia has not been examined. To test whether leptin acts in the brain to influence counterregulation, hyperinsulinemic hypoglycemic (∼45 mg/dl) clamps were performed on rats exposed to or not exposed to recurrent hypoglycemia (3 days, ∼40 mg/dl). Intracerebroventricular artificial cerebral spinal fluid or leptin was infused during the clamp. During acute hypoglycemia, leptin decreased glucagon responses by 51% but increased epinephrine and norepinephrine by 24 and 48%, respectively. After recurrent hypoglycemia, basal plasma leptin levels were undetectable. Subsequent brain leptin infusion during hypoglycemia paradoxically increased glucagon by 45% as well as epinephrine by 19%. In conclusion, leptin acts within the brain to diminish glucagon secretion during acute hypoglycemia but increases epinephrine, potentially limiting its detrimental effects during hypoglycemia. Exposure to recurrent hypoglycemia markedly suppresses plasma leptin, whereas exogenous brain leptin delivery enhances both glucagon and epinephrine release to subsequent hypoglycemia. These data suggest that recurrent hypoglycemia may diminish counterregulatory responses in part by reducing brain leptin action.