bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic Analysis of Serum-Derived Defective Hepatitis C Virus Genomes Revealed Novel Viral
cis
Elements for Virus Replication and Assembly
Authors: Li Qingchao , Tong Yimin , Xu Yongfen , Niu Junqi , Zhong Jin 
Published: January 2018

ABSTRACT

Defective viral genomes (DVGs) of hepatitis C virus (HCV) exist, but their biological significances have not been thoroughly investigated. Here, we analyzed HCV DVGs circulating in patient sera that possess deletions in the structural protein-encoding region. About 30% of 41 HCV clinical isolates possess DVGs that originated from the full-length genome in the same patients. No correlation between DVGs, viremia, and alanine aminotransferase (ALT) levels was found. Sequencing analysis of DVGs revealed the existence of deletion hot spots, with upstream sites in E1 and downstream sites in E2 and NS2. Interestingly, the coding sequences for the core protein and the C-terminal protease domain of NS2 were always intact in DVGs despite the fact that both proteins are dispensable for HCV genome replication. Mechanistic studies showed that transmembrane segment 3 (TMS3) of NS2, located immediately upstream of its protease domain, was required for the cleavage of NS2-NS3 and the replication of DVGs. Moreover, we identified a highly conserved secondary structure (SL750) within the core domain 2-coding region that is critical for HCV genome packaging. In summary, our analysis of serum-derived HCV DVGs revealed novel viral
cis
elements that play important roles in virus replication and assembly.

IMPORTANCE
HCV DVGs have been identified
in vivo
and
in vitro
, but their biogenesis and physiological significances remain elusive. In addition, a conventional packaging signal has not yet been identified on the HCV RNA genome, and mechanisms underlying the specificity in the encapsidation of the HCV genome into infectious particles remain to be uncovered. Here, we identified new viral
cis
elements critical for the HCV life cycle by determining genetic constraints that define the boundary of serum-derived HCV DVGs. We found that transmembrane segment 3 of NS2, located immediately upstream of its protease domain, was required for the cleavage of NS2-NS3 and the replication of DVGs. We identified a highly conserved secondary structure (SL750) within the core-coding region that is critical for HCV genome packaging. In summary, our analysis of serum-derived HCV DVGs revealed previously unexpected novel
cis
elements critical for HCV replication and morphogenesis.
P02 An audit of vancomycin dosing in the neonatal units
Authors: Penny Fletcher , Shruti Patel 
Published: January 2018

AimTo audit the prescribing and monitoring of vancomycin in the neonatal units against the local guideline.The neonatal vancomycin guideline has never been audited. Anecdotally, prescribing and monitoring of this drug is challenging, with pharmacists frequently being asked for advice. The guideline has two ranges depending on which bacteria are being treated, 10–15 mg/L and 15–20 mg/L.The initial dosing frequency is different for babies greater than 10 days of age.MethodData on vancomycin doses, levels, time taken, patient age, weight and renal function, were collected on a data collection form prospectively, from prescriptions and clinical records for all babies on vancomycin on between 17/10/2016 and 16/12/2016. Patients were followed throughout their stay; some had repeated courses. The audit was approved locally. Audit standards were derived from the guideline, with 100% adherence aimed for.Data were entered onto an Excel spreadsheet.ResultsData was collected from 19 patients, 28 vancomycin courses and 31 vancomycin levels.28/28 (100%) prescriptions had the correct initial dose. In one neonate the dose changed from 12 to 8 hourly when they were 10 days old. This change led to a high level.13/15 (87%) had the level taken at the correct time. Two were taken 2–3 hours late. Thirteen courses were stopped before requiring levels.19/31 levels (62%) were within a safe range (10–20 mg/L).All 6 levels>20 mg/L had the next dose held and the level repeated. In two of these cases there was no subsequent dose reduction causing further high levels. In one case a further vancomycin course was prescribed as per guidelines, with no consideration of previous levels, a high level was recorded again.Two levels between 15–20 mg/L were considered too high; a dose was omitted, resulting in two sub-therapeutic levels (below 10 mg/L).Of the other four low levels, three were not acted upon appropriately – no dose or frequency increase, one was acted on correctly with a dose increase.ConclusionThe size of the data set was small but the descriptive findings are interesting.The initial aspects of the guideline are adhered to with all doses prescribed correctly. High levels resulted in doses being held and levels repeated but subsequent actions were suboptimal. Levels appeared to be viewed in isolation and so either no change or an incorrect change was made causing further avoidable high levels. Often low levels were not acted upon appropriately.It is possible that there is limited understanding of pharmacokinetic principles underpinning the adjustment of doses.Changes have been made to the guidelines including a statement that the doses are the initial starting doses only and that dose adjustments are based on levels not age. The different ranges caused confusion and given that the specific bacteria presentmay not be known when initiating treatment, the guidelines have been amended to clarify the safe range of vancomycin to be 10–20 mg/L. Teaching sessions with worked examples will be held with all prescribers and nursing staff.
P12 Factors affecting intravenous fluid bolus administration in paediatrics
Authors: Grace Allport , Stephen Playfor 
Published: January 2018

AimBolus administration of 0.9% sodium chloride solution has been associated with hyperchloraemia, acidosis, acute kidney injury and increased mortality. Such adverse effects are believed to be less likely with balanced electrolyte solutions, such as Plasma- Lyte 148 or Hartmann’s solution. Despite existing evidence, 0.9% sodium chloride solution remains a popular choice for intravenous fluid boluses in paediatrics. This project aims to establish current practice of fluid bolus administration in paediatric patients, and to collect testimony from prescribers to help understand why decisions to prescribe specific fluids were made.MethodPaediatric patients in critical care areas (PICU and PHDU), the Emergency Department (PED) and in general ward areas who had been administered intravenous fluid boluses were identified using a pragmatic data collection technique and the dose, type of fluid, indication and patient’s weight were recorded. Where possible, the prescriber was identified and asked to be interviewed. Prescribers were asked what factors had affected their decision to prescribe the type and dose of fluid administered.ResultsMore than 30 individual episodes of intravenous fluid bolus administration were identified. Most fluid boluses were administered in PICU and PHDU, where balanced electrolyte solutions, specifically Plasma-Lyte 148, were the most popular choice. On general paediatric wards and in PED, 0.9% sodium chloride solution remained the most commonly administered fluid bolus solution. While some prescribers were able to give confident explanations of the factors involved in fluid selection, others referred to clinical guidelines. Individual prescribers described how their prescribing practice would vary according to the clinical setting; with senior clinicians and nursing staff being less accepting of balanced electrolyte solutions in general ward areas. Significant lack of knowledge of intravenous fluid physiology was demonstrated by some prescribers.ConclusionOur findings demonstrate an increase in the administration of balanced electrolyte solutions, such as Plasma-Lyte 148, as fluid boluses; this is in keeping with other international surveys of fluid administration.1,2 Similarly, we have also found significant differences in fluid bolus administration practice across different clinical areas as demonstrated by Jonsson and Perner in 2017.We have demonstrated the importance of on-going multi-disciplinary educational efforts in continuing the evolution of intravenous fluid bolus administration practice to reflect current best practice.ReferencesHammond NE, Taylor C, Finfer S, et al. Patterns of intravenous fluid resuscitation use in adult intensive care patients between 2007 and 2014: An international cross-sectional study. PLoS One2017;12:e0176292.Jonsson AB, Perner A. Changes from 2012 to 2015 in intravenous fluid solutions issued to hospital departments. Acta Anaesthesiol Scand2017;61:532–538.
P13 Medication use and excipient exposure in paediatrics in a secondary care setting
Authors: Paul McCague , Hilary Brennan , Scott Wallace 
Published: January 2018

Background and aimPaediatric patients are widely exposed to a range of excipients which may cause harm to this vulnerable patient group. Legal requirement to disclose quantitative information on excipients changed in 2010,2 however, since most formulations were licensed prior to this date, there is a lack of potentially critical information available to currently practising pharmacists and clinicians. The aim of this study was to quantify excipient exposure to children in a secondary care setting.MethodA cohort study was conducted within Altnagelvin Area Hospital Paediatric Ward (Northern Ireland, Western Health and Social Care Trust) in January 2017. Medicines prescribed to patients throughout the study were recorded and exposure to ethanol, sodium benzoate and propylparaben was quantified.Exposure was then compared to proposed safe limits. Off-label and unlicensed use of medicines was assessed as a secondary aim. This study was classified as a service evaluation and ethical approval was not required.ResultsA total of 91 patients were enrolled in the study. Patient age ranged from 5 days to 15 years. The mean number of items prescribed per patient was 3.0. Analysis revealed that 75.8% of patients were exposed to ≥1 excipient of interest including ethanol, sodium benzoate and propylparabens. Excipient safety levels as proposed by the European Medicines Agency or World Health Organisation (where available) were not exceeded.Quantitative excipient information were not available for two products. There was both off-label and unlicensed use ofmedicines, with off-label prescribing (9.6%) being more common than the use of unlicensed medicines (0.4%).ConclusionThe paediatric population is exposed to potentially harmful excipients contained in commonly prescribed medicines. Although exposure within this study falls within existing safety limits, further research into paediatric specific safe exposure limits are required. It is notable that despite contacting themanufacturer, quantitative excipient information were not available for two products. Safety limits when considered together with quantitative excipient information will allow clinicians to complete an informed risk-benefit analysis for paediatric patients.ReferencesTulec C. Paediatric formulations in practice. In Costello I, Long PF, Wong IK, Tulec C, Yeung V (Ed.), Paediatric drug handling 2007:pp. 43–74. London: Pharmaceutical Press.European Commission. A guideline on summary of product characteristics [Online]2009;2:1–29. http://ec.europa.eu/health//sites/health/files/files/eudralex/vol-2/c/smpc_guideline_rev2_en.pdf [Accessed: 14th April 2017].
SP4 Can text appeal be used to assess pain control?
Authors: Adrian Barker , Lin Lee Poh , Judith Short 
Published: January 2018

AimsCan an automated texting system be used to gather data about analgesia usage after discharge and post-operative pain scores?Our opioid analgesic for post-operative pain control had changed from codeine to morphine two years earlier.Was this dosing and supply adequate or excessive and how could we assess pain control for patients at home? Some surgeons described their technique as ‘relatively painless’ and had as a consequence chosen to stop prescribing any opioid after surgery.Previous audits by post or telephone had achieved a 40% response rate at best. Could we use the smart ‘phones that all parents carry around instead?MethodsWe recruited patients undergoing tonsillectomy ± adenoidectomy, and recorded their age, weight, gender, diagnostic indication for surgery and surgical technique.After overcoming a few IT challenges and with written consent, parents were texted a series of questions for 10 evenings postoperatively, starting the day following surgery.Questions (requiring a single digit response) included the maximum pain score (0–10) experienced, the analgesic drugs administered and any nausea or vomiting (PONV) experienced that day. Responses were stored in a secure database for analysis.Results33 patients were recruited with1 surgical cancellation. 27/32 (84%) parents responded to texts on ≥5 days.2 Patients with poor responses were excluded.Of the 30 studied, 50% were male, with age range 10 months to 15 years, and weight range 6.6 kg to 64 kg. 21 patients had sleep-disordered breathing (SDB) and 14 patients had experienced recurrent tonsillitis, including 5 who also had SDB.All children had paracetamol and ibuprofen available, but 4 patients were discharged without morphine. The average pain score ranged from 4.0 on Day 1 to a peak of 5.5 on Day 6 to a minimum of 2 on Day 10.In total, 69.2% parents gave their children morphine on one or more days in addition to simple analgesia. The rate of PONV was 30%, unrelated to morphine use.ConclusionSMS proved very successful for data collection and has great potential for further audit studies.Our data shows that pain is a significant problem for up to 10 days post-tonsillectomy and has confirmed the requirement for opioid rescue medication for all patients after discharge.We have now re-agreed a standard analgesic regime and staved off any suggestion there was just to recommend that parents buy analgesia.ReferencesWilliams G, et al. The prevalence of pain at home and its consequences in children following two types of short stay surgery: A multicentre observational cohort study. Paediatric Anaesthesia 2015;25:1254–1263.Association of Paediatric Anaesthetists of Great Britain and Ireland. Guidance for the administration of codeine and alternative opioid analgesics in children Nov 2013.
P37 Audit on the quality of documentation of paediatric prescriptions using electronic prescription charts
Authors: Philippa Stilwell , Abimbola Sanu 
Published: January 2018

AimThe aim of this project is to assess the quality of prescribing on all inpatient prescription charts on the paediatric wards in the hospital against the legal prescribing requirements (as stated in Medicines Act, 1968) and trust prescribing standards (as stated in the hospital's Medicines Management Policy).MethodsTen audit standards were identified, based on Generic Medical Record Keeping Standards (RCP, 2017), which incorporated all the legal and trust prescribing standards. A data collection tool was then designed.A single day prospective prevalence audit was conducted; data was collected on a single day from each of four paediatric wards, using the data collection tool. All staff members were blinded to the standards being assessed.Inclusion criteria: all inpatient prescription charts on the paediatric wards and all medicines prescribed on those charts were included (on the single day where data was being collected).Exclusion criteria: dietary products, total parenteral nutrition, embolism stockings and chemotherapy.Results100% compliance was achieved on the majority of patient demographics. 100% compliance was achieved in the majority of standards on prescription item analysis and in all standards for fluids prescriptions. 95% of allergy status´ were documented and 93% of these included the severity of allergy. 73% compliance was achieved in the documentation of patient weight. Improvement is also needed in documenting indication and duration of anti-microbials, where only 81% and 46% compliance was achieved, respectively.Conclusion100% compliance was achieved in many standards (in particular in those which are automated on e-prescribing, for example, patient demographics). More attention is needed to specify the patient´s weight, the allergy status and severity of allergy and the indication and duration of anti-microbials.Comparing with previous audits done when the trust used paper charts for prescribing, electronic prescribing has clearly overall increased adherence to legal prescribing requirements and trust standards which is a significant step towards improving the safety of patient care within the NHS.The results from this audit have been disseminated to remind current users of common prescribing errors. This was done by presenting the results locally and by emailing all departmental staff with the results.Recommendations from this audit include to ensure that all members of staff that have access to electronic prescribing receive the necessary training prior to starting working.Recommendations also include to discuss with pharmacy whether it is possible to make it compulsory to enter weight and allergy status prior to prescribing, with an option for omission in emergency situations.
P39 Continuous vancomycin dosing: an audit and evaluation
Authors: Fiona Robertson , Rachel Walsh , Mildrid Yeo 
Published: January 2018

AimsLate onset sepsis is a major cause of morbidity and mortality within the field of neonatology, with coagulase- negative staphylococci being the most commonly reported pathogens. Due to staphylococcal resistance patterns vancomycin is an essential therapeutic agent. Its efficacy correlates directly with duration of bacterial exposure at therapeutic levels. Some studies have suggested that continuous infusion achieves quicker and more sustained therapeutic levels than traditional intermittent dosing. Continuous dosing was introduced in our neonatal units in September 2015. This piece of work audits adherence to local prescribing and monitoring guidance whilst assessing the effectiveness of the new continuous regimes.MethodAll infants commenced on continuous vancomycin over a six month period were included. Cases were identified via pharmacy records and data collected retrospectively and prospectively. Key areas were: loading and initial continuous doses, therapeutic drug monitoring (TDM), time spent in therapeutic range and the associated effects of gestation and baseline creatinine. Adverse effects were also considered. Data was analysed using Excel and Prism.Results45 treatment episodes were eligible for analysis. Corrected gestation ranged from 24+5 to 41+6. Mean weight was 1450 g and mean duration of therapy 6.5 days. Loading, initial continuous dosing and TDM were generally carried out in line with local guidelines. Regarding the first level measured after commencement of the continuous regime; 9% of levels with continuous infusion were subtherapeutic. A previous audit of intermittent vancomycin dosing showed that 50% of first levels were subtherapeutic. Statistically there was a weak correlation between creatinine level prior to commencement of continuous vancomycin and the first level. Of all 298 levels measured 56% were therapeutic, 19% were supratherapeutic and 25% subtherapeutic. Time spent in therapeutic range was comparable across the range of gestational groups.ConclusionContinuous vancomycin dosing showed promising results in this population. Adherence to local guidelines in terms of prescribing and monitoring was good. The time taken to reach therapeutic range was shorter than previously achieved with intermittent dosing. Maintaining levels with this therapeutic range was also seen to be favourable. More detailed analysis of our results suggests that our dosing guidance is adjusted correctly to take into account important variables in vancomycin pharmacokinetics such as corrected gestational age and renal function. No adverse effects specific to vancomycin were noted during the course of this work.
P7 An audit of the management of resuscitation drugs and trolley contents
Authors: Maidre Mihkel , McVittie Paul , Isaac Rhian 
Published: January 2018

IntroductionEvery clinical area is equipped with either a resuscitation trolley containing a red emergency drug box (2222 box) or only the 2222 box for emergencies such as cardiac arrests. According to national1 and local guidelines each of these trolleys contains a certain set of drugs and a CD size oxygen cylinder.Aims wereto audit compliance of drugs, including the medical gas oxygen, with national1 and local guidelinesto audit compliance with the required daily check of resuscitation trolleys and 2222 boxesto audit frequency of expired medicinesto audit compliance with up to date resuscitation guidelinesThe aims of the audit were to assess the pharmaceutical contents in the resuscitation trolleys, monitor if regular checks are done to the trolleys, compare the pharmaceutical contents in the trolleys to those on the local clinical area’s stock list and review the resuscitation guidelines on the trolley.MethodA data collection form was created which included the drugs and local Trust resuscitation trolley content list. A free text box was included to capture drugs or drug related guidelines found on the trolley that were not officially listed.ResultsForty seven clinical areas were included in the data collection, 32 held a resuscitation trolley and a 2222 box, 15 held a 2222 box only.Compliance of drug content: 50%. Reason found for poor compliance was that most clinical areas (84.4%) did not keep 250 ml sodium chloride bags as routine stock on the ward causing a delay in replenishing following an emergency. Twenty of the trolleys contained drugs not included on the list.Compliance with equipment listCompliance of Oxygen cylinders on trolley: 5/29. Critical care unit trolleys did not keep oxygen cylinder as each bed space keeps a cylinder. One cylinder was found out of date.Compliance rate with daily trolley checks: 29/32Guidelines were found on 31/32 trolleys. Where guidelines were found, revision of the information was required.RecommendationsActions following the audit included changing the trolley content list: 250 mL sodium chloride 0.9 bags to a 500 ml sodium chloride 0.9% w/v bag which is kept routinely in each area. The guidelines are being revised to provide clearer information on dosing and administration for children.The Trust resuscitation committee have agreed to re-audit at least every 6 months.ConclusionAfter the completion of the audit the results were presented to the Resuscitation Committee and implementations were suggested in order to improve the management of resuscitation trolleys in the hospital. Together it was agreed, that a re-audit should be done in the future (3–6 months’ time) to see if these recommendations have improved the current situation.ReferenceResuscitation Council (UK). Acute care: Equipment and drug lists 2013. https://www.resus.org.uk/quality-standards/acute-care-equipment-and-drug-lists/#paed [Accessed: 6 April 2016].