Off-label drug use, medication errors and adverse drug events : among Swedish pediatric inpatients

Background: In pediatrics, treatment with drugs is an important and fully integrated part of everyday medical practice. However, authorized drugs specified to be used in children are often lacking which leads to off-label use, i.e. outside of approved product monographs. Another challenge is medication errors (ME) which is an important cause of adverse drug events (ADE) in hospitalized children. The consequences and effects of these conditions are largely unknown. Studies within the field of pediatric, and especially neonatal, drug safety are lacking. Unsafe drug use may be an important and unrecognized contributor to suboptimal health in this vulnerable group with limited capacity for drug metabolism and excretion. Aim: The general aim of the thesis was to explore the magnitude of drug safety issues within Swedish pediatric inpatients. More specifically we aimed to investigate; I. National extent of off-label drug-use, II. Contents in national ME incident reports, III. Type of ADEs in a pediatric inpatient setting and IV. The views of pediatricians on a clinical decision support system (CDSS) to aid in prescribing drugs. Methods: In the four papers we used different study approaches. In paper I we performed a descriptive cross-sectional study based on collection of drug charts during two time-points. In paper II we used an analytic cross-sectional register-based study on Lex Maria incident reports and complaints from the Health and Social Care Inspectorate. In paper III we carried out a cohort study using a chart review with a pediatric trigger tool covering 600 admissions stratified in four different units, and in paper IV we used qualitative semi-structured interviews with pediatricians. Results: Paper I showed that half of all drug orders received by pediatric inpatients was outside approved product monographs, extemporaneously prepared or unlicensed. In paper II the ME reports indicated frequent occurrence of substances from three previously known high-alert lists with specified error characteristics among the different drug handling processes. In paper III we showed that skin/tissue/vascular harm, omission of analgesic drug therapy and hospital acquired infections are the most abundant ADEs as identified by an extended set of medical record triggers. In paper IV the CDSS-experiences of pediatricians emerged into six categories being: use, benefit, confidence, situations of disregards, misgivings/risks and development potential. Conclusions: Paper I found a similar situation in Sweden regarding off-label and unlicensed drug use as in many other countries. Paper II found that the existing high-alert lists are relevant for pediatric inpatients and suggested the use of process dependent high-alert lists. Paper III found that ADEs are common in pediatric inpatients and that the incidence varied with ADE-type, depending on ward and time after admission. In paper IV the experiences of pediatricians after the implementation of a CDSS gave insights on usability and the need for future developments

Safety Measures to Reduce Medication Administration Errors in Paediatric Intensive Care Unit

Objective: Medicine administration is the last process of the medication cycle. However, errors can happen during this process. Children are at an increased risk from these errors. This has been extensively investigated but evidence is lacking on effective interventions. Therefore, the aim of this research is to propose safety measures to reduce medication administration errors (MAE) in the Paediatric Intensive Care Unit (PICU). Method: The research was carried out over five studies; 1) systematic literature review, 2) national survey of PICU medication error interventions, 3) retrospective analysis of medication error incidents, 4) prospective observation of the administration practice, and 5) survey of PICU healthcare professionals’ opinions on MAE contributory factors and safety measures. Results: Hospital MAE in children found in literature accounted for a mean of 50% of all reported medication error reports (n= 12552). It was also identified in a mean of 29% of doses observed (n= 8894). This study found MAE retrospectively in 43% of all medication incidents (n= 412). Additionally, a total of 269 MAEs were observed (32% per dose observation). The characteristics of the interventions used to reduce MAE are diverse but it illustrated that a single approach is not enough. Also for an intervention to be a success it is fundamental to build a safety culture. This is achieved by developing a culture of collaborative learning from errors without assigning blame. Furthermore, MAE contributing factors were found to include; interruptions, inadequate resources, working conditions and no pre-prepared infusions. The following safety measures were proposed to reduce MAE; 1) dose banding, 2) improved lighting conditions, 3) decision support tool with calculation aid, 4) use of pre-prepared infusions, 5) enhance the double-checking process, 6) medicine administration checklist, and 7) an intolerant culture to interruption. Conclusion: This is one of the first comprehensive study of to explore MAE in PICU from different perspectives. The aim and objectives of the research were fulfilled. Future research includes the need to implement the proposed safety measures and evaluate them in practice

Supporting pharmacists and prescribers in paediatrics:explorations of current practice and electronic systems for medicine related decision support

There is a lack of published literature describing resource and support needs of paediatric prescribers and pharmacists. In order to understand how to support this group of healthcare professionals it is first necessary to identify their current use of resources when prescribing and providing pharmacy services in paediatrics. The methods used in this thesis were mixed. They included: focus groups with prescribers, self-completed questionnaires with paediatric pharmacy staff and paediatric prescribers, interviews with electronic prescribing leaders and documentary analysis of board meeting minutes from paediatric hospitals in England. The resource reported to be used most frequently and most useful by both pharmacists and prescribers was the British National Formulary for Children. The BNFc was reported to be useful due to its current information and ease of use. Pharmacist and prescriber participants reported using a wide range of resources suggesting that there is no single resource that meets their information needs when working in paediatrics. There was general agreement that the current poor availability of some paediatric prescribing information could have an adverse effect on the care of patients. Pharmacy staff reported that an electronic medicines management system improved the supply of medication to inpatients, but described a need for additional development of the system for it to be suitable for all medication supply. Paediatric hospital board minutes reported a range of interventions to improve prescribing, but few reported outcomes. To conclude: this thesis describes the extensive resource needs of both paediatric pharmacists and prescribers. The choice of resource is not affected by the status of its accreditation with NICE, raising a question of the value of this accreditation process. The lack of collaboration between paediatric hospitals regarding strategies used to improve paediatric prescribing is not acceptable and may lead to duplication of work or investment in poor support solutions

Investigating intravenous medication preparation errors in hospital clinical areas.

Medication is a leading cause of iatrogenic injury throughout the world and this has spawned a rapidly growing body of patient safety research. Lack of standardisation of terminology and research methods, and international variations in healthcare delivery pose problems when interpreting study findings. Within the UK, intravenous medicines prepared in hospital clinical areas have been identified as an area requiring further investigation. A Delphi consensus technique was used to agree a practical error definition for intravenous medicines assembly and preparation in hospital clinical areas, suitable for multiprofessional and international use. This included a framework of inclusion and exclusion criteria which, if adopted for future research, would reduce variability and allow comparison of results. The definition and framework was translated into an observational data collection tool and validated for observational audit in adult and paediatric ward areas. In depth interviews were used to elucidate nurses' views and opinions regarding problems they experienced with intravenous medicines assembly and preparation and how they resolved them. They suggested that priority should be given to minimising interruptions, to the design and provision of a dedicated workspace, and to use of needle-free devices. Appropriate information on intravenous preparation needed to be readily accessible within clinical areas. Standardisation of the taxonomy, standards applied, and competency required for intravenous medicines preparation is needed. Pharmaceutical manufacturers should improve product design to minimise the number and complexity of manipulations required in the workplace. A human factors approach should be used to analyse and plan medicines safety solutions

Characterising the types of paediatric adverse events detected by the global trigger tool - CareTrack Kids

Introduction A common method of learning about adverse events (AEs) is by reviewing medical records using the global trigger tool (GTT). However, these studies generally report rates of harm. The aim of this study is to characterise paediatric AEs detected by the GTT using descriptive and qualitative approaches. Methods Medical records of children aged 0–15 were reviewed for presence of harm using the GTT. Records from 2012–2013 were sampled from hospital inpatients, emergency departments, general practice and specialist paediatric practices in three Australian states. Nurses undertook a review of each record and if an AE was suspected a doctor performed a verification review of a summary created by the nurse. A qualitative content analysis was undertaken on the summary of verified AEs. Results A total of 232 AEs were detected from 6,689 records reviewed. Over four-fifths of the AEs (193/232, 83%) resulted in minor harm to the patient. Nearly half (112/232, 48%) related to medication/intravenous (IV) fluids. Of these, 83% (93/112) were adverse drug reactions. Problems with medical devices/equipment were the next most frequent with nearly two-thirds (32/51, 63%) of these related to intravenous devices. Problems associated with clinical processes/procedures comprise one in six AEs (38/232, 16%), of which diagnostic problems (12/38, 32%) and procedural complications (11/38, 29%) were the most frequent. Conclusion Adverse drug reactions and issues with IVs are frequently identified AEs reflecting their common use in paediatrics. The qualitative approach taken in this study allowed AE types to be characterised, which is a prerequisite for developing and prioritising improvements in practice

Medication safety in intravenous drug administration : error causes and systemic defenses in hospital setting

Intravenous administration of drugs is associated with the highest medication error frequencies and more serious consequences to the patient than any other administration route. The bioavailability of intravenously administered medication is high, the therapeutic dose range is often narrow, and effects are hard to undo. Many intravenously administered drugs are high-alert medications, bearing a heightened risk of causing significant patient harm if used in error. Smart infusion pumps with dose error-reduction software can be used to prevent harmful medication errors in high-risk clinical settings, such as neonatal intensive care units. This study investigated intravenous medication safety in hospital settings by identifying recent research evidence related to systemic causes of medication errors (Study I) and systemic defenses to prevent these errors (Study II). The study also explored the development of dose-error reduction software in a neonatal intensive care unit (Study III). A systems approach to medication risk management based on the Theory of Human Error was applied as a theoretical framework. The study was conducted in two phases. In the first phase, a systematic review of recent research evidence on systemic causes of intravenous medication errors (Study I) and systemic defenses aiming to prevent these errors (Study II) was carried out. In Study I, 11 studies from six countries were included in the analysis. Systemic causes related to prescribing (n=6 studies), preparation (n=6), administration (n=6), dispensing and storage (n=5) and treatment monitoring (n=2) were identified. Insufficient actions to secure safe use of high-alert medications, lack of knowledge of the drug, failures in calculation tasks and in double-checking procedures, and confusion between look-alike, sound-alike medications were the leading causes of intravenous medication errors. The number of the included studies was limited, all of them being observational studies and graded as low quality. In Study II, 46 studies from 11 countries were included in the analysis. Systemic defenses related to administration (n=24 studies), prescribing (n=8), preparation (n=6), treatment monitoring (n=2), and dispensing (n=1) were identified. In addition, five studies explored defenses related to multiple stages of the medication use process. Defenses including features of closed-loop medication management systems appeared in 61% of the studies, smart pumps being the defense most widely studied (24%). The evidence quality of the included articles was limited, as 83% were graded as low quality, 13% moderate quality, and only 4% high quality. A mixed-methods study was conducted in the second phase, applying qualitative and quantitative methods (Study III). Medication error reports were used to develop simulation-type test cases to assess the suitability of dosing limits in a neonatal intensive care unit’s smart infusion pump drug library. Of all medication errors reported in the neonatal intensive care unit, 3.5% (n=21/601) involved an error or near-miss related to wrong infusion rate. Based on the identified error mechanisms, 2-, 5-, and 10-fold infusion rates and mix-ups between infusion rates of different drugs were established as test cases. When conducting the pump programming for the test cases (n=226), no alerts were triggered with infusion rates responding to the usual dosages (n=32). Of the erroneous 2-, 5-, and 10-fold infusion rates, 73% (n = 70/96) caused an alert. Mix-ups between infusion rates triggered an alert only in 24% (n=24/98) of the test cases. This study provided an overview of recent research evidence related to intravenous medication safety in hospital settings. Current intravenous medication systems remain vulnerable, which can result in patient harm. While in-hospital intravenous medication use processes are developing towards closed-loop medication management systems, combinations of different defenses and their effectiveness in error prevention should be explored. In addition to improved medication safety, implementing new systemic defenses leads to new error types, emphasizing the importance of continuous proactive risk management as an essential part of clinical practice.Laskimonsisäiseen lääkkeen annosteluun liittyy merkittävä lääkityspoikkeamien ja vakavien haittatapahtumien riski. Sairaaloissa käytetään useita laskimoon annosteltavia suuren riskin lääkkeitä, joiden virheellinen käyttö johtaa muita lääkkeitä todennäköisemmin vakaviin haittoihin. Tässä tutkimuksessa tunnistettiin järjestelmällisen kirjallisuuskatsauksen perusteella lääkityspoikkeamien järjestelmälähtöisiä syitä (osatyö I) sekä lääkehoitoprosessin suojauksia (osatyö II). Lisäksi tutkittiin älyinfuusiopumppujen käyttöönottoa vastasyntyneiden teho-osastolla. Teoreettisena viitekehyksenä käytettiin inhimillisen erehdyksen teoriaa ja järjestelmänäkökulmaa lääkehoitoprosessin riskien hallinnassa. Osatyön I aineistosta (n=11 tutkimusta) tunnistettiin lääkityspoikkeamien syntyyn vaikuttavia järjestelmälähtöisiä syitä, jotka liittyivät lääkehoidon määräämiseen (n=6), käyttökuntoon saattoon (n=6), antoon (n=6), jakeluun ja varastointiin (n=5) sekä seurantaan (n=2). Yleisimpiä syitä olivat riittämättömät toimenpiteet suuren riskin lääkkeiden turvallisen käytön varmistamisessa, ammattilaisten heikot tiedot lääkkeistä, virheet laskutoimituksissa ja kaksoistarkistuksissa sekä toisiltaan näyttävien ja kuulostavien lääkkeiden sekaantuminen keskenään. Osatyön II aineistossa (n=46 tutkimusta) kuvattiin lääkehoitoprosessin suojauksia, jotka liittyivät lääkkeiden annosteluun (n=24), määräämiseen (n=8), käyttökuntoon saattoon (n=6), hoidon seurantaan (n=2) ja jakeluun (n=1). Lisäksi viidessä tutkimuksessa kuvattiin useaan lääkehoitoprosessin vaiheeseen liittyviä suojauksia. Katkeamattoman lääkehoitoprosessin piirteitä tunnistettiin 61 prosentissa tutkimuksista ja älyinfuusiopumput olivat eniten tutkittu suojaus (24 %). Osatyö III toteutettiin monimenetelmätutkimuksena. Vastasyntyneiden teho-osastolla raportoitujen lääkityspoikkeamien pohjalta kehitettiin simulaatiotyyppisiä testitapauksia, joilla arvioitiin annosrajojen sopivuutta älyinfuusiopumppujen lääkekirjastoon. Lääkityspoikkeamista 3,5 % (n=21/601) liittyi väärään infuusionopeuteen ja niiden perusteella testitapauksiksi määritettiin 2-, 5- ja 10-kertaiset infuusionopeudet sekä eri lääkkeiden antonopeuksien sekaantuminen keskenään. Testitapauksissa (n=226) infuusiopumput eivät hälyttäneet tavanomaisia nopeuksia ohjelmoitaessa (n=32), mutta virheellisistä infuusionopeuksista 73 % (n=70/96) aiheutti hälytyksen. Nopeuksien sekaantuminen keskenään laukaisi hälytyksen vain 24 %:ssa (n=24/98) testitapauksista. Sairaaloiden laskimonsisäinen lääkehoitoprosessi kehittyy kohti katkeamatonta lääkehoitoprosessia, mutta se on edelleen altis lääkityspoikkeamille. Kirjallisuuskatsauksiin sisällytettyjen tutkimusten laatu oli pääosin heikko, joten lääkityspoikkeamien riskitekijöitä ja suojauksia tulee edelleen tutkia yhä laadukkaammissa tutkimusasetelmissa. Uusien suojausten käyttöönotto muuttaa myös riskikohtia, mikä korostaa ennakoivan riskienhallinnan merkitystä osana sairaaloiden toimintaa

Prescribing errors at an academic teaching hospital in Johannesburg

A dissertation submitted to the School of Therapeutic Sciences, Faculty of Health Sciences , University of the Witwatersrand in fulfillment of the requirements for the degree of Master of Science in Medicine (Pharmacology) Johannesburg October 2017Prescribing errors are considered the most preeminent error in medicine and currently there have been no South African published studies which investigated the occurrence and types of prescribing errors in our hospitals. Aims To classify and determine the occurrence of medication prescribing errors in selected ward prescriptions in an academic teaching hospital in Johannesburg. In addition to determine the reasons why these errors occur. Methods This study was a mixed methods study that first investigated prescribing error using a retrospective chart review in four wards (medical, surgical, psychiatric and paediatric wards) over a period of two consecutive months. The second part of the study involved using focus groups to determine the systems factors that led to errors taking place in the hospital. Results The adult prescribing error percentage was calculated at 17.9% and the paediatric error rate was 31.8%. There was a statistically significant difference in the error rate between the medical ward and others with an error rate of 19.97% in the medical ward, 13.28% in the surgical ward, 17.48% in the psychiatric ward and 31.80% in the paediatric ward. Clear systems factors such as lack of supervision, long working hours, lack of clinical pharmacology training and even lack of prescriber feedback were present that lead to errors taking place. Conclusions This was the first study in South Africa to compare four wards and to report on adult and paediatric prescribing errors. There were clear systems factors that could be linked to prescribing errors taking place and recommendations to reduce prescribing errors in the hospital are made.MT 201