Adverse drug reactions and off-label and unlicensed medicines in children: a prospective cohort study of unplanned admissions to a paediatric hospital.

AIMS: To examine the impact of off-label and unlicensed (OLUL) prescribing on adverse drug reactions (ADRs) causing unplanned admissions to a paediatric hospital. METHODS: Prescription data from a 12 month prospective cohort study of ADRs detected in children admitted to a paediatric hospital were scrutinized. The relative risk for off-label and unlicensed medicines being implicated in an ADR was calculated. Logistic regression analyses were carried out with exposure to off-label and unlicensed medicines and number of off-label and unlicensed medicines administered as predictor variables. RESULTS: Off-label and unlicensed medicines were more likely to be implicated in an ADR than authorized medicines (relative risk 1.67, 95% CI 1.38, 2.02, P < 0.001). There was a 25% increase in ADR risk (95% CI 1.16, 1.35, P < 0.001) with each additional authorized medicine and 23% (95% CI 1.10, 1.36, P < 0.001) with each additional off-label or unlicensed medicine. Logistic regression analysis focusing on non-oncology patients demonstrated that the number of authorized medicines (odds ratio 1.33, 95% CI 1.23, 1.44, P < 0.001), but not the number of off-label and unlicensed medicine courses, was a predictor of ADR risk. CONCLUSIONS: In a heterogeneous population of children admitted to a secondary/tertiary hospital, off-label and unlicensed medicines are more likely to be implicated in an ADR than authorized medicines. This was largely driven by ADRs related to drugs used in oncological practice, where the usage of off-label or unlicensed medicines was associated with a higher ADR risk than in non-oncological areas.

Adverse drug reactions and off-label and unlicensed medicines in children: a nested case-control study of inpatients in a pediatric hospital.

BACKGROUND: Off-label and unlicensed (OLUL) prescribing has been prevalent in pediatric practice. Using data from a prospective cohort study of adverse drug reactions (ADRs) among pediatric inpatients, we aimed to test the hypothesis that OLUL status is a risk factor for ADRs. METHODS: A nested case?control study was conducted within a prospective cohort study. Details of all medicines administered were recorded, including information about OLUL status. The odds ratio for OLUL medicines being implicated in a probable or definite ADR was calculated. A multivariate Cox proportional hazards regression model was fitted to the data to assess the influence that OLUL medicine use had on the hazard of an ADR occurring. RESULTS: A total of 10,699 medicine courses were administered to 1,388 patients. The odds ratio (OR) of an OLUL medicine being implicated in an ADR compared with an authorized medicine was 2.25 (95% confidence interval (CI) 1.95 to 2.59). Medicines licensed in children but given to a child below the minimum age or weight had the greatest odds of being implicated in an ADR (19% of courses in this category were implicated, OR 3.54 (95% CI 2.82 to 4.44). Each additional OLUL medicine given significantly increased the hazard of an ADR (hazard ratio (HR) 1.3 95% CI 1.2 to 1.3, P <0.001). Each additional authorized medicine given also significantly increased the hazard (HR 1.2 95% CI 1.2 to 1.3, P <0.001). CONCLUSIONS: OLUL medicines are more likely to be implicated in an ADR than authorized medicines. The number of medicines administered is a risk factor for ADRs highlighting the need to use the lowest number of medicines, at the lowest dose for the shortest period, with continual vigilance by prescribers, in order to reduce the risk of ADRs.

Incidence, characteristics and risk factors of adverse drug reactions in hospitalized children - a prospective observational cohort study of 6,601 admissions.

BACKGROUND: Adverse drug reactions (ADRs) are an important cause of harm in children. Current data are incomplete due to methodological differences between studies: only half of all studies provide drug data, incidence rates vary (0.6% to 16.8%) and very few studies provide data on causality, severity and risk factors of pediatric ADRs. We aimed to determine the incidence of ADRs in hospitalized children, to characterize these ADRs in terms of type, drug etiology, causality and severity and to identify risk factors. METHODS: We undertook a year-long, prospective observational cohort study of admissions to a single UK pediatric medical and surgical secondary and tertiary referral center (Alder Hey, Liverpool, UK). Children between 0 and 16 years 11 months old and admitted for more than 48 hours were included. Observed outcomes were occurrence of ADR and time to first ADR for the risk factor analysis. RESULTS: A total of 5,118 children (6,601 admissions) were included, 17.7% of whom experienced at least one ADR. Opiate analgesics and drugs used in general anesthesia (GA) accounted for more than 50% of all drugs implicated in ADRs. Of these ADRs, 0.9% caused permanent harm or required admission to a higher level of care. Children who underwent GA were at more than six times the risk of developing an ADR than children without a GA (hazard ratio (HR) 6.40; 95% confidence interval (CI) 5.30 to 7.70). Other factors increasing the risk of an ADR were increasing age (HR 1.06 for each year; 95% CI 1.04 to 1.07), increasing number of drugs (HR 1.25 for each additional drug; 95% CI 1.22 to 1.28) and oncological treatment (HR 1.90; 95% CI 1.40 to 2.60). CONCLUSIONS: ADRs are common in hospitalized children and children who had undergone a GA had more than six times the risk of developing an ADR. GA agents and opiate analgesics are a significant cause of ADRs and have been underrepresented in previous studies. This is a concern in view of the increasing number of pediatric short-stay surgeries.

The implementation of a Technician Enhanced Administration of Medications [TEAM] model: An evaluative study of impact on working practices in a children's hospital.

BACKGROUND: Children are frequently prescribed unlicensed and off-label medicines meaning dosing and administration of medicines to children is often based on poor quality guidance. In UK hospitals, nursing staff are often responsible for administering medications. Medication Errors [MEs] are problematic for health services, though are poorly reported and therefore difficult to quantify with confidence. In the UK, children's medicines require administration by at least two members of ward staff, known as a 'second check' system, thought to reduce Medication Administration Errors [MAEs]. OBJECTIVES: To assess the impact on working practices of the introduction of a new way of working, using Technician Enhanced Administration of Medications [TEAM] on two specialist wards within a children's' hospital. To evidence any potential impact of a TEAM ward-based pharmacy technician [PhT] on the reporting of MEs. METHODS: A TEAM PhT was employed on two wards within the children's hospital and trained in medicines administration. Firstly, an observational pre-and-post cohort design was used to identify the effect of TEAM on MEs. We analysed the hospital's official reporting system for incidents and 'near misses', as well as the personal incident log of the TEAM PhT. Secondly, after implementation, we interviewed staff about their perceptions of TEAM and its impact on working practices. RESULTS: We affirm MEs are considerably under-reported in hospital settings, but TEAM PhTs can readily identify them. Further, placing TEAM PhTs on wards may create opportunities for inter-professional knowledge exchange and increase nurses' awareness of potential MAEs, although this requires facilitation. CONCLUSIONS: TEAM PhT roles may be beneficial for pharmacy technicians' motivation, job satisfaction, and career development. Hospitals will need to consider the balance between resources invested in TEAM PhTs and the level of impact on reporting MEs. Health economic analyses could provide evidence to fully endorse integration of TEAM PhTs for all hospital settings.

Tick-borne illnesses: identification and management in the emergency department

Tick-borne illnesses are increasing in prevalence and geographic reach. Because the presentation of these illnesses is sometimes nonspecific, they can often be misdiagnosed, especially in the early stages of illness. A detailed history with questions involving recent activities and travel and a thorough physical examination will help narrow the diagnosis. While some illnesses can be diagnosed on clinical findings alone, others require confirmatory testing, which may take days to weeks to result. This issue reviews the emergency department presentation of 9 common tick-borne illnesses and evidence-based recommendations for identification, testing, and treatment.

Growth hormone prescribing and initial BMI SDS: Increased biochemical adverse effects and costs in obese children without additional gain in height.

BACKGROUND: Recombinant human growth hormone (rhGH) treatment in children is usually prescribed using actual body weight. This may result in inappropriately high doses in obese children. METHODS: Retrospective audit of all paediatric patients treated with rhGH 2010-14 at a tertiary paediatric hospital in the UK. Change in height SDS and IGF-I SDS during the first year of treatment was stratified by initial BMI SDS in a mixed cohort, and a subgroup of GH deficient (GHD) patients. Alternative doses for those BMI SDS ≥2.0 (Obese) were calculated using BSA, IBW and LBW. RESULTS: 354 patients (133 female) received rhGH, including 213 (60.2%) with GHD. Obesity was present in 40 patients (11.3%) of the unselected cohort, and 32 (15.0%) of the GHD cohort. For GHD patients, gain in height SDS was directly related to BMI SDS, except in obese patients (p<0.05). For both the entire cohort, and GHD patients only, IGF-1 SDS was significantly higher in obese patients (p<0.0001 for both groups). Cross sectional data identified 265 children receiving rhGH, 81 (30.5%) with a BMI-SDS ≥1.75. Alternate prescribing strategies for rhGH prescribing in obese patients suggest a saving of 27% - 38% annually. CONCLUSIONS: Gain in IGF-I SDS is greater in obese children, and is likely to be related to relatively higher doses of rhGH. Additional gain in height was not achieved at the higher doses administered to obese children. Alternative dosing strategies in the obese patient population should be examined in rigorous clinical trials.

Medicines in schools: a cross-sectional survey of children, parents, teachers and health professionals.

OBJECTIVES: To describe how individual schools manage medicines and strategies for implementation of guidance, to determine the nature of problems perceived by children, parents, teachers and healthcare professionals (HCPs) in relation to medicines management in schools and to highlight differences between these perceptions. DESIGN: A cross-sectional survey study in which questionnaires were completed by children, their parents and carers, groups of HCPs and head teachers. RESULTS: There were 158 respondents to this survey. The management of medicines varies between schools and this reflects how policy guidance is interpreted and is revealed by the differences in experience described. Head teachers acknowledge that there is a lack of expertise about medicines among their staff and they rely on interpretation of and adherence to policy and procedure and compliance with training was used as a measure of good medicines management. There are inconsistencies in how information about medicines is communicated between the healthcare team, families and schools, and there is evidence that this communication is not always timely or effective. This results in problems with medicines at school. Parents emphasised the need for staff at school to understand their child's condition and their medicines. CONCLUSIONS: There are differences between how individual schools manage medicines and interpret policy guidance and discrepancies between the views of each stakeholder group. There is some evidence that medicines management does not always meet the needs of children and their families. Fewer than half of parents and HCPs are satisfied with how medicines are dealt with in schools.

Central auditory processing disorders in children and adults.

Central auditory processing disorders (CAPD) can affect children and adults of all ages due to a wide variety of causes. CAPD is a neurobiologic deficit in the central auditory nervous system (CANS) that affects those mechanisms that underlie fundamental auditory perception, including localization and lateralization; discrimination of speech and non-speech sounds; auditory pattern recognition; temporal aspects of audition, including integration, resolution, ordering, and masking; and auditory performance with competing and/or degraded acoustic signals (American Speech-Language-Hearing Association, 2005a, b). Although it is recognized that central auditory dysfunction may coexist with other disorders, CAPD is conceptualized as a sensory-based auditory disorder. Administration of behavioral and/or electrophysiologic audiologic tests that have been shown to be sensitive and specific to dysfunction of the CANS is critical for a proper diagnosis of CAPD, in addition to assessments and collaboration with a multidisciplinary team. Intervention recommendations for CAPD diagnosis are based on the demonstrated auditory processing deficits and related listening and related complaints. This chapter provides an overview of current definitions and conceptualizations, methods of diagnosis of, and intervention for, CAPD. The chapter culminates with a case study illustrating pre- and posttreatment behavioral and electrophysiologic diagnostic findings.

A pilot randomised controlled trial to assess the utility of an e-learning package that trains users in adverse drug reaction causality.

OBJECTIVES: Causality assessment of adverse drug reactions (ADRs) by healthcare professionals is often informal which can lead to inconsistencies in practice. The Liverpool Causality Assessment Tool (LCAT) offers a systematic approach. An interactive, web-based, e-learning package, the Liverpool ADR Causality Assessment e-learning Package (LACAeP), was designed to improve causality assessment using the LCAT. This study aimed to (1) get feedback on usability and usefulness on the LACAeP, identify areas for improvement and development, and generate data on effect size to inform a larger scale study; and (2) test the usability and usefulness of the LCAT. METHODS: A pilot, single-blind, parallel-group, randomised controlled trial hosted by the University of Liverpool was undertaken. Participants were paediatric medical trainees at specialty training level 1+ within the Mersey and North-West England Deaneries. Participants were randomised (1 : 1) access to the LACAeP or no training. The primary efficacy outcome was score by correct classification, predefined by a multidisciplinary panel of experts. Following participation, feedback on both the LCAT and the LACAeP was obtained, via a built in survey, from participants. KEY FINDINGS: Of 57 randomised, 35 completed the study. Feedback was mainly positive although areas for improvement were identified. Seventy-four per cent of participants found the LCAT easy to use and 78% found the LACAeP training useful. Sixty-one per cent would be unlikely to recommend the training. Scores ranged from 4 to 13 out of 20. The LACAeP increased scores by 1.3, but this was not significant. CONCLUSIONS: Improving the LACAeP before testing it in an appropriately powered trial, informed by the differences observed, is required. Rigorous evaluation will enable a quality resource that will be of value in healthcare professional training.

Clinical coding of prospectively identified paediatric adverse drug reactions--a retrospective review of patient records.

BACKGROUND: National Health Service (NHS) hospitals in the UK use a system of coding for patient episodes. The coding system used is the International Classification of Disease (ICD-10). There are ICD-10 codes which may be associated with adverse drug reactions (ADRs) and there is a possibility of using these codes for ADR surveillance. This study aimed to determine whether ADRs prospectively identified in children admitted to a paediatric hospital were coded appropriately using ICD-10. METHODS: The electronic admission abstract for each patient with at least one ADR was reviewed. A record was made of whether the ADR(s) had been coded using ICD-10. RESULTS: Of 241 ADRs, 76 (31.5%) were coded using at least one ICD-10 ADR code. Of the oncology ADRs, 70/115 (61%) were coded using an ICD-10 ADR code compared with 6/126 (4.8%) non-oncology ADRs (difference in proportions 56%, 95% CI 46.2% to 65.8%; p < 0.001). CONCLUSIONS: The majority of ADRs detected in a prospective study at a paediatric centre would not have been identified if the study had relied on ICD-10 codes as a single means of detection. Data derived from administrative healthcare databases are not reliable for identifying ADRs by themselves, but may complement other methods of detection.