Stephen Tomlin

Risk factors associated with adverse drug reactions in hospitalised children: international multicentre study

BackgroundUnderstanding the epidemiology and risk factors of adverse drug reactions (ADRs) is important in order to develop appropriate prevention strategies. This study aimed to identify risk factors associated with ADRs in hospitalised children and recommend strategies to minimise ADRs.MethodsA prospective multicentre cohort study was conducted on paediatric general medical wards in five European and non-European hospitals. ADRs were identified by intensive chart review. Multivariable logistic regression was used to investigate risk factors associated with ADRs. For the risk factor analysis, prescribed drugs were divided into high-risk and low-risk drug groups. Analgesics, anti-epileptics, antibacterials and antimycotics for systemic use, corticosteroids for systemic use and immunosuppressant agents were considered as high-risk groups whereas the remaining drug classes were defined as low-risk drug groups.ResultsA total of 1,253 paediatric patients were identified [Australia (n = 145), Germany (n = 372), Hong Kong (n = 138), Malaysia (n = 291), UK (n = 307)]. A total of 328 ADRs were observed in 16.7% of patients (186/1,115). Use of five or more low-risk drugs per patient or  three or more high-risk drugs was a strong predictor for ADRs (OR 4.7, 95% CI 2.4–9.3; OR 6.5, 95% CI 2.7–16.0 respectively; p < 0.001). Older children were more likely to experience ADRs; gender was not significantly associated.ConclusionTo reduce the risk of ADRs in children, clinicians and pharmacists should aim to minimise polypharmacy and be aware of higher ADR risks associated with some drug groups.

Medication use in childhood dystonia

BACKGROUND Data around current prescription practices in childhood dystonia is limited. Medication use may be limited by side effects, the incidence of which is uncertain. For a large cohort assessed by our supra-regional service we aimed to: i) Review medications used at the point of referral. ii) Determine the prevalence of adverse drug responses (ADR) resulting in discontinuation of drug use. iii) Identify clinical risk factors for ADR. METHODS Case note review of 278 children with dystonia referred to our service. Data collected on medications, ADR, dystonia aetiology, Gross Motor Function Classification System (GMFCS) level and motor phenotype (pure dystonia/mixed dystonia-spasticity). Logistic regression analysis was used to identify risk factors for ADR. RESULTS At referral 82/278 (29.4%) children were taking no anti-dystonic medication. In the remainder the median number of anti-dystonic medications was 2 (range 1-5). Medications use increased with worsening GMFCS level. The commonest drugs used were baclofen (118/278: 42.4%), trihexyphenidyl (98/278: 35.2%), l-Dopa (57/278: 20.5%) and diazepam (53/278: 19%). Choice of medication appeared to be influenced by dystonia aetiology. ADR had been experienced by 171/278 (61.5%) of children. The commonest drugs responsible for ADR were trihexyphenidyl (90/171: 52.3%), baclofen (43/171: 25.1%) and l-Dopa (26/171: 15.2%). Binary logistic regression demonstrated no clinical risk factors for ADR. CONCLUSIONS ADR is commonly experienced by children with dystonia, regardless of dystonia severity or aetiology. A wide variation in drug management of dystonia was identified. Collectively these findings highlight the need for a rational approach to the pharmacological management of dystonia in childhood.

Adverse Drug Reactions in Children--International Surveillance and Evaluation (ADVISE): a multicentre cohort study

AbstractBackground: A previous meta-analysis reported that 9.5% of hospitalized children suffered from an adverse drug reaction (ADR); however, reported incidences among studies varied. Objective: To enhance the knowledge of ADRs in paediatric hospitalized patients at a global level we investigated the incidence and characteristics of ADRs in hospitalized children in European and non-European countries. Methods: A prospective observational cohort study was conducted in academic and non-academic hospitals in five countries: Australia, Germany, Hong Kong, Malaysia and the UK. Children aged 0–18 years admitted during a 3-month period (between 1 October 2008 and 31 December 2009) were recruited. The main outcome measures were incidence, causality and outcome of ADRs. Results: A total of 1278 patients (1340 admissions) were included [Australia n = 146 (149 admissions), Germany n = 376 (407), Hong Kong n = 143 (149), Malaysia n = 300 (314) and the UK n = 313 (321)]. The median age was 2 years (interquartile range [IQR] 0–7). Patients received a total of 5367 drugs (median 3; IQR 2–5) and median length of hospital stay was 4 days (IQR 3–7). A total of 380 ADRs were identified in 211 patients. The resultant ADR incidence of 16.5% (95% CI 14.5, 18.7) varied significantly between countries (p < 0.001). The highest incidences were observed in Malaysia and the UK. 65.3%(n = 248) of ADRs were found to be probable, and 24% of the ADRs were serious, with one being fatal. Conclusions: By comparing data from five countries in Europe, Asia and Australia we have shown that the incidence of ADRs in hospitalized children is at least as high as incidences published in adults. However, the variation between countries was mainly due to different populations and treatment strategies. Particular attention should be given to opioid use in hospitalized children.

Drug-related problem in children with chronic kidney disease.

Drug therapies in the management of chronic kidney disease (CKD) are complex and specialised and have a high potential for drug-related problem (DRP). In adult CKD populations, the identification and resolution of DRP has been shown to have beneficial effects on disease management, adherence and knowledge of treatment, patient’s quality of life, hospitalisation rate and length of stay and cost to the healthcare system. The focus of this article is the review of published studies on DRP in children with CKD. There is a lack of information on the epidemiology of DRP in this patient group, and research in this area is therefore needed to better understand and manage DRP in children with CKD.

The RCPCH care pathway for children at risk of anaphylaxis: an evidence and consensus based national approach to caring for children with life-threatening allergies

Aims Numerous studies have identified shortcomings in the management of children at risk of severe acute allergic reactions (anaphylaxis). The Science and Research Department at the Royal College of Paediatrics and Child Health (RCPCH) was commissioned by the Department of Health to develop competence based national care pathways for children with allergies. Anaphylaxis is the first completed pathway. Methods The anaphylaxis pathway was developed by a multidisciplinary working group, reviewed by a broad group of stakeholders and approved by the Allergy Care Pathways Project Board and the RCPCH Clinical Standards Committee. Results Pathway development is described under five headings: evidence review, mapping, external review, core knowledge documents and key recommendations. The full pathway can be downloaded from www.rcpch.ac.uk/allergy/anaphylaxis. This document describes the entry points and the ideal pathway of care from self-care through to follow-up. The five key recommendations focus on: (1) prompt administration of adrenaline by intramuscular injection; (2) referral to specialists with competence in paediatric allergies; (3) risk analysis; (4) provision of a self-management plan; and (5) suggested creation of a national anaphylaxis death register. Conclusions We present the first national care pathway for anaphylaxis, which is based on a critique of published evidence, expert consensus and multi-stakeholder input including patient representation via the Anaphylaxis Campaign. The Project Board urges health professionals to work together across networks to improve care for children at risk of anaphylaxis, in particular during the period after an acute reaction. Additionally, the Project Board strongly recommends the funding of a national anaphylaxis register.

An evaluation of the epidemiology of medication discrepancies and clinical significance of medicines reconciliation in children admitted to hospital

Aims To determine the incidence of unintended medication discrepancies in paediatric patients at the time of hospital admission; evaluate the process of medicines reconciliation; assess the benefit of medicines reconciliation in preventing clinical harm. Method A 5 month prospective multisite study. Pharmacists at four English hospitals conducted admission medicines reconciliation in children using a standardised data collection form. A discrepancy was defined as a difference between the patients preadmission medication (PAM), compared with the initial admission medication orders written by the hospital doctor. The discrepancies were classified into intentional and unintentional discrepancies. The unintentional discrepancies were assessed for potential clinical harm by a team of healthcare professionals, which included doctors, pharmacists and nurses. Results Medicines reconciliation was conducted in 244 children admitted to hospital. 45% (109/244) of the children had at least one unintentional medication discrepancy between the PAM and admission medication order. The overall results indicated that 32% (78/244) of patients had at least one clinically significant unintentional medication discrepancy with potential to cause moderate 20% (50/244) or severe 11% (28/244) harm. No single source of information provided all the relevant details of a patients medication history. Parents/carers provided the most accurate details of a patients medication history in 81% of cases. Conclusions This study demonstrates that in the absence of medicines reconciliation, children admitted to hospitals across England are at risk of harm from unintended medication discrepancies at the transition of care from the community to hospital. No single source of information provided a reliable medication history.

Trends and patterns of hormonal contraceptive prescribing for adolescents in primary care in the UK

Background Hormonal contraceptives are the most common method used worldwide by teenagers to prevent unwanted pregnancies. To date there are limited data about such use by teenagers in the UK. This study investigated trends and patterns of hormonal contraceptive prescribing to adolescents aged 12–18 years in UK primary care between 2002 and 2011. Methods A retrospective cohort study using the IMS Disease Analyzer database was conducted. All females aged 12–18 years with ≥1 prescription for a contraceptive drug between 1 January 2002 and 31 December 2011 were included. Annual prevalence of contraceptive drug prescribing was calculated, and indications for prescribing, and types of contraceptive drug prescribed, were examined. Results In 2002, 13.7% (6135/44 532) of female adolescents received prescriptions for hormonal contraceptives, compared to 19.0% (6597/34 676) in 2011. The majority of female adolescents [2002: 76.2% (4676/6135); 2011: 65.7% (4334/6597)] received a contraceptive drug for ‘contraceptive management’. The combined oral contraceptive (COC), ‘progestogen+estrogen’, was the most commonly prescribed. Although use of progestogen-only contraceptives was lower than COCs, the number of patients who received desogestrel pills and etonogestrel implants increased during the study period; levonorgestrel pill use declined. Only one injectable progestogen, long-acting depot medroxyprogesterone acetate, was prescribed. Conclusions Use of hormonal contraceptives among adolescents increased between 2002 and 2011, and COC usage was dominant. The increasing use of hormonal contraceptives in adolescents, especially in younger adolescents, warrants further investigation, including research into the long-term safety of these medicines in this age group.

An evaluation of paediatric medicines reconciliation at hospital discharge into the community

A UK national survey of primary care physicians has indicated that the medication information on hospital discharge summary was incomplete or inaccurate most of the time. Internationally, studies have shown that hospital pharmacists interventions reduce these discrepancies in the adult population. There have been no published studies on the incidence and severity of the discrepancies of the medication prescribed for children specifically at discharge to date. The objectives of this study were to investigate the incidence, nature and potential clinical severity of medication discrepancies at the point of hospital discharge in a paediatric setting.

What is the current practice of medicines reconciliation in children nationally in the UK

The National Institute for Health and Clinical Excellence/National Patient Safety Agency (NICE/NPSA) guidelines for medicines reconciliation (MR) on admission to hospital in adult inpatients were introduced in 2007, but they excluded children less than 16 years of age.

The feasibility of using dose-banded syringes to improve the safety and availability of patient-controlled opioid analgesic infusions in children

Opioid infusions are essential therapy for children in severe pain. Patient controlled analgesia (PCA) is an attractive treatment option because of the multiple benefits it provides: immediate and effective pain relief, titration of analgesia and empowerment of the patient (or nurse) to have a degree of control over their pain which helps to retain autonomy and decrease anxiety. However, opioid infusions for children carry a high risk of medication error. Risks include the complexity in calculating dosages, the manipulation of small volumes to prepare individual infusions and the necessity to deliver the infusion with precision at low flow rates (down to 0.1 mL/h). During PCA additional boluses on top of the baseline infusion rate add to the pharmaceutical and therapeutic complexity. The severe side effects of opioids, including hypoventilation, hypotension and sedation, exacerbate the risk and raise great concern in hospitals, plus limiting the use of PCA in community and hospice settings. At present there is no international standard practice or guideline on the way that PCA is administered. This commentary highlights problems with current practices of preparing and administering PCA in hospitalised children in the UK. Additionally, we advocate a system management approach which we are piloting to address the problems of opioid-based PCA for children in a large (200-bed) hospital, the Evelina London Childrens Hospital, in the hope of developing safer practices for the delivery of opioid analgesia. Intravenous infusions are an important means of administering therapy, yet the technical process is complex with multiple error-prone steps. The errors associated with preparing and administering intravenous infusions in paediatrics (eg, low volume at low flow rate) make drug delivery by infusion a particularly high risk,1 but continuous infusions of opioid are crucial to achieve effective analgesia and avoid uncontrolled pain in neonates and children with conditions such as sickle …