Background 
Adverse drug reactions in children are an important public health problem. We have undertaken a systematic review of observational studies in children in three settings: causing admission to hospital, occurring during hospital stay and occurring in the community. We were particularly interested in understanding how ADRs might be better detected, assessed and avoided.


Methods and Findings 
We searched nineteen electronic databases using a comprehensive search strategy. In total, 102 studies were included. The primary outcome was any clinical event described as an adverse drug reaction to one or more drugs. Additional information relating to the ADR was collected: associated drug classification; clinical presentation; associated risk factors; methods used for assessing causality, severity, and avoidability. Seventy one percent (72/102) of studies assessed causality, and thirty four percent (34/102) performed a severity assessment. Only nineteen studies (19%) assessed avoidability. Incidence rates for ADRs causing hospital admission ranged from 0.4% to 10.3% of all children (pooled estimate of 2.9% (2.6%, 3.1%)) and from 0.6% to 16.8% of all children exposed to a drug during hospital stay. Anti-infectives and anti-epileptics were the most frequently reported therapeutic class associated with ADRs in children admitted to hospital (17 studies; 12 studies respectively) and children in hospital (24 studies; 14 studies respectively), while anti-infectives and non-steroidal anti-inflammatory drugs (NSAIDs) were frequently reported as associated with ADRs in outpatient children (13 studies; 6 studies respectively). Fourteen studies reported rates ranging from 7%–98% of ADRs being either definitely/possibly avoidable.


Conclusions 
There is extensive literature which investigates ADRs in children. Although these studies provide estimates of incidence in different settings and some indication of the therapeutic classes most frequently associated with ADRs, further work is needed to address how such ADRs may be prevented.

Adverse Drug Reactions in Children—A Systematic Review

Objectives: To estimate the extent, nature and consequences of adverse events in a large National Health Service (NHS) hospital, and to evaluate the reliability of a two-stage casenote review method in identifying adverse events.

Design: A two-stage structured retrospective patient casenote review.

Setting: A large NHS hospital in England.

Population: A random sample of 1006 hospital admissions between January and May 2004: surgery (n = 311), general medicine (n = 251), elderly (n = 184), orthopaedics (n = 131), urology (n = 61) and three other specialties (n = 68).

Main outcome measures: Proportion of admissions with adverse events, the proportion of preventable adverse events, and the types and consequences of adverse events.

Results: 8.7% (n = 87) of the 1006 admissions had at least one adverse event (95% CI 7.0% to 10.4%), of which 31% (n = 27) were preventable. 15% of adverse events led to impairment or disability which lasted more than 6 months and another 10% contributed to patient death. Adverse events led to a mean increased length of stay of 8 days (95% CI 6.5 to 9). The sensitivity of the screening criteria in identifying adverse events was 92% (95% CI 87% to 96%) and the specificity was 62% (95% CI 53% to 71%). Inter-rater reliability for determination of adverse events was good (κ = 0.64), but for the assessment of preventability it was only moderate (κ = 0.44).

Conclusion: This study confirms that adverse events are common, serious and potentially preventable source of harm to patients in NHS hospitals. The accuracy and reliability of a structured two-stage casenote review in identifying adverse events in the UK was confirmed.

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Extent, nature and consequences of adverse events: results of a retrospective casenote review in a large NHS hospital

Background: Limited data are available on adverse events among children admitted to hospital. The Canadian Paediatric Adverse Events Study was done to describe the epidemiology of adverse events among children in hospital in Canada. Methods: We performed a 2-stage medical record review at 8 academic pediatric centres and 14 community hospitals in Canada. We reviewed charts from patients admitted from April 2008 through March 2009, evenly distributed across 4 age groups (0 to 28 d; 29 to 365 d; > 1 to 5 yr and > 5 to 18 yr). In stage 1, nurses and health records personnel who had received training in the use of the Canadian Paediatric Trigger Tool reviewed medical records to detect triggers for possible adverse events. In stage 2, physicians reviewed the charts identified as having triggers and described the adverse events. Results: A total of 3669 children were admitted to hospital during the study period. The weighted rate of adverse events was 9.2%. Adverse events were more frequent in academic pediatric centres than in community hospitals (adjusted odds ratio [OR] 2.98, 95% confidence interval [CI] 1.65–5.39). The incidence of preventable adverse events was not significantly different between types of hospital, but nonpreventable adverse events were more common in academic pediatric centres (adjusted OR 4.39, 95% CI 2.08–9.27). Surgical events predominated overall and occurred more frequently in academic pediatric centres than in community hospitals (37.2% v. 21.5%, relative risk [RR] 1.7, 95% CI 1.0–3.1), whereas events associated with diagnostic errors were significantly less frequent (11.1% v. 23.1%, RR 0.5, 95% CI 0.2–0.9). Interpretation: More children have adverse events in academic pediatric centres than in community hospitals; however, adverse events in the former are less likely to be preventable. There are many opportunities to reduce harm affecting children in hospital in Canada, particularly related to surgery, intensive care and diagnostic error.

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Adverse events among children in Canadian hospitals: the Canadian Paediatric Adverse Events Study

Advances in diagnostic tests, technological interventions, and pharmacotherapy have resulted in spectacular results for many intensive care unit (ICU) patients who, in earlier generations, would have succumbed to their critical illness. At the same time, the complexity and intensity of care required for ICU patients is also associated with greater risks for harm resulting from care. As in other inpatient areas, medications are the most common type of therapy in ICUs and are also associated with the most frequent type of ICU adverse events. Critically ill patients are at high risk for adverse drug events for many reasons, including the complexity of their disease that creates challenges in drug dosing, their vulnerability to rapid changes in pharmacotherapy, the intensive care environment providing ample distractions and opportunity for error, the administration of complex drug regimens, the numerous high-alert medications that they receive, and the mode of drug administration. The clinical outcomes of adverse drug events can result in end-organ damage and even death. The costs of an adverse drug event can be substantial to healthcare systems with an additional $6,000-$9,000 for each event. The multiprofessional patient care team is one approach to promoting patient safety in the ICU.

Adverse drug events in intensive care units: risk factors, impact, and the role of team care.

Background: Adverse drug events (ADEs) are an important problem in all hospitalized patients as these events represent medication-related patient harm. Few epidemiologic data exist regarding ADEs in the pediatric inpatient setting and, in particular, the economic impact of such ADEs upon the healthcare sector.

Incidence, preventability, and impact of Adverse Drug Events (ADEs) and potential ADEs in hospitalized children in New Zealand: a prospective observational cohort study.

Background: In medication safety research studies medication related events are often classified by type, seriousness, and degree of preventability, but there is currently no universally reliable “gold standard” approach. The reliability (reproducibility) of this process is important as the targeting of prevention strategies is often based on specific categories of event. The aim of this study was to determine the reliability of reviewer judgements regarding classification of paediatric inpatient medication related events.

Methods: Three health professionals independently reviewed suspected medication related events and classified them by type (adverse drug event (ADE), potential ADE, medication error, rule violation, or other event). ADEs and potential ADEs were then rated according to seriousness of patient injury using a seven point scale and preventability using a decision algorithm and a six point scale. Inter- and intra-rater reliabilities were calculated using the kappa (κ) statistic.

Results: Agreement between all three reviewers regarding event type ranged from “slight” for potential ADEs (κ = 0.20, 95% CI 0.00 to 0.40) to “substantial” agreement for the presence of an ADE (κ = 0.73, 95% CI 0.69 to 0.77). Agreement ranged from “slight” (κ = 0.06, 95% CI 0.02 to 0.10) to “fair” (κ = 0.34, 95% CI 0.30 to 0.38) for seriousness classifications but, by collapsing the seven categories into serious versus not serious, “moderate” agreement was found (κ = 0.50, 95% CI 0.46 to 0.54). For preventability decision, overall agreement was “fair” (κ = 0.37, 95% CI 0.33 to 0.41) but “moderate” for not preventable events (κ = 0.47, 95% CI 0.43 to 0.51).

Conclusion: Trained reviewers can reliably assess paediatric inpatient medication related events for the presence of an ADE and for its seriousness. Assessments of preventability appeared to be a more difficult judgement in children and approaches that improve reliability would be useful.

/pdf/inter-and-intra-rater-reliability-for-classification-of-3hbyu2ezv1.pdf

Inter- and intra-rater reliability for classification of medication related events in paediatric inpatients.

Background
There are few published data analysing risk factors for adverse drug events and medication errors in children.

Aim
To evaluate the factors that influence the risk of adverse drug events and medication errors occurring during a hospital admission for a child.

Method
Prospective cohort study of all paediatric admissions of at least 24 hours duration at Dunedin Hospital over a 12-week period. Suspected events were identified via chart review, multidisciplinary ward meetings, parent interview and voluntary staff reporting. Hypothesis tests were performed using hazard ratios and 95% confidence intervals.

Results
495 patients were included who in total had 520 admissions. There were 67 adverse drug events, of which 38 (57%) were classified as preventable, 77 potential adverse drug events and 255 ‘no-harm’ medication errors. On multivariate analysis, the major independent risk factors for adverse drug events were increasing age (HR 1.2; 95%CI 1.1–1.3) and a greater number of regular medications (HR 6; 95%CI 1.9–19.3). For potential adverse drug events, intravenous infusions conferred the highest risk (HR 32.4; 95%CI 10.9–95.5). For ‘no-harm’ medication errors, greater duration of hospital admission (HR 1.2; 95%CI 1.1–1.3) and a greater number of regular medications (HR 14.6; 95%CI 6.4–33.2), particularly IV infusions (HR 13; 95%CI 2.9–56.9), were the main predictors of occurrence. Sex and weight were not found to be related to adverse drug events or medication errors in this cohort of hospitalised children.

Conclusion
A greater number of regular medications and intravenous infusions were important risk factors for adverse drug events and medication errors occurring during hospital admission for a child. Increasing age also influenced the risk of an adverse drug event, whereas for ‘no harm’ medication errors, a greater duration of hospital admission was important.

Nicola C Austin

Papers

Incidence, preventability, and impact of Adverse Drug Events (ADEs) and potential ADEs in hospitalized children in New Zealand: a prospective observational cohort study.

Inter- and intra-rater reliability for classification of medication related events in paediatric inpatients.

Risk Factors for Adverse Drug Events and Medication Errors in Paediatric Inpatients: Analysis by Admission Characteristics