Stepped-wedge cluster randomised controlled trial to assess the effectiveness of an electronic medication management system to reduce medication errors, adverse drug events and average length of stay at two paediatric hospitals: a study protocol.

INTRODUCTION: Medication errors are the most frequent cause of preventable harm in hospitals. Medication management in paediatric patients is particularly complex and consequently potential for harms are greater than in adults. Electronic medication management (eMM) systems are heralded as a highly effective intervention to reduce adverse drug events (ADEs), yet internationally evidence of their effectiveness in paediatric populations is limited. This study will assess the effectiveness of an eMM system to reduce medication errors, ADEs and length of stay (LOS). The study will also investigate system impact on clinical work processes. METHODS AND ANALYSIS: A stepped-wedge cluster randomised controlled trial (SWCRCT) will measure changes pre-eMM and post-eMM system implementation in prescribing and medication administration error (MAE) rates, potential and actual ADEs, and average LOS. In stage 1, 8 wards within the first paediatric hospital will be randomised to receive the eMM system 1 week apart. In stage 2, the second paediatric hospital will randomise implementation of a modified eMM and outcomes will be assessed. Prescribing errors will be identified through record reviews, and MAEs through direct observation of nurses and record reviews. Actual and potential severity will be assigned. Outcomes will be assessed at the patient-level using mixed models, taking into account correlation of admissions within wards and multiple admissions for the same patient, with adjustment for potential confounders. Interviews and direct observation of clinicians will investigate the effects of the system on workflow. Data from site 1 will be used to develop improvements in the eMM and implemented at site 2, where the SWCRCT design will be repeated (stage 2). ETHICS AND DISSEMINATION: The research has been approved by the Human Research Ethics Committee of the Sydney Children's Hospitals Network and Macquarie University. Results will be reported through academic journals and seminar and conference presentations. TRIAL REGISTRATION NUMBER: Australian New Zealand Clinical Trials Registry (ANZCTR) 370325.

Child and parent satisfaction with the use of spacer devices in acute asthma.

OBJECTIVE: To evaluate child and parent satisfaction with the use of spacers in acute asthma. METHODS: All parents of children presenting to the emergency department of Sydney Children's Hospital over a 3-month period with mild to moderately severe acute asthma who were treated with bronchodilators by spacer device were asked to complete an anonymous questionnaire. Children aged 8 years and older completed a separate questionnaire independently. RESULTS: One hundred and eleven of 158 parents (70%) responded. The majority (84%) found it 'easy' or 'very easy' to use the spacer and 85% reported that they intended to use the spacer at home. Of those parents who had previously used a nebulizer (n = 73), 84% said that the spacer was easier to use, 77% said that the spacer was better tolerated by their child and 84% said that overall they preferred the spacer. Seventeen of 31 children aged 8-14 years treated with a spacer (55%) responded to the satisfaction survey. All respondents found it 'easy' or 'OK' to use the spacer and the majority (82%) 'liked it' or thought 'it was OK'. The majority of children (82%) said that they preferred using spacers because it was quicker (29%) or easier to use (53%). CONCLUSION: The use of spacer devices in mild to moderately severe acute asthma is highly acceptable for children and parents; the majority prefer this mode of drug delivery to nebulization.

EBM in practice: paediatrics.

There is a substantial gap between what we "need to know" and what we "actually know" to practise evidence-based paediatrics. Good evidence from primary research studies about effective child healthcare strategies (for individuals or populations) for a broad range of important issues is lacking. Systematic reviews of existing good-quality research evidence, or evidence-based clinical practice guidelines relevant to child health, are often not readily available or accessible to practising clinicians. Recent initiatives to supply the information needs of paediatricians should lead to improvements in the availability, accessibility and applicability of the "evidence-base". These efforts need wider commitment and further resources. The gap between what we already "know" and what we "actually do" in daily practice is even wider. We need to improve our efforts to implement existing research knowledge, using strategies with demonstrated effectiveness, to promote the timely transfer of research evidence into actual practice. The health outcomes of these efforts need to be systematically evaluated.

Evaluating the effectiveness of evidence-based guidelines for the use of spacer devices in children with acute asthma.

OBJECTIVE: To change standard practice from using nebulisers to metered dose inhalers and holding chambers (spacers) in children presenting with mild to moderate acute asthma. DESIGN: A before-after comparison of children with acute asthma presenting to the emergency department (ED) between August and October 1999 with those presenting between June and August 1997. SETTING: A tertiary care metropolitan children's hospital. INTERVENTIONS: Evidence-based clinical practice guidelines for using spacers were developed by a local multidisciplinary consensus process. A multifaceted guideline implementation program was used in 1999. MAIN OUTCOME MEASURES: Physician prescribing practices (spacer use); clinical outcomes (need for hospitalisation, admission to intensive care unit, and length of stay [LOS]). RESULTS: 75 of 247 children (30%; 95% CI, 25%-36%) required hospital admission in 1999. This was similar to the 1997 study period, when 95 of 326 (29%; 95% CI, 24%-34%) children were admitted. Of those with mild to moderate asthma, 160 (68%) received bronchodilators in the ED; 151 (94%) were initially treated with a spacer device in 1999. In 1997, no children were initially treated with spacers in the ED. The median (range) LOS in hospital for children with asthma of all severities was 1.7 (0.5-19.8) days in 1999 and 1.7 (0.2-7.6) days in 1997 (P=0.85). CONCLUSIONS: We successfully changed standard practice from using nebulisers to spacers for bronchodilator delivery in children with mild to moderate acute asthma, with no difference in the need for or duration of hospitalisation.

Evaluation of a national surveillance unit.

AIM: The Australian Paediatric Surveillance Unit (APSU) facilitates national active surveillance of uncommon childhood conditions. This study assessed whether it fulfilled its objectives and satisfied criteria established by the Centers for Disease Control and Prevention (CDC) for evaluating surveillance systems. METHODS: Anonymous questionnaires were sent to users of the system, individual studies were reviewed, and data were collected from independent sources. RESULTS: Seven hundred and sixty six clinicians, 48 investigators, and 15 public health professionals responded to the questionnaires. Clinicians reported that the APSU was useful, 33% saying information provided by the APSU informed or changed their clinical practice. Most (88%) reported that completing monthly report cards was not a burden. Impact on policy development was limited by suboptimal dissemination of information to public health professionals. Flexibility and timeliness were limited by design. Estimated sensitivity of APSU studies ranged from 92% (congenital rubella) to 31% (drowning/near drowning). Positive predictive value of notified cases was over 70% for most studies. CONCLUSION: The APSU fulfils most of its objectives and meets CDC criteria salient to these. Ways in which the APSU could be improved have been identified, as have methodological challenges and limitations in applying CDC guidelines to this type of unit.

Patient based methods for assessing adverse events in clinical trials in rheumatology. Progress report for the OMERACT Drug Toxicity Working Party. Outcome Measures in Rheumatology.

There has been increasing recognition in recent years that the measurement of drug related toxicities in rheumatology clinical trials has been sub-optimal. The OMERACT Drug Toxicity Working Party was established to address this issue. The first task of the working party was to identify a minimum set of attributes of drug related toxicity that would be important to patients, clinicians, investigators, and policymakers. The working party then developed consensus on a standard set of properties for instruments to measure these attributes. Existing instruments in the field of rheumatology were ascertained by literature review and by contact with experts in the field. Four instruments were ascertained and evaluated using the guidelines developed by the working party. This report outlines the progress and preliminary results of these activities.

Assessment of myocardial perfusion and function in childhood systemic lupus erythematosus.

OBJECTIVES: To determine the prevalence of abnormalities in myocardial perfusion or function in children with systemic lupus erythematosus (SLE), and describe potential factors that may predict their development. STUDY DESIGN: Patients (n = 40; 30 female) were enrolled through the Lupus Clinic at The Hospital for Sick Children between 1990 and 1992. Resting and exercise thallium myocardial perfusion scans, radionuclide angiography with multiple gated acquisition (MUGA), and resting M-mode and two-dimensional echocardiography were performed. RESULTS: All patients were free of symptoms, and none had a history of ischemic heart disease. Their median age was 15.9 years (range 10.5 to 19.8 years) at enrollment. Abnormalities of coronary perfusion were found in 5 (16%) of 31 patients (95% confidence interval: 3%, 29%) and included a large fixed perfusion defect in 1; 5 of 27 MUGA scans showed marginally low left ventricular ejection fractions at rest, whereas all had normal exercise responses. In the group with abnormal thallium scans, three of five patients had antiphospholipid antibodies detected, and two of four had an abnormal plasma lipid profile. This group tended to have a shorter disease duration and had received a lower cumulative dose of corticosteroids; these differences were not statistically significant compared with the group with normal scans. CONCLUSION: Asymptomatic abnormalities of myocardial perfusion occur in children with SLE and are more common than previously suspected. Patients with these abnormalities of myocardial perfusion may be predisposed to the previously recognized early-onset ischemic heart disease seen in adults with SLE.

Hypoparathyroidism associated with systemic lupus erythematosus.

We describe a 15-year-old girl with systemic lupus erythematosus (SLE) who presented with hypocalcemia and a generalized seizure in the setting of an intercurrent illness and active central nervous system lupus. She was subsequently found to have idiopathic hypoparathyroidism. The association of SLE with hypoparathyroidism is extremely rare and this case represents the first pediatric report of this rare association. We suggest there may be a common underlying pathophysiological process linking these diseases.

Experience with misoprostol therapy for NSAID gastropathy in children.

OBJECTIVE: To determine the effect of misoprostol, a synthetic prostaglandin E1 analogue, on the gastrointestinal tract (GIT) symptoms associated with non-steroidal anti-inflammatory drug (NSAID) administration and on the haemoglobin value, in children. METHODS: Retrospective chart review of children attending the paediatric rheumatology clinic at a tertiary referral hospital over a three year period, who were receiving NSAIDs and were prescribed misoprostol for treatment of GIT symptoms or anaemia. RESULTS: Twenty five children (mean age 12.0 (SD 2.8) (range 7-17) years were prescribed misoprostol (mean dose 308.4 (76.5) micrograms/m2/day; 9.8 (2.5) micrograms/kg/day) while NSAID therapy was continued. Of the 22 (88%) patients with GIT complaints, 18 (82%) had complete resolution of symptoms and two (9%) had some improvement. Four patients (18%) had a recurrence of symptoms after initial resolution while still receiving misoprostol. Misoprostol therapy was associated with a statistically significant increase in haemoglobin concentration (mean value before misoprostol 115 (18) g/l; after misoprostol 126 (15) g/l (p = 0.02)). The only adverse effect reported was self limited diarrhoea in one child. CONCLUSION: Misoprostol appeared to be effective in the treatment of GIT symptoms in children receiving NSAIDs and to result in significant increase in the haemoglobin concentration. Further prospective studies are needed to evaluate the role of misoprostol therapy for NSAID associated GIT complaints in the paediatric population.

Acute renal insufficiency in ibuprofen overdose.

Since the introduction of ibuprofen as a nonprescription drug in the US, there have been reports of significant toxicity associated with large ingestions (> 400 mg/kg) in both children and adults. Acute renal insufficiency is a rare, reversible effect of ibuprofen overdose documented in adults, but we could find no published pediatric cases. We report a case of a healthy two-year-old boy, without a previous history of renal problems, who developed reversible acute renal insufficiency after a toxic ingestion of approximately 640 mg/kg ibuprofen. By 11 hours, his initially normal creatinine began to rise, reaching a peak value of 181 mmol/L (2.1 mg/dl) by 27 hours. His urinalysis showed moderate microscopic hematuria without the presence of casts or proteinuria. No problems arose with fluid management. Normalization of his renal function occurred by 72 hours. A serum ibuprofen concentration obtained by high-performance liquid chromatography and drawn approximately four hours after ingestion was 1724 mumol (therapeutic serum concentration, 50-250 mumol). This case demonstrates that acute, reversible renal insufficiency can occur in healthy children after a severe overdose of ibuprofen; hence, renal function should be monitored in such instances.

The "4A" syndrome: adrenocortical insufficiency associated with achalasia, alacrima, autonomic and other neurological abnormalities.

The triad of adrenocortical insufficiency with alacrima and achalasia is an unusual disease entity in paediatrics. The association of autonomic and peripheral neuropathies has more commonly been reported in older individuals. We describe four children (two siblings) with this disorder, aged between 3 and 6 years at diagnosis, all of whom had clinical neurological abnormalities when examined between 6 and 8 years of age. In addition, we performed cardiovascular autonomic testing in three subjects: heart rate variation during deep breathing was abnormal in all three; Valsalva ratio was abnormal in two; and postural systolic blood pressure response was abnormal in one. Pupillary reflexes were abnormal in the only subject in which they could be measured. These results indicate that subtle neurological and, in particular, autonomic abnormalities can be detected at an early age. We propose that autonomic neuropathy be considered as an integral feature of this rare condition and suggest the term "4A" syndrome as a useful mnemonic for the association of adrenocortical insufficiency, achalasia and alacrima with autonomic and other neurological abnormalities.

Penile absorption of EMLA cream in piglets: implications for use of EMLA in neonatal circumcision.

EMLA (eutectic mixture of lidocaine and prilocaine) cream is currently not recommended for use in infants < 1 month of age because of the potential risk of methemoglobinemia as a result of the o-toluidine metabolite of prilocaine. We studied bioavailability and changes in methemoglobin levels following topical penile exposure to 1 g of EMLA cream for 1 hour in piglets. Lidocaine, prilocaine, and o-toluidine concentrations were measured simultaneously using a high-performance liquid chromatography method. The systemic bioavailability of EMLA was low: 4.0 +/- (SD) 4.7% for lidocaine (range 0-13.6; n = 8) and 7.2 +/- 5.7% for prilocaine (range 0-14.5; n = 8). The ratio between exposure to o-toluidine with EMLA versus intravenous administration (i.e., AUCEMLA/AUCIV; see text) was also low: 4.2 +/- 9.3% (range 0-28.6; n = 9). The mean maximum methemoglobin value after intravenous administration was 1.23 +/- 0.64% (range 0.5-3.0; n = 12) and after penile application 0.99 +/- 0.36% (range 0.5-2.0; n = 12). The methemoglobin value was elevated significantly above baseline after intravenous administration (p = 0.03), but not after penile application of EMLA. These findings suggest that penile administration of 1 g of EMLA may be safe for neonatal circumcision, but further study is required.

Safety of the new quinolones in pregnancy.

OBJECTIVE: To investigate the effect on the fetus of intrauterine exposure to quinolones in terms of teratogenicity, with special focus on the musculoskeletal system. METHODS: We studied 38 pregnant women who received quinolones and consulted the Motherisk Program in Toronto from 1989-1992. Perinatal complications, birth weight, birth defects, and developmental milestones, with particular emphasis on the musculoskeletal system, were compared with those of controls matched for both maternal age and indication for antibacterial therapy. RESULTS: Thirty-five women (92%) treated with norfloxacin or ciprofloxacin received therapy during the first trimester. The most common indication for therapy (92%) was urinary tract infection. More pregnancies in the quinolone group resulted in cesarean delivery due to reported fetal distress as compared to the controls (P = .005), without clear reason. Children born to mothers treated with quinolones were significantly heavier (P = .05) than the control infants, possibly because of better control of the urinary tract infection. No malformations were found in the quinolone group, whereas one child in the control group had a ventricular septal defect. No differences were detected between the groups in achievement of developmental milestones or in the musculoskeletal system. CONCLUSION: The use of the new quinolones during the first trimester of pregnancy does not appear to be associated with an increased risk of malformations or musculoskeletal problems; however, longer follow-up and magnetic resonance imaging of the joints may be warranted to exclude subtle cartilage and bone damage.

Simultaneous determination of lidocaine, prilocaine and the prilocaine metabolite o-toluidine in plasma by high-performance liquid chromatography.

An HPLC assay is described for the measurement of prilocaine and lidocaine (components of the local anesthetic cream EMLA) as well as the prilocaine metabolite, o-toluidine, in plasma. The method uses UV detection, is simple, sensitive and most important, only a single 200-microliters plasma sample is needed for simultaneous analysis of prilocaine, lidocaine and o-toluidine with a detection limit of 4 ng/ml. The plasma, together with the internal standard (bupivacaine) is extracted with diethyl ether under alkaline conditions, followed by the extraction of the analytes from the organic phase into dilute sulphuric acid. An aliquot of the acid extract is injected onto the HPLC system and the effluent is monitored by a UV detector.