Alan Graham Stuart

Medication errors in paediatric practice: insights from a continuous quality improvement approach.

Abstract The objective was to assess the incidence and consequences of medication errors, highlight sources of recurrent error and institute changes in practice to prevent their recurrence. Utilising a continuous quality improvement approach, a 2-year prospective cohort study was undertaken using an adverse incident reporting scheme. A multidisciplinary committee analysed medication error reports, classifying them according to type (prescription, supply or administration), severity (serious or not serious) and clinical outcome. Changes in policy and practice were implemented to reduce the frequency of errors. There were 441 reported medication errors in the study period, during which 682 patients were admitted for 5315 inpatient days. Errors were more seven times likely to occur in the intensive care setting. Doctors accounted for 72% of errors and prescription errors doubled when new doctors joined the rotation. Most errors (68%) were detected prior to drug administration. Twenty-four serious medication errors were not detected in advance, but only 4 had overt clinical consequences. Excluding prevented errors and appropriate deviations from prescribed therapy, there were 117 actual medication errors (1/5.8 admissions, or 1/45 inpatient days). During the 2nd year of the scheme, the incidence of all reported errors, administration errors and serious errors fell, but the prescription error rate remained constant. Conclusions Medication errors occurred commonly in this study, but adverse consequences were rare. The non-punitive, multidisciplinary approach to medication errors utilised in this study increased staff vigilance, highlighted sources of recurrent error, and led to changes in drug policies and staff training, which resulted in improved patient safety and quality of care.

Cerebral blood flow and metabolism in children with severe head injury. Part 1: Relation to age, Glasgow coma score, outcome, intracranial pressure, and time after injury.

Understanding the pathophysiology of paediatric head trauma is essential for rational acute management. It has been proposed that the response to severe head injury in children differs from that in adults, with increased cerebral blood flow (cerebral hyperaemia) representing the most common cause of raised intracranial pressure, but this has recently been disputed. The relation between the pathophysiological response and time after injury has not been defined in children. This paper describes 151 serial measurements of cerebral blood flow, arteriojugular venous oxygen difference (AJVDO2), and cerebral metabolic rate for oxygen (CMRO2) that were performed in 21 children with severe head injury, mean age 8 (range 2-16) years, Glasgow coma score < or = 8. Absolute cerebral hyperaemia was uncommon, only 10 (7%) of the 151 cerebral blood flow values being at or above the upper limit of the range published in normal children. There was an inverse correlation between cerebral blood flow and intracranial pressure. (r = -0.24, p = 0.009). Contrary to the widespread assumption that cerebral metabolic rate in patients with head injury is always low, CMRO2 was initially within the normal range in 17/21 (81%) children. Both CMRO2 and AJVDO2 fell significantly between the first and third days after injury. There was a non-significant rise in cerebral blood flow over time. These data represent the first evidence that the temporal change in cerebral metabolic rate reported in experimental models of traumatic brain injury also occurs in patients with head injury. The changes in the pathophysiological response over time suggest that the management may need to be modified accordingly. If cerebral metabolic rate and cerebral oxygen extraction are maximal shortly after injury in children with severe head injury then the children are most likely to sustain secondary damage during this period.

Severe pulmonary hypertension: a frequent complication of stem cell transplantation for malignant infantile osteopetrosis.

This report describes eight infants who developed acute severe pulmonary arterial hypertension (PAH) at days −2 to +89 after allogeneic stem cell transplantation (SCT) for malignant infantile osteopetrosis (MIOP). They were taken from a total of 28 children (frequency 29%) transplanted for this disease at three institutions between 1996 and 2002. Typical presentations were acute dyspnoea, hypoxia and brady/tachycardia usually in the absence of fever, crepitations or other evidence of infection. Six patients (75%) required assisted ventilation and five (62%) died. There was clinical or pathological evidence of veno‐occlusive disease (VOD) in three children, but absence of VOD in the remaining five suggests that a separate disease process may be responsible for the PAH. Responses to nitric oxide (NO), defibrotide (DF), nicardipine and steroids in varying combinations were disappointing. Three children showed sustained improvement after administration of epoprostenol (EP, prostacyclin) in conjunction with NO and/or DF and remain well and free of PAH 25, 31 and 32 months post‐transplant. PAH must therefore be excluded in any child who becomes acutely breathless after SCT for osteopetrosis.

Life expectancy in British Marfan syndrome populations

A total of 206 patients with Marfan syndrome were ascertained throughout genetic clinics in Wales and Scotland during the period 1970–1990. There were 45 deaths representing 22% of the cohort. Mean age at death was 45.3 ± 16.5 years. 50% median cumulative survival in the total cohort (n = 206) was 53 years for males and 72 years for females. Multivariate analysis confirmed severity as the best independent indicator of survival. These findings and survival curves will assist in the counselling of British families and individuals with Marfan syndrome.

Determinants of exercise-induced pulmonary hypertension in patients with normal left ventricular ejection fraction

Background: Pulmonary hypertension (PH) can occur during exercise and has an adverse effect on functional status, exercise tolerance and prognosis. However, the role of cardiac function abnormalities on exercise-induced PH in patients with normal left ventricular ejection fraction (LVEF) is unclear. Objective: To analyse exercise-induced PH determinants in patients with normal LVEF. Methods and results: 396 subjects (160 male, mean age 55 (SD 13)) referred for exercise echocardiography underwent a graded, symptom-limited, supine bicycle exercise with two-dimensional and Doppler echocardiography. Tricuspid regurgitation (TR) velocity was measured at rest and during exercise. Pulmonary artery systolic pressure (PASP) was estimated from TR velocity by adding a right atrial pressure of 10 mm Hg. Patients were classified according to exercise induced PH, defined as present if PASP >50 mm Hg at 50 W of exercise. 135 patients (34%) had PASP >50 mm Hg during exercise. Patients with exercise-induced PH were older, more commonly female and had shorter exercise duration; however, LVEF was significantly higher. The systolic blood pressure at rest and during exercise was significantly higher in patients with exercise-induced PH (rest, 125 (18) vs 132 (18) mm Hg, p = 0.0003; 25 W, 146 (21) vs 157 (21) mm Hg, p<0.0001; 50 W, 157 (24) vs 170 (22) mm Hg, p<0.0001; 75 W, 168 (23) vs 183 (22) mm Hg, p<0.0001). Despite similar resting oxygen saturation, exercise oxygen saturation was significantly lower in subjects with exercise-induced PH than in those without. Numerous echocardiographic variables were significantly different between groups. In multivariate analysis, resting TR velocity (p<0.0001), E/E′ (p = 0.027), age and gender were the strongest predictors of PASP during exercise. Conclusion: Exercise-induced PH is common even in subjects with normal LVEF. It is strongly associated with E/E′ ratio, TR velocity, age, systolic blood pressure during exercise and gender.

Medical treatment of Marfan syndrome: a time for change

It is accepted practice to prescribe β-blockers in order to retard aortic dilatation and prevent aortic dissection and rupture in patients with Marfan syndrome. A critical review of the published pharmacological studies shows this practice to be based on limited evidence. The data from small clinical and experimental studies with surrogate end points suggest greater potential benefit from alternative drug regimens, and a recent experimental study showed that losartan may interrupt the mechanism of disease as well as deal with its functional consequences. It is now essential to perform large, collaborative, randomised controlled trials with clinical end points of new treatments in Marfan syndrome.

Systematic survey of variants in TBX1 in non-syndromic tetralogy of Fallot identifies a novel 57 base pair deletion that reduces transcriptional activity but finds no evidence for association with common variants

Background Tetralogy of Fallot (TOF) is common in individuals with hemizygous deletions of chromosome 22q11.2 that remove the cardiac transcription factor TBX1. Objective To assess the contribution of common and rare TBX1 genetic variants to TOF. Design Rare TBX1 variants were sought by resequencing coding exons and splice-site boundaries. Common TBX1 variants were investigated by genotyping 20 haplotype-tagging SNPs capturing all the common variations present at the locus. Association analysis was performed using the program UNPHASED. Patients TBX1 exons were sequenced in 93 patients with non-syndromic TOF. Single nucleotide polymorphism analysis was performed in 356 patients with TOF, their parents and healthy controls. Results Three novel variants not present in 1000 chromosomes from healthy ethnically matched controls were identified. One of these variants, an in-frame 57 base-pair deletion in the third exon which removed 19 evolutionarily conserved residues, decreased transcriptional activity by 40% in a dual luciferase assay (p=0.008). Protein expression studies demonstrated that this mutation affected TBX1 protein stability. After correction for multiple comparisons, no significant associations between common genetic variants and TOF susceptibility were found. Conclusion This study demonstrates that rare TBX1 variants with functional consequences are present in a small proportion of non-syndromic TOF.

Results of Screening for Intracranial Aneurysms in Patients with Coarctation of the Aorta

BACKGROUND AND PURPOSE: IAs are found in 2.3% of adults; the mean age at detection is 52 years. Prevalence is <0.5% in young adults. Early studies suggest that 10%–50% of patients with aortic coarctation have IAs. Screening recommendations are variable. We sought to examine the prevalence of IAs through screening with MRA. MATERIALS AND METHODS: Consecutive patients older than 16 years of age with coarctation undergoing brain MRA between May 1999 and October 2007 were included. MRA was performed by using a 1.5T scanner with a 3D time-of-flight protocol; simultaneous MR imaging was performed of the heart and aorta. Cerebral MRAs were double-reported by a neuroradiologist. Statistics are described as mean ± SD and median ± range. Continuous variables were compared by using Student t tests and Mann-Whitney U tests (categoric variables, by using the Fisher exact test). RESULTS: One hundred seventeen MRAs were double-reported. The median age was 29 ± 11 years (range, 16–59 years). IAs were found in 12 patients (10.3%). The mean diameter of IAs was 3.9 mm (range, 2.0–8.0 mm). Patients with aneurysms were older (median, 37 years; range, 16–50 years) than those without (median, 23 years; range, 16–59 years; Z = −2.01, P = .04). Hypertension was more common in those with IAs (IA 83% versus no IA 43%, P = .01). There was no association between ascending aortopathy, bicuspid aortic valves, and IAs. CONCLUSIONS: Patients with coarctation have a higher prevalence of IAs, occurring at an earlier age than in population studies. Whether routine screening is appropriate for this group of patients is unclear. Hypertension is likely to be an important pathophysiologic factor.

Marfan’s syndrome and the heart

In recent years, there have been many advances in the treatment of cardiac disease in children with Marfan’s syndrome. Early diagnosis, meticulous echocardiographic follow-up and multidisciplinary assessment are essential. Medical treatment with β-blockers is probably helpful in most children with aortic root dilatation. Research on TGFβ signalling and the potential treatment role of TGFβ antagonists may lead to exciting new treatments, but the results of clinical trials are awaited. In managing the cardiovascular complications of Marfan’s syndrome, the paediatrician has to walk a difficult path. On the one hand, restrictive lifestyle advice and drugs may need to be prescribed, often in the context of a family history of major surgery or even sudden death. On the other hand, it is essential to encourage the often asymptomatic child to develop and mature as normally as possible.

Systemic thromboembolism leading to myocardial infarction and stroke after fenestrated total cavopulmonary connection.

Thromboembolic phenomena involving the caval veins, right atrium, and pulmonary artery are recognised complications after the Fontan operation and other forms of total cavopulmonary connection. A rare case of systemic thromboembolism is reported in a 3 year old girl who had repeated coronary and cerebral thromboembolic events after a fenestrated total cavopulmonary shunt operation. A survey of the 18 paediatric cardiac units in the United Kingdom and Ireland showed a wide discrepancy in anticoagulation policies after Fontan-type operations. Prevention of thrombotic complications by lifelong postoperative anticoagulation may outweigh the risk of haemorrhage.