Biomedical subjects

D M Reith

Publications and source records attributed to D M Reith.

11 recordsLinked to original sources

PubMed2006

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

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 (kappa) statistic. RESULTS: Agreement between all three reviewers regarding event type ranged from "slight" for potential ADEs (kappa = 0.20, 95% CI 0.00 to 0.40) to "substantial" agreement for the presence of an ADE (kappa = 0.73, 95% CI 0.69 to 0.77). Agreement ranged from "slight" (kappa = 0.06, 95% CI 0.02 to 0.10) to "fair" (kappa = 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 (kappa = 0.50, 95% CI 0.46 to 0.54). For preventability decision, overall agreement was "fair" (kappa = 0.37, 95% CI 0.33 to 0.41) but "moderate" for not preventable events (kappa = 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.

Adverse Drug Reaction Reporting Systems↗

PubMed2004

Infant pertussis deaths and the management of cardiovascular compromise.

Infants infected with Bordetella pertussis in the first few weeks of life are at risk of death from 'overwhelming cardiovascular compromise despite intensive care support'. The mechanisms of this severe disease are not completely understood. Three case histories, including that of one infant who survived, are presented. Two of the patients died despite intensive therapy with pressors and, in one child, milrinone. The third child survived following treatment with nitric oxide and sildenafil. Hence, sildenafil in combination with nitric oxide shows promise as a therapy for the haemodynamic consequences of pertussis toxaemia and this should prompt clinical trials for their efficacy for this condition.

Bordetella pertussis↗

PubMed2003

Serious lead poisoning in childhood: still a problem after a century.

OBJECTIVE: To describe a series of patients with clinically significant lead poisoning. METHODOLOGY: A case series of nine patients with lead poisoning who required inpatient management, identified through a Clinical Toxicology Service. RESULTS: Nine children presented with clinically significant lead poisoning. The median serum lead was 2.5 micro mol/L (range 1.38-4.83). Eight of the children were exposed to lead-based paint, with seven due to dust from sanded lead paint during house renovations. Serial blood determinations suggested re-exposure in four of the patients, and in one of these patients the re-exposure was from a different source of lead. Eight of the patients required chelation therapy. CONCLUSIONS: Serious lead poisoning continues to occur and there appears to be complacency regarding the hazard posed by lead paint in old houses.

Chelation Therapy↗

PubMed2001

Population pharmacokinetic modeling of steady state carbamazepine clearance in children, adolescents, and adults.

Carbamazepine (CBZ) clearance decreases from childhood to adulthood and the factors determining this change could include age, size, autoinduction, or maturational changes. This study aims to describe the population pharmacokinetics of CBZ in children and young adults and test the hypothesis that CBZ clearance correlates with weight, surface area, and age. CBZ therapeutic drug monitoring data (sparse data) were collected from child and adult epileptics, and rich data were obtained from a bioequivalence study of CBZ in young adults. Population pharmaco-kinetic analysis was performed using NONMEM V. Forward stepwise, multiple regression was performed on the covariates. Bootstrap validation was performed. A total of 946 observations from 91 subjects, ages 0.7-37 years, were collected and analyzed. A one-compartment, first-order absorption and elimination model, with exponential interindividual error and additive residual error models was developed. The population model was: Clearance (Lhr-1) = ((2.24 x Surface area (m2)) + (0.047 x Dose (mg.kg-1)); Volume of distribution (L) = 0.37 x weight (kg); Absorption rate constant = 0.013 (hr-1). CBZ clearance increased with surface area and dose.

Adolescent↗

PubMed2001

Childhood poisoning in Queensland: an analysis of presentation and admission rates.

OBJECTIVE: To determine the presentation rates for paediatric poisoning by ingestion and the determinants of hospital admission. METHODOLOGY: Cross-sectional survey using an injury surveillance database from emergency departments in South Brisbane, Mackay and Mt Isa, Queensland, from January 1998 to December 1999. There were 1516 children aged 0-14 years who presented following ingestional poisoning. RESULTS: The presentation rates for poisoning were 690, 40 and 67 per 100000 population aged 0-4, 5-9 and 10-14 years, respectively. The admission rates to hospital for poisoning were 144, 14 and 22 per 100000 population aged 0-4, 5-9 and 10-14 years, respectively. Although presentation rates for poisoning were higher in the rural centres the admission rates were disproportionately high for the 0-4 years age group. The agents most frequently ingested were paracetamol, Dimetapp, rodenticides and essential oils. CONCLUSION: There is a need to design and implement interventions aimed at reducing poison exposures and unnecessary hospital admissions in the 0-4 years age group.

Adolescent↗

PubMed2001

Acetazolamide poisoning in a toddler.

Acetazolamide ingestion and its sequelae have not been previously reported in children. A 12-month-old girl, weighing 10 kg, developed metabolic acidosis following ingestion of between 500 and 1250 mg of acetazolamide. The maximum base deficit recorded was 11.6. She was treated with sodium bicarbonate and recovered completely. Accidental poisoning should be included in the differential diagnosis of a child presenting with metabolic acidosis.

Acetazolamide↗

PubMed2001

Valproic acid has temporal variability in urinary clearance of metabolites.

The reasons for the intra- and interindividual variability in the clearance of valproic acid (VPA) have not been completely characterized. The aim of this study was to examine day-night changes in the clearance of 3-oxovalproate (3-oxo-VPA), 4-hydroxy-valproate (4-OH-VPA), and valproic acid glucuronides under steady state. Six diurnally active healthy male volunteers ingested 200 mg sodium valproate 12 hourly, at 0800 and 2000, for 28 days. On the last study day, two sequential 12-h urine samples were collected commencing at 2000 the evening before. Plasma samples were obtained at the end of each collection. Following alkaline hydrolysis, urine was analyzed for concentrations of VPA, 3-oxo-VPA, and 4-OH-VPA. A separate aliquot was assayed for creatinine (CR). The plasma concentrations of VPA, 3-oxo-VPA, 2-en-VPA, and CR were determined. The analysis of VPA and its metabolites was performed by GC-MS. There was an increase in plasma 3-oxo-VPA concentration at 0800, sampling as compared to 2000 sampling (p < .05). The urinary excretion of 3-oxo-VPA and VPA glucuronides were decreased between 2000 and 0800, compared to between 0800, and 2000, by 40% and 50% respectively (p < .05). These results indicate a nocturnal decrease in renal clearance of 3-oxo-VPA rather than a decrease in the beta-oxidation of VPA at night. These differences were not explained by differences between the sampling periods in CR excretion. These results indicate the importance of collecting samples of 24-h duration when studying metabolic profiles of VPA.

Adolescent↗

PubMed2000

The effect of body size on the metabolic clearance of carbamazepine.

OBJECTIVES: To examine the profile of the known pathways of carbamazepine (CBZ) metabolism in a group of children and adolescents, and to test for associations with physical measurements, age and plasma hormonal levels. STUDY DESIGN: Cross-sectional study of children and adolescents attending a neurological outpatients department who were medicated with CBZ. Partial clearances of CBZ to CBZ-epoxide (CBZ-ep), CBZ-10,11-trans-diol (CBZ-diol), 2-hydroxy-CBZ (CBZ-2-OH), 3-hydroxy-CBZ (CBZ-3-OH), CBZ-acridan (CBZ-acr) and their respective glucuronides were calculated by relating 24-h recovery of these metabolites from urine to trough steady-state serum CBZ levels. CBZ and its metabolites were measured by a gradient high performance liquid chromatography (HPLC) method. Serum CBZ-ep, LH, FSH, prolactin, IGF-I, and testosterone or oestradiol and progesterone were also measured. Surface area (SA) and liver volume (LV) were calculated from height and weight. RESULTS: Twelve males and nine females with an age range of 6-17 years participated in the study. Partial clearance to each of the metabolites was most strongly correlated with the calculated size of the liver relative to body weight. These associations persisted when corrected for potential confounders using multiple regression analysis. CONCLUSION: In the age group studied, urinary clearance of CBZ to its known metabolites is proportional to the size of the liver relative to body weight.

Adolescent↗

PubMed2000

Urinary excretion of valproate metabolites in children and adolescents.

The objective of this communication is to describe the changes in the metabolic profile of valproic acid (VPA) from early to late childhood and adolescence. A cross-sectional study of 12 children and adolescents attending a neurological outpatients department, who were medicated with VPA, was carried out. The proportions of daily dose excreted as VPA-glucuronide, 3-oxo-VPA and 4-OH-VPA were calculated by relating 24-h recovery of these metabolites from urine to daily VPA dose. VPA, 3-oxo-VPA and 2-en-valproic acid (2-en-VPA) were measured in trough serum samples. VPA and its metabolites were measured using a capillary gas chromatograpy method. The proportion of daily dose recovered as VPA-glucuronide in children 10 years and younger was smaller than in older children (p<0.05). There were no differences between age groups in the recovery of the other measured metabolites. Lamotrigine (LTG) comedication was also associated with a higher proportion of VPA dose recovered as glucuronide (p<0.01). LTG comedication had a stronger association with a higher proportion of dose being recovered as VPA-glucuronide on multivariate analysis than did the age group (p=0.001 versus p<0.05). In conclusion, older children and adolescents, when compared with younger children, and those comedicated with LTG excrete a higher proportion of VPA dose as VPA-glucuronide.

Adolescent↗

PubMed2000

Acetaminophen causes an increased International Normalized Ratio by reducing functional factor VII.

Acetaminophen may increase International Normalized Ratio (INR) in patients taking anticoagulation medication, and in patients with acetaminophen poisoning without hepatic injury. The objective of this study was to describe and investigate the effect of acetaminophen on INR. The authors studied patients admitted to a regional toxicology treatment center with acetaminophen poisoning with INR and without potentially confounding coingestion or hepatic injury. Exposed and nonexposed (control) cohorts were recruited from admissions with acetaminophen poisoning and psychotropic drug poisoning, respectively. From 1,437 acetaminophen poisonings, after exclusions, there were 143 admissions with 205 estimations of INR. INR showed a time-dependent increase. Fifty percent of all patients and 66% of those with an extrapolated 4-hour acetaminophen concentration > or = 150 mg/L had an abnormal INR at some time. Dose ingested (p = 0.01) and nomogram-based risk (p for trend = 0.005) were correlated with the effect. N-acetylcysteine had a protective effect. Functional factor VII was lower (p = 0.005) in exposed patients (n = 30) than controls (n = 8), and less than antigenic factor VII in exposed patients (p = 0.03). Factor IX was lower (p = 0.02). Factor VIIIc was not significantly different. The authors concluded that an isolated, small rise in INR is common after acetaminophen poisoning without hepatic injury. It appears to be caused by inhibition of Vitamin K-dependent activation of coagulation factors. This effect suggests a possible mechanism for the observed interaction between acetaminophen and warfarin.

Acetaminophen↗

PubMed1996

Relative toxicity of beta blockers in overdose.

OBJECTIVE: To compare the toxicity of beta blockers in overdose and to identify clinical features predictive of serious toxicity. DESIGN: Comparison of clinical data collected prospectively on a relational database of subjects presenting to hospital with self-poisoning, coroner's data and prescription data. SETTING: Newcastle and Lake Macquarie, Australia, 1987-1995. MAIN OUTCOME MEASURES: Death, seizure, cardiovascular collapse, hypoglycemia, coma and respiratory depression. SUBJECTS: Fifty-eight self-poisonings with beta blockers and two deaths investigated by the coroner with evidence of propranolol poisoning. RESULTS: All patients who developed toxicity did so within six hours of ingestion. The use of ipecac was temporally associated with cardiorespiratory arrest in one patient. Propranolol was the only beta blocker associated with seizure; of those who ingested more than 2 g of propranolol, two thirds had a seizure. There was a significant association between a QRS duration of > 100 ms and risk of seizures. Propranolol was over represented in beta blocker poisoning when prescription data were also examined. Propranolol was the only beta blocker associated with death. Propranolol was taken by a younger age group. CONCLUSIONS: Propranolol should be avoided in patients at risk of self-poisoning. Propranolol poisonings should be observed closely for the first six hours post ingestion. Syrup of ipecac should not be used to decontaminate the gastrointestinal tract after beta blocker overdose.

Adolescent↗