Impact of antibiotic allergy labels on patient outcomes in a tertiary paediatric hospital.

AIMS: Antibiotic allergies are reported in 5-15% of children. This study aimed to evaluate the impact of common ß-lactam antibiotic allergy labels (AALs) on hospital treatment, focusing on length of stay and appropriateness of antibiotic prescribing. METHODS: This was a retrospective cohort study over 21 months at the Royal Children's Hospital Melbourne, Australia. A subset of children with the most common ß-lactam allergies, and who required admission for intravenous antibiotics over a 12-month period, was analysed for appropriateness of prescribing. Non-allergic patients were matched to evaluate associations between AALs and hospital treatment. RESULTS: There were 98 912 children admitted over the study period, of whom 938 (1%) had at least one AAL on first admission. Of all encounters, 5145 (2.5%) were for children with AALs. The most common AALs were to amoxicillin and amoxicillin-clavulanic acid combinations (40.8%), cefalexin (14.4%) and trimethoprim-sulfamethoxazole (9.7%). For the subset, there were 66 admissions for children who required intravenous antibiotics. Documentation was adequate for 27% of AALs. Inappropriate prescribing occurred in almost half (47%). Hospital stay was longer for children with AALs (median 4.7 days; IQR 2.3-9.2) compared to non-allergic controls (median 3.9 days; IQR 1.9-6.8; P = .02). Children with AALs were more likely to receive restricted antibiotics (aOR 3.03; 95% CI, 1.45-6.30; P = .003). CONCLUSION: This is the first study to demonstrate high rates of inappropriate prescribing in children with AALs. Children with AALs were significantly more likely to receive restricted antibiotics and had a longer length of stay compared with non-allergic controls.

Medication prescribed by Australian paediatricians: Psychotropics predominate.

AIM: The aims of this study were to examine: (i) medications prescribed by Australian general and community paediatricians, (ii) predictors of prescribing (child age, gender) and (iii) changes in medication prescription between 2008 and 2013. METHODS: Two patient-level practice national audits were conducted by the Australian Paediatric Research Network in 2008 and 2013. General and community paediatricians in outpatient clinics and private practices recorded demographic data, diagnoses and medications prescribed for all patients seen over a 2-week period. RESULTS: In 2008, 199 paediatricians submitted data on 8345 consultations, and in 2013, 180 paediatricians submitted data on 7102 consultations. The most frequently prescribed drug class was psychotropics, prescribed for 46.8% of patients with developmental-behavioural/mental health (DB/MH) diagnoses in 2008 and 49.8% in 2013 (P = 0.015). Within this class, in 2013, the stimulants were prescribed in 35.3% of DB/MH consultations, antidepressants in 7.8% and antipsychotics in 5.6%. The next most frequently prescribed drug classes were laxatives (4.6% of all consultations in 2013), asthma preventers (4.1%), melatonin (3.7%), asthma relievers (2.6%) and proton-pump inhibitors (2.2%), topical corticosteroids (1.8%) and antihistamines (1.4%). Medication prescription was predicted by patient age (P < 0.001, both audits) and male gender (P < 0.01, both audits) but not by measured prescriber variables. The rates of prescribing of psychotropics, melatonin, laxatives and enuresis medications increased between 2008 and 2013. CONCLUSIONS: Australian paediatricians prescribe mostly psychotropic medications, and the amount prescribed appears to be increasing. Paediatricians need good training and professional development in mental health diagnosis and management and the rational prescribing of psychotropic medications.

Chinese herbal medicine granules (PTQX) for children with moderate to severe atopic eczema: study protocol for a randomised controlled trial.

BACKGROUND: Atopic eczema or atopic dermatitis is a chronic inflammatory skin disease. Current conventional medical treatment for moderate and severe atopic eczema is not satisfactory. There is promising evidence derived from randomised clinical trials to support the clinical use of Chinese herbal medicine in the management of atopic eczema. However, the available evidence is compromised by the high risk of bias associated with most of the included trials. Therefore, well-designed and adequately powered randomised clinical trials are needed. The primary aim of this trial is to evaluate the efficacy and safety of oral ingestion of an oral Chinese herbal formula (Pei Tu Qing Xin granules; PTQX) in children aged between 6 and 16 years with moderate to severe atopic eczema. METHODS/DESIGN: We have designed a randomised, double-blind, placebo-controlled, two-arm, parallel clinical trial with 12 weeks of treatment and a 4-week follow-up period. A pilot study with 30 participants will be conducted at the RMIT University in Australia to determine the feasibility of the full-scale randomised clinical trial (N = 124). Eczema Area and Severity Index score will be the primary outcome. Secondary outcome measures include change in symptoms using the Patient-Oriented Eczema Measure, the Children's Dermatology Life Quality Index and the use of concomitant medicines. Safety parameters include report of adverse events and pathology tests during the trial period. DISCUSSION: Key elements for conducting a high-quality randomised clinical trial have been addressed in this protocol. Findings from the proposed trial will provide critical evidence regarding Chinese herbal medicine treatment for atopic eczema. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry Identifier: ACTRN12614001172695. Date of Registration: 7 November 2014.

The addition of tramadol to the standard of i.v. acetaminophen and morphine infusion for postoperative analgesia in neonates offers no clinical benefit: a randomized placebo-controlled trial.

BACKGROUND: Tramadol is used following neonatal cardiac and general surgery. However, its ability to opioid-spare or facilitate earlier extubation in postoperative neonates is unquantified. OBJECTIVE: This randomized placebo-controlled trial aimed to assess whether tramadol's addition to standard analgesia resulted in earlier extubation or reduced analgesic/sedative requirements in postsurgical neonates. METHODS: Neonates born ≥32 weeks postmenstrual age received either tramadol [T] 2 mg·kg(-1) or placebo [P] 6-hourly for up to 5 days postthoracoabdominal surgery in addition to morphine (commenced at 20 mcg·kg(-1) ·h(-1)) and 6-hourly i.v. acetaminophen. Time to extubation, morphine and midazolam amounts, hourly pain scores, and seizure activity were compared using an intention-to-treat and per-protocol analysis. RESULTS: Seventy-one neonates participated. Median survival time to extubation was similar between the groups (T 67 h [95% CI 51, 84] vs P 52 h [95%CI 43, 65]; P = 0.4), and similar numbers were extubated by 96 h (T 69% vs P 77%; difference -8%, 95%CI -28, 13%). Morphine and midazolam exposure was similar, with low pain scores in both groups (mean percentage of time with a pain score >5/20 during the 5 days: T 13% vs P 11%, difference in means 2.8 [95% CI -1.8, 7.6], P = 0.20). Most participants had normal cranial ultrasounds (T 86% vs P 86%); no seizures occurred clinically or electroencephalographically. CONCLUSION: Tramadol's addition to standard analgesia in this small group of postsurgical neonates did not appear to have any positive effect on time to extubation, morphine or midazolam exposure, or pain scores. This questions the benefit of tramadol for postsurgical neonates. Importantly, no seizures occurred in these ill neonates who may potentially be at greater risk of tramadol toxicity compared with adults.

Antibiotic prophylaxis and recurrent urinary tract infection in children.

BACKGROUND: Antibiotics are widely administered to children with the intention of preventing urinary tract infection, but adequately powered, placebo-controlled trials regarding efficacy are lacking. This study from four Australian centers examined whether low-dose, continuous oral antibiotic therapy prevents urinary tract infection in predisposed children. METHODS: We randomly assigned children under the age of 18 years who had had one or more microbiologically proven urinary tract infections to receive either daily trimethoprim-sulfamethoxazole suspension (as 2 mg of trimethoprim plus 10 mg of sulfamethoxazole per kilogram of body weight) or placebo for 12 months. The primary outcome was microbiologically confirmed symptomatic urinary tract infection. Intention-to-treat analyses were performed with the use of time-to-event data. RESULTS: From December 1998 to March 2007, a total of 576 children (of 780 planned) underwent randomization. The median age at entry was 14 months; 64% of the patients were girls, 42% had known vesicoureteral reflux (at least grade III in 53% of these patients), and 71% were enrolled after the first diagnosis of urinary tract infection. During the study, urinary tract infection developed in 36 of 288 patients (13%) in the group receiving trimethoprim-sulfamethoxazole (antibiotic group) and in 55 of 288 patients (19%) in the placebo group (hazard ratio in the antibiotic group, 0.61; 95% confidence interval, 0.40 to 0.93; P = 0.02 by the log-rank test). In the antibiotic group, the reduction in the absolute risk of urinary tract infection (6 percentage points) appeared to be consistent across all subgroups of patients (P > or = 0.20 for all interactions). CONCLUSIONS: Long-term, low-dose trimethoprim-sulfamethoxazole was associated with a decreased number of urinary tract infections in predisposed children. The treatment effect appeared to be consistent but modest across subgroups. (Australian New Zealand Clinical Trials Registry number, ACTRN12608000470392.)

How to use medicines in children: principles of paediatric clinical pharmacology.

Knowledge of drug administration in children and infants has significantly lagged behind that of adults. Despite several paediatric therapeutic mishaps that have been a catalyst for major regulatory reform, the majority of registered medicines do not have indications or dosing for children. This paper will briefly summarise key issues in paediatric pharmacology, including differences in prescribing for children, off-label and unlicensed prescribing and conduct of paediatric clinical trials. A particular emphasis will placed on the situation in Australia.

Prescribing safely for children.

This paper is the second in a series of two and will attempt to highlight important issues in prescribing for children, including principles of safe prescribing, adverse drug reaction assessment and common drugs including paracetamol and ibuprofen. A list of drug information resources is included, which may be useful for clinicians.

Interventions of hospital pharmacists in improving drug therapy in children: a systematic literature review.

Medicines' management or pharmaceutical care in paediatric patients is particularly demanding, mainly because the majority of available drugs have been developed for use in adults. As a result, in children, drugs are often unlicensed or used off-label, suitable formulations or appropriate strengths are lacking, and drugs have to be extemporaneously prepared, liquids and injections diluted, and tablets split. These factors increase the likelihood of medication errors and may lead to a reduction in drug effect. Age-specific changes in pharmacokinetics and pharmacodynamics further complicate drug therapy in children. All these challenges provide unique opportunities for pharmacists to improve the quality of care for paediatric patients. We conducted a systematic literature review examining whether the interventions of hospital pharmacists improve drug therapy in children. Several medical and pharmaceutical databases were searched systematically to identify articles investigating hospital pharmacists' interventions that were intended to improve drug therapy in children. Inclusion criteria were English language, primary research papers and studies in which clinical pharmacists contributed directly to patient care. Exclusion criteria were reviews, editorials, questionnaire studies, modelling studies, letters and studies only available in abstract form. This systematic search identified 18 articles documenting the role of a clinical hospital pharmacist in paediatric care. These articles were divided into the following groups based on study type: (i) studies documenting interventions made by pharmacists and their role in inpatients; (ii) articles presenting the outcomes of a satellite pharmacy; and (iii) articles examining pharmacist involvement in paediatric outpatient clinics. No randomised study comparing pharmacist interventions with standard care was found. In conclusion, although it was difficult to compare the various studies identified because of the different settings, design, duration, size, methodology and definition, all these studies highlighted the importance of hospital pharmacists to medicines' management in paediatric patients. On the basis of this review, we can conclude that pharmacist reviewing of medication charts is very important in identifying medication errors; hence, it is likely to be the most effective method of improving drug therapy in children.

Prevention and treatment of infant and childhood vitamin D deficiency in Australia and New Zealand: a consensus statement.

Vitamin D deficiency has re-emerged as a significant paediatric health issue, with complications including hypocalcaemic seizures, rickets, limb pain and fracture. A major risk factor for infants is maternal vitamin D deficiency. For older infants and children, risk factors include dark skin colour, cultural practices, prolonged breastfeeding, restricted sun exposure and certain medical conditions. To prevent vitamin D deficiency in infants, pregnant women, especially those who are dark-skinned or veiled, should be screened and treated for vitamin D deficiency, and breastfed infants of dark-skinned or veiled women should be supplemented with vitamin D for the first 12 months of life. Regular sunlight exposure can prevent vitamin D deficiency, but the safe exposure time for children is unknown. To prevent vitamin D deficiency, at-risk children should receive 400 IU vitamin D daily; if compliance is poor, an annual dose of 150,000 IU may be considered. Treatment of vitamin D deficiency involves giving ergocalciferol or cholecalciferol for 3 months (1000 IU/day if < 1 month of age; 3000 IU/day if 1-12 months of age; 5000 IU/day if > 12 months of age). High-dose bolus therapy (300,000-500,000 IU) should be considered for children over 12 months of age if compliance or absorption issues are suspected.

Dosing information for paediatric patients: are they really "therapeutic orphans"?

OBJECTIVES: To review the approved product information (PI) of prescription medicines to determine the extent and nature of information available on paediatric dosing and the availability of paediatric dosage formulations in Australia. METHODS: The PIs for all prescription medicines listed in the Australian Monthly Index of Medical Specialties (MIMS) were reviewed. Dosing information for each PI was categorised according to age groupings. PIs claiming suitability for use in paediatric patients were reviewed for information on the availability of paediatric dosage forms. MAIN OUTCOME MEASURES: Proportion of PIs providing paediatric dosing information; availability of dosage forms suitable for children. RESULTS: A total of 1497 PIs were reviewed. The proportions, for each age group, of PIs with inadequate paediatric dosing information were: < 1 month (80.5%), 1-3 months (79.1%), 3 months-2 years (77.5%), 2-6 years (73.2%), and 6-12 years (71.6%). The proportions, for each age group, of PIs that gave specific paediatric dosing information but did not provide a paediatric dosage form were: < 1 month (26.5%), 1-3 months (25.1%), 3 months-2 years (23.3%), 2-6 years (21.9%), and 6-12 years (24.0%). CONCLUSIONS: The PIs for many prescription products listed in MIMS do not adequately detail paediatric doses. Many medicines for which specific paediatric dosing information is given are not available in dosage forms appropriate for children.

Prescribing of psychotropic medications for children by Australian pediatricians and child psychiatrists.

OBJECTIVE: To describe the pattern of prescribing of psychotropic medications for Australian children. DESIGN: Australia-wide cross-sectional postal survey conducted in 2000. PARTICIPANTS: All registered general pediatricians and child and adolescent psychiatrists. RESULTS: The survey was completed by 435 general pediatricians and 187 child and adolescent psychiatrists (response rates 72% and 70%, respectively). Stimulants and clonidine were the most frequently prescribed medications. Seventy-two percent of practitioners reported that they had prescribed a combination of medications. Frequent combinations included a stimulant and clonidine (64% of pediatricians, 51% of child psychiatrists) and a stimulant and a selective serotonin reuptake inhibitor (SSRI; 29% of pediatricians, 36% of child psychiatrists). Pediatricians were more likely than child psychiatrists to report prescribing clonidine for sleep problems (67% vs 36%). Child psychiatrists were more likely than pediatricians to report prescribing SSRIs (93% vs 75%) and mood stabilizers (45% vs 11%) for depression, and SSRIs (74% vs 50%) and tricyclic antidepressants (37% vs 12%) for obsessive compulsive disorder. Off-label prescribing (indication or age not included in the product information) was reported by 40%. Over 5% of practitioners in this study had prescribed clonidine, methylphenidate, dexamphetamine, and typical neuroleptics for children under 3 years of age. CONCLUSIONS: A broad range of psychotropic medications are being prescribed for Australian children, with some medication groups being prescribed frequently. Combinations of psychotropic medications are used regularly, and there is some prescribing for very young children. The safety and efficacy of several of the agents prescribed have not been adequately researched in children. There is an urgent need for pediatric psychopharmacology research to inform current prescribing practice.