Introduction and uptake of electronic growth charts in southern New Zealand.

AIM: The introduction of an electronic system for recording and displaying growth measurements replaces multiple paper growth charts and theoretically improves the availability and consistency of information to support clinical decision-making. Introducing this in a single New Zealand District Health Board provided the opportunity to evaluate usage in hospital settings and determine the uptake of growth recording in a defined population. METHODS: All records between 2010 and 2015 in the Southern District Health Board (SDHB) anthropometry database were downloaded and examined in a retrospective cohort analysis. Records were extracted after matching to demographic and clinical setting data from the hospital patient management system. RESULTS: Analysis included 30 670 data entry points, representing 8551 children. Data entry increased over time to a maximum of 8407 observations in 2015. By the fifth year of use, up to 67% of available clinical encounters had anthropometry recorded in the outpatient department. Rates were lower in the inpatient setting, where only up to 18.4% had anthropometry recorded. The errors identified were low (0.2% of all data). Weight was the most commonly recorded measurement (98.2% of anthropometry entries, 35.1% of available clinical presentations). Height was available for 82.6% of entries and 29.5% of presentations. A body mass index z-score was available for 81.5% of entries and 29.1% of presentations. A head circumference was available for 50.2% of children <2 years age who had anthropometry recorded. CONCLUSIONS: The introduction of an electronic anthropometry database has been successful with increasing rates of use over time, especially in outpatient clinics. Further focus to improve inpatient recording of height and weight is needed.

Management of childhood obesity: An audit of clinical practice in secondary care.

AIM: Childhood obesity continues to be a major health issue for children world-wide, with well-recognised major health effects. This study evaluated the prevalence of obesity in children presenting to secondary care in Southern New Zealand, as well as their clinical management. METHODS: Obesity prevalence was determined by a review of data contained in the electronic anthropometry database in the region for the period 19 July 2010-16 July 2015. All clinical records were further examined using a standard data extraction form for 333 obese children regarding their clinical management. RESULTS: A total of 8551 individuals were identified in the database for review. The prevalence of overweight and obesity was higher than the average national rates but stable over the 5-year period. Children of Maori and Pacific Island ethnicity, those most deprived and males were over-represented in terms of obesity. Of the 333 obese children whose clinical management was examined, 45.0% received a diagnosis of obesity. Of those diagnosed, 24.7% had further investigations related to possible obesity complications, and 72.7% were given management plans. Older females were more likely to receive clinical intervention, while Maori and Pacific Island children were less likely. CONCLUSIONS: Of the children seen in this secondary care setting, 40% are overweight or obese, and yet the rate of clinical intervention left room for improvement, suggesting a need for further staff education and clear guidelines. Maori and Pacific Island children have higher obesity burden but were less likely to receive clinical intervention. This may highlight a need for specific education regarding cultural practices.

Effect of gestational age and blood glucose on C-peptide excretion rate and clearance in neonates.

AIMS: The aim of this study was to measure urinary C-peptide concentrations, and then calculate C-peptide clearance (Cl), and excretion rate (UER) in neonates. In addition, the effect of gestational age (GA) and blood glucose levels (BGL) on C-peptide UER were investigated. METHODS: Insulin concentrations in plasma and C-peptide concentrations were measured in plasma and urine, in 20 neonates. Chemiluminescent immunoassays were used for insulin and C-peptide measurements, with urine diluted to 40% with bovine serum albumin 1% in phosphate buffered saline. Urine volume and time of collection were recorded and used to calculate UER and Cl. RESULTS: The mean Cl of C-peptide was 0.309 ± 0.329 mL/min/kg, and UER was 0.0329 ± 0.0342 pmol/min/kg. Correlations between Cl or UER and GA were not significant (P > 0.05). No significant correlation was shown between Cl or UER and BGL (P > 0.05). CONCLUSIONS: Both Cl and UER were highly variable in neonates, but were not correlated with GA. Additionally, BGL did not appear to affect C-peptide UER and Cl. As GA and BGL did not appear to affect Cl and UER, urinary C-peptide may provide a non-invasive method of measuring insulin production in neonates.

Population pharmacokinetic-pharmacodynamic modelling to describe the effects of paracetamol and N-acetylcysteine on the international normalized ratio.

Paracetamol is one of the most common pharmaceutical agents taken in self-poisonings, and can increase the prothrombin time (PT) through liver injury, and in overdose without hepatic injury by reducing functional factor VII. PT is a measure of hepatic injury used to predict and monitor hepatotoxicity, reported as the international normalized ratio (INR). The antidote for paracetamol poisoning, N-acetylcysteine (NAC), has been reported to have an effect on the PT. This analysis included patients from a retrospective case series, a prospective inception cohort of paracetamol and psychotropic (control) overdoses, and a cross-over clinical trial. A population pharmacokinetic-pharmacodynamic model describing the pharmacodynamic effects of paracetamol and NAC on the INR was developed in Phoenix NLME. The dataset included 172 patients; the median age was 22 years (range 13-71 years). A one-compartment model with first-order input and linear disposition best described paracetamol pharmacokinetics. The population mean estimate of the concentration that induced a response halfway between the baseline and maximal pharmacological effect of paracetamol was 1302 µmol/L (242), the maximum effect of paracetamol was 0.534 (202; from baseline) and the maximum effect of NAC was 0.325 (9.03; from baseline). Both paracetamol and NAC contributed a pharmacological effect to the elevation of INR. The estimated paracetamol concentration that induced a response halfway between the baseline and maximal pharmacological effect was within the range of plasma paracetamol values studied, fivefold greater than the maximum therapeutic concentration, suggesting that an elevated INR would not be expected within the therapeutic range. Simulated 24 and 48 g paracetamol overdoses with NAC administration produced INR values (50th percentile) that reached the upper limit of, or exceeded, the reference range.

Declining newborn intramuscular vitamin K prophylaxis predicts subsequent immunisation refusal: A retrospective cohort study.

AIM: Low rates of childhood immunisation are linked to outbreaks of infectious disease. Identifying and addressing barriers to immunisation may lead to improved immunisation rates. Immunisation and newborn vitamin K prophylaxis have many similarities. We aimed to investigate whether parents who decline newborn vitamin K are also more likely to decline subsequent childhood immunisations. METHODS: We undertook a retrospective cohort study, examining the relationship between vitamin K administration and immunisation uptake by parents of babies born over a 2-year period (January 2010-December 2011) in Dunedin, New Zealand (NZ). Both written and electronic data from a single birthing unit and the NZ National Immunisation Register (NIR) were analysed to ascertain the relationship between declining newborn vitamin K prophylaxis and subsequent immunisation uptake. RESULTS: Records for 3575 babies were examined. Ninety-two per cent of infants received intramuscular, and 5% received oral vitamin K. An increased risk ratio for non-immunisation of 14.1 (95% confidence interval 7.8-25.9) for babies whose parents declined vitamin K was identified. Receiving oral vitamin K was also associated with subsequent non-immunisation, with a risk ratio of 3.5 (95% confidence interval 1.7-7.3). CONCLUSIONS: Parents who decline newborn vitamin K are more likely to decline immunisation for their child. These parents, as well as those that elect for oral vitamin K, are a small but easily identifiable group to whom additional education about the benefits of immunisation could be offered. This is especially pertinent at a time when there is a resurgence of immunisation preventable diseases.

Population pharmacokinetics of intravenous acetaminophen and its metabolites in major surgical patients.

Intravenous acetaminophen is a commonly used analgesic following surgery. The aims of this study were to determine the population pharmacokinetic profile of intravenous acetaminophen and its metabolites in adult surgical patients and to identify patient characteristics associated with acetaminophen metabolism in the postoperative period. 53 patients were included in the dataset; 28 were men, median age (range) 60 years (33-87), median weight (range) 74 kg (54-129). Patients received 1, 1.5 or 2 g of intravenous acetaminophen every 4-6 h. Plasma and urine samples were collected at various intervals for up to 6 days after surgery. Simultaneous modelling of parent acetaminophen and its metabolites was conducted in Phoenix(®) NLME™ to estimate pharmacokinetic parameters. The population mean estimate (CV%) for central (plasma) volume of distribution of parent acetaminophen (VC) was 13.9 (4.41) L, peripheral (tissue) volume of distribution (VT) was 50.9 (2.96) L, and intercompartmental clearance (Q) was 77.5 (9.29) L/h. The population mean (CV%) metabolic clearances for glucuronidation (CLPG) was 8.92 (3.25) L/h, sulfation (CLPS) was 0.903 (3.47) L/h, and oxidation (CLPO) was 0.533 (7.90) L/h. The population mean (CV%) urinary clearances of parent acetaminophen (CLRP) was 0.137 (5.46) L/h, acetaminophen glucuronide (CLRG) was 3.81 (6.71) L/h, acetaminophen sulfate (CLRS) was 3.13 (4.32) L/h, and acetaminophen cysteine + mercapturate (CLRO) was 3.51 (9.98) L/h. Age was found to be a significant covariate on the formation of acetaminophen glucuronide, and renal function (estimated as creatinine clearance) on the urinary excretion of acetaminophen glucuronide.

Treatment Harms in Paediatric Primary Care.

The aim of this study was to describe the epidemiology in children of harms detectable from general practice records, and to identify risk factors. The SHARP study examined 9076 patient records from 44 general practices in New Zealand, with an enrolled population of 210,559 patients. "Harm" was defined as disease, injury, disability, suffering, and death, arising from the health system. The age group studied was ≤20 years of age. There were 193 harms to 141 children and adolescents during the 3-year study period. Harms were reported in one (3.5%) patient aged <2 years, 80 (6.6%) aged 2 to <12 years, 36 (4.9%) aged 12 to <18 years, and 24 (7.5%) aged 18 to ≤20 years. The annualised rates of harm were 36/1000 child and adolescent population for all harms, 20/1000 for medication-related harm (MRH), 2/1000 for severe MRH, and 0.4/1000 for hospitalisation. For MRH, the drug groups most frequently involved were anti-infectives (51.9%), genitourinary (15.4%), dermatologicals (12.5%), and the nervous system (9.6%). Treatment-related harm in children was less common than in a corresponding adult population. MRH was the most common type of harm and was related to the most common treatments used. The risk of harm increased with the number of consultations.

Low dose or very low dose phenylephrine and cyclopentolate microdrops for retinopathy of prematurity eye examinations (The Little Eye Drop Study): a randomised controlled non-inferiority trial.

OBJECTIVE: To determine if very low dose (VLD, 0.5% phenylephrine, 0.1% cyclopentolate) mydriatic microdrop (approximately 7 µL) administration (up to three doses) is non-inferior to low dose (LD, 1% phenylephrine, 0.2% cyclopentolate) mydriatic microdrop administration for ophthalmologist-determined successful retinopathy of prematurity eye examination (ROPEE). DESIGN: Multicentre, prospective, randomised controlled, non-inferiority clinical trial. SETTING: Four neonatal intensive care units in Aotearoa, New Zealand from October 2019 to September 2021. PATIENTS: Infants with a birth weight less than 1250 g or gestational age less than 30+6 weeks and who required a ROPEE. INTERVENTIONS: The intervention: microdrop (approximately 7 µL) of VLD (0.5% phenylephrine and 0.1% cyclopentolate) to both eyes, or the comparison: microdrop of LD (1% phenylephrine and 0.2% cyclopentolate) to both eyes. Up to three doses could be administered. MAIN OUTCOME MEASURES: The primary outcome measure was an ophthalmologist-determined successful ROPEE. RESULTS: One hundred and fifty preterm infants (LD mean GA=27.4±1.8 weeks, mean birth weight=1011±290 g, VLD mean GA=27.5±1.9 weeks, mean birth weight=1049±281 g,) were randomised. Non-inferiority for successful ROPEE was demonstrated for the VLD group compared with the LD group (VLD successful ROPEE=100%, LD successful ROPEE=100%, 95% CI no continuity correction -0.05 to 0.05) and for Maori (95% CI no continuity correction -0.02 to 0.19). CONCLUSION: VLD microdrops enable safe and effective screening for ROPEE in both Maori and non-Maori preterm infants. TRIAL REGISTRATION NUMBER: ACTRN12619000795190.

The pharmacokinetic profile of intravenous paracetamol in adult patients undergoing major abdominal surgery.

BACKGROUND: Intravenous (IV) paracetamol is commonly used in the postoperative period for the treatment of mild to moderate pain. The main pathways for paracetamol metabolism are glucuronidation, sulfation, and oxidation, accounting for approximately 55%, 30%, and 10% of urinary metabolites, respectively. The aim of this study was to describe the pharmacokinetics of IV paracetamol and its metabolites in adult patients after major abdominal surgery. METHODS: Twenty patients were given 1 g of paracetamol by IV infusion at induction of anesthesia (Interval 1) and every 6 hours thereafter, with the final dose given at 48-72 hours (Interval 2). Plasma and urine samples were collected for up to 8 hours after infusion for both intervals. The samples were analyzed by high-performance liquid chromatography to determine the amount of paracetamol and its metabolites. The data were modeled in Phoenix WinNonlin using a user-defined ASCII parent-metabolite model with linear disposition, to obtain the estimates for volume of distribution, metabolic and urinary clearance. RESULTS: Mean (95% confidence interval) metabolic clearance to paracetamol glucuronide increased from 0.06 (0.05-0.08) to 0.14 (0.11-0.18) L · h⁻¹ · kg⁻¹, P value <0.001 and urinary clearance increased from 0.08 (0.07-0.09) to 0.14 (0.10-0.17) L · h⁻¹ · kg⁻¹, P value 0.002. The mean (95% confidence interval) volume of distribution of paracetamol increased from 0.17 (0.12-0.21) to 0.43 (0.27-0.59) L · kg⁻¹, P value 0.032. CONCLUSIONS: After major abdominal surgery, there were apparent increases in the metabolic conversion to paracetamol glucuronide and its urinary clearance suggesting potential induction of paracetamol glucuronidation.

What's in a name? Brand name confusion and generic medicines.

We need an urgent review of medicines labelling in Australia and New Zealand.

Randomised controlled pilot trial comparing low dose and very low- dose microdrop administration of phenylephrine and cyclopentolate for retinopathy of prematurity eye examinations in neonates.

AIMS: To determine ifVery low dose mydriatic eye microdrop regimen sufficiently dilates the pupil (above 4.1 mm) compared with the currently used low dose mydriatic eye microdrop regimen.Cardiovascular, gastrointestinal and respiratory adverse effects occur following eye drop instillation. METHODS: Seventeen premature infants were recruited into this prospective, randomised controlled pilot trial in January 2017 to November 2018. Data were collected from the single-centre Neonatal Intensive Care Unit, Dunedin Hospital, New Zealand. The inclusion criteria were birth weight less than 1500 g or gestational age less than 31 weeks, or any premature infant requiring red reflex testing. Infants were randomised to receive either phenylephrine 1% or 0.5% and cyclopentolate 0.2% or 0.1%, 1 microdrop in both eyes. Efficacy outcome measures were pupil size at retinopathy of prematurity eye examination (ROPEE) and ophthalmologist rating of ease of screen. RESULTS: All participants had sufficient pupillary dilation for a successful ROPEE. Ophthalmologists rated the ROPEE as easy for 90% of all examinations. Pupil dilation measurements at the time of examination, mean±SD, 4.8±0.2 (95% CI 4.5 to 5.2) mm for treatment A and 5±0.2 (95%CI 4.6 to 5.4) mm for treatment B (p=0.61). There were no statistically significant differences between the groups for safety data. CONCLUSIONS: Very low dose microdrop administration of phenylephrine and cyclopentolate appears to be effective at sufficiently dilating the neonatal pupil for ROPEEs. Low dose and very low dose microdrop mydriatic regimens may also reduce the risk of unwanted adverse effects associated with these medicines. TRIAL REGISTRATION NUMBER: Australian New Zealand Clinical Trials Registry (reference ACTRN12616001266459p).

Medication-related harm in New Zealand general practice: a retrospective records review.

BACKGROUND: The extent of medication-related harm in general practice is unknown. AIM: To identify and describe all medication-related harm in electronic general practice records. The secondary aim was to investigate factors potentially associated with medication-related harm. DESIGN AND SETTING: Retrospective cohort records review study in 44 randomly selected New Zealand general practices for the 3 years 2011-2013. METHOD: Eight GPs reviewed 9076 randomly selected patient records. Medication-related harms were identified when the causal agent was prescribed in general practice. Harms were coded by type, preventability, and severity. The number and proportion of patients who experienced medication-related harm was calculated. Weighted logistic regression was used to identify factors associated with harm. RESULTS: In total, 976 of 9076 patients (10.8%) experienced 1762 medication-related harms over 3 years. After weighting, the incidence rate of all medication-related harms was 73.9 harms per 1000 patient-years, and the incidence of preventable, or potentially preventable, medication-related harms was 15.6 per 1000 patient-years. Most harms were minor (n = 1385/1762, 78.6%), but around one in five harms were moderate or severe (n = 373/1762, 21.2%); three patients died. Eighteen study patients were hospitalised; after weighting this correlates to a hospitalisation rate of 1.1 per 1000 patient-years. Increased age, number of consultations, and number of medications were associated with increased risk of medication-related harm. Cardiovascular medications, antineoplastic and immunomodulatory agents, and anticoagulants caused most harm by frequency and severity. CONCLUSION: Medication-related harm in general practice is common. This study adds to the evidence about the risk posed by medication in the real world. Findings can be used to inform decision making in general practice.

Monitoring the use of dabigatran etexilate for stroke prevention: compliance with renal function guidelines.

INTRODUCTION Dabigatran etexilate has become widely used in New Zealand, but information relating to when renal function monitoring is being undertaken is lacking. AIM To investigate if clinically appropriate renal function monitoring is being undertaken in New Zealand primary care for stroke prevention in non-valvular atrial fibrillation patients prescribed dabigatran etexilate. METHODS New Zealand non-valvular atrial fibrillation patients' prescription and primary care health data were extracted from national administrative databases for the period 1 July 2011 to 31 December 2015. The proportion of patients who had serum creatinine measurements at close proximity to treatment initiation and 12-months post initiation were assessed with 95% confidence intervals (CIs) and compared with Fisher's exact test. Log-rank tests for univariate analysis (gender, age, ethnicity and deprivation) effects on serum creatinine testing at dabigatran etexilate treatment initiation and 12-months post initiation were performed. RESULTS Overall, 1,948 patients who had been dispensed dabigatran etexilate with available primary care health data were identified. A total of 1,752 (89.9% [CI: 88.5-91.2]) patients had a renal function test at dabigatran etexilate initiation. There were 929 (72.8% [CI: 70.2-75.2]) patients who received ≥1 year supply of dabigatran etexilate and of these 207 (22.3% [CI: 19.6.6-25.1]) had a serum creatinine test 1 year after initiation. Demographic univariate analysis yielded insignificant log-rank tests for association with having serum creatinine measurements, except for Pacific Peoples. DISCUSSION There appears to be sub-optimal adherence to renal function monitoring for non-valvular atrial fibrillation patients who receive more than 12-months' treatment with dabigatran etexilate in New Zealand primary care.

Fatal Toxicity Indices for Medicine-Related Deaths in New Zealand, 2008-2013.

INTRODUCTION: The fatal toxicity index (FTI) is a measure for assessing the relative risks of death due to the medicines prescribed in a population. This knowledge is useful for prescribers and informs medicine safety initiatives. This study aimed to calculate FTIs for the New Zealand population using three methodologies. METHODS: New Zealand coronial data describing medicine-related deaths from 1 January 2008 to 31 December 2013 were retrospectively extracted from the National Coronial Information System. Three fatal toxicity indices were derived using the number of deaths attributed to each pharmaceutical as the numerator and the total defined daily doses, number of patients and number of prescriptions as denominators. RESULTS: There were 703 medicine-related deaths, of which 627 were assessed as due to one primary contributor. Median decedent age was 48 years (interquartile range 37-58), and 319 (51%) were male. Deaths were intentional in 252 cases (40%), unintentional in 284 (45%) and unknown in 91 (15%). The majority of deaths (n = 486, 78%) occurred in the community. Opioids, antidepressants, antipsychotics and hypnotic-anxiolytics caused most fatalities. While the FTIs for individual medicines varied by denominator applied, methadone and clozapine fatalities were prominent in all three indices. The antidepressants clomipramine, dosulepin and doxepin consistently returned the highest FTIs in their group. CONCLUSION: New Zealand prescribers should be aware of the high relative risk of death associated with methadone and clozapine; that clomipramine, dosulepin and doxepin were identified as the most dangerous antidepressants; and that zopiclone carries a similar fatal risk to benzodiazepines. Varying results were found between the FTIs calculated, making comparisons, particularly between populations, difficult.

Individualised dosing of amikacin in neonates: a pharmacokinetic/pharmacodynamic analysis.

PURPOSE: To examine the pharmacokinetics of amikacin and its pharmacokinetic pharmacodynamic (PKPD) relationship in neonates. To develop an alternative dosing strategy for amikacin in neonates. METHODS: A population PKPD analysis was performed using data collected from 80 neonates with gestational ages from 24 to 41 weeks. The final pharmacokinetic model analysed 358 amikacin concentrations. All neonates were > 72 hours postnatal age. Simulations were performed to develop a new dosing strategy. RESULTS: The final covariate model was clearance = 0.23 x (current weight/2)(0.691) x (postmenstrual age/40)(3.23) and volume of distribution = 0.957 x (current weight/2)(0.89). Following the logistic regression analysis of treatment failure, new amikacin target concentrations were estimated and used in development of an alternative dosing strategy. CONCLUSION: Simulation of a new dosing regimen yielded the following recommendations: 15 mg/kg at 36-h intervals, 14 mg/kg at 24-h intervals and 15 mg/kg at 24-h intervals for neonates < or = 28 weeks, 29-36 weeks and > or = 37 weeks postmenstrual age respectively.

Discrepancies between predicted and observed rates of intravenous gentamicin delivery for neonates.

OBJECTIVES: This study aimed to investigate intravenous infusions as used in the neonatal intensive care setting, to determine the effect of gentamicin dose (mg), gentamicin concentrations (mg/ml), flow rate (ml/h) and flush volume (ml) upon the length of infusion time. METHODS: Intravenous infusions were set up to simulate administration of gentamicin to neonates. Dextrose (10%, w/v) was administered as the primary intravenous fluid at 3.8 or 18.7 ml/h. Gentamicin doses (0.5 mg/0.2 ml, 2 mg/0.2 ml, 2.5 mg/1.0 ml, or 10 mg/1.0 ml) were delivered into the intravenous line at a T-connection using a Graseby pump over 35 min. This was followed by a saline flush of 1 or 2 ml over a further 35 min. At the end of each experiment a 2 ml 0.9% saline bolus was given. Analysis of gentamicin collected at 5-min intervals was by an HPLC method. KEY FINDINGS: The experiment demonstrated that under the infusion conditions neonates weighing 2.5 kg would receive only 80% of the drug at 60 min, increasing to 90-95% by 75 min. In extremely low birth weight neonates (0.5 kg), even lower percentage of gentamicin recovery occurred. At 60 min only 60% of the intended gentamicin dose had been delivered and this increased to only 70% by 75 min. CONCLUSIONS: The delivery of gentamicin administered by intravenous infusion is substantially extended in extremely low birth weight neonates. This appeared to be primarily due to the small volumes and low infusion rates used in these patients.

Evaluation of the effect of intravenous volume expanders upon the volume of distribution of gentamicin in septic neonates.

Sepsis has been reported to increase the volume of distribution of gentamicin in neonates. To determine whether this was caused by the use of intravenous volume expanders a retrospective nested case-control study was performed comparing confirmed septic neonates with non-septic controls. Data were collected on intravenous administration of 0.45% saline/10% dextrose, 0.45% saline/5% dextrose, 0.9% normal saline, red blood cells, platelets, immunoglobulin (Intragam P) and albumin. A population pharmacokinetic analysis was performed using NONMEM for 116 neonates (29 confirmed septic) from which 363 gentamicin serum concentrations were available. The final covariate model was CL=0.097x(current weight/2)(1.3)x(postnatal age/7)(0.29) and V=1.07x(current weight/2)(0.8)+(confirmed sepsis)x0.13. The gentamicin volume of distribution was not significantly influenced by the cumulative intravenous volume expanders. The principal covariates that affected the gentamicin volume of distribution were current body weight and confirmed sepsis.

In vitro validation of a method for neonatal urine collection and analysis.

OBJECTIVE: Urine collection and analysis is important for diagnosis, monitoring of clinical progress, and research in neonates. This study aims to validate a novel methodology for neonatal urine collection, which combines the convenience of cotton ball collection with accurate timing via a urine continence monitor. DESIGN: Laboratory model using a combined cotton ball and urinary incontinence monitor method with and without the presence of an impermeable membrane to prevent desiccation. MAIN OUTCOME MEASURES: Accuracy, bias and precision in measurement of urine volume, electrolytes (sodium, potassium, chloride), creatinine and gentamicin. Changes in analyte concentration over time, and evaporative loss of water, were tested using analysis of variance. The effects of time, temperature and humidity were explored using multivariate analysis of variance. RESULTS: With the use of an impermeable membrane, sodium concentration increased from a mean (SD) of 3.57% (0.68) at 1 min to 5.03% (0.74) at 120 min. There was no significant change in potassium, chloride or creatinine concentrations. Gentamicin concentration decreased by a mean (SD) of 9.05% (1.37) by 30 min. Multivariate analysis found that absolute change in weight, sodium and chloride were only dependent on duration. Gentamicin concentration was affected by duration, humidity and temperature. Relative evaporative loss was minimal at -0.58% (0.31), and the urinary continence monitor was 100% successful at detecting urination for all time points. CONCLUSIONS: This novel methodology provides a standardisable and practical method to collect small volumes of neonatal urine for accurate measurement of both urine output and analyte concentrations.

Systematic review of mydriatics used for screening of retinopathy in premature infants.

INTRODUCTION: Routine retinopathy of prematurity eye examinations are an important part of neonatal care, and mydriatic medicines are essential in dilating the pupil for the eye examination. There are concerns about the level of evidence for efficacy and safety of these mydriatic medicines. OBJECTIVE: This review evaluates both efficacy and safety evidence of mydriatics used during the retinopathy of prematurity eye examination. METHOD: Systematic literature review. RESULTS: There is limited evidence guiding clinical practice for safety and efficacy of mydriatics. The majority of publications are underpowered and with an unclear to high level of bias. There are a wide variety of mydriatic regimens evaluated for efficacy and safety, and multiple regimens are associated with case reports. CONCLUSIONS: Current international guideline seems unnecessarily high, especially when the reviewed literature suggest that lower doses are effective, albiet from underpowered studies. The lowest effective combination regimen appears to be phenylephrine 1% and cyclopentolate 0.2% (1 drop). Microdrop administration of this regimen would further increase the safety profile, however, efficacy needs to be assessed.