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BACKGROUND: Reference change values (RCV) are used to indicate a change in analyte concentration that is unlikely to be due to random variation in the patient or the measurement. Current theory describes RCV relative to a first measurement result (X1). We investigate an alternative view predicting the starting point for RCV calculations from X1 and its location in the reference interval. METHODS: Data for serum sodium, calcium, and total protein from the European Biological Variation study and from routine clinical collections were analyzed for the effect of the position of X1 within the reference interval on the following result from the same patient. A model to describe the effect was determined, and an equation to predict the RCV for a sample in a population was developed. RESULTS: For all data sets, the midpoints of the RCVs were dependent on the position of X1 in the population. Values for X1 below the population mean were more likely to be followed by a higher result, and X1 results above the mean were more likely to be followed by lower results. A model using population mean, reference interval dispersion, and result diagnostic variation provided a good fit with the data sets, and the derived equation predicted the changes seen. CONCLUSIONS: We have demonstrated that the position of X1 within the reference interval creates an asymmetrical RCV. This can be described as a regression to the population mean. Adding this concept to the theory of RCVs will be an important consideration in many cases.
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Sódio , Humanos , Valores de Referência , Sódio/sangue , Cálcio/sangueRESUMO
OBJECTIVES: Laboratory results are increasingly interpreted against common reference intervals (CRIs), published clinical decision limits, or previous results for the same patient performed at different laboratories. However, there are no established systems to determine whether current analytical performance justifies these interpretations. We analysed data from a likely commutable external quality assurance program (EQA) to assess these interpretations. METHODS: The use of CRIs was assessed by evaluating instrument group medians against minimum specifications for bias. The use of clinical decision limits was assessed using specifications from professional bodies, and the monitoring of patients by testing at different laboratories was assessed by comparing all-laboratory imprecision to within-subject biological variation. RESULTS: Five of the 18 analytes with Australasian CRIs did not meet specification for all instrument groups. Among these, calcium and magnesium failed for one instrument group out of seven, while bicarbonate, chloride, and lipase failed for two instrument groups. Of the 18 analytes reviewed currently without CRIs in Australasia, 10 candidates were identified. Among analytes with clinical decision limits, i.e. lipids, glucose, and vitamin D, only triglycerides met both bias and imprecision specifications, while vitamin D met the imprecision specification. Monitoring patients by testing at different laboratories was supported for 15 of the 46 (33â¯%) analyte-method principles groups that met minimum imprecision specifications. CONCLUSIONS: Analysis of data from commutable EQA programs can provide a mechanism for monitoring whether analytical performance justifies the interpretations made in contemporary laboratory practice. EQA providers should establish systems for routinely providing this information to the laboratory community.
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Analytical performance specifications (APS) are used for decisions about the required analytical quality of pathology tests to meet clinical needs. The Milan models, based on clinical outcome, biological variation, or state of the art, were developed to provide a framework for setting APS. An approach has been proposed to assign each measurand to one of the models based on a defined clinical use, physiological control, or an absence of quality information about these factors. In this paper we propose that in addition to such assignment, available information from all models should be considered using a risk-based approach that considers the purpose and role of the actual test in a clinical pathway and its impact on medical decisions and clinical outcomes in addition to biological variation and the state-of-the-art. Consideration of APS already in use and the use of results in calculations may also need to be considered to determine the most appropriate APS for use in a specific setting.
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Controle de Qualidade , Humanos , Técnicas de Laboratório Clínico/normas , Modelos TeóricosRESUMO
Analytical performance specifications (APS) based on outcomes refer to how 'good' the analytical performance of a test needs to be to do more good than harm to the patient. Analytical performance of a measurand affects its clinical performance. Without first setting clinical performance requirements, it is difficult to define how good analytically the test needs to be to meet medical needs. As testing is indirectly linked to health outcomes through clinical decisions on patient management, often simulation-based studies are used to assess the impact of analytical performance on the probability of clinical outcomes which is then translated to Model 1b APS according to the Milan consensus. This paper discusses the related key definitions, concepts and considerations that should assist in finding the most appropriate methods for deriving Model 1b APS. We review the advantages and limitations of published methods and discuss the criteria for transferability of Model 1b APS to different settings. We consider that the definition of the clinically acceptable misclassification rate is central to Model 1b APS. We provide some examples and guidance on a more systematic approach for first defining the clinical performance requirements for tests and we also highlight a few ideas to tackle the future challenges associated with providing outcome-based APS for laboratory testing.
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Técnicas de Laboratório Clínico , Humanos , Técnicas de Laboratório Clínico/normasRESUMO
BACKGROUND: Elevated serum urate levels are associated with progression of chronic kidney disease. Whether urate-lowering treatment with allopurinol can attenuate the decline of the estimated glomerular filtration rate (eGFR) in patients with chronic kidney disease who are at risk for progression is not known. METHODS: In this randomized, controlled trial, we randomly assigned adults with stage 3 or 4 chronic kidney disease and no history of gout who had a urinary albumin:creatinine ratio of 265 or higher (with albumin measured in milligrams and creatinine in grams) or an eGFR decrease of at least 3.0 ml per minute per 1.73 m2 of body-surface area in the preceding year to receive allopurinol (100 to 300 mg daily) or placebo. The primary outcome was the change in eGFR from randomization to week 104, calculated with the Chronic Kidney Disease Epidemiology Collaboration creatinine equation. RESULTS: Enrollment was stopped because of slow recruitment after 369 of 620 intended patients were randomly assigned to receive allopurinol (185 patients) or placebo (184 patients). Three patients per group withdrew immediately after randomization. The remaining 363 patients (mean eGFR, 31.7 ml per minute per 1.73 m2; median urine albumin:creatinine ratio, 716.9; mean serum urate level, 8.2 mg per deciliter) were included in the assessment of the primary outcome. The change in eGFR did not differ significantly between the allopurinol group and the placebo group (-3.33 ml per minute per 1.73 m2 per year [95% confidence interval {CI}, -4.11 to -2.55] and -3.23 ml per minute per 1.73 m2 per year [95% CI, -3.98 to -2.47], respectively; mean difference, -0.10 ml per minute per 1.73 m2 per year [95% CI, -1.18 to 0.97]; P = 0.85). Serious adverse events were reported in 84 of 182 patients (46%) in the allopurinol group and in 79 of 181 patients (44%) in the placebo group. CONCLUSIONS: In patients with chronic kidney disease and a high risk of progression, urate-lowering treatment with allopurinol did not slow the decline in eGFR as compared with placebo. (Funded by the National Health and Medical Research Council of Australia and the Health Research Council of New Zealand; CKD-FIX Australian New Zealand Clinical Trials Registry number, ACTRN12611000791932.).
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Alopurinol/uso terapêutico , Diabetes Mellitus Tipo 1/tratamento farmacológico , Nefropatias Diabéticas/tratamento farmacológico , Inibidores Enzimáticos/uso terapêutico , Taxa de Filtração Glomerular/efeitos dos fármacos , Supressores da Gota/uso terapêutico , Ácido Úrico/sangue , Xantina Oxidase/antagonistas & inibidores , Idoso , Alopurinol/efeitos adversos , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/fisiopatologia , Nefropatias Diabéticas/fisiopatologia , Progressão da Doença , Método Duplo-Cego , Inibidores Enzimáticos/efeitos adversos , Feminino , Supressores da Gota/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência Renal Crônica/tratamento farmacológico , Insuficiência Renal Crônica/fisiopatologia , Sistema Renina-Angiotensina , Falha de TratamentoRESUMO
The role of an External Quality Assurance (EQA) program is generally seen as providing a service to routine laboratories that their analytical performance is satisfactory and stimulating corrective action in the event of poor results. It is recognised that an ideal EQA program uses materials that are commutable with patient samples and have values assigned by higher-order reference methods. Despite this, most routine EQA programs use materials without verified commutability and use consensus means (based on either peer group or all laboratories) as target values. We propose an ongoing role for EQA programs using non-commutable materials and consensus targets to support the measurement services of routine laboratories. This is provided the relevant comparators supplied by the laboratory, e.g. reference intervals and clinical decision points, are based on the same or equivalent measurement system as is used by the laboratory. Materials without verified commutability often have certain practical advantages, which may include the range of analyte concentrations, verified stability, replicate samples and, significantly, lower costs. Laboratories using such programs need to be aware of the limitations, especially comparing results from different measurement systems. However, we also recognise that as well as individual laboratories, data from EQA programs informs manufacturers, professional organisations, clinical guideline writers and other medical bodies For consideration beyond an individual laboratory, proper assessment of differences between measurement systems (results harmonization) and demonstration of correct implementation of metrological traceability (methods trueness) become vital, and for that purpose, commutability of EQA materials and traceability of target values are required.
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Laboratórios , Humanos , Controle de Qualidade , Padrões de ReferênciaRESUMO
OBJECTIVES: To assess interlaboratory variability of total serum bilirubin (TSB) results in newborns. Initiated following a clinical incident in which a neonate was transferred to a tertiary hospital for treatment of severe hyperbilirubinemia but on arrival was reclassified into a lower risk category due to a 20% difference in TSB between laboratories. METHODS: Fresh residual plasma samples from hospital-born infants were pooled to obtain 11 samples across a range of total bilirubin concentrations. Aliquots were light-protected and measured on 7 commercial platforms at 4 accredited medical laboratories. Data from The Royal College of Pathologists of Australasia Quality Assurance Programs' (RCPAQAP) Neonatal Bilirubin program was analysed. RESULTS: Twenty-four to 30% difference in results for individual samples, largely due to calibration differences between assays. When interpreted according to guidelines, results from different platforms would have led to different clinical interventions in some cases. RCPAQAP results showed significant within-method bias but were not shown to be commutable with patient samples. CONCLUSIONS: There are clinically significant method-dependent differences in TSB results from neonatal samples, consistent with our clinical incident. The differences are largely due to lack of standardisation of calibrator values. This has implications for healthcare resource use and possibly for the neurodevelopment of infants. Intervention is needed at a number of levels, including clinical reporting of incidents arising from discordant results, commitment by manufacturers to ensure metrological traceability of methods with sufficiently low uncertainty in the final measurements, and availability of commutable quality assurance material to monitor assay performance, especially at the clinical decision points for neonatal jaundice.
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Hiperbilirrubinemia Neonatal , Icterícia Neonatal , Bilirrubina , Calibragem , Humanos , Hiperbilirrubinemia Neonatal/diagnóstico , Hiperbilirrubinemia Neonatal/terapia , Lactente , Recém-Nascido , Icterícia Neonatal/terapia , Padrões de ReferênciaRESUMO
OBJECTIVE: Graves' disease is an autoimmune disease characterized by production of autoantibodies directed against the thyroid gland. Thyrotropin-receptor antibodies (TRAbs) are clearly pathogenic, but the role of thyroidperoxidase antibodies (TPOAbs) in Graves disease is unknown. METHODS: We retrospectively studied whether TPOAb positivity reduced risk of relapse following antithyroid drug (ATD) treatment in newly diagnosed Graves disease. RESULTS: During follow-up of 204 patients with TRAb-positive Graves disease, 107 (52%) relapsed following withdrawal of ATD. Mean age was 40.0 years, and 82% were female. The average duration of ATD treatment was 23.5 months and was not different between patients who relapsed and those with sustained remission. Absence of TPOAbs significantly increased risk of Graves relapse (odds ratio, 2.21). Male sex and younger age were other factors significantly associated with increased risk of relapse. CONCLUSION: TPOAb positivity significantly improves the odds of remission following ATD treatment in newly diagnosed Graves' disease.
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Antitireóideos , Doença de Graves , Adulto , Antitireóideos/uso terapêutico , Autoanticorpos , Feminino , Doença de Graves/tratamento farmacológico , Humanos , Iodeto Peroxidase , Masculino , Receptores da Tireotropina , Recidiva , Estudos RetrospectivosRESUMO
To determine whether target concentration non-attainment can be anticipated in critically ill patients prior to initiating empiric ß-lactam antibiotic therapy based on readily available clinical factors. Retrospective review of consecutive patients treated with piperacillin or meropenem and who underwent therapeutic drug monitoring (TDM) at St Vincent's Hospital (Sydney, Australia) between January 2013 and December 2015 was performed. Predefined subgroups were patients who received continuous renal replacement therapy (CRRT) and those who did not (non-CRRT). Potential risk factors were evaluated by correlation with ß-lactam antibiotic trough concentrations (Cmin) lower than or equal to targeted minimum inhibitory concentration (MIC). Only the first drug concentration after initiation of the antibiotic treatment was included to reflect empirical dose selection. A total of n = 249 patients (piperacillin, n = 169; meropenem, n = 80) were investigated. For non-CRRT patients (n = 210), multivariate analysis demonstrated the following: male gender (p = 0.006); younger age (p = 0.015); prescribed daily antibiotic dose less than 1.5 times the product information recommendations (p = 0.004); lack of positive microbiology (p = 0.006); lower overall illness severity (p = 0.005); and estimated glomerular filtration rate (eGFR) ≥ 90 mL/min/1.73 m2 (p < 0.001), to be associated with Cmin ≤ MIC. No predictor variable was found to be significantly associated with Cmin ≤ MIC for the CRRT cohort. Evaluating the risk of target concentration non-attainment using simple clinical factors is possible at the bedside for non-CRRT patients prior to empiric antibiotic initiation. Clinicians should be wary of selecting doses based on the product information especially when treating younger male patients with apparently 'normal' renal function.
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Antibacterianos/uso terapêutico , Estado Terminal/terapia , beta-Lactamas/uso terapêutico , Adulto , Idoso , Antibacterianos/farmacologia , Biomarcadores , Cromatografia Líquida de Alta Pressão , Feminino , Humanos , Unidades de Terapia Intensiva , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Razão de Chances , Fatores de Risco , Espectrometria de Massas em Tandem , beta-Lactamas/farmacologiaRESUMO
The results of medical laboratory testing are only useful if they lead to appropriate actions by medical practitioners and/or patients. An underappreciated component of the medical testing process is the transfer of the information from the laboratory report into the reader's brain. The format of laboratory reports can be determined by the testing laboratory, which may issue a formatted report, or by electronic systems receiving information from laboratories and controlling the report format. As doctors can receive information from many laboratories, interpreting information from reports in a safe and rapid manner is facilitated by having similar report layouts and formats. Using Australia as an example, there is a wide variation in report formats in spite of a body of work to define standards for reporting. In addition to standardising of report formats, consideration needs to be given to optimisation of report formatting to facilitate rapid and unambiguous reading of the report and also interpretation of the data. Innovative report formats have been developed by some laboratories; however, wide adoption has not followed. The need to balance uniformity of reporting with appropriate innovation is a challenge for safe reporting of laboratory results. This paper discusses the current status and opportunity for improvement in safety and efficiency of the reading of laboratory reports, using current practise and developments in Australia as examples.
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Documentação/normas , Laboratórios/organização & administração , Laboratórios/normas , Austrália , Eficiência Organizacional , Humanos , Segurança do Paciente , Padrões de ReferênciaRESUMO
The Australasian Association of Clinical Biochemists (AACB) has over the past 5 years been actively working to achieve harmonized reference intervals (RIs) for common clinical chemistry analytes using an evidence-based checklist approach where there is sound calibration and metrological traceability. It has now recommended harmonized RIs for 18 common clinical chemistry analytes which are performed in most routine laboratories and these have been endorsed by the Royal College of Pathologists of Australasia (RCPA). In 2017 another group of analytes including urea, albumin and arterial blood gas parameters were considered and suggested harmonized RIs proposed. This report provides an update of those harmonization efforts.
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Testes de Química Clínica/normas , Adulto , Albuminas/análise , Albuminas/normas , Australásia , Gasometria/normas , Medicina Baseada em Evidências , Humanos , Valores de Referência , Sociedades Médicas , Ureia/sangue , Ureia/normasRESUMO
Reference intervals are a vital part of the information supplied by clinical laboratories to support interpretation of numerical pathology results such as are produced in clinical chemistry and hematology laboratories. The traditional method for establishing reference intervals, known as the direct approach, is based on collecting samples from members of a preselected reference population, making the measurements and then determining the intervals. An alternative approach is to perform analysis of results generated as part of routine pathology testing and using appropriate statistical techniques to determine reference intervals. This is known as the indirect approach. This paper from a working group of the International Federation of Clinical Chemistry (IFCC) Committee on Reference Intervals and Decision Limits (C-RIDL) aims to summarize current thinking on indirect approaches to reference intervals. The indirect approach has some major potential advantages compared with direct methods. The processes are faster, cheaper and do not involve patient inconvenience, discomfort or the risks associated with generating new patient health information. Indirect methods also use the same preanalytical and analytical techniques used for patient management and can provide very large numbers for assessment. Limitations to the indirect methods include possible effects of diseased subpopulations on the derived interval. The IFCC C-RIDL aims to encourage the use of indirect methods to establish and verify reference intervals, to promote publication of such intervals with clear explanation of the process used and also to support the development of improved statistical techniques for these studies.
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Padrões de Referência , Química Clínica/normas , HumanosRESUMO
External Quality Assurance (EQA) is vital to ensure acceptable analytical quality in medical laboratories. A key component of an EQA scheme is an analytical performance specification (APS) for each measurand that a laboratory can use to assess the extent of deviation of the obtained results from the target value. A consensus conference held in Milan in 2014 has proposed three models to set APS and these can be applied to setting APS for EQA. A goal arising from this conference is the harmonisation of EQA APS between different schemes to deliver consistent quality messages to laboratories irrespective of location and the choice of EQA provider. At this time there are wide differences in the APS used in different EQA schemes for the same measurands. Contributing factors to this variation are that the APS in different schemes are established using different criteria, applied to different types of data (e.g. single data points, multiple data points), used for different goals (e.g. improvement of analytical quality; licensing), and with the aim of eliciting different responses from participants. This paper provides recommendations from the European Federation of Laboratory Medicine (EFLM) Task and Finish Group on Performance Specifications for External Quality Assurance Schemes (TFG-APSEQA) and on clear terminology for EQA APS. The recommended terminology covers six elements required to understand APS: 1) a statement on the EQA material matrix and its commutability; 2) the method used to assign the target value; 3) the data set to which APS are applied; 4) the applicable analytical property being assessed (i.e. total error, bias, imprecision, uncertainty); 5) the rationale for the selection of the APS; and 6) the type of the Milan model(s) used to set the APS. The terminology is required for EQA participants and other interested parties to understand the meaning of meeting or not meeting APS.
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Técnicas de Laboratório Clínico/normas , Garantia da Qualidade dos Cuidados de Saúde/métodos , Humanos , Guias de Prática Clínica como AssuntoRESUMO
BACKGROUND: Hyperfiltration (HF) has been linked to the development of diabetic kidney disease (DKD), but the causative or predictive role of HF in the pathogenesis of DKD still remains unclear. To date, there have been no studies of HF in Indigenous Australians, a population with high rates of both diabetes and end-stage kidney disease. We aimed to compare the characteristics and frequency of HF in Indigenous Australians with and without type 2 diabetes. METHODS: Indigenous Australian participants, recruited across five pre-defined strata of health, diabetes status and kidney function, had a reference glomerular filtration rate (GFR) measured using plasma disappearance of iohexol [measured GFR(mGFR)] over 4 h. HF was defined in various ways: (i) mGFR > 144 mL/min/1.73 m(2), which is mGFR > 1.96 × SD above the mean of the mGFR in non-diabetic participants with normal albuminuria and normal renal function (mGFR > 90 mL/min/1.73 m(2)); (ii) age-corrected mGFR (>144 mL/min/1.73 m(2)) to account for the effect of ageing on GFR in subjects over 40 years of age with cut-off 1 mL/min/1.73 m(2) lower for every year; (iii) mGFR > 144 mL/min, without correction for body surface area or age, as well as (iv) mGFR > 125 mL/min/1.73 m(2), without adjustment for age. RESULTS: A total of 383 Indigenous participants, 125 with and 258 without diabetes, with mGFR > 90 mL/min/1.73 m(2) were studied. The proportion of participants with HF was 7% using mGFR > 144 mL/min/1.73 m(2), 11% using the age-adjusted definition, 19% using mGFR > 144 mL/min and 27% using mGFR > 125 mL/min/1.73 m(2). Diabetes was more common in participants with HF (40-74%) compared with normofiltering participants (28-31%), regardless of the definition of HF. CONCLUSIONS: HF exists in Indigenous Australians with and without diabetes. A greater proportion of participants had diabetes in HF group compared with normofiltration group. Long-term follow-up of this cohort is necessary to determine if HF plays a role in the development of DKD and non-DKD.
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Albuminúria/diagnóstico , Diabetes Mellitus Tipo 2/fisiopatologia , Nefropatias Diabéticas/fisiopatologia , Taxa de Filtração Glomerular , Havaiano Nativo ou Outro Ilhéu do Pacífico , Insuficiência Renal Crônica/diagnóstico , Adulto , Albuminúria/etiologia , Austrália/epidemiologia , Superfície Corporal , Estudos Transversais , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/etnologia , Nefropatias Diabéticas/etnologia , Nefropatias Diabéticas/etiologia , Feminino , Serviços de Saúde do Indígena , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência Renal Crônica/etiologiaRESUMO
BACKGROUND: Steroid immunoassays originally required solvent extraction, chromatography, and structurally authentic tracers to avoid interference from steroid cross-reactivity and matrix effects. The demand for steroid assays has driven assay simplification, bypassing this triplet of validity criteria to allow use of unextracted serum, which has introduced bias and nonspecificity at low steroid concentrations. We aimed to evaluate the performance of commercial direct estradiol (E2) immunoassays relative to the reference method of LC-MS and compared serum E2 measurements from each assay with biomarkers of estrogen action. METHODS: We measured serum E2 in duplicate using 5 commercial direct immunoassays and LC-MS in a nested cohort of 101 healthy, asymptomatic men >40 years old from the Healthy Man Study. For each immunoassay, we evaluated the detectability and distribution of serum E2 measurements, CV, and bias (relative to LC-MS) by Passing-Bablok regression and deviance plots. RESULTS: Three assays detected E2 in all samples, whereas E2 was detected in only 53% and 72% of samples by 2 other assays. All 5 assays had positive biases, ranging from 6% to 74%, throughout their ranges. CVs were lower with 4 immunoassays than with LC-MS. LC-MS, but none of the direct immunoassays, correlated with serum testosterone and sex steroid-binding globulin. CONCLUSIONS: The positive bias of direct E2 immunoassays throughout their working range reflects the nonspecific effects of steroid cross-reactivity and/or matrix interference arising from the violation of the triplet validity criteria for steroid immunoassay.
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Estradiol/sangue , Cromatografia Líquida/normas , Humanos , Imunoensaio/normas , Masculino , Espectrometria de Massas/normas , Pessoa de Meia-Idade , Valores de ReferênciaAssuntos
Biomarcadores , Insuficiência Renal Crônica/diagnóstico , Albuminúria , Biomarcadores/sangue , Biomarcadores/urina , Técnicas de Laboratório Clínico/métodos , Técnicas de Laboratório Clínico/normas , Creatinina/sangue , Cistatina C/sangue , Complicações do Diabetes , Taxa de Filtração Glomerular , Humanos , Hipertensão/complicações , Testes de Função Renal , Educação de Pacientes como Assunto , Fatores de Risco , Sensibilidade e EspecificidadeRESUMO
A working party (WP) from the Australasian Association of Clinical Biochemists, Australasian Society of Clinical and Experimental Pharmacologists and Toxicologists, Royal College of Pathologists of Australasia and Royal Australasian College of Physicians recommends the following: *mass units should be used for reporting therapeutic drug concentrations in Australia and New Zealand; and the litre (L) should be used as the denominator when expressing concentration. Examples of these units are mg/L and µg/L Exceptions to these principles include: *drugs for which there is current uniformity of reporting and supporting information using molar units, notably lithium (mmol/L) and methotrexate (µmol/L); *drugs that are also present as endogenous substances, where the units used routinely should continue to be used. This applies to many substances, including minerals (eg, iron; µmol/L), vitamins (eg, vitamin D; nmol/L) and hormones (eg, thyroxine; pmol/L). *drugs for which the denominator is not a 198 of fluid and there is international uniformity of reporting (eg, thiopurine metabolites; per 109 red blood cells). These recommendations relate to drugs that are used therapeutically, whether measured for therapeutic drug monitoring purposes or for assessment of overdose. Other substances, such as drugs of misuse, heavy metals or environmental toxins, were not considered by the WP and are thus not covered by this document. These recommendations should also be applied to other supporting documentation such as published guidelines, journal articles and websites. The implementation of these recommendations in New Zealand is subject to local confirmation.