A prospective multi-centre study assessing the safety and effectiveness following the implementation of an accelerated chest pain pathway using point-of-care troponin for use in New Zealand rural hospital and primary care settings.

AIMS: Most rural hospitals and general practices in New Zealand (NZ) are reliant on point-of-care troponin. A rural accelerated chest pain pathway (RACPP), combining an electrocardiogram (ECG), a structured risk score (Emergency Department Assessment of Chest Pain Score), and serial point-of-care troponin, was designed for use in rural hospital and primary care settings across NZ. The aim of this study was to evaluate the safety and effectiveness of the RACPP. METHODS AND RESULTS: A prospective multi-centre evaluation following implementation of the RACPP was undertaken from 1 July 2018 to 31 December 2020 in rural hospitals, rural and urban general practices, and urgent care clinics. The primary outcome measure was the presence of 30-day major adverse cardiac events (MACEs) in low-risk patients. The secondary outcome was the percentage of patients classified as low-risk that avoided transfer or were eligible for early discharge. There were 1205 patients enrolled in the study. 132 patients were excluded. Of the 1073 patients included in the primary analysis, 474 (44.0%) patients were identified as low-risk. There were no [95% confidence interval (CI): 0-0.3%] MACE within 30 days of the presentation among low-risk patients. Most of these patients (91.8%) were discharged without admission to hospital. Almost all patients who presented to general practice (99%) and urgent care clinics (97.6%) were discharged to home directly. CONCLUSION: The RACPP is safe and effective at excluding MACEs in NZ rural hospital and primary care settings, where it can identify a group of low-risk patients who can be safely discharged home without transfer to hospital.

Implementation and evaluation of a rural general practice assessment pathway for possible cardiac chest pain using point-of-care troponin testing: a pilot study.

OBJECTIVES: To assess the feasibility and acceptability, and additionally to preliminarily evaluate, the effectiveness and safety of an accelerated diagnostic chest pain pathway in rural general practice using point-of-care troponin to identify patients at low risk of acute myocardial infarction, avoiding unnecessary patient transfer to hospital and enabling early discharge home. DESIGN: A prospective observational pilot evaluation. SETTING: Twelve rural general (family) practices in the Midlands region of New Zealand. PARTICIPANTS: Patients aged ≥18 years who presented acutely to rural general practice with suspected ischaemic chest pain for whom the doctor intended transfer to hospital for serial troponin measurement. OUTCOME MEASURES: The proportion of patients managed using the low-risk pathway without transfer to hospital and without 30-day major adverse cardiac event (MACE); pathway adherence; rate of 30-day MACE; patient satisfaction with care; and agreement between point-of-care and laboratory measured troponin concentrations. RESULTS: A total of 180 patients were assessed by the pathway. The pathway classified 111 patients (61.7%) as low-risk and all were managed in rural general practice with no 30-day MACE (0%, 95% CI 0.0% to 3.3%). Adherence to the low-risk pathway was 95.5% (106 out of 111). Of the 56 patients classified as non-low-risk and referred to hospital, 9 (16.1%) had a 30-day MACE. A further 13 non-low-risk patients were not transferred to hospital, with no events. The sensitivity of the pathway for 30-day MACE was 100.0% (95% CI 70.1% to 100%). Of low-risk patients, 94% reported good to excellent satisfaction with care. Good concordance was observed between point-of-care and duplicate laboratory measured troponin concentrations. CONCLUSIONS: The use of an accelerated diagnostic chest pain pathway incorporating point-of-care troponin in a rural general practice setting was feasible and acceptable, with preliminary results suggesting that it may safely and effectively reduce the urgent transfer of low-risk patients to hospital.

A typical presentation of type B insulin resistance syndrome with isolated hypoglycaemia and suppressed insulin.

Type B insulin resistance syndrome is a rare autoimmune disorder affecting glucose homeostasis characterised by the presence of serum autoantibodies to the insulin receptor. Typically, these patients present with severe insulin resistance although a mixed hyperglycaemic and hypoglycaemic phenotype may also occur, as can an exceptionally rare isolated hypoglycaemia presentation. The classic biochemical pattern comprises elevated insulin levels despite significant hypoglycaemia. We report an adult man presenting with isolated hypoglycaemia and suppressed serum insulin and C-peptide levels. He demonstrated evidence of autoimmunity with positive antinuclear antibodies, reactive lymphadenopathy and cytopaenias but did not meet the criteria for systemic lupus erythematosus and underlying malignancy was not identified despite extensive investigation. Insulin receptor antibodies were present. Treatment with prednisone led to resolution of hypoglycaemia, with no recurrence after 36 months of follow-up. However, 42 months after initial presentation, he represented with high-grade lymphoma.

Study protocol for an observational study to evaluate an accelerated chest pain pathway using point-of-care troponin in New Zealand rural and primary care populations.

INTRODUCTION Accelerated diagnostic chest pain pathways are used widely in urban New Zealand hospitals. These pathways use laboratory-based troponin assays with good analytical precision. Widespread implementation has not occurred in many of New Zealand's rural hospitals and general practices as they are reliant on point-of-care troponin assays, which are less sensitive and precise. An accelerated chest pain pathway using point-of-care troponin has been adapted for use in rural settings. A pilot study in a low-risk rural population showed no major adverse cardiac events at 30 days. A larger study is required to be confident that the pathway is safe. AIMS To assess the safety and effectiveness of an accelerated chest pain pathway adapted for rural settings and general practice using point-of-care troponin to identify low-risk patients and allow early discharge. METHODS This is a prospective observational study of an accelerated chest pain pathway using point-of-care troponin in rural hospitals and general practices in New Zealand. A total of 1000 patients, of whom we estimate 400 will be low risk, will be enrolled in the study. OUTCOME MEASURES The primary outcome is the proportion of patients identified by the pathway as low risk for a 30-day major adverse cardiac event. Secondary outcomes include the proportion of low-risk patients who were discharged directly from general practice or rural hospitals, the proportion of patients reclassified as having acute myocardial infarction by the pathway and the proportion of patients with low and intermediate risk safely managed in the rural hospital.

How comparable are total human chorionic gonadotropin (hCGt) tumour markers assays?

Background Total human chorionic gonadotropin (hCGt) tumour marker testing is regarded as an "off label" application for most commercial methods. We compared four assays in patients with a hCGt tumour marker request. We hypothesised that regression slopes would be altered and that outliers would be more common with tumour marker than with pregnancy samples if the detection of malignancy associated hCG molecular forms differed amongst assays. Further such systematic differences would be obvious and large enough to change clinical management decisions. Results We measured hCGt in 390 samples from 137 females and 253 males with a tumour marker request and 208 pregnancy controls with the following methods: Access Total ßhCG, Architect Total-ßhCG, Cobas hCG + ß and Immulite HCG. The between method regressions determined on tumour marker and pregnancy samples were not significantly different. The outlier rates were similar for male and female tumour marker and the pregnancy groups: 1.6% (95% confidence interval [CI] 0%-3.1%), 2.2% (95% CI 0%-4.7%) and 2.9% (95% CI 0.6%-5.2%). The outliers were randomly distributed amongst the methods and we were confident that they would not adversely influence clinical decisions. Conclusions The hCGt results were clinically equivalent with no systematic difference amongst the four assays.

ICare-ACS (Improving Care Processes for Patients With Suspected Acute Coronary Syndrome): A Study of Cross-System Implementation of a National Clinical Pathway.

BACKGROUND: Efforts to safely reduce length of stay for emergency department patients with symptoms suggestive of acute coronary syndrome (ACS) have had mixed success. Few system-wide efforts affecting multiple hospital emergency departments have ever been evaluated. We evaluated the effectiveness of a nationwide implementation of clinical pathways for potential ACS in disparate hospitals. METHODS: This was a multicenter pragmatic stepped-wedge before-and-after trial in 7 New Zealand acute care hospitals with 31 332 patients investigated for suspected ACS with serial troponin measurements. The implementation was a clinical pathway for the assessment of patients with suspected ACS that included a clinical pathway document in paper or electronic format, structured risk stratification, specified time points for electrocardiographic and serial troponin testing within 3 hours of arrival, and directions for combining risk stratification and electrocardiographic and troponin testing in an accelerated diagnostic protocol. Implementation was monitored for >4 months and compared with usual care over the preceding 6 months. The main outcome measure was the odds of discharge within 6 hours of presentation RESULTS: There were 11 529 participants in the preimplementation phase (range, 284-3465) and 19 803 in the postimplementation phase (range, 395-5039). Overall, the mean 6-hour discharge rate increased from 8.3% (range, 2.7%-37.7%) to 18.4% (6.8%-43.8%). The odds of being discharged within 6 hours increased after clinical pathway implementation. The odds ratio was 2.4 (95% confidence interval, 2.3-2.6). In patients without ACS, the median length of hospital stays decreased by 2.9 hours (95% confidence interval, 2.4-3.4). For patients discharged within 6 hours, there was no change in 30-day major adverse cardiac event rates (0.52% versus 0.44%; P=0.96). In these patients, no adverse event occurred when clinical pathways were correctly followed. CONCLUSIONS: Implementation of clinical pathways for suspected ACS reduced the length of stay and increased the proportions of patients safely discharged within 6 hours. CLINICAL TRIAL REGISTRATION: URL: https://www.anzctr.org.au/ (Australian and New Zealand Clinical Trials Registry). Unique identifier: ACTRN12617000381381.

A note on marginalization of regression parameters from mixed models of binary outcomes.

This article discusses marginalization of the regression parameters in mixed models for correlated binary outcomes. As is well known, the regression parameters in such models have the "subject-specific" (SS) or conditional interpretation, in contrast to the "population-averaged" (PA) or marginal estimates that represent the unconditional covariate effects. We describe an approach using numerical quadrature to obtain PA estimates from their SS counterparts in models with multiple random effects. Standard errors for the PA estimates are derived using the delta method. We illustrate our proposed method using data from a smoking cessation study in which a binary outcome (smoking, Y/N) was measured longitudinally. We compare our estimates to those obtained using GEE and marginalized multilevel models, and present results from a simulation study.

Factitious Graves' Disease Due to Biotin Immunoassay Interference-A Case and Review of the Literature.

CONTEXT: Biotin (vitamin B7) is an essential co-factor for four carboxylases involved in fatty acid metabolism, leucine degradation, and gluconeogenesis. The recommended daily intake (RDI) of biotin is approximately 30 µg per day. Low-moderate dose biotin is a common component of multivitamin preparations, and high-dose biotin (10 000 times RDI) has been reported to improve clinical outcomes and quality of life in patients with progressive multiple sclerosis. Biotin is also a component of immunoassays, and supplementation may cause interference in both thyroid and non-thyroid immunoassays. OBJECTIVE: To assess whether biotin ingestion caused abnormal thyroid function tests (TFTs) in a patient through assay interference. DESIGN: We report a patient with biotin-associated abnormal TFTs and a systematic review of the literature. SETTING: A tertiary endocrine service in Hamilton, New Zealand. RESULTS: The patient had markedly abnormal TFTs that did not match the clinical context. After biotin cessation, TFTs normalized far more rapidly than possible given the half-life of T4, consistent with assay interference by biotin. Multiple other analytes also tested abnormal in the presence of biotin. CONCLUSION: Biotin ingested in moderate to high doses can cause immunoassay interference. Depending on the assay format, biotin interference can result in either falsely high or low values. Interference is not limited to thyroid tests and has the potential to affect a wide range of analytes. It is important for clinicians to be aware of this interaction to prevent misdiagnosis and inappropriate treatment.

Vitamin D status of psychiatric inpatients in New Zealand's Waikato region.

BACKGROUND: Vitamin D deficiency is widespread in New Zealand, confers multiple health risks, and may be particularly common among people with psychiatric illness. We studied vitamin D status in an unselected sample of adult psychiatric inpatients in Hamilton (latitude 37.5 S) during late winter. METHODS: We recruited 102 consenting subjects and measured 25-hydroxy vitamin D3 levels in venous blood using a competitive electrochemiluminescence immunoassay. In addition to descriptive statistics, we used one-sample t-tests to determine the extent to which ethnic and diagnostic subgroups fell below the vitamin D deficiency threshold of 50 nM. RESULTS: 75 subjects (74%) had vitamin D levels <50 nM and thus had at least mild deficiency, while 19 (19%) were severely deficient with levels <25 nM. Rates of deficiency were comparable for men and women; only the former showed a correlation of vitamin D levels with age (r = 0.45, p < 0.01). Maori participants constituted half the sample (n = 51) and were more likely to be deficient than their European counterparts (p = 0.04). Vitamin D also varied by diagnosis, with schizophrenia associated with markedly lower levels than mania and depression (p < 0.001). CONCLUSIONS: Vitamin D deficiency is prevalent in the psychiatric inpatient setting in New Zealand and may be relevant to poor physical health outcomes, notably among Maori and those with schizophrenia. These findings support proposals to provide vitamin D supplementation, particularly during the winter months.

Inappropriate trace element testing in the Auckland region.

AIM: To understand recent changes in trace element test usage in the Auckland region of New Zealand. METHODS: Laboratory records of trace element tests between 2004 and 2008 were analysed. A questionnaire was sent to a frequent requestor group to elicit reasons for requesting trace element tests. RESULTS: The annual number of trace element test requests increased by 3.5-fold over the study period. The increase was largely due to a 2.8-fold increase in serum copper, a 3.8-fold increase in serum zinc, and a 3.4-fold increase in serum selenium tests. Most of the increase was accounted for by a small number of requestors, mainly general practitioners. An outlier group of 24 requestors was identified who were responsible for ordering 55% of serum copper, 61% of serum zinc, 63% of serum selenium and 66% of blood mercury tests in the last year of the study. Responses to the questionnaire suggest that among the outlier group the reasons for requesting serum zinc, copper and selenium tests are not evidence-based. CONCLUSION: The majority of trace element tests performed in the Auckland region appear to be non-evidence-based, and represent a significant wastage of public laboratory resources. This suggests that laboratories could achieve significant savings in expenditure by clearly defining appropriate indications for performing trace element tests.

Structural Equation Modeling of Multivariate Time Series.

The covariance structure of a vector autoregressive process with moving average residuals (VARMA) is derived. It differs from other available expressions for the covariance function of a stationary VARMA process and is compatible with current structural equation methodology. Structural equation modeling programs, such as LISREL, may therefore be employed to fit the model. Particular attention is given to assumptions concerning the process before the first observation. An application to a repeated time series is used to demonstrate the effect of these assumptions on the structure of the reproduced covariance matrix.

Fitting Partially Nonlinear Random Coefficient Models as SEMs.

The nonlinear random coefficient model has become increasingly popular as a method for describing individual differences in longitudinal research. Although promising, the nonlinear model it is not utilized as often as it might be because software options are still somewhat limited. In this article we show that a specialized version of the model can be fit to data using SEM software. The specialization is to a model in which the parameters that enter the function in a linear manner are random, whereas those that are nonlinear are common to all individuals. Although this kind of function is not as general as is the fully nonlinear model, it still is applicable to many different data sets. Two examples are presented to show how the models can be estimated using popular SEM computer programs.

Mental retardation and ataxia due to normotriglyceridemic hypobetalipoproteinemia.

A 12-year-old boy with mental retardation, obesity, ataxia, and visual impairment was shown to have normal fasting plasma triglyceride but low cholesterol and vitamin E levels. Investigations indicated that he was compound heterozygous for two mutations in the apolipoprotein B gene (APOB), resulting in a failure to express apolipoprotein B-100, yet retain apolipoprotein B-48 production. The proband therefore was able to form chylomicrons, but not a low-density lipoprotein capable of receptor-mediated endocytosis. This resulted in chronic vitamin E deficiency. We suggest the term normotriglyceridemic hypobetalipoproteinemia for this easily recognizable condition.

A Version of Quadratic Regression with Interpretable Parameters.

The quadratic regression model is popular and effective in describing a wide variety of data, but it is based on a function whose parameters are not easy to interpret. We suggest an alternative form of the quadratic model that has the same expectation function, but also has the useful feature that its parameters are interpretable. Examples are provided of a simple regression problem and also of a nonlinear mixed-effects model. The models can be estimated with available software.