Practical approaches to the detection of macrotroponin.

INTRODUCTION: Macrotroponin is increasingly recognised as a cause of confusion in interpreting high-sensitivity cardiac troponin (hs-cTnI) results. In this study, we sought to evaluate two practical approaches to detecting macrotroponin. These two approaches are PEG precipitation and SVM (support vector machine) analysis to classify discrepancies between hs-cTn assays. METHOD: Residual serum and heparin plasma specimens (n = 483) with initially elevated hs-cTnI from hospital and community laboratories were retested on multiple hs-cTn platforms before and after PEG precipitation and Protein A immunoglobulin depletion. SVM analysis was conducted to identify a linear equation that best discriminated specimens with macrotroponin using a combination of results from two different hs-cTn assays. FINDINGS: The diagnostic performance of PEG precipitation was carried out using Protein A immunoglobulin depletion as the reference comparator. When a cutoff residual activity after PEG precipitation of ≤ 20% was used, this threshold carried a high specificity of 92% (confidence interval 83-98%; n = 189) using the Siemens hs-cTnI Vista assay and 95% specificity (86%-98%; n = 242) using the Abbott hs-cTnI Architect assay. SVM analysis generated a linear equation identifying macrotroponin specimens from results obtained on two hs-cTn assays. This approach can be highly specific, comparable to PEG precipitation when certain assay combinations and concentrations are used. CONCLUSION: We describe and identify practical alternatives to detecting macrotroponin. These approaches can be optimised for high specificity, reducing the need for more complex laboratory methods.

Effect of Macrotroponin in a Cohort of Community Patients with Elevated Cardiac Troponin.

BACKGROUND: Macrotroponin is an important cause of discrepancy between current high-sensitivity cardiac troponin (hs-cTn) assays, however, its clinical significance is unclear. This study examined the effects of macrotroponin and repeat testing by different hs-cTnI assays in a cohort of community patients with elevated hs-cTnI. METHODS: The first residual serum specimen from each patient in the community admitted to hospital with elevated hs-cTnI (Siemens hs-cTnI Centaur) was retested after immunoglobulin depletion and by 5 other hs-cTn assays. Low recovery of cTnI (<40%) following immunoglobulin depletion was considered as macrotroponin. A retrospective chart review was performed for these participants. Investigator-adjudicated diagnosis served as the reference standard. RESULTS: In our cohort of community patients with elevated troponin (n = 188), participants with macrotroponin (n = 99) often had a multifactorial or indeterminate myocardial injury (56% vs 25%) and were less likely to have acute coronary syndrome (9% vs 28%). On repeat testing of cTn on other platforms, better diagnostic performance (c-statistics) for ischemic and non-ischemic cardiac causes was observed on the Beckman Access hs-cTnI (0.74; 95% confidence interval [CI] 0.67-0.81) or the Abbott hs-cTnI Architect (0.75; CI 0.68-0.82) compared to the Siemens hs-cTnI Vista (0.62; CI 0.54-0.70; P < 0.05). This could be attributed to differences in assay reactivity for macrotroponin. Interestingly, better diagnostic performance was observed in patients without macrotroponin. Although a small number of deaths occurred (n = 16), participants with macrotroponin had better overall survival. CONCLUSIONS: In the low-risk setting, the presence of macrotroponin was clinically associated with multifactorial or indeterminate causes of troponin elevation.

Inter- and intra-rater reliability of knee flexion angle measurements on X-ray and MRI.

Background: Range of motion (ROM) is an important aspect of orthopaedic patient assessment. It can be measured at the knee joint by determining the knee flexion angle (KFA) a patient can achieve at extremes of flexion and extension. As with any measurement, the accuracy and reliability of the method used determine its validity. The consistency of magnetic resonance imaging (MRI) scans as compared to the current gold standard of X-ray remains unknown in terms of KFA evaluation. The aim of this study was to assess and compare the reliability of measuring KFA between X-ray and MRI scans. Methods: This study included 80 patients (94 knees) who had attended a specialist knee clinic due to varying knee pathologies and undergone both X-ray and MRI scans. Lateral and T1-weighted sagittal imaging views (respectively) were used to measure KFA by two trained observers independently at two separate time points, 8 weeks apart. The data was then statistically analysed and intra- and inter-observer reliability calculated using the intraclass correlation coefficient (ICC). Results: The intra-observer reliability for X-ray was 0.96 (P<0.001) and that for MRI was 0.83 (P<0.001). The inter-observer reliability for X-ray was 0.99 (P<0.001) and that for MRI was 0.81 (P<0.001). All the intra-class correlation coefficients were graded as excellent in both the intra- and inter-observer reliability analysis. Overall, the mean KFA was notably higher on X-ray measurements than that on MRI scans. There was a statistically significant difference between Time 1 and Time 2 measurements (17.7° vs. 16.8°) for MRI data (P=0.022). No significant difference was found for X-ray measurements (46.4° vs. 45.6°) in this regard (P=0.182). Conclusions: Both X-ray and MRI allow KFA to be measured with an excellent degree of reliability. However, X-ray measurements were overall superior to that of MRI mainly due to the larger field of view of the visible on-screen image which more readily identifies the anatomical landmarks required to measure KFA.

Identification of macrotroponin T: findings from a case report and non-reproducible troponin T results.

OBJECTIVES: Macrotroponin is due to cardiac troponin (cTn) binding to endogenous cTn autoantibodies. While previous studies showed a high incidence of macrotroponin affecting cTnI assays, reports of macrotroponin T, particularly without cTnI reactivity, have been rare. Although the clinical significance of macrotroponin is not fully understood, macroenzymes and complexes are recognised to cause confusion in interpretation of laboratory results. The potential for adverse clinical consequences due to misinterpretation of affected results is very high. METHODS: We describe four cases of macrotroponin T with persistently low high sensitivity cTnT (hs-cTnT) by the 9 min compared to the 18 min variant of the assay. Three cases were serendipitously identified due to the use of a lot number of Roche hs-cTnT affected by non-reproducible results, necessitating measurement of cTnT in duplicate. We identified and characterised these macrotroponin specimens by immunoglobulin depletion (Protein A and PEG precipitation), mixing studies with EDTA and recombinant cTnT. RESULTS: In cases of macro-cTnT, a lower result occurred on the hs-cTnT using the 9 min compared to 18 min variant assay (ratio of 9-18 min hs-cTnT <0.80). Mixing studies with recombinant cTnT or EDTA demonstrated a difference in recovery vs. controls. One of these patients demonstrated a high molecular weight complex for cTnI and cTnT demonstrating a macrocomplex involving both cTn. This patient demonstrated a rise and fall in cTn when measured by several commercial assays consistent with genuine acute cardiac injury. CONCLUSIONS: We identified several cases of macro-cTnT and described associated clinical and biochemical features.

Effect of macrotroponin on the utility of cardiac troponin I as a prognostic biomarker for long term total and cardiovascular disease mortality.

Macrotroponin is a complex formed between endogenous cardiac troponin autoantibodies and circulating cardiac troponin (cTn). It is a recognised cause of discrepancy between current high sensitivity troponin (hs-cTn) assays; and immunoglobulin-bound (macrotroponin) and unbound cTn can coexist in varying proportions in the acute setting. Increasingly it is considered when laboratory cTn results do not match a patient's clinical picture. However, despite the better understanding of macrotroponin as an analytical interference, its clinical significance remains unclear. The aim of this study was to determine the potential impact of macrotroponin on the use of cTn as a long-term prognostic marker. We repeated cTnI testing after polyethylene glycol (PEG) precipitation on consecutive participants (n=159) with a first elevated cTn above 0.2 µg/L during their hospital admission episode. Because this paper is looking at outcomes in years, the initial data were generated at a time when non-hs-cTn assays were in use. We divided the cohort into two groups based on an exploratory PEG recovery cut-off of <34.6% to indicate the presence of possible macrotroponin and compared the overall and cardiovascular related mortality. The median follow-up time for the overall cohort was 8.35 years (8.32-8.40 interquartile range) with no difference between the two groups. The overall median survival was 8.1 years. Our findings indicate a hazard ratio of 0.54 (0.32-0.91 95% CI) for all-cause mortality and 0.48 (0.24-0.95) for cardiovascular mortality in patients with possible macrotroponin compared to those patients with troponin elevation without evidence of macrotroponin, after adjustment for common cardiovascular disease risk factors. Furthermore, an association was observed between PEG% recovery and all-cause mortality (p<0.05). This study showed that patients with macrotroponin have comparatively favourable long-term all-cause and cardiovascular mortality in a cohort of patients with elevated troponin. We illustrate the importance of recognising cTn results as being a summation of heterogeneous components, including those bound to antibodies, and the potential role of macrotroponin to further improve our interpretation and use of cTn as a biomarker.

A three-way comparison of glycated haemoglobin: are results from the three platforms interchangeable?

AIMS: To determine whether glycated haemoglobin (HbA1c) results from three commonly used platforms can be interpreted cumulatively and used interchangeably in individuals with common haemoglobinopathies. A secondary goal was to assess the relationship between HbA1c concentrations, and haemoglobin and mean corpuscular volume in this population. METHODS: One hundred and forty-five samples, mostly with haemoglobinopathies, were tested by each of: Roche Gen.3 Cobas c513, Capillarys 2 Flex-Piercing and Bio-Rad D-100 platforms. Statistical comparisons and limits of performance based on biological variation, international recommendations, and local diagnostic cut-offs were drawn upon to determine comparability of results. RESULTS: Inter-platform measurements were not significantly different for the large majority of results. The four HbA1c results that showed maximum discrepancy between triplicates had the following abnormalities: heterozygous haemoglobin S/ beta thalassemia, heterozygous haemoglobin S/ alpha thalassemia, beta thalassemia trait and alpha thalassemia trait. Six triplicates of results in the thalassemia groups (7.5% of thalassemia samples) had levels that misclassified patients' glycaemic status. There was no correlation between HbA1c concentration and mean corpuscular volume, and a weak negative correlation between HbA1c concentration and haemoglobin concentration. CONCLUSION: HbA1c concentrations measured by Cobas c513, Capillarys 2 Flex-Piercing and the Bio-Rad D-100 were found to be comparable in the large majority of samples. While discordance was due to assay imprecision in some cases, in others no biological or analytical explanation could be found.

Change in troponin concentrations in patients with macrotroponin: An in vitro mixing study.

INTRODUCTION: Macrotroponin is a complex formed between endogenous cardiac troponin autoantibodies (cTnAABs) and circulating cardiac troponin (cTn). The potential effect of macrotroponin on current high sensitivity cTn assays has not been fully explored but has recently been identified as a major cause of discrepancy in cTn results between assays. In this study we investigated the effects of mixing troponin (cTn) standards to specimens with and without macrotroponin. METHOD: Macrotroponin was identified in specimens by a recovery of cTnI < 40% following protein A immunoglobulin depletion. Troponin standards containing cTn-IC and cTn-TIC complexes were mixed with serum samples, with (n = 20) and without (n = 10) the presence of macrotroponin. Specimens were tested for cTn before and after mixing by three commercially available high sensitivity cTn assays. Gel filtration chromatography was carried out on five specimens with macrotroponin and each fraction was analzyed by multiple cTn assays. FINDINGS: Following mixing with cTn-TIC standard, all specimens with macrotroponin had a markedly reduced absolute increase in cTnI, indicating negative analytical interference due to macrotroponin. Following mixing with the cTn-IC standard, specimens with macrotroponin demonstrated highly variable changes in cTnI, suggesting significant heterogeneity in macrotroponin complex reactivity between individuals. When the ratio of change, calculated by dividing the absolute change between two cTn assays, was compared between specimens with and without macrotroponin, significant differences were observed (p < 0.001). These findings were supported by variable migration of peak cTn activity on gel filtration chromatography. CONCLUSION: Macrotroponin leads to assay dependent analytical interference affecting current high sensitivity troponin I assays. Furthermore, endogenously occurring cTnAABs are conformationally specific and the analytical effects vary between assays and individuals.

Discrepancy between Cardiac Troponin Assays Due to Endogenous Antibodies.

BACKGROUND: Despite well-described analytical effects of autoantibodies against cardiac troponin (cTn) I on experimental assays, no study has systematically examined their impact on cTn assays in clinical use. We determined the effects of endogenous antibodies on 5 different cTnI assays and a cTnT assay. METHODS: cTn was measured by 6 methods: Siemens hs-cTnI Centaur, Siemens hs-cTnI Vista, Abbott hs-cTnI Architect, Beckman hs-cTnI Access, Beckman cTnI Access, and Roche hs-cTnT Elecsys. Measurements were repeated on 5 assays (all except Siemens hs-cTnI Vista) following immunoglobulin depletion by incubation with protein A. Low recovery of cTnI (<40%) following immunoglobulin depletion was considered positive for macro-cTnI. Protein A findings were validated by gel filtration chromatography and polyethylene glycol precipitation. RESULTS: In a sample of 223 specimens selected from a community laboratory that uses the Siemens hs-cTnI Centaur assay and from which cTn was requested, 76% of samples demonstrated increased cTnI (median, 88 ng/L; interquartile range, 62-204 ng/L). Macro-cTnI was observed in 123 (55%) of the 223 specimens. Comparisons of cTnI assays markedly improved once patients with macro-cTnI were removed. Passing-Bablok regression analysis between hs-cTnI assays demonstrated different slopes for patients with and without macro-cTnI. In patients with macro-cTnI, 89 (72%) showed no effect on the recovery of cTnT, whereas 34 (28%) had reduced recovery of cTnT. The proportion of results above the manufacturers' 99th percentile varied with the cTn assay and macro-cTnI status. CONCLUSION: We suggest that the observed discrepancy between hs-cTnI assays may be attributed in part to the presence of macro-cTnI.

The impact of a national COVID-19 lockdown on acute coronary syndrome hospitalisations in New Zealand (ANZACS-QI 55).

BACKGROUND: Countries with a high incidence of coronavirus 2019 (COVID-19) reported reduced hospitalisations for acute coronary syndromes (ACS) during the pandemic. This study describes the impact of a nationwide lockdown on ACS hospitalisations in New Zealand (NZ), a country with a low incidence of COVID-19. METHODS: All patients admitted to a NZ Hospital with ACS who underwent coronary angiography in the All NZ ACS Quality Improvement registry during the lockdown (23 March - 26 April 2020) were compared with equivalent weeks in 2015-2019. Ambulance attendances and regional community troponin-I testing were compared for lockdown and non-lockdown (1 July 2019 to 16 February 2020) periods. FINDINGS: Hospitalisation for ACS was lower during the 5-week lockdown (105 vs. 146 per-week, rate ratio 0•72 [95% CI 0•61-0•83], p = 0.003). This was explained by fewer admissions for non-ST-segment elevation ACS (NSTE-ACS; p = 0•002) but not ST-segment elevation myocardial infarction (STEMI; p = 0•31). Patient characteristics and in-hospital mortality were similar. For STEMI, door-to-balloon times were similar (70 vs. 72 min, p = 0•52). For NSTE-ACS, there was an increase in percutaneous revascularisation (59% vs. 49%, p<0•001) and reduction in surgical revascularisation (9% vs. 15%, p = 0•005). There were fewer ambulance attendances for cardiac arrests (98 vs. 110 per-week, p = 0•04) but no difference for suspected ACS (408 vs. 420 per-week, p = 0•44). Community troponin testing was lower throughout the lockdown (182 vs. 394 per-week, p<0•001). INTERPRETATION: Despite the low incidence of COVID-19, there was a nationwide decrease in ACS hospitalisations during the lockdown. These findings have important implications for future pandemic planning. FUNDING: The ANZACS-QI registry receives funding from the New Zealand Ministry of Health.

The decision to discontinue screening for carnitine uptake disorder in New Zealand.

When screening for carnitine uptake disorder (CUD), the New Zealand (NZ) newborn screening (NBS) service identified infants as screen-positive if they had initial and repeat free carnitine (C0) levels of less than 5.0 µmol/L. Since 2006, the NBS service has identified two infants with biochemical and genetic features consistent with neonatal CUD and nine mothers with features consistent with maternal CUD. A review of the literature suggests that these nine women reflect less than half the true prevalence and that CUD is relatively common. However, the NZ results (two infants) suggest a very low sensitivity and positive predictive value of NBS. While patients presenting with significant disease due to CUD are well described, the majority of adults with CUD are asymptomatic. Nonetheless, treatment with high-dose oral L-carnitine is recommended. Compliance with oral L-carnitine is likely to be poor long term. This may represent a specific risk as treatment could repress the usual compensatory mechanisms seen in CUD, such that a sudden discontinuation of treatment may be dangerous. L-carnitine is metabolized to trimethylamine-N-oxide (TMAO) and treated patients have extremely high plasma TMAO levels. TMAO is an independent risk factor for atherosclerosis and, thus, caution should be exercised regarding long-term treatment with high-dose carnitine of asymptomatic patients who may have a biochemical profile without disease. Due to these concerns, the NZ Newborn Metabolic Screening Programme (NMSP) initiated a review via a series of advisory and governance committees and decided to discontinue screening for CUD.

Apparent Hyperthyroidism Caused by Biotin-Like Interference from IgM Anti-Streptavidin Antibodies.

BACKGROUND: Exclusion of analytical interference is important when there is discrepancy between clinical and laboratory findings. However, interferences on immunoassays are often mistaken as isolated laboratory artefacts. The mechanism of a rare cause of interference in two patients that caused erroneous thyroid function tests, and also affects many other biotin dependent immunoassays, was characterized and reported. PATIENT FINDINGS: Patient 1 was a 77-year-old female with worsening fatigue while taking carbimazole over several years. Her thyroid function tests, however, were not suggestive of hypothyroidism. Patient 2 was a 25-year-old female also prescribed carbimazole for apparent primary hyperthyroidism. Despite an elevated free thyroxine, the lowest thyrotropin on record was 0.17 mIU/L. In both cases, thyroid function tests performed by an alternative method were markedly different. Further characterization of both patients' serum demonstrated analytical interference on many immunoassays using the biotin-streptavidin interaction. Sandwich assays (e.g., thyrotropin, follicle-stimulating hormone, troponin T, beta-human chorionic gonadotropin) were falsely low, while competitive assays (e.g., free thyroxine, free triiodothyronine, TSH binding inhibitory immunoglobulin) were falsely high. Pre-incubation of serum with streptavidin microparticles removed the analytical interference, initially suggesting the cause of interference was biotin. However, neither patient had been taking biotin. Instead, a ∼100 kDa immunoglobulin M (IgM) immunoglobulin with high affinity to streptavidin was isolated from each patient's serum. The findings confirm IgM anti-streptavidin antibodies as the cause of analytical interference. SUMMARY: Two patients with apparent hyperthyroidism as a result of analytical interference caused by IgM anti-streptavidin antibodies are described. CONCLUSION: Analytical interference identified on one immunoassay should raise the possibility of other affected results. Characterization of interference may help to identify other potentially affected immunoassays. In the case of anti-streptavidin antibodies, the pattern of interference mimics that due to biotin ingestion. However, the degree of interference varies between individual assays and between patients.

Falsely elevated plasma metanephrine in patients taking midodrine.

Plasma metanephrines have become the biochemical test of choice for suspected phaeochromocytomas and paragangliomas in many institutions. We encountered two separate cases of significantly elevated plasma metanephrines in patients taking midodrine, a sympathomimetic drug used in the treatment of severe postural hypotension, in the absence of a diagnosis of phaeochromocytomas and paragangliomas. Upon stopping midodrine treatment, plasma metanephrine concentrations returned to normal in both patients. To explore the hypothesis that midodrine or its metabolite desglymidodrine might interfere with the metanephrines assay, we tested the interaction of midodrine with metanephrine assays from two different centres. High-performance liquid chromatography tandem mass spectrometry on plasma samples and on methanolic extract of midodrine demonstrated co-elution of the metabolite desglymidodrine with metanephrine. We conclude that patients taking midodrine may have falsely elevated plasma metanephrine as a result of analytical interference, and clinicians need to be aware of this problem.

A novel frameshift mutation in the lipoprotein lipase gene is rescued by alternative messenger RNA splicing.

BACKGROUND: Type I hyperlipoproteinemia, manifesting as chylomicronemia and severe hypertriglyceridemia, is a rare autosomal recessive disorder usually caused by mutations in the lipoprotein lipase gene (LPL). OBJECTIVE: We sought to determine whether mutations in LPL could explain the clinical indications of a patient presenting with pancreatitis and hypertriglyceridemia. METHODS: Coding regions of LPL were amplified by polymerase chain reaction and analyzed by nucleotide sequencing. The LPL messenger RNA transcript was also analyzed to investigate whether alternative splicing was occurring. RESULTS: The patient was homozygous for the mutation c.767_768insTAAATATT in exon 5 of the LPL gene. This mutation is predicted to result in either a truncated nonfunctional LPL, or alternatively a new 5' donor splice site may be used, resulting in a full-length LPL with an in-frame deletion of 3 amino acids. Analysis of messenger RNA from the patient showed that the new splice site is used in vivo. CONCLUSION: Homozygosity for a mutation in the LPL gene was consistent with the clinical findings. Use of the new splice site created by the insertion mutation rescues an otherwise damaging frameshift mutation, resulting in expression of an almost full-length LPL that is predicted to be partially functional. The patient therefore has a less severe form of type I hyperlipoproteinemia than would be expected if she lacked any functional LPL.

Utilization of Reflex Testing for Direct Bilirubin in the Early Recognition of Biliary Atresia.

BACKGROUND: Delayed diagnosis of biliary atresia is an important cause of pediatric end-stage liver failure and liver transplantation. We sought to determine whether direct bilirubin is underutilized by retrospectively reviewing patients with biliary atresia. Further, we aimed to determine the role of reflex testing for direct bilirubin in patients suspected for jaundice. METHODS: The time intervals between total bilirubin and direct bilirubin measurements were retrospectively reviewed in patients with biliary atresia. We also audited the results of two major laboratories that had implemented reflex testing for direct bilirubin. We evaluated the clinical impact and cost of reflex testing in infants with increased direct bilirubin (>1.5 mg/dL; >25 µmol/L). RESULTS: In patients with known biliary atresia, an isolated total bilirubin measurement preceded direct bilirubin measurement in 46% (40/87) of patients; with a median delay of 19 days (interquartile range 3-44 days). In the community setting, direct bilirubin had a higher clinical specificity for biliary atresia than in the hospital setting. Reporting direct bilirubin results in 1591 infants younger than 2 weeks of age in the community was associated with three admissions to the hospital, one of whom was diagnosed with biliary atresia. The cost for the two laboratories for direct-bilirubin testing was estimated at US$3200 (NZ$4600) for each newly diagnosed case of biliary atresia. CONCLUSIONS: We identified underutilization of direct bilirubin as a cause of delay in the recognition of biliary atresia and show that reflex testing for direct bilirubin in jaundiced infants is a cost-effective solution.

The Risk of Fatty Acid Oxidation Disorders and Organic Acidemias in Children with Normal Newborn Screening.

New Zealand has undertaken expanded newborn screening since 2006. During that period there have been no reported cases of fatty acid oxidation disorders or organic acidemias that have been diagnosed clinically that the screening programme missed. However there may have been patients that presented clinically that were not diagnosed correctly or notified.In order to investigate the false-negative screening rate a case-control study was undertaken whereby the clinical coding data and relevant medical records were reviewed for 150 controls and 525 cases. The cases had normal newborn screening but with key analytes and/or ratios just below the notification level for individual disorders and thus in theory were most at risk of having metabolic disease.Two cases had medical histories suggestive of metabolic disease and thus could represent a false-negative screen. One of these had marginally elevated octanoyl carnitine levels and thus possible medium-chain acyl Co-A dehydrogenase deficiency (MCADD) while the other had elevated isovaleryl carnitine and thus may have been a case of isovaleric acidemia (IVA). However, subsequent molecular analysis revealed that the diagnosis of MCADD and IVA was unlikely.Despite relatively high cut-offs the New Zealand Newborn Metabolic Screening Programme does not appear to have missed any confirmed cases of fatty acid oxidation disorders and organic acidemias in its first 8 years of expanded newborn screening. This would suggest a similar low false-negative screening rate in centres with comparable screening protocols and would indicate that the risk of fatty acid oxidation disorders and classical organic acidemias in children who had normal newborn screening is low.

Rheumatoid factor measurement--continuing problems 70 years after discovery.

There have been long-standing unpublished differences in rheumatoid factor (RF) results, based on the Royal College of Pathologists of Australasia external quality assurance program. This study compared RF results between two commonly used commercial instruments. Serum samples were exchanged between a laboratory using a Beckman Immage immunonephelometer and another using a Roche Modular immunoturbidimeter. The World Health Organization (WHO) reference standard for RF (W1066) was then used to compare the two methods. The Roche immunoturbidimeter appears to have superior sensitivity. Furthermore, there is significant bias between the two instruments as levels of RF increase. Results from the WHO RF reference preparation correlated most closely with the results from the Roche immunoturbidimeter. Standardization for RF measurement is not optimal and has not been achieved between these two commonly used instruments. This may have clinical implications for patient management.

Effects of calcium supplementation on lipids, blood pressure, and body composition in healthy older men: a randomized controlled trial.

BACKGROUND: Calcium supplementation has been suggested to have beneficial effects on serum lipids, blood pressure, and body weight, but these possibilities have not been rigorously assessed in men. OBJECTIVE: This study evaluated the effect of calcium supplementation on the change in the ratio of HDL to LDL cholesterol (primary endpoint) and on changes in cholesterol fractions, triglycerides, blood pressure, and body composition (secondary endpoints). DESIGN: We carried out a randomized controlled trial of calcium supplementation in 323 generally healthy men over a period of 2 y. Subjects were randomly assigned to take placebo, 600 mg Ca/d, or 1200 mg Ca/d. RESULTS: There was no significant treatment effect on the ratio of HDL to LDL cholesterol (P = 0.47) nor on weight, fat mass, lean mass, triglycerides, or total, LDL, or HDL cholesterol (P > 0.28 for all). There were downward trends in systolic and diastolic blood pressures within the calcium-supplemented groups, but there were no significant treatment effects over the whole trial period (P > 0.60). In a post hoc analysis of those with baseline calcium intakes below the median value (785 mg/d), blood pressures showed borderline treatment effects (P = 0.05-0.06 for changes at 2 y in those who received 1200 mg Ca/d compared with placebo: systolic, -4.2 mm Hg; diastolic, -3.3 mm Hg). Low magnesium intake showed a similar interaction. No treatment effects on weight or body composition were found. CONCLUSIONS: These data do not show significant effects of calcium supplementation on serum lipids or body composition. Calcium supplementation in those with low dietary intakes may benefit blood pressure control. This trial was registered with the Australian Clinical Trials Registry as ACTRN 012605000274673.

Personal impact of type 2 diabetes decreased over 5 years: implications for motivating patients.

AIM: To investigate the change in personal impact of diabetes, in the same patients, over 5 years. METHODS: Subjects were 144 Europeans and 63 Polynesians. Personal impact was measured by closed questions asking if diabetes affected work, interests, home life, social life and home relationships. RESULTS: After 5 years participants had deteriorated metabolic measures and more frequent and severe complications. Nevertheless, the personal impact from having any problem caused by diabetes reduced by 60%. Knowledge of diabetes and self-blood glucose monitoring had improved. People were more likely to accept their diagnosis and were less concerned if others knew. They wanted to know more about diabetes, they felt more in control of the condition and found food restrictions less onerous, but were more worried by their diabetes. CONCLUSION: Personal impact of diabetes decreased over 5 years. This and associated attitudinal changes, probably explained by 'response shift', produce both challenges and opportunities for clinicians seeking to educate and motivate patients. We need to ask patients directly rather than presume how diabetes is impacting on their life. Only then can we construct joint knowledge with our patients in ways that are personalized to their current attitudes and concerns.