Biomarkers of ageing in New Zealand VLBW young adults and controls.

BACKGROUND: There is individual variation in physiological ageing. Former very low birthweight (VLBW; birthweight < 1500 g) young adults may have less satisfactory measurements on some physiological parameters than term controls. We hypothesized that a summation score of physiological biomarkers that change with age would show VLBW adults to have a more advanced physiologic age than controls. METHODS: VLBW adults (229; 71% survivors of a national VLBW cohort) and term-born controls (100) were clinically assessed at 26-30 years. Ten measured physiological biomarkers were selected and measurements converted to z-scores using normative reference data. Between-group comparisons were tested for statistical significance for individual biomarker z-scores and a summation score. RESULTS: Nine of 10 biomarkers showed a mean z-score suggestive of older physiological age in the VLBW group versus controls. The observed mean difference in the summation score was highly significant (p < 0.001), representing a mean shift of 0.47 SD in the distribution of test scores for VLBW relative to controls. CONCLUSIONS: Utilizing a 10-biomarker score, VLBW young adults have a score indicative of poorer physiological functioning than term-born controls. Repeating these measures after an interval could provide insights into the comparative pace of ageing between VLBW and term-born adults. IMPACT: A summation score of 10 physiological biomarkers that are known to change with age shows that former very low birthweight adults have significantly poorer physiological functioning by the end of their third decade than term-born controls. This result adds to existing literature showing very preterm and very low birthweight young adults often have physiological and metabolic test results that are less satisfactory than those from term controls, despite mostly being in the normal range for age; for instance, higher systolic blood pressure. Although the pace of ageing in later years is yet to be established, the implications of this study are that preventative measures and lifestyle choices that impact on physiological ageing might have even greater importance for very preterm and very low birthweight graduates.

Laboratory performance of sweat conductivity for the screening of cystic fibrosis.

BACKGROUND: There are several complementary English-language guidelines for the performance of the sweat chloride test. These guidelines also incorporate information for the collection of conductivity samples. However, recommendations for the measurement and reporting of sweat conductivity are less clear than for sweat chloride. The aim of the study was to develop an understanding of the testing and reporting practices of sweat conductivity in Australasian laboratories. METHODS: A survey specifically directed at conductivity testing was sent to the 12 laboratories registered with the Royal College of Pathologists of Australasia Quality Assurance Programs. RESULTS: Nine (75%) laboratories participated in the survey, seven of whom used Wescor Macroduct® for collecting sweat and the Wescor SWEAT·CHEK™ for conductivity testing, and the remaining two used the Wescor Nanoduct®. There was considerable variation in frequency and staffing for this test. Likewise, criteria about which patients it was inappropriate to test, definitions of adequate collection sweat rate, cutoffs and actions recommended on the basis of the result showed variations between laboratories. CONCLUSIONS: Variations in sweat conductivity testing and reporting reflect many of the same issues that were revealed in sweat chloride test audits and have the potential to lead to uncertainty about the result and the proper action in response to the result. We recommend that sweat testing guidelines should include clearer statements about the use of sweat conductivity.

Electrolytes in sick neonates - which sodium is the right answer?

INTRODUCTION: Hypoproteinaemia leads to spuriously high-sodium values when measured by indirect ion-selective electrodes (ISE) as used in main laboratory analysers compared with direct ISE employed in point-of-care analysers (POCT). The authors, therefore, investigated the occurrence of hypoalbuminaemia and its effect on measured sodium from POCT and the main laboratory analyser of neonatal intensive-care samples. METHOD: Sodium, in paired retrospective samples, measured by the main laboratory and neonatal unit blood-gas (POCT) analysers were compared. RESULTS: Hypoalbuminaemia (<30 g/l) was present in 1400/2420 paired results. Sodium was higher when measured by laboratory analyser, the difference increased with decreasing albumin; sodium (laboratory - POCT)=7.6 (±1.1)-0.22 (±0.04)×albumin. A difference >3 mmol/l was present in 31% and consequently underestimated (9.4%) hyponatraemia and overestimated (3.8%) hypernatraemia. CONCLUSION: Hypoalbuminaemia is common in sick neonates and monitoring electrolytes using POCT and laboratory analysers frequently yield significantly different results with consequent misclassification. In these patients, measurement of electrolytes by direct ISE (blood-gas analyser) may be more accurate.

BCS1L gene mutation presenting with GRACILE-like syndrome and complex III deficiency.

The clinical presentation of a neonate with GRACILE-like syndrome, complex III deficiency and BCS1L mutations is discussed. This case is compared and contrasted with the original Finnish reports of GRACILE syndrome and other cases with a similar phenotype. This case confirms the pathogenicity of the BCS1L gene mutation c.166C>T, and provides support for the pathogenicity of a sequence variation, c.-588T>A, previously reported.

Trimethylaminuria: causes and diagnosis of a socially distressing condition.

Trimethylaminuria is a disorder in which the volatile, fish-smelling compound, trimethylamine (TMA) accumulates and is excreted in the urine, but is also found in the sweat and breath of these patients. Because many patients have associated body odours or halitosis, trimethylaminuria sufferers can meet serious difficulties in a social context, leading to other problems such as isolation and depression. TMA is formed by bacteria in the mammalian gut from reduction of compounds such as trimethylamine-N-oxide (TMAO) and choline. Primary trimethylaminuria sufferers have an inherited enzyme deficiency where TMA is not efficiently converted to the non-odorous TMAO in the liver. Secondary causes of trimethylaminuria have been described, sometimes accompanied by genetic variations. Diagnosis of trimethylaminuria requires the measurement of TMA and TMAO in urine, which should be collected after a high substrate meal in milder or intermittent cases, most simply, a marine-fish meal. The symptoms of trimethylaminuria can be improved by changes in the diet to avoid precursors, in particular TMAO which is found in high concentrations in marine fish. Treatment with antibiotics to control bacteria in the gut, or activated charcoal to sequester TMA, may also be beneficial.

Comparison of high sensitivity and contemporary troponin assays for the early detection of acute myocardial infarction in the emergency department.

BACKGROUND: Current guidelines define acute myocardial infarction (AMI) by the rise and/or fall of cardiac troponin with ≥1 value above the 99th percentile. Past troponin assays have been unreliable at the lower end of the range. Highly sensitive assays have therefore been developed to increase the clinical sensitivity for detection of myocardial injury. METHODS: Three hundred and thirty-two patients with chest pain suggestive of AMI were prospectively recruited between November 2006 and April 2007. Serial blood samples were analysed to compare Roche Elecsys high sensitivity troponin T (hsTnT), Abbott Architect troponin I 3rd generation (TnI 3) and Roche Elecsys troponin T (TnT) for the diagnosis of AMI. RESULTS: One hundred and ten (33.1%) patients were diagnosed with AMI. Test performance for the diagnosis of AMI, as quantified by receiver operating characteristic area under the curve (95% confidence intervals) for baseline/follow-up troponins were as follows: hsTnT 0.90 (0.87-0.94)/0.94 (0.91-0.97), TnI 3 0.88 (0.84-0.92)/0.93 (0.90-0.96) and TnT 0.80 (0.74-0.85)/0.89 (0.85-0.94). hsTnT was superior to TnT (P < 0.001/0.013 at baseline/follow-up) but equivalent to TnI 3. For patients with a final diagnosis of AMI, baseline troponins were raised in more patients for hsTnT (83.6%) than TnI 3 (74.5%) and TnT (62.7%). A delta troponin of ≥20% increased the specificity of hsTnT from 80.6% to 93.7% but reduced sensitivity from 90.9% to 71.8%. CONCLUSION: hsTnT was superior to TnT but equivalent to TnI 3 for the diagnosis of AMI. Serial troponin measurement increased test performance. hsTnT was the most likely to be raised at baseline in those with AMI. A delta troponin increases specificity but reduces sensitivity.

Asthma prevalence in European, Maori, and Pacific children in New Zealand: ISAAC study.

The International Study of Asthma and Allergies in Childhood (ISAAC) demonstrated that the highest prevalence of asthma in the world is in English-speaking countries, including New Zealand. In this paper, we compare asthma symptom prevalence in the three major ethnic groups (Maori, Pacific, and European) in the six participating centers in New Zealand. Hospital admission rates for asthma are higher among Maori and Pacific children compared to European children. The working hypothesis was that there were important differences in prevalence of asthma symptoms or diagnosis between ethnic groups which might explain these observed differences in asthma morbidity. In each center in 1992-1993, we sampled approximately 3000 children at each of the age brackets 6-7 years and 13-14 years. There were 37592 participants. Maori children had higher rates of diagnosed asthma and reported asthma symptoms than Pacific children in both age groups (diagnosed asthma in 6-7-year-olds: Maori, 31.7%; Pacific, 21.2%; 95% confidence interval on difference (CID), 7.2, 13.8; P < 0.001; 13-14-year-olds: Maori, 24.7%; Pacific, 19.2%; CID 2.5, 8.5; P < 0.001; recent wheeze in 6-7-year-olds: Maori, 27.6%; Pacific, 22.0%; CID, 2.6, 8.6; P < 0.001; 13-14-year-olds: Maori, 30.8%; Pacific, 21.1%; CID, 4.8, 14.5; P < 0.001;). European children had rates intermediate between those of Maori and Pacific children (6-7-year-olds) or similar to those of Maori children (13-14-year-olds), but had the lowest prevalence of night waking with wheeze in both age groups (e.g., 6-7-year-olds: European, 2.6%; Maori, 5.8%; Pacific, 5.7%; European-Maori CID: -4.2, -2.2, P < 0.001; European-Pacific CID: -4.7, -1.7, P < 0.001; Maori-Pacific CID: -1.7, 1.8, P = 1.0). The pattern of differences closely resembled that in a 1985 Auckland study, despite a 1.5-1.7-fold overall increase in prevalence. In conclusion, there are important differences in asthma prevalence among Maori, Pacific, and European children. These differences are small compared to worldwide variation, but their pattern is stable over time. The higher rate of severe asthma symptoms that Maori and Pacific children report may be one reason for the increased asthma morbidity in these groups. Further studies are needed to determine the reasons for these apparent differences in asthma severity.