Falsely elevated parathyroid hormone in a patient with osteoporosis: a case report and review.

BACKGROUND: Parathyroid hormone (PTH) measurements can be falsely elevated due to the hormone binding to other molecules (macro-PTH) or immunoassay interference with heterophile, human anti-animal or other antibodies. This is rare but could lead to incorrect diagnosis, unnecessary investigations or avoidance of teriparatide treatment. We report a case of falsely high PTH levels due to assay interference and review the literature on cases of spuriously elevated PTH. CASE REPORT: An 87-year-old woman attending our bone health clinic with osteoporosis had persistently elevated PTH (383-784 pg/ml) using the Roche Cobas e801 immunoassay despite having normal serum calcium, phosphate, 25 hydroxyvitamin D (> 50 nmol/l) and eGFR (> 60 ml/min). To rule out falsely elevated PTH, a polyethylene glycol precipitation (PEG) test was performed which recovered less than 10% of the hormone resulting in a normal level. PTH was also tested on a different assay (Atellica Siemens) that identified a result of 27 pg/ml. The findings were consistent with immunoassay interference likely due to heterophile antibodies giving rise to a spuriously high PTH. DISCUSSION: The presence of unexpectedly high PTH levels should alert physicians to the possibility of false results due to assay interference or macro-PTH. This highlights the importance of clinically correlating results and of good communication with the testing laboratory. Here, we present the case of an 87-year-old woman with spuriously elevated PTH levels due to immunoassay interference likely mediated by heterophile antibodies. The presence of unexpectedly high PTH levels should prompt consideration of the possibility of false results due to assay interference or macro-PTH.

Vitamin D: determinants of status, indications for testing and knowledge in a convenience sample of Irish adults.

Vitamin D deficiency is common in Irish adults, though there is limited research on its determinants, knowledge of vitamin D or indications for testing. We aimed to explore the determinants of vitamin D status in adults and examine knowledge and reasons for testing. The study population comprised adults who had serum 25-hydroxyvitamin D tested by general practitioners request at a Dublin Hospital in 2020. Questionnaires detailing dietary intake, sun exposure, ethnicity, biophysical factors and vitamin D knowledge were sent to a sample stratified by age, sex and vitamin D status. In total, there were 383 participants, mean age 56·0 (sd 16·6) years. Wintertime deficiency disproportionally affected non-white v. white (60 % v. 24 %, P < 0·001). The greatest predictors of deficiency were low vitamin D intake (< 10 µg/d) (P < 0·001) and non-white ethnicity (P = 0·006), followed by sun avoidance (P = 0·022). It was also more prevalent in those with lower body exposure when outdoors. The majority (86 %) identified vitamin D as important for bone health. However, 40 % were tested for non-clinical indications and half were not aware of the recommended daily allowance (RDA). Low vitamin D intake was the most important determinant of deficiency, but ethnicity and sun exposure habits were also significant predictors. The majority had no clear indication for testing and were not aware of the RDA. Public health policies to improve knowledge and vitamin D intake, especially for those of non-white ethnicity and with reduced sun exposure, should be considered.

Vitamin D retesting by general practitioners: a factor and cost analysis.

OBJECTIVES: Vitamin D testing by Primary Care doctors is increasing, placing greater workloads on healthcare systems. There is little data though on vitamin D retesting in Ireland. This study aims to investigate the factors associated with vitamin D retesting by Irish General Practitioners (GPs) and examine the resulting costs. METHODS: This is a retrospective analysis over 5 years (2014-2018) of GP requested 25-hydroxyvitamin D (25(OH)D) results in 36,458 patients at a major city hospital in Dublin, Ireland. Those with one test were compared with individuals who were retested and samples categorised to determine changes in status between tests. RESULTS: Nearly one in four patients (n=8,305) were retested. Positive predictors of retesting were female (p<0.001), age (60-69 years, p<0.001), location (Co. Kildare, p<0.001) and initial deficiency (<30 nmol/L, p<0.001) or insufficiency (30-49.9 nmol/L, p<0.001). Vitamin D status improved on retesting, with deficiency halving on first retest (9 vs. 18%, p<0.001) and dropping to 6% on further retests. About 12.2% of retests were done within 3 months and 29% had ≥2 retests within 1 year. 57% of retests were in those initially vitamin D replete (>50 nmol/L). The annual cost of inappropriate testing was €61,976. CONCLUSIONS: One in four patients were retested and this varied by age, gender and patient location. Over 10% of retests were inappropriately early (<3 months), a third too frequent and over half were in replete individuals incurring significant costs. Clear guidance for GPs on minimum retesting intervals is needed, as well as laboratory ordering systems to limit requests using pre-defined criteria.

Waist circumference provides an indication of numerous cardiometabolic risk factors in adults with cerebral palsy.

OBJECTIVE: To report the prevalence of cardiometabolic risk factors in a cohort of adults with cerebral palsy (CP) and to investigate the ability of anthropometric measures to predict these factors. DESIGN: Cross-sectional study. SETTING: Testing took place in a laboratory setting. PARTICIPANTS: Adults with CP (N=55; mean age, 37.5±13.3 y; Gross Motor Function Classification System levels, I-V) participated in this study. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, glucose, insulin, and C-reactive protein levels were measured from a fasting venous blood sample. Insulin resistance was calculated using the Homeostasis Model Assessment (HOMA-IR) index. Blood pressure, body mass index (BMI), waist circumference (WC), waist-hip ratio, and waist-height ratio were also measured. The metabolic syndrome (MetS) was defined according to the 2009 Joint Interim Statement. RESULTS: The prevalence of the MetS was 20.5% in ambulatory adults and 28.6% in nonambulatory adults. BMI was associated with HOMA-IR only (ß=.451; P<.01). WC was associated with HOMA-IR (ß=.480; P<.01), triglycerides (ß=.450; P<.01), and systolic blood pressure (ß=.352; P<.05). Receiver operating characteristic curve analysis revealed that WC provided the best indication of hypertensive blood pressure, dyslipidemia, HOMA-IR, and the presence of multiple risk factors (area under the curve, .713-.763). CONCLUSIONS: A high prevalence of the MetS was observed in this relatively young sample of adults with CP. WC was a better indicator of a number of risk factors than was BMI and presents as a clinically useful method of screening for cardiometabolic risk among adults with CP.

Risk Factors and Modifiers for Cardiovascular Disease Assessment of Patients with Heterozygous Familial Hypercholesterolaemia.

Background: The assessment of the risk of cardiovascular disease (CVD) in patients with heterozygous familial hypercholesterolemia (HeFH) is determined by conventional risk factors. However, factors modifying CVD, or risk modifiers, beyond conventional risk factors may inform their CVD risk assessment and the subsequent use of new therapies. This work identifies and characterises patients within a lipid clinic cohort with regards to conventional CVD risk factors and risk modifiers with a focus on those with HeFH. Methods: A study of consecutive adult patients attending our specialist lipid clinic was performed over a six-month period. The patient data recorded included demographics, clinical characteristics, risk factors and risk modifiers, biochemical profiles and genetic testing results. Risk modifiers were identified based on ESC/EAS guidance, and those with HeFH were compared to those without. Results: A total of 370 patients were included. Of these, 98 HeFH patients were identified (26%). Then, 52% of HeFH patients were stratified into the very-high risk category due to the presence of CVD risk factors. Risk modifiers were present in 73%. These included a family history of premature CVD (56%), obesity (28%), a sedentary lifestyle (13%) and a major psychiatric disorder (12%). Compared to the rest of the cohort, those with HeFH were less likely to have hypertension and more likely to have a family history of premature CVD. Conclusions: Half of patients with HeFH are categorised as having very high CV risk. Consideration of risk modifiers, particularly a family history of premature CV disease, increases this very-high-risk category further. This may have implications for the clinical application and access to novel treatments.

Hepatitis C community prevalence is over-estimated: a prospective, birth cohort study.

BACKGROUND: Hepatitis C virus infection is often asymptomatic, and many patients may be unaware they are infected. Community-based, birth cohort screening has been advocated to identify these patients. It has been estimated that 0.7-1% of individuals born between 1965 and 1985 in Ireland are infected. The cost-effectiveness of screening is critically dependent on the population prevalence. AIMS: The aim is to determine the community prevalence of hepatitis C virus infection in the birth cohort 1965-1985. METHODS: Residual serum samples from blood tests ordered by community general practitioners were anonymised and analysed for the presence of hepatitis C antibody ± antigen. Twelve large general hospitals throughout the country participated. RESULTS: A total of 14,320 samples were tested, 9347 of which were from the birth cohort 1965-1985. Seventy-two samples were positive for hepatitis C antibody of which 12 were positive for hepatitis C antigen (17%). The overall prevalence of hepatitis C antigen in the birth cohort was 0.09%. A higher prevalence (0.39%) was identified in males in two urban areas of Dublin. CONCLUSIONS: Hepatitis C virus seroprevalence was much lower than previously estimated. The proportion of antibody positive patients with hepatitis C antigen was also lower than expected suggesting the effects of treatment and/or high spontaneous viral clearance. Universal birth cohort screening is unlikely to be cost-effective. Targeted birth cohort screening in high prevalence areas could be considered.

Postprandial effect of dietary fat quantity and quality on arterial stiffness and wave reflection: a randomised controlled trial.

BACKGROUND: Arterial stiffness is a component of vascular function and an established risk factor for cardiovascular disease. There is a lack of conclusive evidence on the effect of a meal rich in monounsaturated fat (MUFA) compared with an isoenergetic meal rich in saturated fat (SFA) on postprandial vascular function and specifically on arterial stiffness. METHODS: Twenty healthy, non-smoking males (BMI 24 ± 2 kg/m2; age 37.7 ± 14.4 y) participated in this single-blind, randomised, cross-over dietary intervention study. Each subject was randomised to receive a high-fat test-meal (3 MJ; 56 ± 2 g fat) at breakfast on 2 separate occasions, one rich in oleic acid (MUFA-meal) and one rich in palmitic acid (SFA-meal), and the meals were isoenergetic. Blood pressure (BP), arterial stiffness (PWV) and arterial wave reflection (augmentation index, AIx) were measured using applanation tonometry at baseline and every 30 minutes up to 4 hours after the ingestion of the test-meals. RESULTS: All subjects completed both arms of the dietary intervention. There was no significant difference in BP parameters, PWV or AIx at baseline between the two treatments (P > 0.05). There was a significant increase in brachial and aortic BP, mean arterial pressure (MAP), heart rate and PVW (time, P < 0.05) over the four hours after consumption of the fat-rich test-meal although the increase in PWV was no longer significant when adjusted for the increase in MAP. There was no difference in PWV between the two treatments (treatment*time, P > 0.05). There was a significant reduction in AIx (time, P < 0.05) over the four hour postprandial period although this was no longer significant when adjusted for the increase in heart rate and MAP (time, P > 0.05). There was no difference in AIx between the two treatments (treatment*time, P > 0.05). However, the reduction in heart rate corrected augmentation index (AIx75) was significant when corrected for the increase in MAP (time, P < 0.01) with no differential effect of the treatments (treatment*time, P > 0.05). CONCLUSIONS: This study has demonstrated a BP dependent increase in PWV and a decrease in arterial wave reflection in the four hour period in response to a high-fat meal. There was no evidence however that replacement of some of the SFA with MUFA had a differential effect on these parameters. The study highlights the need for further research to understand the effects of the substitution of SFA with MUFA on non-serum, new and emerging risk factors for CVD such as arterial stiffness.

Low socioeconomic status predicts vitamin D status in a cross-section of Irish children.

Vitamin D is essential for bone and muscle health with adequate status in childhood crucial for normal skeletal development. We aimed to investigate vitamin D status in a convenience sample (n = 1226) of Irish children (aged 1-17 years) who had serum 25-hydroxyvitamin D (25(OH)D) tested by request of their GP at a Dublin Hospital between 2014 and 2020. We examined predictors including age, sex, season and socioeconomic status (SES). Vitamin D deficiency (<30 nmol/l) was prevalent affecting 23 % and was more common in disadvantaged areas (34 %) and in those aged >12 v. ≤12 years (24 % v. 16 %, P = 0⋅033). The greatest predictor was SES (disadvantaged v. affluent, OR 2⋅18, CI 1⋅34, 3⋅53, P = 0⋅002), followed by female sex (OR 1⋅57, CI 1⋅15, 2⋅14, P = 0⋅005) and winter season (October to February, OR 1⋅40, CI 1⋅07, 1⋅84, P = 0⋅015). A quarter of our sample of children were deficient, rising to one-third in those in disadvantaged areas. Females and those aged over 12 years had a higher prevalence of deficiency. Public health strategies to improve vitamin D status in Irish children, including systematic food fortification may need to be considered to address this issue.

Porphyria cutanea tarda precipitated by ovarian stimulation during oocyte retrieval in a genetically susceptible female.

We report a case of 33-year-old female with underlying genetic susceptibility for familial porphyria cutanea tarda due to novel UROD variant (c.636 + 2 dupT) unmasked by transient exposure to supraphysiological oestrogen concentrations following a single cycle of successful controlled ovarian stimulation for oocyte retrieval. Use of oral oestrogen in the form of oral contraceptive pills and hormone replacement therapy has been well known to trigger active porphyria cutanea tarda phenotype in susceptible women. However, to date, the emergence of clinically overt porphyria cutanea tarda has not been reported in association with fertility treatment in the literature before.

SARS-CoV-2 Antibody Testing in Health Care Workers: A Comparison of the Clinical Performance of Three Commercially Available Antibody Assays.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies are an excellent indicator of past COVID-19 infection. As the COVID-19 pandemic progresses, retained sensitivity over time is an important quality in an antibody assay that is to be used for the purpose of population seroprevalence studies. We compared 5,788 health care worker (HCW) serum samples by using two serological assays (Abbott SARS-CoV-2 anti-nucleocapsid immunoglobulin G (IgG) and Roche anti-SARS-CoV-2 anti-nucleocapsid total antibody) and a subset of samples (all Abbott assay positive or grayzone, n = 485) on Wantai SARS-CoV-2 anti-spike antibody enzyme-linked immunosorbent assay (ELISA). For 367 samples from HCW with a previous PCR-confirmed SARS-CoV-2 infection, we correlated the timing of infection with assay results. Overall, seroprevalence was 4.2% on Abbott and 9.5% on Roche. Of those with previously confirmed infection, 41% (150/367) and 95% (348/367) tested positive on Abbott and Roche, respectively. At 21 weeks (150 days) after confirmed infection, positivity on Abbott started to decline. Roche positivity was retained for the entire study period (33 weeks). Factors associated (P ≤ 0.050) with Abbott seronegativity in those with previous PCR-confirmed infection included sex (odds ratio [OR], 0.30 male ; 95% confidence interval [CI], 0.15 to 0.60), symptom severity (OR 0.19 severe symptoms; 95% CI, 0.05 to 0.61), ethnicity (OR, 0.28 Asian ethnicity; 95% CI, 0.12 to 0.60), and time since PCR diagnosis (OR, 2.06 for infection 6 months previously; 95% CI, 1.01 to 4.30). Wantai detected all previously confirmed infections. In our population, Roche detected antibodies up to at least 7 months after natural infection with SARS-CoV-2. This finding indicates that the Roche total antibody assay is better suited than Abbott IgG assay to population-based studies. Wantai demonstrated high sensitivity, but sample selection was biased. The relationship between serological response and functional immunity to SARS-CoV-2 infection needs to be delineated. IMPORTANCE As the COVID-19 pandemic progresses, retained sensitivity over time is an important quality in an antibody assay that is to be used for the purpose of population seroprevalence studies. There is a relative paucity of published literature in this field to help guide public health specialists when planning seroprevalence studies. In this study, we compared results of 5,788 health care worker blood samples tested by using two assays (Roche and Elecsys, anti-nucleocapsid antibody) and by testing a subset on a third assay (Wantai enzyme-linked immunosorbent assay [ELISA] anti-spike antibody). We found significant differences in the performance of these assays, especially with distance in time from PCR-confirmed COVID-19 infection, and we feel these results may significantly impact the choice of assay for others conducting similar studies.

Geomapping Vitamin D Status in a Large City and Surrounding Population-Exploring the Impact of Location and Demographics.

Vitamin D status was assessed in a large urban area to compare differences in deficiency and to geomap the results. In total, 36,466 participants from 28 geographical areas were identified in this cross-sectional, retrospective analysis of general practitioner (GP)-requested 25(OH)D tests at St James's Hospital, Dublin between 2014 and 2018. The population were community-dwelling adults, median age 50.7 (18-109 years) with 15% of participants deficient (<30 nmol/L), rising to 23% in the winter. Deficiency was greatest in younger (18-39 years) and oldest (80+ years) adults, and in males versus females (18% vs. 11%, p < 0.001). Season was the biggest predictor of deficiency (OR 4.44, winter versus summer, p < 0.001), followed by location (west Dublin OR 2.17, north Dublin 1.54, south Dublin 1.42 versus rest of Ireland, p < 0.001) where several urban areas with an increased prevalence of deficiency were identified. There was no improvement in 25(OH)D over the 5-year period despite increased levels of testing. One in four adults were vitamin D deficient in the winter, with significant variations across locations and demographics. Overall this study identifies key groups at risk of 25(OH)D deficiency and insufficiency, thus providing important public health information for the targeting of interventions to optimise 25(OH)D. Mandatory fortification may be necessary to address this widespread inadequacy.

A High Prevalence of Vitamin D Deficiency Observed in an Irish South East Asian Population: A Cross-Sectional Observation Study.

At northern latitudes, non-ethnic population groups can be at an increased risk of vitamin D deficiency (defined as a 25-hydroxyvitamin D [25(OH)D] status ≤30 nmol/L). The vitamin D status of ethnic minority groups has been examined both in UK and European populations, but not in the Irish context. The aim of this study is to assess the vitamin D status from a selection of the Dublin population of South East Asian descent. A search was conducted, using the laboratory information system of St James's Hospital, Dublin, for vitamin D requests by General practitioners. From 2013 to 2016, 186 participants were identified and 25(OH)D analysis was quantified using liquid chromatography-tandem mass spectrometry (LC-MS-MS). Overall, the median age was 32 years, 51% were male, and the 25(OH)D concentration ranged from 10 to 154 nmol/L. In total, 66.7% of the total sample were vitamin D deficient and 6.7% had a 25(OH)D status greater than 50 nmol/L (the 25(OH)D concentration defined by the EU as 'sufficient'). Females had a significantly higher 25(OH)D concentration than males (25.0 vs. 18.0 nmol/L; p = 0.001) but both groups had a significant proportion with deficient status (56% and 76.8%, respectively). Seasonal variation of 25(OH)D was not evident while high rates of deficiency were also observed in those aged <18 years and >50 years. Given the importance of vitamin D for health, this sub-population could be at a significantly increased risk of rickets, impaired bone metabolism, and osteoporosis. In addition, vitamin D deficiency has been associated with several non-bone related conditions, including cardiovascular disease and diabetes. Currently, there is no unique vitamin D intake or vitamin D status maintenance guidelines recommended for adults of non-Irish descent; this needs to be considered by the relevant public health bodies in Ireland.

Acute haemodynamic response to sleeping head-up at 6 inches in older inpatients.

OBJECTIVE: Our aim was to investigate the effect of monotherapy of sleeping head-up (SHU) at 6 in. in a group of older inpatients with OH from all causes. METHODS: We recruited nine consecutive inpatients (mean age (SD) 76(5) years) with persistent, symptomatic OH with a mean systolic blood pressure (SBP) drop on standing and nadir SBP of 68 (27.8) and 94 (19.2) mmHg respectively. All patients underwent SHU for 1 week. Beat-to-beat haemodynamics during lying and standing, 24-hour ambulatory blood pressure, supine haematocrit, urea/electrolytes, plasma renin activity and aldosterone were measured before and after intervention. RESULTS: One week after SHU, SBP, stroke volume and cardiac output increased significantly (all P < 0.05) by 12 mmHg, 15 ml and 1.3 l/minutes respectively while heart rate and total peripheral resistance were significantly reduced by 3.6 bpm and 0.355 dynes/s/cm(5) respectively during 2 minute of standing. Serum creatinine was also significantly lower. Five patients improved in their mobility following SHU. INTERPRETATIONS: SHU for 1 week at 6 in. was well tolerated by older in-patients with OH, associated with improved orthostatic tolerance, and with haemodynamic changes in keeping with increased extracellular volume. SHU at 6 in. has a role in the acute treatment of OH for patients in hospital, but its longer-term effects and in the out-patient setting require further study.

Overview of human obesity and central mechanisms regulating energy homeostasis.

Obesity is now regarded as a global epidemic affecting both adults and children, and is associated with significant morbidity and mortality. Thus the effective management of obesity has become an important clinical focus. Therefore, an understanding of the pathways controlling appetite, satiety and food intake is critical for gaining an insight into the pathogenesis of obesity and also for the development of diagnostic tests and therapeutic agents for use in the clinical management of this condition. Over the last decade or more research using both mouse and human genetic models has elucidated the critical role of the leptin-melanocortin pathway in the hypothalamus, in regulating mammalian energy balance. In tandem with this, a clearer understanding of the regulation of gut-derived hormones and their interaction with the central nervous system has further illuminated the complex interplay between central and peripheral aspects of energy regulation. The obesity epidemic and the expanded knowledge base relating to its aetiopathogenesis have specific implications for clinical biochemistry. In particular, an increase in workload may be expected due to biochemical investigation of obesity and its co-morbidities. Moreover, advice on the in-depth investigation of complex cases of obesity may be sought, including information on newer diagnostic tests, such as serum leptin or molecular genetic analysis. There may also be a substantive role for chemical pathologists in establishing and running clinical obesity services. Finally, clinical biochemistry has a role in research pertaining to obesity and cardiometabolic risk.

Undetectable high-density lipoprotein cholesterol in acute malaria.

We report the case of a 39-year-old West African man in whom high-density lipoprotein cholesterol (HDL-C) was identified as undetectable at <0.08 mmol/L. Total cholesterol in the same sample was 2.85 mmol/L; triglycerides were only mildly elevated at 2.32 mmol/L. He was admitted with a 2-week history of polydipsia, polyuria, weight loss and hyperpyrexia. Dual malarial infection with Plasmodium ovale and falciparum was identified and attributed to a recent trip to Nigeria without chemoprophylaxis. Also, he was diagnosed with diabetes mellitus with random hyperglycemia of 39 mmol/L but no ketonemia. Subsequent investigation revealed a low apolipoprotein A1 of 0.38 g/L (1.04-2.02), confirming a true HDL-C deficit. On clinical examination, he had neither orange tonsils consistent with Tangier disease nor corneal opacification consistent with lecithin-cholesterol acyltransferase deficiency. The patient was an avid gym goer but denied anabolic steroid abuse, a fact supported by a transient primary testosterone deficiency at presentation (testosterone 6.56 nmol/L, RR 8.6-29; follicle-stimulating hormone high at 9.2 mU/L, luteinising hormone high at 11.9 mU/L). He was treated for malaria and started on metformin for diabetes. At 8-week follow-up, his HDL-C was entirely normal at 1.38 mmol/L. We believe this severe drop in HDL-C level to be due to acute inflammation caused by malaria. As extreme drops in HDL-C have been found to be associated with the poorest prognosis, prospective identification of HDL-C and prompt clinical liaison may be of benefit.

Obesity therapy: altering the energy intake-and-expenditure balance sheet.

Obesity is associated with numerous health complications, which range from non-fatal debilitating conditions such as osteoarthritis, to life-threatening chronic diseases such as coronary heart disease, diabetes and certain cancers. The psychological consequences of obesity can range from lowered self-esteem to clinical depression. Despite the high prevalence of obesity and the many advances in our understanding of how it develops, current therapies have persistently failed to achieve long-term success. This review focuses on how fat mass can be reduced by altering the balance between energy intake and expenditure.

Verification of Abbott 25-OH-vitamin D assay on the architect system.

OBJECTIVES: Analytical and clinical verification of both old and new generations of the Abbott total 25-hydroxyvitamin D (25OHD) assays, and an examination of reference Intervals. METHODS: Determination of between-run precision, and Deming comparison between patient sample results for 25OHD on the Abbott Architect, DiaSorin Liaison and AB SCIEX API 4000 (LC-MS/MS). Establishment of uncertainty of measurement for 25OHD Architect methods using old and new generations of the reagents, and estimation of reference interval in healthy Irish population. RESULTS: For between-run precision the manufacturer claims 2.8% coefficients of variation (CVs) of 2.8% and 4.6% for their high and low controls, respectively. Our instrument showed CVs between 4% and 6.2% for all levels of the controls on both generations of the Abbott reagents. The between-run uncertainties were 0.28 and 0.36, with expanded uncertainties 0.87 and 0.98 for the old and the new generations of reagent, respectively. The difference between all methods used for patients' samples was within total allowable error, and the instruments produced clinically equivalent results. The results covered the medical decision points of 30, 40, 50 and 125 nmol/L. The reference interval for total 25OHD in our healthy Irish subjects was lower than recommended levels (24-111 nmol/L). CONCLUSION: In a clinical laboratory Abbott 25OHD immunoassays are a useful, rapid and accurate method for measuring total 25OHD. The new generation of the assay was confirmed to be reliable, accurate, and a good indicator for 25OHD measurement. More study is needed to establish reference intervals that correctly represent the healthy population in Ireland.

Septic shock is correlated with asymmetrical dimethyl arginine levels, which may be influenced by a polymorphism in the dimethylarginine dimethylaminohydrolase II gene: a prospective observational study.

INTRODUCTION: Asymmetrical dimethyl arginine (ADMA) is an endogenous non-selective inhibitor of nitric oxide synthase that may influence the severity of organ failure and the occurrence of shock secondary to an infectious insult. Levels may be genetically determined by a promoter polymorphism in a regulatory gene encoding dimethylarginine dimethylaminohydrolase II (DDAH II), which functions by metabolising ADMA to citrulline. The aim of this study was to examine the association between ADMA levels and the severity of organ failure and shock in severe sepsis and also to assess the influence of a promoter polymorphism in DDAH II on ADMA levels. METHODS: A prospective observational study was designed, and 47 intensive care unit (ICU) patients with severe sepsis and 10 healthy controls were enrolled. Serum ADMA and IL-6 were assayed on admission to the ICU and seven days later. Allelic variation for a polymorphism at position -449 in the DDAH II gene was assessed in each patient. Clinical and demographic details were also collected. RESULTS: On day 1 more ADMA was detectable in the ICU group than in the control group (p = 0.005). Levels subsequently increased during the first week in ICU (p = 0.001). ADMA levels were associated with vasopressor requirements on day one (p = 0.001). ADMA levels and Sequential Organ Failure Assessment scores were directly associated on day one (p = 0.0001) and day seven (p = 0.002). The degree of acidaemia and lactaemia was directly correlated with ADMA levels at both time points (p < 0.01). On day seven, IL-6 was directly correlated with ADMA levels (p = 0.006). The variant allele with G at position -449 in the DDAH II gene was associated with increased ADMA concentrations at both time points (p < 0.05). CONCLUSION: Severity of organ failure, inflammation and presence of early shock in severe sepsis are associated with increased ADMA levels. ADMA concentrations may be influenced by a polymorphism in the DDAH II gene.