Comparison of two (data mining) indirect approaches for between-subject biological variation determination.

Background: Between-subject biological variation (CV) is an important parameter in several aspects of laboratory practice, including setting of analytical performance specification, delta checks and calculation of index of individuality. Using simulations, we compare the performance of two indirect (data mining) approaches for deriving CV.

Methods: The expected mean squares (EMS) method was compared against that proposed by Harris and Fraser.

Comparison of 8 methods for univariate statistical exclusion of pathological subpopulations for indirect reference intervals and biological variation studies.

Background: Indirect reference intervals and biological variation studies heavily rely on statistical methods to separate pathological and non-pathological subpopulations within the same dataset. In recognition of this, we compare the performance of eight univariate statistical methods for identification and exclusion of values originating from pathological subpopulations.

Methods: The eight approaches examined were: Tukey's rule with and without Box-Cox transformation; median absolute deviation; double median absolute deviation; Gaussian mixture models; van der Loo (Vdl) methods 1 and 2; and the Kosmic approach.

Comparison of four indirect (data mining) approaches to derive within-subject biological variation.

Objectives: Within-subject biological variation ( ) is a fundamental aspect of laboratory medicine, from interpretation of serial results, partitioning of reference intervals and setting analytical performance specifications. Four indirect (data mining) approaches in determination of were directly compared.

Methods: Paired serial laboratory results for 5,000 patients was simulated using four parameters, the percentage difference in the means between the pathological and non-pathological populations, the within-subject coefficient of variation for non-pathological values, the fraction of pathological values, and the relative increase in of the pathological distribution.

Sporadic late onset nemaline myopathy (SLONM) in an adult presenting with progressive muscle weakness.

Sporadic late onset nemaline myopathy (SLONM) is a rare, intractable acquired myopathy that is characterised by progressive muscle weakness and the presence of nemaline rods in myofibres. Unlike the congenital form of nemaline myopathy (NM), there are only few case reports and series on SLONM in the scientific literature. We present a case report of SLONM in a 62-year-old male from a rural town in Western Australia, without any of the conditions often associated with SLONM such as monoclonal gammopathy of uncertain significance or HIV infection.

25-Hydroxyvitamin D C3-epimer is universally present in neonatal Western Australian samples but is unlikely to contribute to diagnostic misclassification.

Background: The presence of C3-epimer (C-3-epi-25-hydroxyvitamin D) in infant serum may complicate 25-hydroxyvitamin D (25(OH)D) measurement when using liquid chromatography tandem mass spectrometry assays that do not separately measure the epimer. We measured the concentration of C3-epi-25(OH)D in neonatal samples in Western Australian using umbilical cord blood samples and a liquid chromatography tandem mass spectrometry assay that separately quantifies 25(OH)D and C3-epi-25(OH)D.

Methods: A total of 120 anonymized cord blood samples were analysed using a liquid chromatography tandem mass spectrometry assay that utilizes two CSH fluoro-phenyl columns in series.

Long-term efficacy, safety, and patient acceptability of ibandronate in the treatment of postmenopausal osteoporosis.

Several second-generation bisphosphonates (BPs) are approved in osteoporosis treatment. Efficacy and safety depends on potency of farnesyl pyrophosphate synthase (FPPS) inhibition, hydroxyapatite affinity, compliance and adherence. The latter may be influenced by frequency and route of administration.

Systematic detection of familial hypercholesterolaemia in primary health care: a community based prospective study of three methods.

Background: Familial hypercholesterolaemia (FH), a co-dominantly inherited disease of cholesterol that markedly increases risk of premature coronary artery disease (CAD), is significantly under-diagnosed. Primary health care is increasingly seen as a setting in which to increase the detection rate of index cases. We report a prospective study of three methods of case detection using pre-existing primary health care services in one community.

Can patients be accurately assessed for familial hypercholesterolaemia in primary care?

Objective: Familial Hypercholesterolaemia (FH) is the most prevalent monogenic condition causing premature coronary artery disease, although the majority of individuals remain undiagnosed. We sought to investigate whether individuals with FH could be accurately identified in primary care.

Methods: The Dutch Lipid Clinic Network Criteria scores (DLCNCS) assessed by general practitioners (GPs) were compared with DLCNCS assessed by specialists using primary care data in 153 individuals.

Detecting familial hypercholesterolaemia in the community: impact of a telephone call from a chemical pathologist to the requesting general practitioner.

Objective: To determine whether a telephone call from a chemical pathologist to the requesting general practitioner (GP) of individuals at high risk of familial hypercholesterolaemia (FH) increases specialist referral and detection of FH.

Method: Individuals with an LDL-cholesterol ≥ 6.5 mmol/L without secondary causes were identified from a community laboratory; 100 cases and 96 historical controls.

Serum 25-hydroxyvitamin D levels in vitamin D-insufficient hip fracture patients after supplementation with ergocalciferol and cholecalciferol.

Vitamin D insufficiency is commonly associated with hip fracture. However, the equipotency of ergocalciferol and cholecalciferol supplementation in this patient group has not been studied in a randomized trial using high-performance liquid chromatography (HPLC) measurement of serum 25-hydroxyvitamin D (25OHD). The objective of this study was to determine if ergocalciferol and cholecalciferol are equipotent therapies in vitamin D-insufficient hip fracture patients.

Salivary paracetamol: evaluation of a colorimetric method in assessing deliberate self-poisoning.

Background: In the laboratory evaluation of suspected paracetamol poisoning, a non-invasive sample type that avoids venepuncture would be an attractive alternative to plasma, particularly in the paediatric setting. Salivary paracetamol measurement has not previously been evaluated in the published medical literature in the setting of deliberate self-poisoning (DSP).

Methods: In-house validation experiments (recovery, stability and lower limit-of-detection) were performed on pooled saliva samples using a Roche Acetaminophen assay on a Roche/Hitachi 917 analyser.

Directions for clinical practice improvement in HFE gene mutation testing.

Objective: To audit the clinical indications for HFE gene mutation testing in a consecutive series of requests.

Design: Retrospective audit of reasons prompting 187 HFE test requests received between June 2003 and June 2005, by examination of the request form, hospital notes (when available) and, when required, information from the referring doctor.

Setting: A tertiary care public teaching hospital laboratory, Perth, Western Australia.

The identification and characterisation of a novel null HLA-DRB1 allele.

Since the introduction of DNA-based human leukocyte antigen (HLA) typing a number of discrepancies with serological typing have been documented. At the time of submission of this abstract (July 2005 ImMunoGeneTics project (IMGT) project database release) 42 HLA class I and II null alleles had been described characterised by a lack of expression of cell surface antigen. These null alleles can be accounted for by a number of demonstrated molecular mechanisms including insertion, deletion and point mutation and may lead to a nonsense codon, splicing defect or premature stop codon.

Urinary NTX results rarely alter the clinical management of patients with osteoporosis in the tertiary hospital.

Aim: Urinary levels of cross-linked N-terminal telopeptide of type I collagen (NTX) are used as a marker of bone resorption and are useful for monitoring response of patients treated with anti-resorptive agents. We aimed to determine how urinary NTX results alter clinical decision making by physicians treating patients with osteoporosis in a tertiary hospital setting.

Methods: We reviewed patient notes of all new NTX requests in 2002 and 2003 with at least one subsequent repeat measurement.