Christopher P. Price

Point of care testing.

Point of care testing, otherwise referred to as near patient, bedside, or extra laboratory testing, is not new. Many of the early “diagnostic tests” were first done at the bedside—for example, urine testing. Over the past few years, however, analytical systems have been developed that enable a wide range of tests to be done quickly and simply without the need for sophisticated laboratory equipment.1 The key objective of point of care testing is to generate a result quickly so that appropriate treatment can be implemented, leading to an improved clinical or economic outcome (figure). This article sets out the requirements for delivering an effective point of care testing service and reviews the evidence of the clinical and economic effectiveness of point of care testing. #### Summary points Point of care testing requires trained operators to ensure a good quality service Testing is effective only if action taken on the result Testing has been shown to reduce hospital stay, improve adherence to treatment, and reduce complications Although point of care testing is more expensive than laboratory testing, it produces wider economic benefits I searched the literature with Medline and Embase using the key phrases “point of care testing,” “bedside testing,” “near patient testing,” and “extra laboratory testing.” I also hand searched relevant laboratory medicine and disease related journals (such as those on diabetes) and health technology assessment reports. Two broad types of technology support point of care testing: small bench top analysers (for example, blood gas and electrolyte systems) and hand held, single use devices (such as urine albumin, blood glucose, and coagulation tests). The bench top systems are smaller versions of laboratory analysers in which vulnerable operator dependent steps have been automated—for example, automatic flushing of sample after analysis, calibration, and quality control. Hand held devices have been developed using microfabrication techniques. …

Adult reference ranges for serum cystatin C, creatinine and predicted creatinine clearance

Serum cystatin C measurement has been previously shown by ourselves and others to be a better indicator of changes in glomerular filtration rate (GFR) than serum creatinine. However, the available literature on reference values for cystatin C concentration remains surprisingly sparse; we thus set out to determine an adult reference range. Blood was taken from 309 healthy blood donors and creatinine and cystatin C concentrations were measured using commercially available automated methodologies. In addition, predicted creatinine clearances were calculated using the Cockcroft and Gault formula. The 95% reference intervals for creatinine, predicted creatinine clearance and cystatin C for all blood donors, regardless of gender, were 68-118 µmol/L, 58-120 ml/min/1·73 m 2 and 0·51-0·98 mg/L, respectively. For women, the intervals were 68-98 µmol/L, 60-119 ml/min/1·73 m 2 and 0·49-0·94 mg/ L; for men, they were 78-123 µmol/L, 57-122 ml/min/1·73 m 2 and 0·56-0·98 mg/L. The mean 95% reference interval for cystatin C in all donors under 50 years of age was 0·53-0·92 mg/L; for those over 50 years of age it was 0·58-1·02 mg/L. The small difference between male and female ranges meant that a single reference range for cystatin C could be established for all adults under 50 years of age without adjustment for body surface area. Serum cystatin C measurement offers a simpler and more sensitive screening test than serum creatinine for early changes in GFR.

Potential Clinical Utility of Serum HER-2/neu Oncoprotein Concentrations in Patients with Breast Cancer

BACKGROUND The HER-2/neu oncogene and its p185 receptor protein are indicators of a more aggressive form of breast cancer. HER-2/neu status guides Herceptin therapy, specifically directed to the extracellular domain (ECD) of the HER-2/neu oncoprotein. The HER-2/neu ECD is shed from cancer cells into the circulation and is measurable by immunoassay. METHODS We performed a systematic review of the peer-reviewed literature on circulating ECD with respect to prevalence, prognosis, prediction of response to therapy, and monitoring of breast cancer. RESULTS The prevalence of increased ECD in patients with primary breast cancer varied between 0% and 38% (mean, 18.5%), whereas in metastatic disease the range was from 23% to 80% (mean, 43%). Some women with HER-2/neu-negative tumors by tissue testing develop increased ECD concentrations in metastatic disease. Increased ECD has been correlated with indicators of poor prognosis, e.g., overall survival and disease-free survival. Increased ECD predicts a poor response to hormone therapy and some chemotherapy regimens but can predict improved response to combinations of Herceptin and chemotherapy. Many studies support the value of monitoring ECD during breast cancer progression because serial increases precede the appearance of metastases and longitudinal ECD changes parallel the clinical course of disease. CONCLUSIONS The monitoring of circulating HER-2/neu ECD provides a tool for assessing prognosis, for predicting response to therapy, and for earlier detection of disease progression and timely intervention with appropriate therapy.

Developments in the assessment of glomerular filtration rate

The assessment of the glomerular filtration rate (GFR) is the most commonly used test of renal function. The accepted reference procedure employs an exogenous clearance marker whilst the most popular test is that of serum or plasma creatinine. All of these tests have limitations, although the surrogate endogenous markers are the most practical. Cystatin C, a low molecular weight protein which can be measured by light scattering immunoassay, possesses many of the attributes required of the ideal GFR marker. Data on reference ranges indicate that circulating cystatin C levels reflect the variation in GFR throughout life and the marker demonstrates a better correlation with the reference procedure than serum creatinine.

MULTIPLE FORMS OF HUMAN SERUM ALKALINE PHOSPHATASE : DETECTION AND QUANTITATION

The measurement of serum alkaline phosphatase (EC 3.1.3.1 ALP) has been popular in clinical practice for over 50 years despite a limited knowledge of the structure, function and pathophysiology of this enzyme family. The existence of multiple forms of the enzyme has provided a great deal of opportunity for research and this has helped to refine ideas on the clinical utility of measurement of the enzymes in serum as well as to elucidate their structure and function. 1,2

REFERENCE VALUES FOR ANALYTES OF 24-H URINE COLLECTIONS KNOWN TO BE COMPLETE

One hundred and twenty two 24-h urine collections were obtained from a representative sample of men and women in the general population aged 25–44 years. The collections were verified for their completeness by urine recovery of oral doses of para-amino benzoic acid. Means (with 0·95 reference intervals) for both sexes for 24-h urinary output were determined for nitrogen, urea, creatinine, urate, ammonia, sodium, potassium, volume, and pH. Within person variation in nitrogen, urea, creatinine, ammonia, sodium and potassium was estimated for a consecutive 28-day series of 24-h urine collections for eight individuals. Within person variation was greatest for sodium and least for creatinine. These differences when compared with the between person variation in the analytes studied have implications for the precision with which a result from a single specimen can be used to place an individual within a distribution of values for epidemiological purposes. In clinical biochemistry, the population results reported here should be appropriate as a reference base for comparison with individual patient results.

The use of urinary dipstick tests to exclude urinary tract infection: a systematic review of the literature.

Several systematic reviews have examined the use of dipstick tests to diagnose or rule in urinary tract infection (UTI). We examined the evidence relating to the use of urine leukocyte esterase and nitrite tests in adults to exclude or rule out UTI. A search of the literature from 1966 to 2003 revealed 30 studies as containing relevant and suitable information and 23 of these, which used a cut-off of 108 colony-forming units per liter, were combined in a meta-analysis. The leukocyte esterase or nitrite test combination, with one or the other test positive, was used in 14 studies, showed the highest sensitivity and the lowest negative likelihood ratio. While there was significant heterogeneity between the studies, 7 of 14 demonstrated significant decreases in pretest to posttest probability with a pooled posttest probability of 5% for the negative result. In certain circumstances, there is evidence for the use of urinalysis as a rule-out test for UTI.

Current and future use of point-of-care tests in primary care: an international survey in Australia, Belgium, The Netherlands, the UK and the USA

Objective Despite the growing number of point-of-care (POC) tests available, little research has assessed primary care clinician need for such tests. We therefore aimed to determine which POC tests they actually use or would like to use (if not currently available in their practice). Design Cross-sectional survey. Setting Primary care in Australia, Belgium (Flanders region only), the Netherlands, the UK and the USA. Participants Primary care doctors (general practitioners, family physicians). Main measures We asked respondents to (1) identify conditions for which a POC test could help inform diagnosis, (2) from a list of tests provided: evaluate which POC tests they currently use (and how frequently) and (3) determine which tests (from that same list) they would like to use in the future (and how frequently). Results 2770 primary care clinicians across five countries responded. Respondents in all countries wanted POC tests to help them diagnose acute conditions (infections, acute cardiac disease, pulmonary embolism/deep vein thrombosis), and some chronic conditions (diabetes, anaemia). Based on the list of POC tests provided, the most common tests currently used were: urine pregnancy, urine leucocytes or nitrite and blood glucose. The most commonly reported tests respondents expressed a wish to use in the future were: D-dimer, troponin and chlamydia. The UK and the USA reported a higher actual and desired use for POC tests than Australia, Belgium and the Netherlands. Our limited data suggest (but do not confirm) representativeness. Conclusions Primary care clinicians in all five countries expressed a desire for POC tests to help them diagnose a range of acute and chronic conditions. Rates of current reported use and desired future use were generally high for a small selection of POC tests, but varied across countries. Future research is warranted to explore how specific POC tests might improve primary care.

The Early Fall in Levels of S-100 β in Traumatic Brain Injury

Abstract Protein S-100 β has been suggested as a prognostic marker in traumatic brain injury. However, little is known of its behaviour in the immediate post-injury period. With Ethics Committee approval, we recruited 30 patients with a history of head injury presenting to our Accident and Emergency Department. Blood was taken on arrival and at four hours post-injury. Serum S-100 β was estimated using an immunoluminometric assay. Levels of S-100 β were seen to fall rapidly with time. Half-time was distributed non-parametrically with a median of 198 minutes. Using the Mann–Whitney U test we found a statistically significant difference between non-desirable (Glasgow Outcome Score 1–3) and desirable (Glasgow Outcome Score 4–5) outcome on admission (p = 0.0155) but not at four hours (p = 0.1336). Levels of S-100 β fell rapidly after its release following traumatic brain injury. Time after injury is therefore critical in assessing the significance of levels of S-100 β, and sampling should be as early as possible to gain maximum information. If S-100 β is to be assessed as a monitor of ongoing brain injury in the intensive therapy unit sampling must be frequent (e.g. every 4 hours) to be able to detect rises in serum levels before they have decayed to baseline.

Significant and persistent loss of bone mineral density in the femoral neck after haematopoietic stem cell transplantation: long-term follow-up of a prospective study.

Summary. Reduced bone mineral density (BMD) has been reported following allogeneic stem cell transplantation (alloSCT) but the effects of autologous SCT (autoSCT) are less well characterized. We performed a prospective study of BMD changes and its determinants in 44 SCT recipients (38 auto and six allo; 30 peripheral blood SCT and 14 bone marrow transplantation). Serial measurements of BMD at the lumbar spine and femoral neck were performed at baseline and at 3, 6, 12 and 24 months, and spinal radiographs were performed at baseline and 12 months. Mean baseline BMD values at the femoral neck and spine were within normal limits. At 3 months, there was a significant decline of BMD at the femoral neck (P = 0·011) and a non‐significant trend towards reduction at the spine. BMD loss persisted for up to 2 years at the femoral neck (P = 0·005), but values returned to baseline at the spine. Reflecting the rapid initial decline in BMD, bone‐specific alkaline phosphatase (a serum marker of bone formation) showed a significant initial decline at 1 month but had recovered to pretransplant levels by 3 months. No new fractures were detected at 1 year post transplant. Sex, diagnosis, use of total body irradiation, stem cell source and type of graft (auto versus allo) did not significantly predict BMD change over the first 12 months. In conclusion, significant and persistent bone loss at the femoral neck was demonstrated in this group of patients following stem cell transplantation. The implications of these findings for future fracture risk require further study.