Point-of-care testing (POCT): Current techniques and future perspectives.

Point-of-care testing (POCT) is a laboratory-medicine discipline that is evolving rapidly in analytical scope and clinical application. In this review, we first describe the state of the art of medical-laboratory tests that can be performed near the patient. At present, POCT ranges from basic blood-glucose measurement to complex viscoelastic coagulation assays. POCT shortens the time to clinical decision-making about additional testing or therapy, as delays are no longer caused by transport and preparation of clinical samples, and biochemical-test results are rapidly available at the point of care. Improved medical outcome and lower costs may ensue. Recent, evolving technological advances enable the development of novel POCT instruments. We review the underlying analytical techniques. If new instruments are not yet in practical use, it is often hard to decide whether the underlying analytical principle has real advantage over former methods. However, future utilization of POCT also depends on health-care trends and new areas of application. But, even today, it can be assumed that, for certain applications, near-patient testing is a useful complement to conventional laboratory analyses.

Point-of-care testing in hospitals and primary care.

BACKGROUND: Many medical laboratory tests can now be done near the patient (point-of-care testing, POCT), ranging from basic blood glucose measurement to complex coagulation testing. Switching from conventional laboratory testing to POCT shortens the time to decision-making about further testing or treatment, as delays are no longer caused by specimen transport and preparation, and the test results are rapidly available at the point of care. Better medical outcomes and lower costs may ensue. METHOD: Selective literature review. RESULTS: The available methods and equipment enable persons not specially trained in laboratory medicine to perform high-quality laboratory testing at the point of care, under certain conditions. Before POCT is introduced in a hospital or outpatient practice, a cost-benefit analysis should be performed, because the introduction is costly and requires a certain amount of organizational work especially for quality management. The potential medical and economic benefits should be assessed individually in each case. CONCLUSION: POCT for certain applications is a useful complement to conventional laboratory testing. The future utilization of POCT will depend not only on technical advances, but also on developments in costs and reimbursement.

Point-of-care determination of neonatal bilirubin with the blood gas analyzer RapidLab 1265.

BACKGROUND: The aim of the study was to evaluate the comparability of the new neonatal bilirubin method on the RapidLab 1265 blood gas analyzer. This point-of-care testing (POCT) device has the option for the determination of neonatal bilirubin, making it potentially valuable for use in neonate intensive care units or in outpatient ambulances. METHODS: We paired 240 patient samples for intermethod comparisons between the new POCT method and the routine laboratory method (Vitros 350 chemistry system with BuBc slide). In parallel, a transcutaneous jaundice meter (JM-103) was applied to the newborns. Low birthweight and premature neonates were excluded from the trial. The turn-around-time (TAT) for the POCT method was also compared with the routine method, and the practicality of the new analyzer was evaluated for clinical purposes. RESULTS: Bilirubin measurements using the RapidLab 1265 are suitable for the application in newborns. For imprecision, coefficients of variation between 5.6% and 23% were found. The correlation between the Vitros 350 (x) and RapidLab 1265 (y) was y=1.0x-0.1 (r=0.91), with a mean bias of +0.1 mg/dL and a 95% limit of agreement of ±2.5 mg/dL. As in all POCT methods, the TAT was significantly lower than that of the core laboratory. CONCLUSIONS: In contrast to the JM-103, the results of the RapidLab 1265 correlated closely with the Vitros 350, although occasional results of both methods were more different than expected. In general, the RapidLab 1265 blood gas analyzer provides clinically useful bilirubin results using neonatal whole blood samples, although imprecision data are higher than for the laboratory method. The POCT device is suitable for neonatal intensive care units after thoroughly training the employees that will use the device.

Vaccination of patients with advanced ovarian carcinoma with the anti-idiotype ACA125: immunological response and survival (phase Ib/II).

PURPOSE: A Phase I/IIb multicenter study was conducted to evaluate the safety and immunogenicity of the anti-idiotypic antibody vaccine ACA125 that functionally imitates the tumor antigen CA125 in 119 patients with advanced ovarian carcinoma. A preliminary report on the initial 42 patients demonstrated safety and immunogenicity. EXPERIMENTAL DESIGN: Using the complete intention-to-treat population (n = 119) who received a mean of 9.7 ACA125 applications, survival was analyzed with respect to immunological responses. RESULTS: In 81 patients (68.1%), a specific anti-anti-idiotypic antibody (Ab3) response could be induced. Additionally, the development of CA125-specific antibodies (Ab1') and antibody-dependent cell-mediated cytotoxicity of CA125-positive tumor cells was observed in 50.4% and 26.9% of patients, respectively. The median survival of all patients was 19.4 months (range, 0.5-56.1 months). Ab3-positive patients showed a significantly longer survival (median, 23.4 months; P < 0.0001) as compared with Ab3-negative patients (median, 4.9 months). A positive Ab3 response remained associated with longer survival when controlling for other prognostic factors including FIGO (International Federation of Gynecologists and Obstetricians) stage, response to and type of first-line chemotherapy, number of previous treatments, or concomitant antitumor therapy. With regard to safety, repeated vaccination was well tolerated. No serious adverse events related to the application of ACA125 occurred. CONCLUSIONS: Although the uncontrolled design of this study prevents definitive conclusions with respect to subgroups, the data support a relationship between Ab3 response and survival time. Thus, the need for further randomized, controlled clinical trials to establish efficacy of the vaccine ACA125 seems to be indicated.

Adhesion molecules, activin and inhibin--candidates for the biochemical prediction of hypertensive diseases in pregnancy?

BACKGROUND: The aim of the prospective study was to compare standard parameters as Doppler ultrasound and 24-h blood pressure measurement with possible maternal serological markers regarding their prognostic value in predicting hypertensive diseases in pregnancy. MATERIALS: Twenty-four-hour blood pressure measurement was performed before and after 32+0 gestational week in 57 pregnant women with either chronic hypertension ( n=13), preeclampsia ( n=21), pregnancy-induced hypertension (PIH; n=12) or normotension ( n=11). Blood samples were taken and the concentrations of soluble intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), activin A and inhibin A were determined as well as serum uric acid, creatinine, total serum protein and serum albumin. Doppler ultrasound of the uterine arteries was examined before 32+0 gestational week in the same patients. For the statistical evaluation Kruskal-Wallis-Test and Mann-Whitney-U-Test were performed. Differences in the predictive value were evaluated by receiver-operating characteristics. RESULTS: VCAM-1 was significantly elevated in women developing hypertensive diseases as compared to normotensive women (preeclampsia: p<0.001; PIH: p<0.05; chronic hypertension: p<0.001). In early pregnancy activin A and inhibin A were significantly higher in preeclamptic patients than in the other groups (activin A: normotension: p<0.005; PIH: p<0.001; chronic hypertension: p<0.005) (inhibin A: normotension: p<0.005; PIH: p<0.001; chronic hypertension: p<0.01), thus suggesting them to be specific markers for the development of preeclampsia. Mean arterial pressure was significantly elevated in preeclampsia ( p<0.001) and chronic hypertension ( p<0.005) as compared to normotensives. CONCLUSION: Twenty-four-hour blood pressure monitoring with determination of mean arterial pressure and measurement of VCAM-1, activin A and inhibin A as serum parameters can be suggested as useful tests in the specific prediction of different types of hypertensive diseases in pregnancy.

Interleukin-6 fused to an anti-idiotype antibody in a vaccine increases the specific humoral immune response against CA125+ (MUC-16) ovarian cancer.

Anti-idiotypic (Id) monoclonal antibodies can serve as surrogate for tumor-associated antigens in vaccination strategies. The murine anti-Id monoclonal antibody ACA125 that mimics the CA125 carbohydrate antigen expressed on ovarian cancer cells induces an anti-anti-Id antibody (Ab3) response that is associated with prolonged survival of ovarian cancer patients. To increase the Ab3 antibody response, we evaluated two strategies in a mouse model: (a) coinjection of human interleukin (IL)-6 together with the fusion protein chACA125, which consists of the anti-Id ACA125 single-chain Fv antibody joined to the human IgG1 CH2/CH3 domain; and (b) injection of the fusion protein chACA125-IL-6, which consists of the ACA125 single-chain Fv fused to human IL-6 via the IgG1 CH2/CH3 domain. Vaccination of mice with the chACA125-IL-6 fusion protein resulted in higher titers of anti-CA125 (Ab3) antibodies compared with application of the chACA125 antibody with or without systemic coadministration of IL-6. Application of the chACA125-IL-6 fusion protein did not elicit detectable antihuman IL-6 antibody titers, whereas coinjection of human IL-6 did. Taken together, these data suggest that the chACA125-IL-6 fusion protein directly stimulates ACA125-specific B cells via the IL-6 domain, whereas coinjection of IL-6 leads to an overall immune stimulation. Antigen-IL-6 fusion proteins will improve vaccination regimens and anticancer immunotherapeutic strategies by increasing the antigen-specific humoral immune response.

A double-blind, placebo-controlled study of vitamin A and zinc supplementation in persons with tuberculosis in Indonesia: effects on clinical response and nutritional status.

BACKGROUND: The results of cross-sectional studies indicate that micronutrient deficiencies are common in patients with tuberculosis. No published data exist on the effect of vitamin A and zinc supplementation on antituberculosis treatment. OBJECTIVE: Our goal was to investigate whether vitamin A and zinc supplementation increases the efficacy of antituberculosis treatment with respect to clinical response and nutritional status. DESIGN: In this double-blind, placebo-controlled trial, patients with newly diagnosed tuberculosis were divided into 2 groups. One group (n = 40) received 1500 retinol equivalents (5000 IU) vitamin A (as retinyl acetate) and 15 mg Zn (as zinc sulfate) daily for 6 mo (micronutrient group). The second group (n = 40) received a placebo. Both groups received the same antituberculosis treatment recommended by the World Health Organization. Clinical examinations, assessments of micronutrient status, and anthropometric measurements were carried out before and after 2 and 6 mo of antituberculosis treatment. RESULTS: At baseline, 64% of patients had a body mass index (in kg/m(2)) < 18.5, 32% had plasma retinol concentrations < 0.70 micromol/L, and 30% had plasma zinc concentrations < 10.7 micromol/L. After antituberculosis treatment, plasma zinc concentrations were not significantly different between groups. Plasma retinol concentrations were significantly higher in the micronutrient group than in the placebo group after 6 mo (P < 0.05). Sputum conversion (P < 0.05) and resolution of X-ray lesion area (P < 0.01) occurred earlier in the micronutrient group. CONCLUSION: Vitamin A and zinc supplementation improves the effect of tuberculosis medication after 2 mo of antituberculosis treatment and results in earlier sputum smear conversion.

Vaccination with autologous tumour antigen-pulsed dendritic cells in advanced gynaecological malignancies: clinical and immunological evaluation of a phase I trial.

Dendritic cell (DC)-based therapy has proven to be effective in patients with malignant lymphoma, melanoma, and renal and prostate carcinoma. In this phase I clinical trial, we have shown that patients with advanced gynaecological malignancies can be effectively vaccinated with DC pulsed with keyhole limpet haemocyanin (KLH) and autologous tumour antigens. Two patients with uterine sarcoma and six subjects with ovarian carcinoma received three to 23 intracutaneous injections of antigen-pulsed DC at 10-day or 4-week intervals. Three patients showed stable disease lasting 25 to 45 weeks, and five experienced tumour progression within the first 14 weeks. KLH- and tumour lysate-specific delayed-type hypersensitivity (DTH) reactions were observed in six and one patient, respectively. Lymphoproliferative responses to KLH and to tumour lysate stimulation were recorded in six patients and in two patients respectively. Tumour antigen-stimulated interferon-gamma (IFN-gamma) secretion by peripheral blood mononuclear cells (PBMC) in one patient was consistent with a T(H) type 1 cytokine bias. The treatment was safe, well tolerated, immunologically active and except for local cutaneous hypersensitivity devoid of significant adverse effects.