Relevance of laboratory investigations in monitoring patients with psoriasis on etanercept or adalimumab.

BACKGROUND: Guidelines concerning biological treatment of patients with psoriasis recommend different pretreatment and monitoring laboratory panels in variable frequencies to monitor treatment. OBJECTIVES: To investigate the relevance of laboratory investigations in monitoring patients with psoriasis on etanercept or adalimumab. METHODS: A prospective cohort study over 5 years was conducted in all consecutive patients with psoriasis on etanercept or adalimumab. All laboratory investigations performed for monitoring treatment were analysed. Laboratory abnormalities were graded according to the Common Terminology Criteria for Adverse Events v4.03. The primary endpoint was the percentage of patients with a grade 3 or grade 4 laboratory abnormality. The secondary endpoints were defined as: (i) significant changes in laboratory parameters during etanercept or adalimumab treatment and (ii) the percentage of patients having a laboratory abnormality requiring discontinuation of etanercept or adalimumab treatment. RESULTS: Laboratory parameters were available for 162 patients treated with etanercept and/or adalimumab. The number of treatment episodes was 155 for etanercept and 58 for adalimumab. Follow-up was 316 patient-years for etanercept and 54 patient-years for adalimumab. Thirty-eight of 146 patients treated with etanercept (26%) had one or more grade 3 and/or grade 4 laboratory abnormalities. For adalimumab, this was eight of 58 (14%). These were predominantly considered unrelated to biologic therapy. For both biologics, significant changes were observed in mean laboratory parameters during treatment compared with pretreatment as well as significant trends. However, mean values during treatment remained within normal ranges. Laboratory abnormalities did not lead to permanent discontinuation of biologic treatment in any patient. CONCLUSIONS: In this cohort, the incidence of biologic therapy-related serious laboratory abnormalities was low. Our findings do not support a need for routine laboratory testing in patients with psoriasis on etanercept or adalimumab beyond the laboratory testing required for concomitant therapies or comorbidities.

Glandularity and mean glandular dose determined for individual women at four regional breast cancer screening units in the Netherlands.

The nationwide breast cancer screening programme using mammography has been in full operation in The Netherlands since 1997. There is concern that the mean glandular doses due to mammography might be differing between different regions of the country due to differences in glandularity and compressed breast thickness. To investigate regional differences, glandularity, compressed breast thickness and mean glandular dose were determined for individual breasts during screening at mammography units at four locations in The Netherlands. Differences in glandularity were observed, which could be related qualitatively to differences in age of the participants at the different locations. Mean glandular dose depends on compressed breast thickness, glandularity and technical conditions of screening. The lowest average value of the mean glandular dose was found for the unit in Amsterdam. This is most likely due to the use of the Mo/Rh anode/filter combination at this unit, in addition to the Mo/Mo combination. At the other three units, almost exclusively the Mo/Mo anode/filter combination was used. Differences in mean glandular dose averaged per unit could be related mainly to differences in tube-current exposure-time product values. Consequently, it is concluded that differences in mean glandular dose at different units are marginal.

Method for determination of the mean fraction of glandular tissue in individual female breasts using mammography.

The nationwide breast cancer screening programme using mammography has been in full operation in the Netherlands since 1997. Quality control of the screening programme has been assigned to the National Expert and Training Centre for Breast Cancer Screening. Limits are set to the mean glandular dose and the centre monitors these for all facilities engaged in the screening programme. This procedure is restricted to the determination of the entrance dose on a 5 cm thick polymethylmethacrylate (PMMA) phantom. The mean glandular dose for a compressed breast is estimated from these data. Individual breasts may deviate largely from this 5 cm PMMA breast model. Not only may the compressed breast size vary from 2 to 10 cm, but breast composition varies also. The mean glandular dose is dependent on the fraction of glandular tissue (glandularity) of the breast. To estimate the risk related to individual mammograms requires the development of a method for determination of the glandularity of individual breasts. A method has been developed to derive the glandularity using the attenuation of mammography x-rays in the breast. The method was applied to a series of mammograms at a screening unit. The results, i.e., a glandularity of 93% within the range of 0 to 1, were comparable with data in the literature. The glandularity as a function of compressed breast thickness is similar to results from other investigators using differing methods.

Fatty acids and atherosclerotic risk.

Most research concerning the effects of dietary fatty acids on atherosclerotic risk has focused on their effects on lipid and lipoprotein metabolism. However, it is known that fatty acids also influence a number of other relevant mechanisms involved in atherosclerosis such as lipid peroxidation, inflammation and haemostasis. The most favourable distribution of cholesterol over the various lipoproteins is achieved when saturated and trans fatty acids are replaced by a mixture of cis-unsaturated fatty acids. Furthermore, fatty acids from fish oil lower triacylglycerol concentrations. Effects on other atherosclerotic risk markers are less evident. Monounsaturated fatty acids maybe preferable above other fatty acids with respect to low-density lipoprotein oxidation as measured by indirect in vitro assays. The relevance of these assays for the in vivo situation is, however, limited. With respect to inflammation, mainly the effects of n-3 polyunsaturated fatty acids from fish oil have been studied, but results were inconsistent. Also results from studies evaluating the effects of fatty acids on haemostatic risk markers were inconsistent, which may be partly related to the use of different analytical methods. The most consistent finding however is the potential beneficial effect of moderate intakes of fish oil on platelet aggregation. Furthermore, reducing total fat intake rather than changing the fatty acid composition of the diet may beneficially affect the coagulation system. In conclusion, while beneficial effects on atherosclerotic risk are mainly ascribed to cis-unsaturated fatty acids, it remains debateable whether trans and saturated fatty acids in the diet have to be replaced by cis-unsaturated fatty acids or by carbohydrates. To answer this question adequately more validated methods are needed that reflect in vivo lipid peroxidation, inflammation and haemostasis.

Do non-specific minimal signs in a biennial mammographic breast cancer screening programme need further diagnostic assessment?

Mammographic features such as small vague densities, indefinable microcalcifications, subtle architectural distortions, alone or in combination, are non-specific appearances for breast cancer. These features sometimes precede malignancy and a decisive strategy on how to deal with non-specific minimal signs in a breast cancer screening programme is therefore desirable. After studying the prevalence of these signs in a Dutch Breast Cancer Screening Centre and estimating the risk of participants with these signs acquiring breast cancer within 2 years, we have developed such a strategy. Non-specific minimal signs were seen on the mammograms of 53 of 500 (10.6%) participants, aged 50-70 years, in this programme. After retrospective analysis of the mammograms of 254 patients with screen-detected or interval carcinoma, non-specific minimal signs were detected in 77 cases. Combining the incidence of breast cancer with the difference between the expected number of non-specific minimal signs in the screening programme and its actual occurrence in previous mammograms of patients with breast cancer, the risk of cancer in women with these signs, additional to that of screened women in general (additional risk), is calculated as being 0.5%. Invasive breast cancer in women with previously detected non-specific minimal signs demonstrated a favourable stage at diagnosis (axillary metastasis in 23% vs 37% in cancers without these previous signs, p < or = 0.05). Our strategy for follow-up in case of non-specific minimal signs remains unchanged because of the low additional risk and favourable staging, and is restricted to an invitation for the next screening round in 2 years time.

PACS in practice: the status of the PACS project at the St. Radboud University Hospital. Part A: Introduction and the picture system.

A so-called bottom-up approach of a Picture Archiving and Communication System (PACS) is initiated by existing clinical questions. It is investigated how far existing Data-Acquisition (DA) modalities combined with the existing computer infrastructure of the hospital can provide soil to a, at first local, PACS system. Examples of current research projects in Digital Subtraction Angiography (DSA), Computed Tomography (CT) and Magnetic Resonance Imaging (MRI) demonstrate how image and raw data processing evolve from applications based on a general matrix manipulation software package to projects within the field of PACS. Starting from the existing facilities a stepwise increase of connections and expansions of required features is going to be brought about by separately considering the picture system, the communication system and the archive system. A three step phasing is proposed: (1) Software linking; (2) Hardware linking: small scale; and (3) Hardware linking: local area network. Examples are given from the first phase, i.e. the development and expansion of software on existing DA-modalities or processing hardware to receive the data on floppy disk, hard disk or tape. Data are converted and transported for further processing: (a) within the department; (b) between hospital departments; and (c) between research centres. With regard to the picture system special attention has to be given to the requirements for digitizing analogue film images and the reading of images from monitor screens instead of films on lightboxes.

Improvement of IVDSA of the brachiocephalic arteries using a non-ionic contrast medium.

The introduction of IVDSA provides a safer method of angiographic investigation of the aortic arch and brachiocephalic arteries than conventional angiography in patients with cerebro-vascular disease. The quality of visualization however decreases. Instead of changing over to IADSA we find it worthwile to try to improve IVDSA in different ways. One of them is represented in this prospective double blind cross-over study in which we have investigated the effects of using an isotonic non-ionic contrast medium, iohexol (omnipaque), in comparison to meglumin-sodium-diatrizoate (urografin) which is widely used. Iohexol causes less severe side-effects, less severe artifacts and a better image quality. A statistical relation between parameters could not be established. A lag-effect exists for side-effects. The necessity of using low osmolar contrast media is discussed.

Comparison of brachiocephalic angiography and IVDSA in the same group of patients.

In this investigation for the first time conventional angiography (CA) and intravenous digital subtraction angiography (IVDSA) of the aortic arch and brachiocephalic vascular territory is compared in the same group of 25 patients. The quality of the image derived from IVDSA is inferior to that of CA and, moreover, varies with the location. If sufficiently good, IVDSA has an accuracy of 81 to 91% in comparison to CA for stenotic lesions depending on the site. Ulcerations are missed more frequently than with CA. Discrepancies between IVDSA and CA are caused mainly by misregistration. According to our investigation there are multiple stenotic lesions in the brachiocephalic territory in 84% of the patients. Adequate assessment of the need for surgery in symptomatic patients can therefore only be made after complete visualization of the aortic and brachiocephalic vascular territory. If non-invasive methods, like duplex-scanning, cannot fulfill this requirement, IVDSA is the only semi-invasive method that can provide the information. It is therefore desirable to improve IVDSA technique in the near future instead changing to intra-arterial DSA (IADSA). Now already the advantages outweight the drawbacks.

Quality analysis of DSA equipment.

In the framework of a quality analysis project for the improvement of digital subtraction angiography (DSA) equipment, an inventory was made of the image quality and radiation dose of DSA equipments in six hospitals in the Netherlands. The image quality was investigated with a contrast detail (CD) phantom. The entrance dose of the radiation on this phantom and the skin dose at the level of the eye lenses and the thyroid gland were measured in these hospitals using a human phantom during a standardised simulated DSA examination of the aortic arch and brachiocephalic arteries, by means of thermo-luminescence dosimeters (TLD). To establish the relation of these measurements on the human phantom and real patient examinations, the same measurements were carried out in our own hospital on 16 patients during a comparable DSA examination. To find the difference from the dose in conventional angiography (CA) the same measurements were carried out in our hospital on 11 patients during a comparable examination. These dose measurements were also carried out on the human phantom with the use of the same CA equipment. We found large differences in image quality in the various hospitals. Within one hospital, monitor images were better than hard copy images. These differences were strongly related to the amount of radiation used, to the technique of storing the images (digital or analogue) and to the quality of the equipment used to make hard copies (the imager). Recommendations are made for improvement and quality control.

Assessment of intra-abdominal and subcutaneous abdominal fat: relation between anthropometry and computed tomography.

The ability to distinguish between intra-abdominal and subcutaneous abdominal fat may be important in epidemiologic and clinical research. In this study anthropometric measurements were taken from 71 men and 34 women presenting for routine computed tomography (CT). Areas of abdominal fat were calculated from CT scans made at the level of the L4 vertebra. The amounts of intra-abdominal and subcutaneous abdominal fat could be accurately predicted from several circumferences, skinfold measurements, body mass index, and age (R2 ranged from 0.79 to 0.84). In addition, it was found that the area of intra-abdominal fat on the CT scan was related to the waist:hip circumference ratio (r = 0.75 in men, r = 0.55 in women) and to the waist:thigh circumference ratio (r = 0.55 in men, r = 0.70 in women). The correlations of the circumference ratios with the areas of subcutaneous fat were invariably lower.

Receiver operating characteristic curves in diagnostic imaging.

The evaluation of medical imaging systems is normally done by quantifying the physical properties of the equipment. Since a diagnosis by the radiologist is the result of a combination of equipment and radiologist, it is preferable to evaluate the system as a whole by the use of receiver operating characteristic curves. The aid of this article is to explain this evaluation technique to the radiologist and indicate why this technique in many cases is the proper way to evaluate imaging systems.