Methotrexate polyglutamates as a marker of patient compliance and clinical response in psoriasis: a single-centre prospective study.

BACKGROUND: Methotrexate is activated by the sequential addition of glutamic acid residues to form methotrexate polyglutamates (MTXPG(1-5)). MTXPG(1-5) inhibit enzymes of the folate-purine-pyrimidine pathways, and longer-chain MTXPG(3-5) species are more active. OBJECTIVES: To determine the pattern of erythrocyte MTXPG(1-5) in patients initiated on oral methotrexate for psoriasis, and to investigate the potential utility of MTXPGs as markers of compliance and/or clinical response. METHODS: This was a single-centre, prospective study of 55 adult patients with chronic plaque psoriasis initiated on weekly oral methotrexate. Erythrocyte MTXPG(1-5) concentrations were measured (at weeks 4, 8, 12, 24 and 52) using high-performance liquid chromatography. Methotrexate responders achieved ≥ 50% improvement in Psoriasis Area and Severity Index or physician's global score of 'clear'/'nearly clear' at 24 weeks. RESULTS: MTXPG levels were measured in 14-33 patients at each time point. All MTXPG(1-5) species were detected at week 4 of therapy. Steady state for long-chain MTXPG(3-5) and total MTXPG(1-5) was achieved by week 24. MTXPG(3) emerged as the predominant MTXPG species (from week 12 onwards) and reflected overall polyglutamate status (correlating strongly with MTXPG(2-5) , MTXPG(3-5) and MTXPG(4-5) ; R = 0·76-0·95, P < 1·55 × 10(-5)). Age, renal function and sex were not significant determinants of MTXPG(3) concentration. No significant association was identified between MTXPG and adverse events or responder status. CONCLUSIONS: This is the first study to demonstrate the prospective accumulation of MTXPG(1-5) in patients with psoriasis. The detection of MTXPGs early in therapy and the establishment of a steady state with continuous treatment may offer measuring of MTXPG as a test to monitor patient compliance with therapy. Larger studies are required to determine the role of MTXPG as a potential biomarker of clinical response.

Multicentre comparison of the Glasgow Blatchford and Rockall Scores in the prediction of clinical end-points after upper gastrointestinal haemorrhage.

BACKGROUND: The Glasgow Blatchford Score (GBS) is increasingly being used to predict intervention and outcome following upper gastrointestinal haemorrhage (UGIH). AIM: To compare the GBS with both the admission and full Rockall scores in predicting specific clinical end-points following UGIH. PATIENTS AND METHODS: Data on consecutive patients presenting to four UK hospitals were collected. Admission history, clinical and laboratory data, endoscopic findings, treatment and clinical follow-up were recorded. Using ROC curves, we compared the three scores in the prediction of death, endoscopic or surgical intervention and transfusion. Results A total of 1555 patients (mean age 56.7years) presented with UGIH during the study period. Seventy-four (4.8%) died, 223 (14.3%) had endoscopic or surgical intervention and 363 (23.3%) required transfusion. The GBS was similar at predicting death compared with both the admission Rockall (area under ROC curve 0.804 vs. 0.801) and full Rockall score (AUROC 0.741 vs. 0.790). In predicting endo-surgical intervention, the GBS was superior to the admission Rockall (AUROC 0.858 vs. 0.705; P<0.00005) and similar to the full Rockall score (AUROC 0.822 vs. 0.797). The GBS was superior to both admission Rockall (AUROC 0.944 vs. 0.756; P<0.00005) and full Rockall scores (AUROC 0.935 vs. 0.792; P<0.00005) in predicting need for transfusion. CONCLUSIONS: Despite not incorporating age, the GBS is as effective as the admission and full Rockall scores in predicting death after UGIH. It is superior to both the admission and full Rockall scores in predicting need for transfusion, and superior to the admission Rockall score in predicting endoscopic or surgical intervention.

Fecal calprotectin predicts the clinical course of acute severe ulcerative colitis.

OBJECTIVES: Calprotectin is a granulocyte neutrophil-predominant cytosolic protein. Fecal concentrations are elevated in intestinal inflammation and may predict relapse in quiescent inflammatory bowel disease. We aim to investigate fecal calprotectin (FC) as a biomarker in predicting the clinical course of acute severe ulcerative colitis (ASUC). METHODS: In 90 patients with ASUC requiring intensive in-patient medical therapy (January 2005-September 2007), we investigated the discriminant ability of FC to predict colectomy and corticosteroid and infliximab nonresponse. All patients received parenteral corticosteroids as first-line treatment; 21 (23.3%) were also treated with infliximab (5 mg/kg), after failure of corticosteroid therapy. RESULTS: Of 90 patients, 31 (34.4%) required colectomy, including 11 (52.4%) of those treated with infliximab. Overall FC was high (1,020.0 microg/g interquartile range: 601.5-1,617.5). FC was significantly higher in patients requiring colectomy (1,200.0 vs. 887.0; P=0.04), with a trend toward significance when comparing corticosteroid nonresponders and responders (1,100.0 vs. 863.5; P=0.08), as well as between infliximab nonresponders and responders (1,795.0 vs. 920.5; P=0.06). Receiver-operator characteristic curve analysis yielded an area under the curve of 0.65 to predict colectomy (P=0.04), with a maximum likelihood ratio of 9.23, specificity 97.4%, and sensitivity 24.0% at a cutoff point of 1,922.5 microg/g. Kaplan-Meier analyses showed that using 1,922.5 microg/g over a median follow-up of 1.10 years, 87% of patients will need subsequent colectomy. CONCLUSIONS: This is the first data set to demonstrate that FC levels are dramatically elevated in severe UC. These data raise the possibility that this biomarker can predict response to first or second-line medical therapy in this setting.

Efficacy and complications of adalimumab treatment for medically-refractory Crohn's disease: analysis of nationwide experience in Scotland (2004-2008).

BACKGROUND: Adalimumab is a second generation humanized anti-tumour necrosis factor (TNF) monoclonal antibody with established efficacy in Crohn's disease (CD). AIMS: To evaluate the efficacy and safety of adalimumab on a nationwide clinical setting. METHODS: We used the Scottish Society of Gastroenterology network to identify and follow up the clinical outcomes of patients with CD treated with adalimumab over a 4-year period (2004-2008). RESULTS: A total of 98 patients received adalimumab - 100.5 patient follow-up years were recorded (64.3% females; median age at diagnosis of 20.7 years; 88.8% treated with 80/40 mg induction regimen. Eighty eight (89.8%) had previous infliximab with 29 (32.9%) primary nonresponders; 32 (32.6%) were corticosteroid-dependent; 47 (47.9%) were intolerant/resistant to most immunosuppressive therapies (two or more). In all, 60% of patients were in clinical remission at 1-year follow-up, with 30% and 55% requiring dose escalation to weekly therapy at 1-and 2-year follow-up respectively. Overall, 29 (29.6%) patients developed complications with eight nonfatal serious (8.2%) adverse events and 2 (2.0%) case fatalities (sepsis following perforation and disseminated colorectal cancer, respectively). CONCLUSIONS: Adalimumab is efficacious in severe and refractory CD in the clinical setting, although there remain significant therapy- and disease-related risks of serious complications.

Environmental risk analysis of ultraviolet phototherapy centres in Ireland.

BACKGROUND: Ultraviolet (UV) radiation is commonly used in the treatment of dermatological conditions such as psoriasis. It is known that high levels of exposure to UV radiation (UVR) will increase the risk of adverse biological effects. Exposure limit values for UVR have been developed by the International Commission on Non-Ionising Radiation Protection (ICNIRP) and occupational exposure to phototherapy staff should be kept within these limits. The use of environmental controls such as warning signs, good ventilation and UV-opaque curtains will significantly reduce the risks to staff, patients and members of the public. AIMS: The aim of the study is to identify hazards in phototherapy centres and present recommendations for reducing risks. METHODS: An environmental risk assessment has been carried out at eleven phototherapy centres in the Republic of Ireland. The study assessed a number of areas such as patient safety, staff safety, room design and UV leakage measurements. RESULTS: The majority of clinics are well designed and there is consistent use of protective equipment. CONCLUSIONS: The results show that on the whole there is a satisfactory level of risk management in phototherapy centres. Recommendations on maintaining good safety standards are presented.

Synchronized, interactive teleconferencing with digital cardiac images.

St James's Hospital is a tertiary referral center for percutaneous intervention and cardiothoracic surgery for a number of referring hospitals. This article reports on the development and implementation of a synchronized, interactive teleconferencing system for cardiac images that links St. James's Hospital with a remote site (Sligo General Hospital) and overcomes the problems of transmission of large image files. Teleconferencing was achieved by setting up lossless auto transmission of patient files overnight and conferencing the next morning with linked control signals and databases. As a suitable product was not available, a commercially new software was developed. The system links the imaging databases, monitors and synchronizes progress through imaging sequences, and links a range of image processing and control functions. All parties to the conference are ensured that they are looking at the same images as they are played or at specific aspects of an image that the other party is highlighting. The system allows patient management decisions to be made at a weekly joint teleconference with cardiothoracic surgeons and interventional cardiologists from both sites. Rapid decision making was facilitated with 70% of decisions obtained within 24 h, and 88% within 1 week of their procedure. In urgent cases, data can be transmitted within 20 min of the diagnostic procedure. The system allows increased access to angiography for patients living in rural areas, and provides a more focused referral for revascularization. Participation of the referring cardiologist has improved the quality of decision making.

Development and application of a quality control procedure for short-wave diathermy units.

Short-wave diathermy (SWD) is a form of radiofrequency (RF) radiation, operating at 27.12 MHz, that is used therapeutically by physiotherapists. Although this form of therapy is widely available, the management of the equipment is not often addressed by either physiotherapists or by medical physics/clinical engineering. A quality control protocol for SWD units, examining power output and electrical and mechanical condition, was developed and applied to 20 units used in clinical practice. In addition, an environmental assessment of where the units were used was also included. Results showed that the power output was generally stable (coefficient of variation range 0-8.8%) and reproducible (coefficient of variation range 0-6.8%). When the outputs from 12 similar units were compared, it was found that the relationship between the units' intensity settings and power output measurements was non-linear. Two units with mechanical timers were found to have inaccuracies that could contribute, under a 'worst-case' scenario, to a dosage error of up to 45%. Environmental analysis found that all treatment plinths in use contained metal parts, which could constitute a fire hazard, and no department examined was equipped with an RF screened room, a facility that would ensure that other persons in the vicinity were not exposed to excessive stray radiation.

Analysis of ultraviolet phototherapy and photochemotherapy resources in Ireland.

BACKGROUND: Ultraviolet (UV) phototherapy is widely used and very successful in the treatment of skin conditions. As such a safe and efficient service is essential. At present, there are no standard Irish guidelines regarding the operation, calibration or inspection of UV equipment nor is there an Irish policy on staff/patient safety or training issues. AIM: To survey all known phototherapy centres in Ireland. METHODS: A postal questionnaire was sent to all known phototherapy centres in Ireland addressed to the consultant dermatologist or the physiotherapist-in-charge. It was divided into six sections: Instrumentation, Quality Assurance, UV meters, equipment maintenance, patient/staff safety and training. Comments on current practice were invited. Non-respondents were contacted by telephone, in some cases the survey was mailed a second time. RESULTS: This study demonstrated a substantial quantity of suboptimal equipment in use and a lack of consensus regarding quality assurance inspection and UV meter calibration frequency. CONCLUSIONS: Guidelines must be established for calibration of UV equipment and standardisation of phototherapy protocols in Ireland.

Development of a quality assurance protocol for peripheral subtraction imaging applications.

Peripheral subtraction scanning is used to trace the blood vessels of upper and lower extremities. In some modern C-arm fluoroscopy systems this function is performed automatically. In this mode the system is programmed to advance and stop in a series of steps taking a mask image at each point. The system then repeats each step after the contrast agent has been injected, and produces a DSA image at each point. Current radiographic quality assurance protocols do not address this feature. This note reviews methods of measuring system vibration while images are being acquired in automated peripheral stepping. The effect on image quality pre- and post-image processing is assessed. Results show that peripheral stepping DSA does not provide the same degree of image quality as static DSA. In examining static test objects, the major cause of the reduction in image quality is misregistration due to vibration of the image intensifier during imaging.

Evaluation of renal function following treatment with 5-aminosalicylic acid derivatives in patients with ulcerative colitis.

BACKGROUND: A number of cases of nephrotoxicity have been reported in patients with inflammatory bowel disease taking oral 5-aminosalicylic acid (5-ASA). AIM: To evaluate the effects of 9 months of therapy with mesalazine or olsalazine on renal function in patients with ulcerative colitis in remission. METHODS: Forty patients with ulcerative colitis in complete remission for 6 months were randomized to either olsalazine (n=20) or mesalazine (n=20 for nine months). Thirty-six of the 40 patients were on prior salicylate therapy. Disease activity was the measure ofclinical efficacy and was assessed by the Harvey-Bradshaw Index (HBI). Laboratory efficacy measurements included glomerular filtration rate (GFR), microalbuminuria, urinary gluthathione S-transferase (GST) and serum C-reactive protein (CRP). Safety analysis consisted of documentation of adverse events and laboratory values. RESULTS: There was no significant reduction in the GFR overall on therapy. The levels of GFR adjusted for baseline were similar in the two treatment groups after 3, 6 and 9 months. A significantly higher percentage of mesalazine-treated patients experienced drug related adverse events, all of a minor nature. The incidence of adverse events causing early withdrawal was similar in the two treatment groups. CONCLUSION: Treatment with mesalazine or olsalazine for 9 months had no significant impact on GFR.

Superior epithelial arcuate lesions with soft contact lens wear.

BACKGROUND: Superior epithelial arcuate lesions (SEALs) are an infrequent and often asymptomatic complication of conventional soft contact lens wear. The characteristic arcuate pattern of the full-thickness corneal epithelial lesion usually occurs in the area covered by the upper eyelid, within 2 to 3 mm of the superior limbus in the 10- and 2-o'clock region. METHODS: Literature on SEALs and recent clinical records from clinical trials using two types of prototype high Dk soft contact lenses were reviewed to gain greater insights into the etiology of SEALs. RESULTS AND CONCLUSIONS: The reported low incidence of SEALs is partly because SEALs are not usually symptomatic. The etiology of SEALs is multifactorial. Our current hypothesis is that SEALs are produced by mechanical chaffing at the peripheral cornea. This chaffing occurs as a result of inward pressure of the upper lid, in an area where the peripheral corneal topography and lens design, rigidity, and surface characteristics combine to create excessive "frictional" pressure and abrasive shear force on the epithelial surface. Patient characteristics such as gender, age, and specific corneal and lid topographies also appear to influence the occurrence of SEALs. Prototype silicone hydrogel lenses are made from higher modulus materials with surfaces that seem to differ subtly in wettability in some patients. The prevalence of SEALs may well increase with the first generations of these lenses.

Development of a novel method for assessing balance: the quantitative posturography system.

Balance is the ability to maintain equilibrium while sitting or standing. There are a number of different methods which are used to assess balance: technical methods such as sway magnetometry, ataxia meter and force platforms, and clinical methods such as the functional reach test, Berg balance test and fall risk index. The most frequently used technical method is the force platform. There are two types of force platform, a static and a dynamic force platform, of which the dynamic force platform has been found to be more sensitive to detect impaired balance. The quantitative posturography system (QPS) described in this paper is a type of dynamic force platform; however, it has a simpler design than the currently available dynamic force platforms and can match the subject's sway exactly for tilting in the anterio-posterior and medio-lateral directions with its novel design. This paper describes the novel design of the QPS and its calibration.

A quality control procedure for force platforms.

A force platform is a technical method of quantitatively assessing balance indirectly. The use of force platforms in physiotherapy departments has become more prominent over the last few years. However, the main drawback in the use of force platforms is the lack of comprehensive calibration procedures, which casts doubt on the results obtained with these systems. Existing calibration tests are limited to testing the spatial accuracy of the force platform. This paper describes a comprehensive quality control test procedure which was developed. It is proposed that the developed quality control test procedure could be used to test all types of force platform and it includes a description of how the tests should be carried out, the frequency with which they should be carried out and the expected performance for each of the tests as recommended for the most part by the Association Francaise de Posturologie.

The development of a phantom to determine foetal organ doses from 131I in the foetal thyroid.

Iodine can accumulate in the foetal thyroid from the twelfth week of gestation onwards. If the iodine taken up by the foetal thyroid is in the form of 131I then the thyroid and its proximal tissues and organs will be irradiated. Several mathematical models exist in the literature on foetal/maternal iodine kinetics. However, very few studies have been performed where the foetal thyroid had been physically modelled thus allowing the determination of foetal organ dosimetry from 131I in the foetal thyroid. Here, the development of such a physical model or phantom is described and dosimetry results obtained from the phantom are discussed. The phantom is of Perspex construction, the dimensions of which are sufficient to incorporate models of the foetus at 16, 24 and 36 weeks' gestational age. The dosimetry of two organs is presented, that of the brain and the thymus. The results show that the measured absorbed dose is comparable with that calculated using modified MIRD dosimetry and traditional methods. The results also show that the dose to the thymus is greater than that of the brain by a factor of almost 30 for 16 weeks' gestational age.

Thyroid dosimetry in Europe following the Chernobyl accident.

Thyroid dose estimates for European populations following the Chernobyl accident in 1986 have been presented in the literature. These dose estimates used standard values for parameters such as thyroid mass, iodine uptake and biological half-life. Previous work has shown that these values are not representative of European populations and that local values should be utilized. Using published data on revised thyroid dose estimates, thyroid dosimetry data arising as a result of the Chernobyl accident are presented for 22 European countries. When these are compared with previously published estimates it is found that in all cases the previous results underestimate the thyroid dose by up to a factor of 4. Risk estimates on the incidence of fatal and non-fatal thyroid cancers are also determined from this new data and, again, the results are underestimated. The results show an increase in the number of fatal cancers, rising from 149 as predicted by the NEA to 310 under the new estimates, and from 180 as predicted by UNSCEAR to the new estimate of 380.

Digitized mammograms: a preliminary clinical evaluation and the potential for telemammography.

We performed a preliminary clinical evaluation of digitized mammograms to assess whether digital images suitable for telemammography could be obtained. Thirty mammograms were digitized at a resolution of 4000 x 4000 pixels and 12 bit/pixel. The series contained 17 carcinomas in 16 patients. Five consultant radiologists reported both the original mammograms and the digitized images. There was agreement between the reports of the mammograms and the digitized images in relation to whether a suspicious lesion was present or not in 95% of cases. No study considered benign on viewing the film images was interpreted as malignant on reporting the digitized images. This suggests that film digitizers may allow a digital image of a mammogram of acceptable quality for telemammography to be obtained in the absence of a purpose-built digital mammography system.

Gadopentetate dimeglumine as a contrast agent in peripheral angioplasty. A case report.

Gadopentetate dimeglumine (Gd-DTPA) is widely used as a contrast agent in MR imaging. We report on a case in which Gd-DTPA was used as the contrast agent during angioplasty in a patient who had recently had an adverse reaction to a non-ionic iodinated contrast medium. Gd-DTPA allowed a diagnostic angiogram to be performed with no side effects, and may thus be a useful contrast agent at angioplasty in patients with contra-indications to iodinated contrast media.

Calibration and assessment of a fluid-filled catheter-transducer system for the measurement of ventricular diastolic pressures.

A concise set of experiments is described which detail the calibration of a fluid-filled catheter-transducer system and the assessment of a widely used industrial algorithm for determining end-diastolic pressures using that system. First, the static response of the catheter-transducer system was evaluated in vitro by inserting the catheter into a graduated cylinder of saline. Twelve observations revealed a systematic undervaluation of pressure by the system of 1.78 mmHg with 95% limits of agreement ranging from -6.22 to 2.66 mmHg. Next, the dynamic response was evaluated in vivo by performing a transient step-response test. The system had an adequate dynamic response (fn = 11.12 Hz) for intraventricular pressure waveform replication but was considerably underdamped (beta = 0.16). Finally, the ability of the analysis software to detect the point of end-diastole and evaluate end-diastolic pressure was assessed by comparing system output with manual measurements of end-diastolic pressure in 12 patients. The mean difference between manually determined end-diastolic pressure and system output was 0.83 +/- 1.68 mm Hg. This difference is clinically insignificant and shows that the more noteworthy source of error is in the manometer-transducer emphasizing the importance of calibration and quality assurance of fluid-filled catheter-transducer systems for use in clinical cardiology or research.

Thyroid dosimetry of adult European populations.

Radioactive iodine, in the form of iodine-131, behaves similarly to stable iodine in small quantities, thus resulting in a radiation dose to the thyroid. Under the Medical Internal Radiation Dosimetry Committee formulation for radiation dose calculation to an organ, the resulting dose to the thyroid gland is dependent on the organ mass, its isotope uptake and the effective half-life of the element in the gland. Traditionally, values have been used for these parameters which, in some cases, were determined some decades previous. Iodine supply is a primary contributor to correct thyroid function and ultimately these values of mass, uptake and half-life. Recently, new data have become available on iodine kinetics throughout Europe. Here, the influence of the highly variable iodine supply in Europe on projected thyroid doses is determined. Thyroid mass values ranged from 9 g (Sweden) to 28 g (Poland) while uptake measurements were found to range from 18% (Finland) to approximately 60% (Germany and Poland). Resulting dose estimates ranged from 0.5 Gy MBq-1 (Finland) injested to 1.3 Gy MBq-1 (Czechoslovakia) injested. It was also found that among European populations the highest dose burden was to those populations with mild iodine deficiency. The results show that the use of generic metabolic data for the thyroid can lead to a misrepresentation of the absorbed dose to the thyroid. Thus, the data presented provide a better reflection of the actual thyroid dose following ingestion of iodine-131 for European countries.