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PubMed2026

Identification and characterization of anti-chikungunya virus compounds using a biosafe toolkit.

Chikungunya virus (CHIKV) is a re-emerging mosquito-borne alphavirus for which no specific antiviral therapy is currently available. During the large outbreak in Foshan, Guangdong Province, China, in July 2025, CHIKV rapidly spread to neighboring regions and caused more than 16,000 confirmed cases. In this study, the predominant outbreak strain of CHIKV was selected as the reference sequence to establish a panel of complementary biosafe tools for antiviral compound screening and mechanistic investigation. A virus replicon particle (VRP) system for CHIKV was first constructed and applied to compound library screening, resulting in the identification of three candidate antiviral compounds: MDL-12330A, bazedoxifene acetate, and anidulafungin. To further validate their antiviral activities and investigate their potential mechanisms, CHIKV functional evaluation systems were subsequently established, including vesicular stomatitis virus (VSV)- and murine leukemia virus (MLV)-based pseudovirus systems for viral entry, a replicon RNA system for post-entry replication-associated processes, a replication-defective nsP4 mutant replicon RNA system for primary translation, and a virus-like particle (VLP) system for viral particle assembly and budding assessment. Using these complementary systems, we systematically evaluated the antiviral profiles of the three candidate compounds across multiple stages of the CHIKV life cycle. This analysis revealed distinct stage-specific inhibitory patterns and provided insights into their potential antiviral mechanisms, which warrant validation using authentic CHIKV infection to assess their translational potential.

Chikungunya virus↗

PubMed2003

Measurement of copper release rates from antifouling paint under laboratory and in situ conditions: implications for loading estimation to marine water bodies.

The release of biocides, such as copper (Cu), from antifouling (AF) coatings on vessel hulls represents a significant proportion of overall Cu loading in those harbors and estuaries where substantial numbers of small craft or large vessels are berthed. Copper release rates were measured on several self-polishing, tin-free coatings and an ablative Cu reference coating applied to steel panels using three measurement methods. The panels were exposed in natural seawater in San Diego Bay, and release rates were measured both in the laboratory and field over 2 years. Results with the static (20 cm x 30 cm) panels indicated that Cu release rates were initially high (25-65 microg Cu cm(-2)day(-1)), with a large range of values between paint types. Release rates declined to substantially lower rates (8-22 microg cm(-2)day(-1)) with reduced variability within 2 months. Release rates continued to decrease over time for approximately 6 months when relatively constant release rates were observed for most coatings. Over time, relative differences in Cu release rates measured by three exposure methods decreased, with all coatings exhibiting similar behavior toward the end of the study. Lowest overall Cu release rates were observed with the self-polishing experimental paint no. 7 in static-dynamic and in situ treatments. The highest periodic release rates were measured from panels that experienced periods of both static and dynamic exposure (8.7 ms(-1) rotation). The lowest release rates were measured from panels that experienced static, constant depth exposure, and where release rates were evaluated in situ, using a novel diver-deployed measurement system. Results from this in situ technique suggests that it more closely reflects actual Cu release rates on vessel hulls measured with intact natural biofilms under ambient conditions than measurements using standardized laboratory release rate methods. In situ measurements made directly on the AF surface of vessels demonstrated typically lower release rates than from the panel studies, averaging 8.2 microg cm(-2)day(-1) on pleasure craft, and 3.8 microg cm(-2)day(-1) on Navy vessels. The data suggest that the presence of an established biofilm likely serves to moderate the release of Cu from field-exposed antifouling coatings both on panels and hull surfaces.

Biofilms↗

PubMed2002

Guidelines on bladder cancer.

OBJECTIVES: On behalf of the European Association of Urology (EAU) guidelines for diagnosis, therapy and follow-up of bladder cancer patients were established. Criteria for recommendations were evidence based, and included aspects of cost-effectiveness and clinical feasibility. METHOD: A systematic literature research using Medline Services was conducted. References were weighted by a panel of experts. RESULTS: TNM 1997 classification and WHO grading 1998 are recommended. Recommendations are developed for diagnosis for bladder cancer in general, treatment of superficial and infiltrative bladder cancer, and follow-up after different types of treatment modalities, such as intravesical instillations, radical cystectomy, urinary diversions, radiotherapy and chemotherapy.

Follow-Up Studies↗

PubMed2006

Automated detection of lung nodules in multidetector CT: influence of different reconstruction protocols on performance of a software prototype.

PURPOSE: To evaluate the accuracy of software for computer-aided detection (CAD) of lung nodules using different reconstruction slice thickness protocols in multidetector CT. MATERIALS AND METHODS: Raw image data sets for 15 patients who had undergone 16-row multidetector CT (MDCT) for known pulmonary nodules were reconstructed at a reconstruction thickness of 5.0, 2.0 and 1.0 mm with a reconstruction increment of 1.5, 1.0 and 0.5 mm, respectively. The "Nodule Enhanced Viewing" (NEV) tool of LungCare for computer-aided detection of lung nodules was applied to the reconstructed images. The reconstructed images were also blinded and then evaluated by 2 radiologists (A and B). Data from the evaluating radiologists and CAD was then compared to an independent reference standard established using the consensus of 2 independent experienced chest radiologists. The eligible nodules were grouped according to their size (diameter > 10, 5 - 10, < 5 mm) for assessment. Statistical analysis was performed using the receiver operating characteristic (ROC) curve analysis, t-test and two-rater Cohen's Kappa co-efficient. RESULTS: A total of 103 nodules were included in the reference standard by the consensus panel. The performance of CAD was marginally lower than that of readers at a 5.0-mm reconstruction thickness (AUC = 0.522, 0.517 and 0.497 for A, B and CAD, respectively). In the case of 2.0-mm reconstruction slices, the performance of CAD was better than that of the readers (AUC = 0.524, 0.524 and 0.614 for A, B and CAD, respectively). CAD was found to be significantly superior to radiologists in the case of 1.0-mm reconstruction slices (AUC = 0.537, 0.531 and 0.675 for A, B and CAD, respectively). The sensitivity at a reconstruction thickness of 1.0 mm was determined to be 66.99 %, 68.93 % and 80.58 % for A, B and CAD, respectively. The time required for detection was shortest for CAD at reconstruction slices of 1.0 mm (mean t = 4 min). The performance of radiologists was greatly enhanced when using CAD: sensitivity 91.26 % and 94.17 % for CAD+A and CAD+B, respectively (AUC = 0.889 and 0.917). CAD was most advantageous in the detection of nodules < 10 mm. CONCLUSION: At a 1.0-mm reconstruction thickness, CAD's ability to detect nodules < 10 mm is superior to that of radiologists and its relatively short evaluation time makes it a viable second reader.

Diagnosis, Computer-Assisted↗

PubMed2004

Detection and antigenic characterization of salmonid alphavirus isolates from sera obtained from farmed Atlantic salmon, Salmo salar L., and farmed rainbow trout, Oncorhynchus mykiss (Walbaum).

A simple method of detecting the presence of the salmonid alphaviruses (SAVs), salmon pancreas disease virus (SPDV) and sleeping disease virus (SDV), from serum samples is described. Using a 96-well tissue-culture plate format, test sera are diluted in medium and added to chinook salmon embryo (CHSE-214) cells. After incubation for 3 days at 15 degrees C, plates are fixed and stained using a monoclonal antibody (mAb)-based immunoperoxidase (IPX) detection system, and virus-infected cells are observed microscopically by white light. Application of this screening test, which is now used routinely in our laboratory in conjunction with an IPX-based virus neutralization (IPX-VN) test for detecting antibodies to SAVs, has resulted in the recovery of 12 additional isolates from salmon sera and four additional isolates from trout sera. A low level of antigenic variation was detected when these SAV isolates were investigated by indirect immunofluorescence using a panel of mAbs raised to reference SPDV and SDV isolates.

Alphavirus↗

PubMed2005

Antioxidant properties of minocycline: neuroprotection in an oxidative stress assay and direct radical-scavenging activity.

Minocycline is neuroprotective in animal models of a number of acute CNS injuries and neurodegenerative diseases. While anti-inflammatory and anti-apoptotic effects of minocycline have been characterized, the molecular basis for the neuroprotective effects of minocycline remains unclear. We report here that minocycline and a number of antioxidant compounds protect mixed neuronal cultures in an oxidative stress assay. To evaluate the role of minocycline's direct antioxidant properties in neuroprotection, we determined potencies for minocycline, other tetracycline antibiotics, and reference antioxidant compounds using a panel of in vitro radical scavenging assays. Data from in vitro rat brain homogenate lipid peroxidation and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assays show that minocycline, in contrast to tetracycline, is an effective antioxidant with radical scavenging potency similar to vitamin E. Our findings suggest that the direct antioxidant activity of minocycline may contribute to its neuroprotective effects in some cell-based assays and animal models of neuronal injury.

Animals↗

PubMed2002

Quantitation of immunoglobulin to hepatitis E virus by enzyme immunoassay.

We developed a quantitative enzyme immunoassay (EIA) for antibody to hepatitis E virus (HEV) by using truncated HEV capsid protein expressed in the baculovirus system to improve seroepidemiology, to contribute to hepatitis E diagnosis, and to enable vaccine evaluations. Five antigen lots were characterized; we used a reference antiserum to standardize antigen potency. We defined Walter Reed antibody units (WR U) with a reference antiserum by using the four-parameter logistic model, established other reference pools as assay standards, and determined the conversion factor: 1 WR U/ml = 0.125 World Health Organization unit (WHO U) per ml. The EIA performed consistently; median intra- and inter-test coefficients of variation were 9 and 12%, respectively. The accurate minimum detection limit with serum diluted 1:1,000 was 5.6 WR U/ml; the test could detect reliably a fourfold antibody change. In six people followed from health to onset of hepatitis E, the geometric mean antibody level rose from 7.1 WR U/ml to 1,924.6 WR U/ml. We used the presence of 56- and 180-kDa bands by Western blotting as a confirmatory test and to define true-negative and -positive serum specimens. A receiver-operating characteristics plot identified 30 WR U/ml as an optimum cut-point (sensitivity, 86%; specificity, 89%). The EIA detected antibody more sensitively than a commercially available test. The EIA was transferred to another laboratory, where four operators matched reference laboratory results for a panel of unknowns. Quantitation of antibody to HEV and confirmation of its specificity by Western blotting make HEV serology more meaningful.

Capsid↗

PubMed1997

Molecular tracking of Candida albicans in a neonatal intensive care unit: long-term colonizations versus catheter-related infections.

Nosocomial neonatal candidiasis is a major problem in infants requiring intensive therapy. The subjects of this retrospective study were nine preterm infants admitted to the neonatal intensive care unit of the Hospital Central de Asturias between March 1993 and August 1994. The infants were infected with or colonized by Candida albicans. Five patients developed C. albicans bloodstream infections. A total of 36 isolates (including isolates from catheters and parenteral nutrition) were examined for molecular relatedness by PCR fingerprinting and restriction fragment length polymorphism (RFLP) analysis. The core sequence of phage M13 was used as a single primer in the PCR-based fingerprinting procedure, and RFLP analysis was performed with C. albicans-specific DNA probe 27A. Both techniques were evaluated with a panel of eight C. albicans reference strains, and each technique showed eight different patterns. With the 36 isolates from neonates, each technique enabled us to identify by PCR and RFLP analysis seven and six different patterns, respectively. The combination of these two methods (composite DNA type) identified eight different profiles. A strain with one of these profiles was present in three patients and in their respective catheters. Patients infected with or colonized by this isolate profile were clustered in time. Among the other patients, each patient was infected over time and at multiple anatomic sites with a C. albicans strain with a distinct DNA type. We conclude that C. albicans was most commonly producing long-term colonizations, although horizontal transmission probably due to catheters also occurred.

Base Sequence↗

PubMed2003

Evaluation of the Vitek 2 ID-GNB assay for identification of members of the family Enterobacteriaceae and other nonenteric gram-negative bacilli and comparison with the Vitek GNI+ card.

We evaluated the Vitek 2 ID-GNB identification card (bioMérieux, Inc., Durham, N.C.) for its ability to identify members of the family Enterobacteriaceae and other gram-negative bacilli that are isolated in clinical microbiology laboratories. Using 482 enteric stock cultures and 103 strains of oxidase-positive, gram-negative glucose-fermenting and nonfermenting bacilli that were maintained at -70 degrees C and passaged three times before use, we inoculated cards according to the manufacturer's directions and processed them in a Vitek 2 instrument using version VT2-R02.03 software. All panel identifications were compared to reference identifications previously confirmed by conventional tube biochemical assays. At the end of the initial 3-h incubation period, the Vitek 2 instrument demonstrated an accuracy of 93.0% for the identification of enteric strains; 414 (85.9%) were correctly identified at probability levels ranging from excellent to good, and an additional 34 (7.1%) strains were correctly identified but at a low level of discrimination. Nineteen (3.9%) strains were unidentified, and 15 (3.1%) were misidentified. The 19 unidentified strains were scattered among 10 genera. Three of the 15 misidentified strains were lactose-positive Salmonella spp. and were identified as Escherichia coli; another was a lactose-positive, malonate-negative Salmonella enterica subsp. arizonae strain that was identified as E. coli. Of the 103 glucose-fermenting and nonfermenting nonenteric strains, 88 (85.4%) were correctly identified at probability levels ranging from excellent to good, and 10 (9.7%) were correctly identified, but at a low level of discrimination, for a total of 95.1% accuracy with this group. Two strains were unidentified and three were misidentified. The errors occurred for strains in three different genera. With the increased hands-off approach of the Vitek 2 instrument and accuracies of 93% for the identification of enteric organisms and 95.1% for the identification of nonenteric organisms with the ID-GNB card, use of this product presents an acceptable method for the identification of most gram-negative organisms commonly isolated in the clinical laboratory. A comparison of these results to those obtained by testing 454 of the same strains with the Vitek GNI+ card revealed no significant difference in the abilities of the two cards to identify these organisms accurately.

Bacterial Typing Techniques↗

PubMed2006

Anti-proteasome autoantibodies contribute to anti-nuclear antibody patterns on human larynx carcinoma cells.

BACKGROUND: Autoantibodies to the 20S proteasome represent an unspecific but common serological phenomenon in patients with systemic autoimmune diseases. Interestingly, a high prevalence of these antibodies have been observed in patients with connective tissue diseases, where anti-nuclear antibodies (ANAs) serve as an important diagnostic screening test. OBJECTIVE: To disclose interference of anti-proteasome antibodies with known ANA patterns. METHODS: Anti-proteasome antibodies were isolated for comprehensive immunofluorescence analyses. The immunofluorescence pattern of human anti-proteasome antibodies was compared with a panel of monoclonal and polyclonal reference antibodies, and colocalisation was analysed using confocal microscopy. RESULTS: Anti-proteasome antibodies clearly contributed to the ANA patterns of their respective serum samples from patients with different rheumatic disorders. In addition to the nuclear pattern, proteasomal staining was also detectable in the cytoplasm, at the endoplasmic reticulum and perinuclear regions showing features overlapping with other known autoantibodies such as those to mitochondria. The specificity of anti-proteasome antibodies was proved by competition experiments and by colocalisation with monoclonal reference antibodies in confocal microscopy. CONCLUSION: In ANA diagnostics, interference of anti-proteasome antibodies will have to be taken into account, especially in the differentiation of anti-cytoplasmatic autoantibodies.

Adult↗

PubMed1975

The HL-A system in asbestos workers.

In a study of the HL-A system in 56 selected asbestos workers referred to the Pneumoconiosis Medical Panel with definite or suspected asbestosis, the W 27 antigen was found more often than among a control population. Six of the 10 asbestos workers with the W 27 antigen had definite radiographic evidence of asbestosis compared to 13 out of 46 without the W 27 antigen. These observations, if confirmed, suggest that the W 27 antigen may provide a useful marker of an enhanced susceptibility to the tissue-damaging effects of asbestos dust.

Adult↗

PubMed2026

Epigenetic Liquid Biopsy Enables Universal Mutation-Agnostic Molecular Surveillance for High-Risk Neuroblastoma.

PURPOSE: Liquid biopsy monitoring in pediatric solid tumors is limited by low mutational burden and lack of trackable genomic drivers. We sought to develop a mutation-agnostic, methylation-based liquid biopsy framework enabling universal molecular surveillance of high-risk neuroblastoma. EXPERIMENTAL DESIGN: Using whole-genome Oxford Nanopore Technologies sequencing of high-risk neuroblastoma tumors, we compared tumor-derived methylation profiles with a comprehensive atlas of normal human cell types and identified 72 neuroblastoma-specific differentially methylated regions (meNBL) that were reliably detectable in cell-free DNA (cfDNA). Marker robustness and specificity were validated using independent neuroblastoma methylation datasets and assessed against methylation profiles from other cancer types. We established neuroblastoma as a distinct methylation entity within the reference atlas by integrating a panel of 25 meNBLs, enabling quantitative estimation of tumor-derived cfDNA. Assay performance was evaluated across diagnostic, remission, relapse, and healthy control samples and compared with mutation-based and copy number-based approaches. RESULTS: Neuroblastoma-derived cfDNA was consistently detected at diagnosis and relapse but was absent in healthy controls and during confirmed remission. Methylation-based deconvolution demonstrated high specificity, with no detectable background signal in controls, and improved performance relative to copy number-based tumor fraction estimation. Longitudinal profiling enabled early molecular detection of relapse and reliable disease monitoring. CONCLUSIONS: We establish a robust, mutation-independent methylation-based liquid biopsy strategy for neuroblastoma that enables accurate, quantitative disease monitoring across all high-risk patients, including those lacking trackable genomic alterations. This approach supports the clinical translation of methylation-based cfDNA deconvolution as a broadly applicable platform for pediatric precision oncology.

Humans↗

PubMed2001

Guidelines on renal cell cancer.

OBJECTIVES: On behalf of the European Association of Urology (EAU), Guidelines for Diagnosis, Therapy and Follow-Up of Renal Cell Carcinoma Patients were established. Criteria for recommendations were evidence based and included aspects of cost-effectiveness and clinical feasibility. METHOD: A systematic literature research using Medline Services was conducted. References were weighted by a panel of experts on renal cell carcinoma (RCC). RESULTS: RCC is characterised by a constant rise in incidence over the last 50 years, with a predominance of men over women and an incidence peak in the 6th and 7th decade. There is no risk factor established and the current TNM system (UICC, 1997) is endorsed for staging purposes. Clinical signs and symptoms of RCC are becoming less frequent, incidental discovery constitutes already a majority of cases. Diagnosis is established by ultrasound and abdominal CT, extension assessment in routine cases is done by chest X-ray. Additional examinations may be required in select cases. The therapy of choice in organ-confined RCC is surgery. Radical tumour nephrectomy is considered as a standard. Efficacy and side-effects of organ-sparing surgery, lymphadenectomy and inclusion/omission of ipsilateral adrenalectomy in selected cases is a matter of ongoing clinical research. In metastatic cases, tumour nephrectomy should only be considered in the context of modern systemic immunotherapy. A follow-up at regular intervals is recommended because certain cases of recurrences may be candidates for surgery and/or immunomodulating therapy. CONCLUSION: A rise in incidence, improved diagnostic procedures, and evolving multimodality therapeutic concepts justify the need for rational guidelines on this most challenging urologic malignancy.

Carcinoma, Renal Cell↗

PubMed2001

Non-Hodgkin's lymphoma after primary Hodgkin's disease in the German Hodgkin's Lymphoma Study Group: incidence, treatment, and prognosis.

PURPOSE: The cumulative incidence for non-Hodgkin lymphoma's (NHL) after primary Hodgkin's disease (HD) ranges between 1% and 6%. To investigate the course of disease for secondary NHL, we retrospectively analyzed patients treated within clinical trials of the German Hodgkin's Lymphoma Study Group (GHSG) since 1981. PATIENTS AND METHODS: From 1981 to 1998, the GHSG conducted three generations of clinical trials for the treatment of primary HD involving a total of 5,406 patients. Reference histology by an expert panel was obtained for 4,104 of the patients. Data on incidence, treatment, and outcome of secondary NHL were updated in March 1999. RESULTS: At first diagnosis of HD, the pathologists rejected 114 (2.1%) of 5,520 cases initially diagnosed as HD and rediagnosed them as primary NHL. Fifty-two (0.9%) of the remaining 5,406 patients developed a secondary NHL. One patient was excluded from further analyses because of insufficient documentation. Six patients had no further therapy because of patient refusal (n = 1) or rapidly progressive disease (n = 5). For the remaining 45 patients, overall response rate was 43% (36% complete response and 7% partial response). The actuarial 2-year freedom from treatment failure (FFTF) and overall survival (OS) for all patients was 24% and 30%, respectively, and for patients with diffuse large-cell lymphoma, it was 28% and 35%, respectively. Time of occurrence of secondary NHL after first diagnosis of HD and variables employed in the age-adjusted International Prognostic Factor Index (IPFI) significantly influenced treatment outcome. CONCLUSION: In the GHSG, the incidence of secondary NHL with 0.9% is relatively low compared with previously reported series. The prognosis of secondary NHL seems dismal and is significantly influenced by time of occurrence and the age-adjusted IPFI. In a subset of patients with secondary NHL, long-term disease-free survival could be achieved.

Actuarial Analysis↗

PubMed2002

Cytohistologic discrepancies: a means to improve pathology practice and patient outcomes.

The use of cytohistologic discrepancies to investigate and reduce error seldom is studied. All gynecologic discrepancies (n = 283; 0.87% and 7.37% of all cytologic and histologic cases, respectively) and nongynecologic discrepancies (n = 146; 2.26% and 0.44% of all cytologic and histologic cases, respectively) for 26 months were classified as sampling or interpretive. Specimen type and pathologist discrepancy percentages, effect of discrepancies on patient outcome, and interobserver agreement of discrepancies were evaluated. Discrepancies were interpretive in 67% and 34% of gynecologic and nongynecologic cases, respectively. Statistically significant associations were seen between individual pathologist and discrepancy percentages. Breast (1.2%) and bronchial (0.8%) cytologic diagnoses had the highest discrepancy percentages. The kappa scores ranged from 0.02 to 0.45 for pairwise agreement of discrepant cases. Of nongynecologic interpretive discrepancies available for review, 63% (27/43) and 14% (6/43) were of no or minor clinical significance, respectively. Cytohistologic correlation is a useful tool to monitor performance and to identify specimen types prone to error.

Biopsy↗

PubMed2001

The cost-effectiveness of magnetic resonance imaging for investigation of the knee joint.

OBJECTIVES: This study considered the role of magnetic resonance imaging (MRI) in the diagnosis of knee injuries in a district general hospital (DGH) setting. The principal objective was to identify whether the use of MRI had a major impact on the clinical management of patients presenting with chronic knee problems, in whom surgery was being considered, whether it reduced overall costs and whether it improved patient outcome. In addition, the research: (1) explored the 'diagnostic accuracy' of initial clinical investigation of the knee by an orthopaedic trainee, consultant knee specialist and consultant radiologist; (2) considered the variability and diagnostic accuracy of interpretations of knee MRI investigations between radiologists; (3) measured the strength of preference for the potential diagnostic/therapeutic impact of knee MRI (i.e. the avoidance of surgery). METHODS - RANDOMISED CONTROLLED TRIAL: The research was based on a single-centre randomised controlled trial conducted at Kent and Canterbury Hospital. Patients attending with knee problems in whom surgery was being considered were recruited from routine orthopaedic clinics. Most patients had been referred by their general practitioner. Patients were randomised to either investigation using an MRI scan (MRI trial arm) or investigation using arthroscopy (no-MRI trial arm). The study investigated the benefits of knee MRI at two levels: diagnostic/therapeutic impact (i.e. avoidance of surgery) and patient outcome (using the Short Form with 36 items and EQ-5D quality-of-life measurement instruments). Quality of life was assessed at baseline and at 6 and 12 months. Costs were assessed from the perspectives of the NHS and patients. All analyses were by intention to treat. METHODS - SUBSTUDIES (INVESTIGATION OF DIAGNOSTIC ACCURACY): For the investigation of diagnostic accuracy of initial clinical investigation, the sample comprised 114 patients recruited in a separate study conducted at St Thomas' Hospital. The sample was drawn from patients presenting at the Accident and Emergency Department with an acute knee injury. All study patients received an MRI scan, but initial diagnosis was made without access to the scan or the radiologist's report. After 12 months, all clinical notes and MRI scans of study patients were reviewed and a final 'reference standard' diagnosis for each patient was reached. Comparison was made between the diagnosis recorded by each clinician (i.e. orthopaedic trainee, knee specialist and consultant radiologist) and the reference diagnosis. METHODS - SUBSTUDIES (INVESTIGATION OF THE GENERALISABILITY OF RESULTS): For this substudy, the MRI images from 80 patients (recruited at St Thomas' Hospital) were interpreted independently by seven consultant radiologists at DGHs and the St Thomas' Hospital MRI radiologist. For each area of the knee, the level of agreement (measured using weighted kappa) between the responses of the eight radiologists and the reference standard diagnosis was assessed. METHODS - SUBSTUDIES (INVESTIGATION OF PREFERENCES): The investigation of potential patient preferences for the diagnostic/therapeutic impact of MRI was explored using a discrete choice conjoint measurement research design. Choices involved selecting between two alternative scenarios described using four attributes, and data were collected from 585 undergraduate sports science students and analysed using a random-effects probit model. RESULTS - RANDOMISED CONTROLLED TRIAL: The trial recruited 118 patients (59 randomly allocated to each arm). The two groups were similar in important respects at baseline. The central finding was of no statistically significant differences between groups in all measures of health outcome, although a trend in favour of the no-MRI group was observed. However, the use of MRI was found to be associated with a positive diagnostic/therapeutic impact: a significantly smaller proportion of patients in the MRI group underwent surgery (MRI = 0.41, no-MRI = 0.71; p = 0.001). There was a similar mean overall NHS cost for both groups. RESULTS - SUBSTUDIES (INVESTIGATION OF DIAGNOSTIC ACCURACY): The exploration of diagnostic accuracy found that, when compared to orthopaedic trainees (44% correct diagnoses) or to radiologists reporting an MRI scan (68% correct diagnoses), the accuracy rate was higher for knee specialists (72% correct diagnoses). RESULTS - SUBSTUDIES (INVESTIGATION OF THE GENERALISABILITY OF RESULTS): This generalisability study indicated that, in general terms, radiologists in DGHs provide accurate interpretations of knee MRI images that are similar to a radiologist at a specialist centre. The one area of the knee for which this did not hold was the lateral collateral ligament. RESULTS - SUBSTUDIES (INVESTIGATION OF PREFERENCES): The central finding for this substudy was that, on average and within the range specified, choices in this group of potential patients were not significantly influenced by variation in the chance of avoiding surgery. CONCLUSIONS - IMPLICATIONS FOR HEALTHCARE: The evidence presented in this report supports the conclusions that the use of MRI in patients presenting at DGHs with chronic knee problems in whom arthroscopy was being considered did not increase NHS costs overall, was not associated with significantly worse outcomes and avoided surgery in a significant proportion of patients. CONCLUSIONS - RECOMMENDATIONS FOR FURTHER RESEARCH (IN PRIORITY ORDER): (1) The trial data demonstrated that the use of MRI in patients with chronic knee problems reduced the need for surgery. However, the link between diagnostic processes and changes in health outcome is indirect and the finding of no-MRI-related effect on health outcome may, therefore, be a consequence of the limited power of the trial. Further research to confirm (or contradict) these findings would be valuable. (2) The investigation of diagnostic accuracy involved comparison with a reference diagnosis established by a panel of two clinical members of the research team. It would be interesting to explore the extent to which the results would differ using an external panel. (3) The result from the preference study, indicating that the potential diagnostic/therapeutic impact of knee MRI was not highly valued, is a surprising finding that would be important to explore in general public or patient populations. (4) The focus for the trial-based aspects of this research was the DGH and patients presenting with chronic knee problems who were being considered for surgery. Care should be taken in generalising from these results to other patient groups (e.g. acute knee injuries) or to other settings (e.g. specialist centres). Further clinical trials would be required in order to answer such questions.

Adolescent↗

PubMed2006

Practice parameters for sublingual immunotherapy.

The efficacy and safety of sublingual immunotherapy (SLIT) are currently supported by clinical trials, meta-analysis and post-marketing surveys. Practice parameters for clinical use of SLIT are proposed here by a panel of Italian specialists, with reference to evidence based criteria. Indications to SLIT include allergic rhinoconjunctivitis, asthma, and isolated conjunctivitis (strength of recommendation: grade A). As to severity of the disease, SLIT is indicated in moderate/severe intermittent rhinitis, persistent rhinitis and mild to moderate asthma (grade D). SLIT may be safely prescribed also in children aged three to five years (grade B), and its use in subjects aged more than 60 years is not prevented when the indications and contraindication are ascertained (grade D). The choice of the allergen to be employed for SLIT should be made in accordance with the combination of clinical history and results of skin prick tests (grade D). Polysensitisation, i.e. the occurrence of multiple positive response does not exclude SLIT, which may be done with the clinically most important allergens (grade D). As to practical administration, co-seasonal, pre co-seasonal, and continuous schedules are available, being the latter recommended for perennial allergens or for pollens with particularly prolonged pollination, such as Parietaria (grade D). For pollens with relatively short pollination, such as grasses and trees (cypress, birch, alder, hazelnut, olive) the pre co-seasonal and perennial schedules are preferred (grade C). The build-up phases suggested by manufacturers can be safely used (grade A), but they can be modified according to the patient's tolerance (grade C). A duration of SLIT of 3-5 years is recommended to ensure a long-lasting clinical effect after the treatment has been terminated (grade C).

Administration, Sublingual↗

PubMed2000

[Can the degree of renal artery stenosis be automatically quantified?].

The objective of the reported study is to validate a computer system, QUASAR, dedicated to the quantification of renal artery stenoses. This system estimates automatically the reference diameter and calculates the minimum diameter to compute a degree of stenosis. A hundred and eighty images of atheromatous stenoses between 10% and 80% were collected from two French independent protocols. For the 49 images of the EMMA protocol, the results from QUASAR were compared with the visual estimation of an initial investigator and with the results from a reference method based on a panel of fixe experienced experts. For the 131 images of the ASTARTE protocol, the results from QUASAR were compared with those from a semi-automatic quantification system and with those from a system based on densitometric analysis. The present work validates QUASAR in a population of narrow atheromatous stenoses (> 50%). In the context of the EMMA protocol, QUASAR is not significantly different from the mean of the fixe experts. It is unbiased and more precise than the estimation of a single investigator. In the context of the ASTARTE protocol, there is no significant difference between the three methods for the stenoses higher than 50%, however, globally, QUASAR surestimates significantly (up to 10%) the degree of stenosis.

Aged↗