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Flow cytometric detection of B-clonal excess in fine needle aspirates for enhanced diagnostic accuracy in non-Hodgkin's lymphoma in adults.

Fine needle aspiration (FNA) cytology is a valuable aid to diagnosis and tumour staging in patients with non-Hodgkin's lymphoma. These tumours are often multicentric and involve sites such as the liver or the spleen which are not easily accessible to surgical biopsy. Particularly with splenic involvement, there is a diagnostic problem of morphologically distinguishing the lymphoma cells in an admixture of normal lymphocytes. Since most lymphomas in adults are of B-cell origin, we studied the diagnostic value of adding a surface immunoglobulin (sIg) light chain analysis to the cytological evaluation of FNAs. B-clonal excess was determined by flow cytometric analysis of the sIg light chain distribution and a monoclonal finding was considered diagnostic of lymphoma. In primary diagnostic procedures the light chain analysis established a diagnosis of lymphoma in 5/14 (36%) aspirates from patients with poorly differentiated tumours. Fine needle aspirates performed as part of staging procedures were morphologically normal or inconclusive in 19 cases; in seven of these (37%) lymphoma involvement was diagnosed by the light chain analysis. Diagnostic precision was enhanced by combining morphological and immunological evaluation of fine needles aspirates in patients with established or suspected non-Hodgkin's lymphoma.

B-Lymphocytes↗

Recombinant DNA technology and its diagnostic applications.

As yet recombinant DNA technology does not appear to have widespread diagnostic application in pathology. However, it does have a useful role to play in specific circumstances in at least three main areas: a it can provide precise diagnostic information about genetic diseases, allowing appropriate counselling, and indicating future directions for research on therapeutic intervention, e.g. gene therapy; b micro-organisms can be identified more sensitively and specifically, in fresh or fixed tissue samples, and their genomes can be analysed in fine detail, providing information relevant to the aetiology, epidemiology and pathogenesis of many diseases; c in tumour pathology the main application so far has been to resolve diagnostic problems associated with leukaemias and lymphomas, when other diagnostic procedures have been inconclusive. Specific chromosomal translocations, involving recognized genes, are particularly amenable to diagnosis by these means. Diagnostic applications to solid tumours are yet to be identified, although significant insights into tumorigenesis have been obtained, and these may ultimately lead to the development of useful markers for prognostic and therapeutic purposes.

Base Sequence↗

Diagnostic accuracy of the care dependency scale.

AIM: This paper reports an investigation of the diagnostic accuracy of the Care Dependency Scale (CDS). BACKGROUND: Assessment tools can be described in terms of diagnostic accuracy, or the ability to correctly classify subjects into clinically relevant subgroups. Diagnostic accuracy can be determined by several techniques as sensitivity, specificity, receiver operating curve analysis and likelihood ratios. METHOD: A cross-sectional design was used with data from 237 patients from two studies. Data were collected using a questionnaire consisting of the CDS and the Barthel Index (BI). The CDS is a relatively new instrument and should be validated by comparison against an established gold standard, in this case the BI. Measures to quantify the validity of diagnostic tests, such as sensitivity, specificity, positive and negative predictive values, prevalence and likelihood ratios were calculated. In addition, the receiver operating characteristics (ROC) curve analysis was used to report the test accuracy of the CDS and to determine an appropriate cut-off point for care dependency detection. FINDINGS: The prevalence in the sample study was very high (84%). The area under the ROC curve for the CDS was 0.81, which indicates moderate diagnostic accuracy. Patients with a CDS sumscore </=68 (rule-out cut-off point) were classified as care dependent, all others as independent. The determination of the appropriate cut-off point was based on sensitivity (0.85) and positive predictive valued (0.90). CONCLUSION: The CDS may be used for to estimate care dependency among hospital patients with various conditions.

Activities of Daily Living↗

Diagnosing the diagnostic process.

Experimental results obtained by examining the diagnostic performance of students and doctors in different medical schools and different cultural environments are presented. The pertinent data were obtained using tests of diagnostic skills based on real cases. The technique requires asking questions (tactics) to obtain the information needed to reach a diagnosis so that the subject becomes an active searcher of information and the final answer is not the only element used to evaluate tactics. The results show significant differences in performance according to medical experience. Experts ask fewer questions than students or less-experienced doctors but maximize the information value by asking them at the proper time in the sequence. New evaluation procedures are described to characterize quantitatively each diagnostic tactic. Experimentally based theoretical considerations are made concerning the prediction and development of diagnostic talent, the structure of diagnostic processes and its training. New approaches to the problem are briefly sketched.

Argentina↗

Diagnostic value of a glass fibre-based histamine analysis for allergy testing in children.

The aim of this study was to compare the diagnostic value of common allergy tests with basophil histamine release in 124 children with symptoms of asthma. The patients were evaluated by case history, skin prick test, RAST-analysis, and basophil histamine release using a glass fibre-based histamine assay to 10 common inhalant allergens. The bronchial provocation test was used as a reference of "true" IgE-mediated asthma. To compare the various diagnostic parameters each absolute test value was classified into a scoring system. The concordance between the tests varied between 85-97%. In general, the best concordance was found between basophil histamine release and RAST. Sensitivity, specificity and predictive values were calculated on the basis of 104 bronchial provocation tests. It was found that histamine release was the best single analysis, followed by RAST and prick testing. The sensitivity of RAST and histamine release was very high (1.00) for pollen and house dust mites. Histamine release showed a predictive value between 0.91 and 1.00 for pollen and house dust mites, thus indicating the possibility of omitting the bronchial provocation test. In the dander group histamine release gave the best sensitivity (0.91), however at the expense of specificity (0.64), whereas RAST and skin prick test gave a specificity of 1.00. In the mould group histamine release also showed the best diagnostic value. The combination of skin testing with histamine release or RAST was of no additional diagnostic help. It is concluded that the glass fibre-based histamine analysis, which makes routine histamine release testing possible, is a reliable diagnostic test in children.

Asthma↗

Unproven diagnostic procedures in IgE-mediated allergic diseases.

A considerable body of literature on therapeutic aspects of complementary and alternative medicine has been published in recent years, but little is known on diagnostic procedures. This short review lists complementary and alternative diagnostic procedures for the diagnosis of allergic diseases and presents an assessment of their usefulness for the daily practice. The review of the literature revealed that neither the determination of specific immunoglobulin G-antibodies in serum, the hair-analysis, the cytotoxic test, kinesiology, iridology, or electrodermal testing represent useful tests for the daily practice. To date, no complementary or alternative diagnostic procedure can be recommended as a meaningful element in the diagnostic work-up of allergic diseases. This is especially true for food allergy: properly performed oral food challenges still represent the gold standard for implementing specific diets in food allergic individuals. Ineffective diagnostic approaches may be costly for the consumer and delay appropriate therapy.

Animals↗

Diagnostic pitfalls in food allergy in children.

Currently, the diagnostic work-up of suspected food allergy includes skin prick tests, the measurement of food specific immunoglobulin E (IgE), and the atopy patch test, and double-blind, placebo-controlled food challenges. However, all of these methods, even double-blind, placebo-controlled food challenges (DBPCFC), may sometimes be misleading. This overview describes several pitfalls for standard diagnostic methods such as problems with irritative skin reactions mimicking IgE-mediated symptoms, the problem of non-IgE-mediated reactions, pitfalls arising from the way foods are prepared or processed, effects of the route of exposure, the role of augmentation factors lowering the threshold value for clinical reactions, the noncomparability of specific IgE decision points, the influence of the timing of diagnostic measures. In addition, the problem of alternative diagnostic measures is discussed. In conclusion, there are several pitfalls in the diagnostic work-up of food allergy, which may be misleading for the physician. Properly performed controlled oral food challenges still represent the gold standard for implementing specific diets in food allergic individuals in order to avoid both unjustified diets, which may lead to severe impairments in growth and development, and to avoid unnecessary symptoms if an underlying food allergy is not correctly identified as a cause for the symptoms of the patient.

Child↗

The diagnostic yield of intravenous urography: a demographic study.

OBJECTIVE: To examine the impact of intravenous urography (IVU) on patient management in unselected patients in an effort to identify groups in which the use of urography could be reduced. PATIENTS AND METHODS: The results of IVU in 235 consecutive unselected patients were assessed prospectively to establish the value of IVU in patient management. Patients were divided into subgroups on the basis of age, sex, presenting symptoms and source of referral. The percentage of examinations with findings affecting patient management was taken as the 'positive diagnostic yield.' Differences between the positive diagnostic yields of IVU in the various groups were examined using the chi 2 test. RESULTS: For all patients the diagnostic yield was 37.4%. In patients over 50 years of age the yield was 46% while below that age the yield fell to 20%. This difference was significant (chi 2 = 13.88, P < 0.001). There were no significant differences between the other defined groups. Specifically, patients referred by general practitioners were as likely to have an IVU abnormality as were patients referred by a hospital practitioner. Patients with painless microscopic haematuria had a lower diagnostic yield (20%) than the other groups examined but this was not significant. CONCLUSION: IVU has a high diagnostic yield in an unselected population. Although the yield is lower in younger patients IVU offers advantages over other techniques in the investigation of urolithiasis--the commonest positive diagnosis in this study. We argue that it should retain its position as the primary investigation for the majority of patients with urological disease, particularly those suffering loin pain or haematuria.

Adolescent↗

Effects of a shared protocol between urologists and general practitioners on referral patterns and initial diagnostic management of men with lower urinary tract symptoms in Italy: the Prostate Destination study.

OBJECTIVE: To assess whether adopting a shared protocol between urologists and general practitioners (GPs) might change diagnostic procedures and referral patterns in the management of men with lower urinary tract symptoms (LUTS). SUBJECTS AND METHODS: Forty-five urological centres and 263 GPs in Italy participated in this prospective study. Procedures adopted by GPs for evaluating five consecutive patients (aged > or = 50 years) were compared before (phase 1) and after (phase 2) implementation of the shared protocol. An evidence-based diagnostic algorithm was developed and approved by participating urologists and presented to local GPs at a training session. Protocol modifications were allowed after discussion with GPs. Direct costs of diagnostic procedures carried out before and after implementing the protocol were calculated from the perspective of the national health service. RESULTS: In all, 903 patients were evaluable in phase 1 and 856 in phase 2. Implementation of the protocol did not change referral patterns, with about half the patients being managed entirely by GPs. The use of a digital rectal examination by GPs increased from 32% to 41%, use of transrectal and suprapubic ultrasonography decreased from 33% to 23% and 53% to 44%, respectively, (all P < 0.001) and use of the International Prostate Symptom Score increased from 4.5% to 23.1% (P < 0.001). Overall, protocol-recommended tests were used more frequently, while those not recommended decreased after implementing the protocol. However, overuse of the tests not recommended (i.e. urine culture and free/total prostate specific antigen ratio) remained high. The mean cost per patient of diagnostic procedures ordered by GPs decreased from Euros 71.82 to Euros 61.93, with Euros 9.9 saved for each patient. CONCLUSION: Our intervention failed to decrease the percentage of cases of LUTS being referred to specialists, but was moderately effective in inducing changes in the diagnostic management by GPs that were indicative of increased compliance with best-practice principles, and produced cost savings of 13.8%.

Aged↗

From clinical observation to long-term monitoring: diagnostic developments in conservative epileptology.

The diagnostic goals in nonsurgical (conservative) epileptology differ from presurgical diagnostic aims. The resulting development of diagnostic methods in a tertiary-level epilepsy center is shown and the major technical and organizational consequences of this difference for diagnostic long-term monitoring (LTM) as opposed to presurgical LTM are investigated. A total of 133 consecutive daytime LTM investigations using radio telemetry were reviewed and seizure parameters such as type, duration, method of seizure detection, and need of mobility were evaluated and compared to presurgical LTM. Compared to presurgical LTM, partial seizures were relatively rare (17.8%) and short epileptic or nonepileptic motor events lasting <1 s, such as myoclonic, atonic, short tonic seizures, spasms, tics, or startle reactions, are frequent (34.9%). Of all seizures, 23% had no or minor ictal EEG changes, subtle symptomatology without signaling by a patient or accompanying person, and could be detected only by continuous online surveillance by an experienced EEG technician. Due to the nature of the patient population in diagnostic LTM, there is an increased need for ictal and interictal mobility (radio telemetry). LTM in conservative epileptology requires more intense human surveillance for seizure detection and increased patient mobility compared to presurgical LTM.

Adolescent↗

Analysis accuracy and susceptibility to faults of Holter functions in diagnostic pacemakers.

The analysis accuracy and susceptibility to faults of the additional diagnostic functions were tested in 16 patients (eight men, eight woman, average age 61.5 +/- 10.8 years, 14 VVI, 2 AAI) with diagnostic pacemakers (Quintech DPG 921). The average observation period was 19.7 months. With 109 follow-up intervals of an average duration of 87 +/- 39 days, this meant an observation period of 25.9 patient years. A stage-by-stage test structure over several intervals of time was applied in order to validate the data acquired through pacemaker Holter functions by means of control ECGs and mathematical test methods. The only fault to occur in the diagnostic functions was a loss of stored data. This was observed in 10% of the follow-up intervals and was on the average 28% (16%-38%) of the total events. Forty-four percent (7/16) of the pacemakers were affected by this malfunction. Our results show that the diagnostic data are certainly correctly acquired. The clinical value of the diagnostic functions is clearly reduced by this potential loss of data.

Adult↗

Comparison of Three Different Protocols for Dobutamine Stress Echocardiography: Does the Addition of Atropine Increase Complications, and Does It Improve Diagnostic Accuracy?

The addition of atropine during dobutamine stress echocardiography (DSE) is increasingly used for detecting coronary artery disease (CAD), but its safety and whether it has added diagnostic accuracy have not been well defined. The aim of this study was to retrospectively compare the complication rate and diagnostic accuracy of three different protocols in the same laboratory. DSE was performed in 1090 patients over a 5-year period. The protocol had included (1) 5' stages up to 30 µg/kg/min of dobutamine in the first 184 patients, (2) 3' stages up to 40 µg/kg/min in the next 274 patients, and (3) 3' stages up to 40 µg/kg/min with atropine, when required in the last 632 patients. A large number of patients (n = 938) underwent coronary angiography within 2 weeks, and 524 patients had a significant coronary stenosis (> 50%). In the whole group of 1090 patients, serious complications developed in 5 patients (one acute myocardial infarction, one sustained ventricular tachycardia, and three prolonged ischemia). Although the incidence was low, there were no detectable differences between protocols. Hypotension, which was defined as a >/= 20 mmHg decrease in systolic blood pressure from the baseline, was observed in 68 patients. Premature ventricular contraction was the most common arrhythmia. The complication rate was similar among three protocols. The diagnostic accuracy for detecting CAD was nearly the same among three protocols (30 µg, 86%; 40 µg, 84%; and 40 µg with atropine, 84%), but the prevalence of CAD was higher with the 30-µg protocol (65%) than the 40-µg protocol (55%) or 40-µg-with-atropine protocol (53%, P < 0.01). In 469 patients without a previous myocardial infarction, the prevalence of CAD was the same (38-42%). Sensitivity increased with more aggressive protocols (71%, 76%, and 84%). However, it was associated with the loss of specificity (92%, 92%, and 85%). Thus, the diagnostic accuracy was similar among groups (84%, 85%, and 84%). In conclusion, the addition of atropine during DSE does not increase the rate of complication compared with previous conservative protocols and shows the same diagnostic accuracy with a small increase in sensitivity at the cost of a small and matched decrease in specificity.

Journal Article↗

The cost-effectiveness of diagnostic testing strategies for Helicobacter pylori.

OBJECTIVE: Several noninvasive methods are now available for diagnosing Helicobacter pylori infection. Because the prevalence of H. pylori infection is variable in patients requiring testing, the optimal testing strategies may vary under different conditions. The aim of this study was to evaluate the cost-effectiveness of competing diagnostic strategies for H. pylori in patients with varying H. pylori prevalence. METHODS: A decision analysis was performed comparing the costs per number of correct diagnoses achieved by alternative sequential testing strategies. Estimates of H. pylori prevalence and test characteristics were derived from a systematic review of the MEDLINE bibliographic database. Cost estimates were derived from the 2000 Medicare Fee Schedule. RESULTS: The enzyme-linked immunosorbent assay (ELISA) test had the lowest cost per correct diagnosis at low (30%), intermediate (60%), and high (90%) prevalence ($90-$95/correct diagnosis), but its diagnostic accuracy was low (80-84%). At low and intermediate prevalence the stool test was more accurate (93%), with an average cost of $126-$127 per correct diagnosis. Additional confirmatory testing of positive or negative tests increased the diagnostic accuracy of the stool test, but had high incremental costs. ELISA testing was preferable when prevalence rates were very high (90%), and using a confirmatory urea breath test for negative ELISA tests increased the diagnostic accuracy to 96%, with modest incremental costs. If the cost of the breath test was <$50 or if the cost of the stool test is >$82, breath testing became preferable to stool testing. If the cost of the stool test fell to <$20, it became preferable to ELISA. Similarly, if the cost of the ELISA serology was >$39 then stool testing became preferable at all prevalence rates. Fingerstick whole blood tests were not cost-effective. CONCLUSIONS: The choice of an initial test for H. pylori detection depends on the prevalence of H. pylori infection and the value placed on increased diagnostic accuracy. Although ELISA results in the lowest cost-effectiveness ratios, in patients at low-intermediate pretest probability of infection, the stool test provides increased accuracy, with modest incremental costs.

Cost-Benefit Analysis↗

The utility of diagnostic tests in irritable bowel syndrome patients: a systematic review.

OBJECTIVE: The aim of this study was to determine the pretest probability of organic GI disease and the accuracy of diagnostic tests for organic GI disease in patients who meet symptom-based criteria for irritable bowel syndrome (IBS). METHODS: After a comprehensive literature search for studies examining the accuracy of diagnostic tests for organic GI disease among patients who meet symptom-based criteria for IBS, two independent observers qualitatively assessed the methodology of selected studies and extracted data. Data on the pretest probability of organic GI disease in this population and the accuracy of currently recommended diagnostic tests were converted to descriptive tables. RESULTS: Among patients meeting symptom-based criteria for IBS, the pretest probability of inflammatory bowel disease, colorectal cancer, or infectious diarrhea is less than 1%. Currently recommended diagnostic tests rarely identify organic GI disease in patients fulfilling symptom-based criteria for IBS. However, the pretest probability of celiac disease in patients meeting symptom-based criteria for IBS was 10 times higher than the prevalence of celiac disease in the general population. CONCLUSIONS: There is insufficient evidence to recommend the routine performance of a standardized battery of diagnostic tests in patients who meet symptom-based criteria for IBS. Based upon the increased pretest probability of celiac disease, routine performance of serological tests for celiac disease may be useful in this patient population, though additional study is needed in this area.

Autoantibodies↗

Clinical diagnosis of Parkinson's disease. Proposal of diagnostic subgroups classified at different levels of confidence.

The objective of this paper is to evaluate the accuracy of conventional diagnostic criteria for Parkinson's disease and give an overview of alternative causes to parkinsonian syndromes. We also propose a new approach to the clinical diagnosis of Parkinson's disease, which may improve the diagnostic accuracy. The available information on autopsy findings in patients clinically diagnosed as Parkinson's disease shows that 20 to 30% of these patients do not have the typical neuropathological features with Lewy bodies and cell loss in the substantia nigra. The use of selected additional clinical criteria improves the diagnostic accuracy, however, at the cost of rejecting a rather large group of patients with idiopathic disease verified by autopsy. Based on this fact and a review of the literature on parkinsonian syndromes that may be confused with idiopathic Parkinson's disease, we propose criteria for diagnostic subgroups of the disease classified at different levels of confidence. The suggested diagnostic subgroups are clinical definite, probable and possible Parkinson's disease with a decreasing level of specificity and an increasing level of sensitivity in the different patient categories. The clinical features given special importance in this classification includes presence of resting tremor, asymmetrical disease, response to dopamine agonism and presence of atypical clinical features like dementia and clinical autonomic failure at onset and pyramidal or cerebellar signs at examination. In addition, a history indicating possible etiology for another parkinsonian syndrome will exclude the diagnosis.

Diagnosis, Differential↗

Validation of diagnostic criteria for solitary cerebral cysticercus granuloma in patients presenting with seizures.

OBJECTIVE: To evaluate a set of clinical and computed tomographic (CT) criteria (previously described by us) to predict the diagnosis of a solitary cerebral cysticercus granuloma (SCCG) at initial presentation, in patients presenting with seizures. MATERIAL AND METHODS: The diagnostic criteria were applied prospectively to patients presenting with seizures and solitary lesion on the CT scan. The clinical diagnostic criteria were as follows: seizures should be the presenting complaint; there should be no evidence of persistent raised intracranial pressure, progressive neurological deficit or an active systemic disease. The CT diagnostic criteria were: evidence of a solitary contrast enhancing lesion measuring 20 mm or less in its maximal dimension without a shift of the midline structures due to the surrounding oedema. A diagnosis of SCCG was made only when all the clinical and CT criteria were fulfilled. Over a period of 36 months, we managed 401 patients presenting with seizures and a solitary mass on the CT scan; 215 met the criteria for the diagnosis of an SCCG. RESULTS: Of the 215 patients initially diagnosed to have an SCCG, 197 were ultimately determined to have that diagnosis (true positive diagnosis) while 16 were excluded because of lack of follow-up CT assessment. Two of the 215 patients with the initial diagnosis of an SCCG subsequently had histological diagnosis of a secondary metastasis and a pyogenic abscess (false positive diagnosis). Our set of diagnostic criteria for SCCG had a sensitivity of 99.5%; specificity of 98.9%; a positive predictive value of 99%; and a negative predictive value of 99.5%. The likelihood ratios for the positive and negative tests were 92.99 and 0.005 respectively. CONCLUSIONS: Our diagnostic criteria help in not only accurately identifying an SCCG but also in differentiating it from a solitary tuberculoma and other brain masses. However, confirmation of the diagnosis of an SCCG is only obtained at follow-up evaluation and therefore careful clinical and CT re-evaluation is essential in all patients initially diagnosed to have an SCCG.

Albendazole↗

The reliability of child psychiatric diagnosis. A comparison among Danish child psychiatrists of traditional diagnoses and a multiaxial diagnostic system.

The study was conducted to compare an experimental multiaxial diagnostic system (MAS) with traditional multicategorical diagnoses in child psychiatric work. Sixteen written case histories were circulated to 21 child psychiatrists, who made diagnoses independently of one another, using two different diagnostic systems. Diagnostic reliability was measured as percentage of interrater agreement. The highest diagnostic reliability was obtained in psychotic disorders, the lowest in personality disorders. The MAS implied improved diagnostic reliability of mental retardation, somatic disorders and developmental disorders. Adjustment reaction (reactio maladaptiva) was the diagnosis most commonly used, but with varying reliability in both systems. The reliability of the socio-economic and psychosocial axes were generally high.

Adjustment Disorders↗

Dental caries paradigms in diagnosis and diagnostic research.

In this article, the fundamentals of caries diagnosis are reviewed from the three component perspectives, namely the strategy, the logics, and the tactics. Strategy concerns the objectives of the diagnostic process (i.e. why we diagnose caries). The logics describe how we assemble and evaluate the information collected and how this leads to an assessment of diagnostic value. Finally, tactics are about how we collect the information necessary to arrive at a correct diagnosis. We argue that the hitherto-dominant essentialistic caries paradigm should be replaced by a nominalistic caries concept. This allows us to circumvent the problem of a lack of a caries gold standard and to proceed in caries-diagnostic research to find the diagnostic methods that result in the best health outcomes for our patients. We also demonstrate the limitations of the medical model when attempting to understand caries diagnosis, and adhere to the Bader & Shugars caries script model. It is concluded that the current caries profile, characterized by lower prevalence and extent, and slower progression, has increased the need for an academic strengthening of the dental curriculum with respect to diagnostic reasoning and clinical decision-making processes.

Decision Making↗