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Background: “Diagnostic accuracy” refers to the ability of medical tests to provide accurate information about diagnosis, prognosis, risk of disease, and other clinical issues. Published reports on diagnostic accuracy of medical tests frequently fail to adhere to minimal clinical epidemiological standards, and such failures lead to overly optimistic assessments of evaluated tests. Our aim was to enumerate key items for inclusion in published reports on diagnostic accuracy, with a related aim of making the reports more useful for systematic reviews. Methods: We examined published reports on shortcomings of studies of diagnostic accuracy. We prepared an initial draft of a checklist to address common errors and presented it at a meeting of editors. After incorporation of comments from editors, we published a revised version in Clinical Chemistry in 1997 for comment from readers. One of us (E.M.) additionally circulated copies of the draft to methodologists and others interested in Evidence-Based Medicine. We updated the checklist with input from these sources. Results: The updated document lists items for inclusion in the title, abstract, methods, results, and discussion sections of published papers. Depending on the nature of the study, the total number of items for a single paper is ∼40. We invite comments on this document, which is freely available at Clinical Chemistry Online, where it can accessed readily from the Table of Contents for the July 2000 issue at www.clinchem.org/content/vol46/issue7/. Comments (eLetters) can be posted there for general reading. Conclusions: The suggested revisions incorporated in this report appear useful to ensure inclusion of additional information that can allow assessment of the validity of the conclusions and the applicability of the study in other settings. The list can be useful in formulating guidelines and a checklist, which will require testing by authors and study of their effect on published studies of diagnostic accuracy.

Patients with Type II (non-insulin-dependent) diabetes mellitus have an increased risk of cardiovascular and all-cause mortality compared to the background population [1,2]. Microalbuminuria is a well-known predictor of increased mortality in patients with Type II diabetes [2±6]. The excess mortality is mainly caused by cardiovascular diseases [1,2,6].Orosomucoid is a glycoprotein (41 000 M r , content of carbohydrate 42 %) with a low isoelectric point of 2.7 [7]. Orosomucoid is synthesized in the liver and its serum concentrations are raised in conditions of inflammation and tissue repair [8]. The specific function of the protein is not known. In renal physiological investigations orosomucoid has been classified as a marker of increased glomerular permeability [9]. Diabetologia (2002) Abstract Aims/hypothesis. Urinary orosomucoid excretion rate is increased in a substantial proportion of patients with Type II (non-insulin-dependent) diabetes mellitus and normal urinary albumin excretion rate. The aim of this study was to determine whether increased urinary orosomucoid excretion rate is predictive of increased mortality in patients with Type II diabetes.Methods. In a cohort study including 430 patients with Type II diabetes, baseline urinary samples were analysed for orosomucoid and albumin. Mean follow-up was 2.4 years. Results. We found that 188 (44 %) patients had normal and 242 (56 %) patients had increased urinary orosomucoid excretion rates. During the study period 41 patients died; out of these 23 patients died of cardiovascular diseases. Odds ratio for all-cause mortality was 2.50 (95 % CI 1.00±6.22) and odds ratio for cardiovascular mortality was 9.81 (1.31±73.6) having increased urinary orosomucoid excretion rate at baseline (odds ratios adjusted for age, sex, duration of diabetes, cardiovascular diseases, weight, medication, HbA 1 c , plasma creatinine and urinary albumin excretion rate). Urinary albumin excretion rate was an independent predictor of all-cause mortality when urinary orosomucoid excretion rate was not included in the analysis. Subgroup analysis revealed that 39 % of the patients with normal urinary albumin excretion rate (n = 251) had increased urinary orosomucoid excretion rates and that these patients had a higher cardiovascular mortality (p = 0.007) than patients with normal urinary albumin excretion rate and normal urinary orosomucoid excretion rates. Conclusion/interpretation. We found that urinary orosomucoid excretion rate predicted all-cause and cardiovascular mortality in patients with Type II diabetes independently from other risk factors. [Diabetologia (2002)

Background: Inflammation-associated proteinuria in acute, nonrenal disease is a common but poorly understood phenomenon. We performed an observational study of the urinary excretion of orosomucoid (␣ 1 -acid glycoprotein), albumin, ␣ 1 -microglobulin (protein HC), and IgG to obtain quantitative and temporal data on these 4 proteins. Methods: Urine samples were collected at daily intervals for up to 23 days from 6 patients with surgeryinduced inflammation and at hourly intervals for a 24-h period from 7 sepsis patients. Urinary protein concentrations were assessed by immunoturbidimetry. Results: During surgery-induced inflammation, the increase and decrease in orosomucoid excretion mirrored changes in plasma C-reactive protein. Values for all 4 urinary proteins were increased in sepsis patients. The observed maximum increases in urinary protein excretion relative to the upper reference values were 280-fold for orosomucoid, 98-fold for ␣ 1 -microglobulin, 33-fold for albumin, and 26-fold for IgG. Conclusions: Orosomucoid, usually present in plasma and urine in much lower concentrations than albumin, is increased in urine to concentrations equal to or higher than albumin in proteinuria associated with acute inflammation. The pathophysiologic mechanisms responsible for this markedly increased excretion are unknown. Monitoring of urinary excretion of orosomucoid and other specific proteins, expressed as protein/creatinine ratios, may provide a window for clinically rele-

Aims/hypothesis: To study whether urinary orosomucoid excretion rate (UOER) predicts mortality in normoalbuminuric patients with diabetes at 5 years of follow-up, and to investigate the relationship between orosomucoid in serum and urine. Methods: A cohort of 578 patients with diabetes (430 type 2, 148 type 1) was followed prospectively for an average of 5 years. UOER was measured in timed overnight urine samples. Results: Eightytwo patients with type 2 diabetes and 17 patients with type 1 diabetes died. Among patients with type 2 diabetes, 251 (58%) had normoalbuminuria; increased UOER independently predicted cardiovascular mortality (OR 4.94, 95% CI 1.60−15.22; p<0.006) in those with normoalbuminuria and in the entire cohort of patients with type 2 diabetes (odds ratio 3.63, 95% CI 1.50−8.81; p<0.005). Patients with increased UOER had a higher all-cause mortality than those with normal UOER (log-rank test, p<0.001 for type 2 patients; p<0.04 for type 1 patients). In patients with type 1 diabetes, there were five cardiovascular deaths and no significant predictive value of UOER. Patients with increased UOER had a subclinical increase in serum orosomucoid. Conclusion/interpretation: Increased UOER was an independent, powerful predictor of cardiovascular mortality in normoalbuminuric patients with type 2 diabetes and in the entire cohort of patients with type 2 diabetes. There were indications of UOER as being a valuable marker in type 1 diabetes that showed differences in survival between patients with normal versus increased UOER. Serum orosomucoid was associated with UOER; UOER may be a marker of lowgrade inflammation in patients with diabetes.

Asymptomatic patients with type 2 diabetes and increased UOER displayed signs of chronic low-grade inflammation and endothelial dysfunction. UOER was independently related to markers of proinflammation and endothelial dysfunction in patients with type 2 diabetes. The previously shown relation between increased UOER and cardiovascular mortality is proposed to be caused by chronic low-grade inflammation and early endothelial dysfunction.

The present study was undertaken to investigate the effect of adrenergic agents on secretion of amylase from the salivary glands in vivo. Saliva was collected from the distal oesophagus in conscious rats. Adrenaline increased the concentration of amylase in saliva and serum significantly. The result of infusion of alpha- and beta-adrenergic antagonists as well as noradrenaline and isoproterenol showed that secretion of salivary amylase is predominantly mediated by stimulation of beta-adrenergic receptors, especially of the beta₁-subtype. Investigation of the isoenzyme pattern in saliva, pancreatic juice and serum demonstrated that the major component in serum is salivary amylase. This study has shown that beta-adrenergic agents stimulate secretion of amylase from the salivary glands in rats. Though the secretion is mainly exocrine small amounts of amylase is found in serum, which seems to originate from the salivary glands.

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