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PubMed2005

Diagnostic precision and accuracy in interpretation of specimens from cancer screening programs.

Few areas in modern medicine provide a better example of evidence-based data than the anatomic pathologists' classification of fully developed malignancies. Beginning with the Papanicolaou (Pap) smear, morphologic tools also were applied to specimens obtained in cancer screening programs directed at large, asymptomatic patient populations. The Papanicolaou test was quickly responsible for a reduction in the incidence of invasive squamous cell carcinoma of the cervix, proving the concept that screening could interdict the development of advanced malignancy. Other screening programs followed the Papanicolaou test initiative, producing a revolutionary change in the specimens submitted to pathologists. Cancer screening generates specimens containing morphologic deviations from normal that are thought to put currently healthy patients at risk of future malignancy. However, translating morphologic findings in such samples into risk estimates raises a number of statistical and ethical problems. When diagnostic thresholds are set to favor specificity, unwanted false-negative results accrue. Conversely, aiming at sensitivity over specificity is associated with biologically false-positive results, which are likewise undesirable. Pathologists interpreting these specimens find themselves facing a screening paradox. These screening programs attempt to discover the very earliest changes of neoplastic transformation, but these same earliest changes are inherently the most difficult to identify with precision and accuracy. This paper discusses these challenges.

Data Interpretation, Statistical↗
PubMed2004

Creating a pandemic of prediabetes: the proposed new diagnostic criteria for impaired fasting glycaemia.

AIMS/HYPOTHESIS: In November 2003 the American Diabetes Association expert committee on the diagnosis and classification of diabetes mellitus suggested a revision of the diagnostic criteria for IFG, lowering the diagnostic threshold from 6.1 to 5.6 mmol/l. The aim of the present study was to evaluate the consequences of this change with respect to: (i) the prevalence of IFG in five different countries; (ii) the concordance between IFG and IGT (classification of individuals); and (iii) the cardiovascular risk profile of these groups. Finally we discuss the likelihood that intervention for cardiovascular risk and prevention strategies developed for individuals with IGT are applicable to subjects with IFG. METHODS: The first part of the study is based on the population-based Danish Inter99 study, where 6265 individuals, aged 30 to 60 years and without previously diagnosed diabetes, underwent an oral glucose tolerance test. The second part is based on the DETECT-2 project, in which studies from China, India, France and USA were used to analyse the impact of the proposed revision of the diagnostic criteria in different ethnic groups. RESULTS: The proposed change in diagnostic criteria would increase the prevalence of IFG in Denmark from 11.8 to 37.6%. The proposed IFG category would identify 60.0% of all subjects with IGT compared to 29.2% with the old criteria, but among individuals with the new IFG category only 18.5% would also have IGT. Individuals with isolated IFG had lower insulin levels and a lower cardiovascular risk profile with the proposed criteria compared with the current WHO criteria. Data from the DETECT-2 study confirmed the marked increase in the prevalence of IFG, and the estimated number of individuals in the age range 40 to 64 years with IFG in urban India, urban China and the USA would increase by 78%, 135% and 193% respectively. CONCLUSIONS/INTERPRETATION: The proposed revised diagnostic criteria will lead to a dramatic increase in the prevalence of IFG, but the concordance rate between IFG and IGT remains low. This new IFG group will have a more favourable cardiovascular risk profile than the current IFG group as defined by the WHO. This seriously questions whether the existing intervention strategies are applicable to the new category of individuals with IFG.

Adult↗
PubMed2003

Who are the comorbid adolescents? Agreement between psychiatric diagnosis, youth, parent, and teacher report.

The investigators examined the rates of psychiatric comorbidity for externalizing and internalizing behavior problems, using semistructured diagnostic interview and parent, teacher, and youth report on the Achenbach checklists. The study also evaluated the effects of conjunctive, compensatory, and disjunctive data combination strategies. Using the same data and identical diagnostic thresholds, between 5 and 74% of 189 youths presenting to an outpatient clinic were identified as having comorbid internalizing and externalizing problems. Parent report and semistructured interview indicated the highest comorbidity rates. Despite good cross-source agreement (rs .29-.58), there was very little agreement about which specific youths presented with comorbid internalizing and externalizing problems (kappas .14-.40). Results also indicate that single DSM-IV disorders, such as bipolar disorder, can manifest "comorbid" patterns of behavior problems on checklists.

Adolescent↗
PubMed2003

Agreement and error rates using blinded review to evaluate surgical pathology of biopsy material.

Blinded review has been shown to be an excellent method to detect disagreements and errors and improve performance in gynecologic cytology. Preliminary studies suggest it may be valuable in surgical pathology. We reviewed 5,000 sequential outpatient surgical pathology biopsy cases without knowledge of the original diagnosis or history and compared the results with those of the original diagnosis. Complete agreement was obtained in 91.12% of cases. The technique of blinded review of surgical pathology biopsy material had a sensitivity of more than 99%, failing to identify an abnormality in 19 cases. Although there was a significant level of diagnostic disagreement (444 cases), primarily due to differences in diagnostic thresholds (292 cases), diagnoses that resulted in a change in the original report (true errors) were present in only 5 cases, and only 4 were clinically significant. This clinically significant error rate of 0.08% is significantly lower than previously published error rates. Blinded review is a sensitive (99%) and effective method to identify areas of disagreement and errors in surgical pathology biopsy material. The relatively high rate of disagreement found with blinded review coupled with the very low rate of error highlights the substantial potential for bias in nonblinded reviews.

Biopsy↗
PubMed2006

Minor depression in adolescence: phenomenology and clinical correlates.

BACKGROUND: Depressions that fail to meet the diagnostic criteria for major depressive disorder (MDD) may be underdiagnosed and undertreated in adolescent population. Traditionally, they are not considered as serious conditions and the phenomenological nature and clinical correlates of these disorders are largely unknown. In the present study, we used a large, representative and age-standardized sample of adolescents to examine the phenomenology and clinical correlates of minor depression, a poorly understood condition included in the category of Depressive Disorder Not Otherwise Specified in Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition-Text Revised (DSM-IV-TR). METHODS: 909 girls and 945 boys, with mean age of 14, were interviewed by professionals using the Semi-Structured Assessment for the Genetics of Alcoholism (SSAGA). RESULTS: Although clearly milder condition than MDD, minor depression was associated with marked suicidal thoughts, plans and attempts, recurrences and a high degree of comorbidity. At this early age, despite that 14% of adolescents under 15 had suffered from depressive conditions with severe clinical implications, most of them failing to meet the diagnostic threshold for MDD, only 1.7% had received any psychiatric treatment. 40% of depressive adolescents who had attempted suicide had no contact with mental health services. LIMITATIONS: Analyzed in a cross-sectional setting, no conclusions about long-term implications could be made. CONCLUSIONS: The results highlight the clinical and public health significance of non-MDD depressions, e.g. minor depression, which need to be more carefully identified and treated at early age.

Adolescent↗
PubMed1996

Adenosine deaminase (ADA) isoenzyme analysis in pleural effusions: diagnostic role, and relevance to the origin of increased ADA in tuberculous pleurisy.

The rise in adenosine deaminase (ADA) activity in the pleural fluid of tuberculous pleurisy patients, though used for diagnosis, is of unknown origin. In this work, we determined ADA activity and the activities of 2'-deoxyadenosine deaminase and ADA-2 in 350 patients. We also considered whether the results throw light on the origin of high pleural fluid ADA in tuberculous pleurisy and estimated the diagnostic efficiency of 2'-deoxyadenosine deaminase, ADA-2 and total ADA activities with and without the inclusion of the 2'-deoxyadenosine deaminase/ADA activity ratio in a combined criterion. The 350 pleural effusions were classified by previously established criteria as transudates (60 males/18 females) or as tuberculous (49 males/27 females), neoplastic (50 males/39 females), parapneumonic (36 males/19 females), empyematous (11 males/3 females), or miscellaneous (25 males/13 females) exudates. Total ADA, ADA-2 and 2'-deoxyadenosine deaminase activities were, respectively, 127.5 +/- 2.9, 103 +/- 29.5 and 42.8 +/- 14 U.L-1 in tuberculous exudates. With diagnostic thresholds of 47, 40 and 22 U.L-1 respectively, the sensitivities of ADA, ADA-2 and 2'-deoxyadenosine deaminase for tuberculosis were 100, 100 and 95%; their specificities 91, 96 and 92%; and their efficiencies 93, 97 and 93%, respectively. One hundred and one effusions (all 76 tuberculous, 12 neoplastic, 4 parapneumonic and 9 empyematous exudates) had total ADA levels > 47 U.L-1; of these, 8 neoplastic, 1 parapneumonic and all the tuberculous exudates had a 2'-deoxyadenosine deaminase/ADA activity ratio < 0.49. The criterion of simultaneously having ADA > 47 U.L-1, ADA-2 > 40 U.L-1 and a 2'-deoxyadenosine deaminase/ADA activity ratio < 0.49 was satisfied by all the tuberculous effusions but only eight others (all neoplastic) (sensitivity 100%, specificity 97%, efficiency 98%). We conclude that: 1) high total ADA activity in tuberculous pleural effusions is due mainly to an increase in ADA-2, and, therefore, originated from the only known source monocytes and macrophages; 2) ADA-2 was a more efficient diagnostic marker of tuberculous pleurisy than total ADA activity, although the difference was not statistically significant; and 3) among effusions with high total ADA the 2'-deoxyadenosine deaminase/ADA activity ratio differentiates tuberculous effusions from empyemas and parapneumonic effusions, but fails to discriminate well between tuberculous and neoplastic effusions.

Adenosine Deaminase↗
PubMed2002

Gender differences in depression. Epidemiological findings from the European DEPRES I and II studies.

BACKGROUND: While there is ample evidence that the prevalence rates for major depressive disorder (MDD) in the general population are higher in women than in men, there is little data on gender differences as regard to symptoms, causal attribution, help-seeking, coping, or the consequences of depression. METHOD: The large DEPRES Study dataset covering representative population samples of six European countries (wave I: 38,434 men and 40,024 women; wave II: 563 men and 1321 women treated for depression) was analyzed for gender differences. RESULTS: In wave I marked gender differences were found in the six-month prevalence rate for major depression but less so for minor depression; the gender differences for major depression persisted across all age groups. Even after stratification by clinically significant impairment and paid employment status, men reported fewer symptoms than women; as a consequence, men reached the diagnostic threshold less often. In wave II there were clear gender differences in causal attribution and in coping. Men coped by increasing their sports activity and consumption of alcohol and women through emotional release and religion. Women felt the effects of depression in their quality of sleep and general health, whereas men felt it more in their ability to work. LIMITATIONS: The second wave of the study comprises treated depressives only and may be less representative than the first wave.

Adaptation, Psychological↗
PubMed2005

Changing the definition of impaired fasting glucose: impact on the classification of individuals and risk definition.

OBJECTIVE: This study evaluates the impact of lowering the diagnostic threshold for impaired fasting glucose (IFG) from 6.1 to 5.6 mmol/l as proposed by the American Diabetes Association (ADA) on the prevalence of the condition, classification of individuals, and risk definition. RESEARCH DESIGN AND METHODS: A total of 1,285 employees of the Italian Telephone Company aged 35-59 years without known diabetes underwent an oral glucose tolerance test (OGTT). BMI, serum cholesterol, triglycerides, and blood pressure were measured. Medication use was recorded. RESULTS: With the new ADA criterion, the proportion of people diagnosed with IFG increased from 3.2 to 9.7%. The newly proposed IFG category identified 41% of all subjects with impaired glucose tolerance (IGT) compared with 16.2% identified with the use of the World Health Organization criterion for IFG; the improvement in accuracy has been achieved at the cost of classifying more previously "normal" subjects as having IFG (from 2.3 to 7.3%). Both IFG and IGT were associated with an unfavorable risk profile for diabetes and cardiovascular disease, with a higher estimated risk for IGT than IFG. CONCLUSIONS: Even with the revised diagnostic criterion, IFG and IGT identify distinct groups that have a different background risk. The cost/benefit of preventive measures tested in people with IGT may not apply to the new IFG category.

Adult↗
PubMed2001

Diabetes complicating pregnancy.

Despite the well-documented relationship between morbidity in pregnancy and pregestational maternal diabetes, the corrected perinatal outcome is, in most series, equal to or better than that of the general reference obstetric population. No single aspect or element of contemporary management is responsible for this improvement; rather, a combination of interventions seems responsible. Targeting delivery early in term, improved compliance, better glycemic control during pregnancy, improved control at conception, improved neonatal care, family planning, and early screening for fetal abnormalities all likely contribute to improved outcome. The currently observed rates of perinatal mortality suggest that an irreducible minimum mortality rate may be reached; however, large disparities in access to care and treatment continue to result in a wide range in rates of morbidity and mortality, a fact that pertains to outcomes in general as well as to pregnancies complicated by diabetes. The identification of women with lesser degrees of hyperglycemia as diabetic by lowering the thresholds for glucose tolerance test abnormality suggests an importance of the diagnosis that is not supported by evidence of either related morbidity or therapeutic benefit. The extrapolation of risk to women with lesser degrees of hyperglycemia seems to have little basis, and the management of women with mild glucose intolerance as if they had overt diabetes is unwarranted. The excess of resources dedicated to the identification and monitoring of an increasing number of women with mild abnormalities of glucose metabolism should prompt a reevaluation of these practices. Perinatal benefits of this expenditure are difficult to document or nonexistent, and there is a predictable increase in iatrogenic morbidities associated with the diagnosis. The exception in the most recent recommendations is the addition of a random glucose measure to screen for the rare women with overt undiagnosed diabetes who presents for prenatal care, because these women are at increased risk of morbidities related to diabetes. A curious statement was made in the summary and recommendations of the fourth International Congress on Gestational Diabetes: "There remains a compelling need to develop diagnostic criteria for GDM [gestational diabetes mellitus] that are based on the specific relationships between hyperglycemia and risk of adverse outcome." If these relationships are undefined, what is the import of the diagnosis? At the author's center, application of the new diagnostic thresholds for the diagnosis of gestational diabetes mellitus has increased the incidence to over 6%. Without a clear expectation of benefit, this increase represents an unsupportable investment of resources. What are the prospects for improving understanding of the relationships between glucose intolerance and pregnancy risks? The direction of new guidelines and recommendations seems to be moving away from resolution of the relationships. The new criteria result in the diagnosis of gestational diabetes in an increasing number of women who were previously normal. It is easier to differentiate women at an extreme of hyperglycemia from normal. Investigations will be even less able to identify attributable effects of glucose intolerance in pregnancy with the inclusion of women with lesser degrees of hyperglycemia. As evidenced in O'Sullivan's original series, women with fasting hyperglycemia in pregnancy are still presumed to be at increased risk of fetal death. This risk factor remains important in clinical management if insulin treatment, fetal surveillance, and early term delivery can reduce the risk of fetal loss. At the author's center, the relationships among outpatient measures of fasting glycemia, glucose tolerance testing results, and perinatal outcomes are evaluated. Preliminary results suggest that fasting glycemia measured at the time of a 50-g glucose tolerance test is significantly correlated with and as sensitive and predictive of morbidity as the glucose tolerance test diagnosis of gestational diabetes. If these results are confirmed, it will be difficult to rationalize continued glucose tolerance testing.

Delivery, Obstetric↗
PubMed2003

Clinical significance of eosinophils in suspicious or borderline renal allograft biopsies.

AIMS: Renal allograft biopsies play a critical role in renal transplantation. Acute rejection characterized by tubulitis and intimitis is of primary concern. There is an association between eosinophilic infiltrates and irreversible acute rejection; however, the significance of eosinophils in biopsies that fall short of the diagnostic threshold for acute rejection has not been well studied. This report describes clinical course, treatment and long-term outcome of 5 transplant recipients with biopsy histology that showed borderline changes associated with eosinophilic infiltrates. METHODS: Clinical records were selected for review on the basis of biopsy histology satisfying the following criteria: presence of interstitial infiltrates with eosinophils, absence of definitive criteria for acute rejection and absence of findings suggestive of infection or cyclosporine toxicity. RESULTS: All identified biopsies occurred within the first month of transplantation, and histology showed varying degrees of patchy mononuclear cell infiltrates composed of lymphocytes, with eosinophilic infiltrates, but no evidence of acute rejection based on Banff criteria. These patients were taking trimethoprim-sulfamethoxazole and ranitidine at the time of biopsy. Serum creatinine returned to baseline levels in each case after stopping both drugs, and remained stable during the duration of follow-up without any documented episode of acute rejection. No patient received specific therapy for acute rejection. CONCLUSION: This report suggests that independent of decisions on treatment with high-dose steroids or anti-lymphocyte antibody preparations, the management algorithm should include stopping drugs associated with acute interstitial nephritis when non-diagnostic biopsies show eosinophilic infiltrates.

Adult↗
PubMed1997

The role and clinical significance of subsyndromal depressive symptoms (SSD) in unipolar major depressive disorder.

Analyses conducted in 10,526 community respondents investigated by the NIMH Epidemiological Catchment Area (ECA) Program, revealed the 1-month point prevalence of depressive symptoms and disorders in the general population, at the first ECA interview (Wave 1) to be 10%, as follows: 2.3% major depressive disorder (MDD); 2.3% dysthmic disorder (DD); 1.5% minor depressive disorder (MinD); and 3.9% subsyndromal depressive symptoms (SSD, defined as two or more depressive symptoms beneath the diagnostic threshold of MinD, DD or MDD). There appears to be two classes of SSD in this community sample: first, SSD, which occurred as an integral component of the course of unipolar major depressive disorder (MDD); and, second, SSD occurring spontaneously in non-unipolar depressed community subjects. In the first instance, SSD was frequently prodromal to episodes of MinD or MDD or residual to resolving episodes. Analyses also support the conclusion that SSD is a clinically significant, interepisode, depressive subtype of unipolar MDD, since SDD is associated with harmful dysfunction in five of six measures of adverse outcome, has a significantly increased prevalence of past histories of major depressive episodes, and an elevated lifetime prevalence of suicide attempts. Comparison of subsyndromal depressive symptomatology or depressive disorder diagnoses at Wave 1 with diagnoses obtained, 1 year later, at the Wave 2 interview, confirm the persistent and chronic nature of depression in this large representative sample of community respondents, in which 71% of subjects with depressive symptoms or disorders at Wave 1 continued to be symptomatic at Wave 2. In addition, subjects experienced a surprising degree of change in depressive symptom and disorder diagnoses during the 1-year observational window between Wave 1 and Wave 2, in which a remarkable percentage of individuals, who began the year in a depressive symptom or disorder diagnostic category, ended the year in another. This has led us to hypothesize that the typical clinical picture of unipolar MDD is dynamic and pleomorphic in nature, characterized by substantial symptomatic fluidity, in which patients frequently change diagnoses from one depressive subtype to another during their courses of illness.

Adolescent↗
PubMed2004

Conventional measures underestimate glycaemia in cystic fibrosis patients.

AIMS: Diabetes mellitus is an increasingly important complication of cystic fibrosis (CF). The association with increased morbidity of cystic fibrosis-related diabetes (CFRD) has emphasized the need for accurate monitoring of glycaemia in all CF patients. The diagnosis has relied on conventional thresholds in an oral glucose tolerance test (OGTT) derived from epidemiological studies in non-CF subjects. However, it has not been established if these values are equivalent in CF and non-CF populations. METHODS: We compared glycaemia in 21 non-diabetic CF subjects with 21-age and BMI-matched non-CF controls using HbA(1c), OGTT and a subcutaneous continuous glucose monitoring system (CGMS) that measures interstitial glucose levels. RESULTS: All conventional measures of glycaemia were similar in the two groups: HbA(1c) mean CF vs. controls (5.5 vs. 5.3%P = 0.4), fasting glucose (4.8 vs. 4.7 mmol/l P = 0.7) and 2-h glucose (5.8 vs. 5.7 mmol/l P = 0.8). However, these conventional measures did not accurately reflect glycaemia 30-, 60- and 90-min. Glucose values and area under the curve in OGTT were all higher in CF subjects than controls (P = 0.01-0.0001). Mean CGMS value [5.9 (0.8) vs. 5.1 (0.5) mmol/l, P = 0.004], and the proportion of subjects with peak CGMS values > 11.1 mmol/l (33 vs. 5%P = 0.00001) were also higher in CF subjects than controls. These results remained significantly different when only subjects with normal glucose tolerance in the two groups were studied. CONCLUSIONS: We have shown that overall glycaemia, as shown by both the response during an OGTT and CGMS, is higher in CF subjects who have similar HbA(1c), fasting and 2-h glucose values. These results question whether it is appropriate to use the diagnostic thresholds and OGTT time points derived from the non-CF population for a diagnosis of diabetes in patients with cystic fibrosis.

Adult↗
PubMed2006

Calcaneus ultrasonometry and dual-energy X-ray absorptiometry for the evaluation of vertebral fracture risk.

The aim of this retrospective, cross-sectional, controlled, non-population-based study was to evaluate the specificity and sensitivity of quantitative ultrasonometry (QUS) of the heel and of dual-energy X-ray absorptiometry (DXA) in the prediction of morphometric vertebral fracture in postmenopausal women and to establish whether the combination of the two devices could improve the capacity to identify the presence of vertebral fracture. Also, we tried to identify the best T-score threshold for high risk of vertebral fracture for both QUS and DXA, highlighting the discrepancies between the two methodologies and between the various sites examined with DXA. From 6,300 patients examined by DXA (total body, lumbar spine, total femur, femoral neck), QUS and DXA vertebral morphometry (MXA), we selected 764 postmenopausal women with nontraumatic vertebral fractures; 770 postmenopausal women with normal morphometry were chosen as a control group. Logistic regression analysis yielded odds ratios (ORs) for bone mineral density (BMD) measurements and QUS that were comparable: BMD-total body 4.16, BMD-lumbar spine 4.80, BMD-total femur 3.77, BMD-femoral neck 3.86, and QUS 4.41, without statistical differences even after correction for different confounding variables (menopausal years, weight, height, body mass index, and age). The ORs obtained from different combinations of QUS and DXA results did not show statistically significant differences compared to those from a single method alone. The sensitivity and specificity of all measurements were determined by area using the receiver operating characteristic curve; these were 0.94 for total body, 0.95 for lumbar spine, 0.86 for total femur, 0.89 for femoral neck, and 0.93 for QUS, without statistical difference. The areas under the curve obtained from the combination of QUS and DXA were higher but without statistical significance compared to QUS alone. In conclusion, both QUS and DXA were able to discriminate women with fracture from women without fracture and independently contributed to determining the association with fracture. The combination of QUS and BMD did not improve the diagnostic ability of either individual technique. We found different diagnostic thresholds for QUS and DXA.

Absorptiometry, Photon↗
PubMed1996

The DSM-IV panic disorder field trial: panic attack frequency and functional disability.

The goal of the DSM-IV panic disorder field trial was to provide an empirical basis for choosing between alternate proposals (DSM-III-R and proposed DSM-IV) for the diagnostic threshold for panic disorder, in particular the number and frequency of panic attacks required for diagnosis. The two criteria sets were compared with respect to their ability to identify individuals whose panic attacks were associated with distress, impairment, or help-seeking. Subjects were a convenience sample screened in three geographically diverse primary care clinics for presence (past 6 months) or absence (lifetime) of panic attacks. Each underwent a clinician-administered semistructured interview which included assessment of panic frequency, panic-related impairment, psychiatric diagnosis, health services utilization, and medical illness. Self-perceived health-related quality of life was assessed using the Medical Outcome Study SF-36 Health Survey Questionnaire. Although both proposals diagnosed the same proportion of panic-impaired individuals, they were not completely overlapping. Twenty percent of subjects diagnosed by each criteria set were excluded by the other. Subjects who had been excluded by the DSM-III-R but included by the DSM-IV proposal were those with fewer than 4 attacks in 4 weeks who also denied worry about the "next" attack. Broadening the worry criterion to include concerns about the health implications of attacks enabled diagnosis of this group. Subjects who met DSM-III-R, but not the proposed DSM-IV criteria, had 4 attacks in 4 weeks but denied any panic related worry. Modification of the DSM-IV proposal to include a month of worry or "a significant change in behavior related to the attacks" allowed inclusion of this group in the diagnostic category. These data suggest that the finalized DSM-IV panic disorder criteria will diagnose a greater proportion of individuals whose panic attacks are associated with impairment without inflating the diagnostic category or significantly reducing specificity.

Adult↗
PubMed2005

The partial area under the summary ROC curve.

The area under the curve (AUC) is commonly used as a summary measure of the receiver operating characteristic (ROC) curve. It indicates the overall performance of a diagnostic test in terms of its accuracy at various diagnostic thresholds used to discriminate cases and non-cases of disease. The AUC measure is also used in meta-analyses, where each component study provides an estimate of the test sensitivity and specificity. These estimates are then combined to calculate a summary ROC (SROC) curve which describes the relationship between-test sensitivity and specificity across studies. The partial AUC has been proposed as an alternative measure to the full AUC. When using the partial AUC, one considers only those regions of the ROC space where data have been observed, or which correspond to clinically relevant values of test sensitivity or specificity. In this paper, we extend the idea of using the partial AUC to SROC curves in meta-analysis. Theoretical and numerical results describe the variation in the partial AUC and its standard error as a function of the degree of inter-study heterogeneity and of the extent of truncation applied to the ROC space. A scaled partial area measure is also proposed to restore the property that the summary measure should range from 0 to 1. The results suggest several disadvantages of the partial AUC measures. In contrast to earlier findings with the full AUC, the partial AUC is rather sensitive to heterogeneity. Comparisons between tests are more difficult, especially if an empirical truncation process is used. Finally, the partial area lacks a useful symmetry property enjoyed by the full AUC. Although the partial AUC may sometimes have clinical appeal, on balance the use of the full AUC is preferred.

Area Under Curve↗
PubMed2003

Increased medical costs of a population-based sample of depressed elderly patients.

BACKGROUND: We examined whether older adults with depressive symptoms below the diagnostic threshold and those with DSM-IV major depression and/or dysthymia have higher medical costs than those without depression. METHODS: We mailed the PRIME-MD 2-item depression screen to the patients of 2 large primary care clinics of a staff-model health maintenance organization in Seattle, Wash. All 11 679 patients 60 years and older with primary care providers at the participating clinics were included, and 8894 (76.2%) were successfully enrolled. An additional 107 patients were referred to the study by their primary care physician. Nonrespondents were slightly younger and had higher inpatient medical costs in the previous 6 months. Patients with positive findings on at least 1 item or referred by their family physician were offered an interview with the Structured Clinical Interview for DSM-IV. The total cost of medical services for the 6 months before the study was obtained from the cost accounting system of the health maintenance organization. RESULTS: Total ambulatory costs were 43% to 52% higher and total ambulatory and inpatient costs were 47% to 51% higher in depressed compared with nondepressed elderly patients after adjustment for chronic medical illness. This increase was seen in every component of health care costs, with only a small percentage due to mental health treatment. In mean costs, depressed elderly patients averaged an increase of 763 US dollars to 979 US dollars in ambulatory costs and 1045 US dollars to 1700 US dollars in ambulatory and inpatient costs. No differences in costs were noted between patients with subthreshold depressive syndromes and those with DSM-IV depressive disorders. CONCLUSION: Depressive symptoms and DSM-IV depressive disorders in elderly patients are associated with significantly higher health care costs, even after adjustment for chronic medical illness.

Age Factors↗
PubMed2004

Bulimia nervosa in adolescents: a disorder in evolution?

BACKGROUND: There are few reports that describe the manifestation of bulimia nervosa (BN) among adolescents. Moreover, none make reference to the comparative clinical manifestation of adolescent BN and adolescent anorexia nervosa. Nor are any reports available of how distinct partial-syndrome BN cases are from those that meet full diagnostic criteria for BN. OBJECTIVES: To describe 3 groups of adolescents, those with a full-syndrome eating disorder (BN and anorexia nervosa) or partial-syndrome BN, and to compare these groups along demographic, general psychopathology, and eating disorder variables. DESIGN: The study population included 120 adolescents with eating disorders who were initially seen at The University of Chicago Eating Disorders Program, Chicago, Ill, for treatment. All participants completed an assessment prior to treatment. MEASURES: Weight and height were obtained from all participants. Participants also completed a baseline demographic questionnaire (eg, menstrual status, ethnicity, family status), Beck Depression Inventory, Rosenberg Self-Esteem Scale, and the Eating Disorder Examination. RESULTS: Partial-syndrome BN cases are clinically quite similar to their full-syndrome counterparts. Only objective binge eating episodes and purge frequency distinguished BN and partial-syndrome BN cases. Anorexia nervosa cases, on the other hand, were quite distinct from BN and partial-syndrome BN cases on almost all variables. CONCLUSION: Early recognition and swift treatment of eating disorders in adolescents, regardless of whether a diagnostic threshold is met, are imperative because they will lead to early intervention thereby potentially improving eating disorder recovery rates.

Adolescent↗
PubMed1997

Diagnostic practice and the estimated prevalence of craniosynostosis in Colorado.

BACKGROUND: In the late 1980s, evidence of an epidemic of craniosynostosis in Colorado included reports of clusters from selected high-altitude communities and an investigation showing the high and rapidly rising rates of surgically corrected synostosis. Some evidence suggested that local diagnostic practice could account for the epidemic. OBJECTIVE: To determine the contributions of any excess rates of disease occurrence, surgery-based ascertainment, and diagnosis to the reported epidemic. DESIGN: Population-based birth prevalence study with diagnostic evaluation. SETTING: The Colorado Department of Health, April 15, 1986, to July 14, 1989. PATIENTS OR OTHER PARTICIPANTS: Children in the Craniosynostosis Registry or state birth record files. MAIN OUTCOME MEASURES: Birth prevalence was estimated from registry and birth record data; case classification by suture type and malformation patterns were determined by review of radiographs and medical records. RESULTS: The period birth prevalence of radiographically confirmed nonsyndromic synostosis was 14.1 per 10,000 live births. Of a total of 605 children, 307 (51%) had definite radiographic evidence of synostosis, for which the intrarater reliability was good (except for the coronal suture on plain films) and the interrater reliability was fair or good (except for the metopic suture on plain films). Between the first and third years, case reports fell from 347 to 103. CONCLUSIONS: Diagnostic criteria strongly influenced the rate of synostosis. The rate of radiographically confirmed synostosis was within the range of published estimates. Low diagnostic thresholds, which changed over time, created the semblance of a severe statewide epidemic and may have obscured excess rates of disease at high altitude.

Colorado↗