Single Cutoff Point Research Articles

A meta-analysis derivation of continuous likelihood ratios for diagnosing pleural fluid exudates.

In evaluating pleural effusions, clinicians perform thoraceninstance, recommend measuring pleural fluid-to-serum albumin gradients when patients with congestive heart failure have tesis and pleural fluid analysis most often by Light’s criteria to establish the exudative or transudative nature of the effuan exudative effusion by Light’s criteria (7). A Bayesian approach addresses these limitations of binary sion (1). Light’s criteria (2) dichotomize effusions into exudative or transudative categories with the use of three pleural testing strategies (10). Rather than diagnosing the presence or absence of a condition, a Bayesian strategy uses test results test criteria: pleural fluid-to-serum protein ratio, pleural fluid lactate dehydrogenase (LDH) concentration, and pleural fluidto generate likelihood ratios that increase or decrease a clinician’s pretest estimate of the probability of disease. Likelito-serum LDH ratio. Several other pleural fluid test criteria have similar diagnostic accuracies as compared with each of hood ratios represent the likelihood that a positive test result would be found in a patient with as opposed to without the individual tests within Light’s criteria (3). These criteria include pleural fluid cholesterol, pleural fluid-to-serum cholesdisease (10). Likelihood ratios are usually calculated using a single test result cutoff point. These binary likelihood ratios terol ratio, pleural fluid protein, and pleural fluid-to-serum have values above 1 for test results that increase the likelialbumin gradient. All of these tests dichotomize effusions into hood of an exudative effusion and values below 1 that deexudative or transudative categories by determining whether crease the likelihood. We previously published multilevel the test results are above or below a single cutoff point. likelihood ratios for pleural fluid test criteria commonly used Problems exist, however, with these pleural fluid test criteria to diagnose exudative pleural effusions (11). Multilevel likelias commonly used in clinical practice. First, dichotomizing hood ratios are calculated by using two or more cutoff points effusions into exudates and transudates by using a single for the range of possible test results. These multiple cutoff cutoff point loses much of the information contained in pleupoints demarcate test result intervals that are each associated ral fluid tests, which generate continuous numeric results (4). with a different likelihood that the patient has an exudative Test results just beyond and those extremely beyond a cutoff effusion. Although breaking up continuous test result values point are treated the same in that both establish the presence into ordinal intervals with multiple cutoff points improves of an exudative effusion. This binary diagnostic strategy exdiagnostic precision as compared with using a single cutoff plains why Light’s criteria frequently misclassify as exudates point, they only provide an average value for the range of the pleural effusions associated with congestive heart failure likelihood ratios that exist within each of the test result inter(5–7), which usually have borderline pleural fluid test results vals (4). A more precise diagnostic approach would calculate when in the exudative range. It also contributes to the misclassian exact likelihood ratio for each possible discrete pleural fluid fication that occurs in 1 to 10% of patients with malignant test result. Such discrete likelihood ratios are called continuous pleural effusions who appear to have transudative effusions likelihood ratios (12). Methods for calculating continuous likeby Light’s criteria (8). Second, combining two or more tests lihood ratios have been reported for very few conditions. using a single cutoff point for each test, as done by Light’s In this study, we analyze with logistic regression a multicencriteria, increases sensitivity but decreases specificity because ter registry of pleural fluid test values from patients with estabonly one of the tests needs to be positive to define an exudative lished diagnoses to derive equations that calculate continuous effusion (9). Finally, the lower specificity caused by combining likelihood ratios for pleural fluid test criteria for exudative several criteria encourages physicians to commonly order addieffusions. We also compare continuous likelihood ratios with tional—and usually unnecessary—pleural fluid tests when inimultilevel and binary likelihood ratios to determine whether tial test results do not fit clinical circumstances. Experts, for continuous likelihood ratios provide statistically significant and clinically important advantages.

Mediterranean diet and reduction in the risk of a first acute myocardial infarction: an operational healthy dietary score.

Although an important secondary prevention trial reported an impressive protection by a Mediterranean dietary pattern on reinfarction and cardiovascular death, scarce direct epidemiologic evidence is currently available regarding the role of the Mediterranean diet in the aetiology of coronary heart disease. The aim of the study was to quantify the risk reduction of incident myocardial infarction provided by a Mediterranean dietary pattern. We included 342 subjects (171 patients who suffered their first acute myocardial infarction and 171 matched controls) in a case-control study. A validated semi-quantitative food frequency questionnaire (136 items) was used. We defined an a priori Mediterranean dietary pattern. We assessed six food items that we considered protective: 1) olive oil, 2) fiber, 3) fruits, 4)vegetables, 5) fish and 6) alcohol. For each of these six dietary factors, we calculated the distribution according to quintiles within the study and assigned each participant a score of 1 to 5 corresponding to the quintile of intake, with 1 representing the lowest and 5 representing the highest quintile. We also estimated the quintiles of two other elements assumed to be associated with a higher risk: 7) meat/meat products and 8) some items with high glycaemic load (white bread, pasta and rice). For these two elements we inversely ranked the score, with 1 representing the highest and 5 representing the lowest quintile. Finally, we summed up the eight quintile values for each participant.A second score ( post hoc pattern) was built using only a single cut-off point for these eight elements. The cut-off points for each element in this post hoc pattern were decided according to the dose-response relationships between the consumption of each food item and the risk of myocardial infarction observed in the analyses that used quintiles of each food item. For both patterns, we found that the higher the score, the lower the odds ratio of myocardial infarction. A significant linear trend was apparent after adjustment for the main cardiovascular risk factors. For each additional point in the a priori Mediterranean pattern (observed range: 9-38) the odds ratio (95 % confidence intervals) was 0.92 (0.86-0.98). This estimate was 0.55 (0.42-0.73) when we used the post hoc pattern (range: 0-8). Our data support the hypothesis that a Mediterranean diet (that emphasizes olive oil, fiber, fruits, vegetables, fish and alcohol and reduces meat/meat products) can be an effective measure for reducing the risk of myocardial infarction. However, our results support the exclusion of refined cereals with a high glycaemic load as healthy elements of this pattern.

Spatially resolved derivative spectroscopy of vertical-cavity surface-emitting lasers using near-field scanning optical microscopy

A near-field scanning optical microscope was used in collection mode to generate spatially resolved maps of the first derivative with respect to operating current of power emission from vertical-cavity surface-emitting lasers (VCSELs). This technique is highly sensitive to the formation of new modes and can be used to identify mode cutoff points. An example of the usefulness of this technique is demonstrated as we estimate the index of refraction profile of the VCSEL under study at the single mode cutoff point. This profile is a primary feature of the waveguiding characteristics of such lasers.

Application of stratum-specific likelihood ratios in mental health screening.

The accuracy of a diagnostic procedure is commonly assessed by measuring sensitivity, specificity and positive and negative predictive values. Likelihood ratios provide an alternative method for describing these results, though they are typically reported only for dichotomized outcomes. However, likelihood ratios can also be applied to ordinal or continuous results. The present paper discusses the application of stratum-specific likelihood ratios in a primary care setting using the General Health Questionnaire (GHQ-12) and the Symptom Check List 90-R (SCL-90-R). A randomly selected sample (n = 408) of adult outpatients from primary care offices in Düsseldorf was screened using the German versions of the GHQ-12 and the SCL-90-R. Logistic regression analysis indicated that stratum-specific or multilevel likelihood ratios preserve more information than a fixed threshold approach with a single cutoff point. For each test, five clinically useful strata with monotonically increasing stratum-specific likelihood ratios were selected. Stratum-specific likelihood ratios have enormous practical value, and they are becoming an important way of expressing and comparing the usefulness of different tests. Stratum-specific likelihood ratios reduce the spectrum bias that might arise if only two categories (cases and non-cases) are chosen. Additionally, multilevel likelihood ratios can be used as bedside information to obtain the post-test probability from the pre-test probability of the disorder.

RETRACTED: Prostate cancer screening in the Tyrol, Austria: experience and results

This article summarises the experience and results of different prostate carcinoma screening projects using total prostate specific antigen (PSA) and per cent free PSA as the initial test. Of the 21078 volunteers 1618 (8%) had elevated PSA levels. Of these men 778 (48%) underwent biopsies; 197 (25%) biopsies were positive for prostate carcinoma and 135 (17%) underwent radical prostatectomy. 95 were found to be organ-confined. A PSA cut-off of 2.5 ng/ml in men aged 45-49 years and of 3.5 ng/ml in men aged 50-59 years resulted in an 8% increase in the detection rate of organ-confined disease. 284/2272 men (13%) had elevated PSA levels and prostate carcinoma was detected in 62 men (3%). All patients underwent radical prostatectomy and histological examination revealed organ-confined tumour in all but 8 men. 98/340 men (29%) had biopsies positive for carcinoma; 28 of these patients (29%) had carcinoma that originated in the transition zone only. In the retrospective study, receiver operating characteristic curve analysis showed that by using a per cent free PSA of less than 18% as a biopsy criterion, 37% of the negative biopsies could be eliminated although 94% of all carcinomas would still be detected. In the first prospective study, 106/158 men (67%) with elevated PSA levels below 10.0 ng/ml were further evaluated and 37 (35%) prostate carcinomas were detected. By using a per cent free PSA of <22% as a biopsy criterion, 30% of the negative biopsies could be eliminated although 98% of the carcinomas would still be detected. In the second prospective study, 120/465 men (26%) with total PSA levels between 1.25 and 6.49 ng/ml and a per cent free PSA<18% were further evaluated and 27 (23%) were found to have prostate carcinomas. Receiver operating characteristic curve analysis for PSA transition zone (TZ) density showed that by using a PSA transition zone density of >22 ng/ml/cc as a biopsy criterion, 24.4% of negative biopsies could be avoided without missing a single carcinoma. In the prescreening era the incidence of T1a Grade 1 and 2 carcinomas was 3.1% and the incidence of T1a and T1b Grade 3 carcinoma was 2.3% whereas in the years after the establishment of PSA-based screening the incidence was 4.6 and 1.03% respectively. The rate of organ-confined tumours increased from 28.7% in 1993 to 65.7% in 1997. In this evaluation a new approach, to proceed with a prostate biopsy based upon the individual risk of having prostate cancer rather than a single PSA cut-off point was developed. High total PSA levels, PSA density and PSA transition zone density correlated significantly with high Gleason scores, capsular penetration, a high percentage of cancer in the prostatectomy specimen and a high cancer volume. In this evaluation all of the 95 patients with PSA levels below 3.99 ng/ml who underwent radical prostatectomy showed clinically significant, organ-confined prostate cancer with negative surgical margins. The results of this evaluation suggest that older men have larger tumour volumes compared with younger men with the same PSA levels. These data suggest that PSA-based screening with low PSA cut-off values increase the detection rate of clinically significant, organ confined and potentially curable prostate cancer. Per cent free PSA and PSA transition zone density provide an additional diagnostic benefit over total PSA.

Mid-arm circumference for detecting malnutrition during infancy.

Mid-arm circumference (MAC) has been extensively used at 1-5 years of age as an age-independent indicator of protein-energy malnutrition (PEM). Its role below 12 months of age has not been studied adequately and a search for a clinically reliable cut-off point has not been systematically done. This study was planned to establish the age-independent character of MAC within the 6-12 month age group and identify a cut-off point demonstrating the maximum sensitivity and specificity in detection of PEM. Two hundred and forty malnourished infants [< 80% weight for age (W/A) of 50th percentile of NCHS standard] were included with even distribution into 6 subgroups; 240 healthy infants were taken as controls. MAC within the age of 6-12 months was found to be age independent with an overall increase of 5.1%. By using various cut-off points a value of < or = 12.5 cm of MAC proved to be having maximum sensitivity (92.1%) and specificity (88.3%). MAC is, therefore, a simple, age independent, informative measurement for early assessment of PEM by using single cut-off point < or = 12.5 cm, and can serve as a screening test for targeting infants for meaningful utilization of nutritional programmes. Since nearly all MAC tapes in current use already have < or = 12.5 cm colour coded cut-off, no new tapes are necessary.

Vergleichende Analyse des L/S-Verfahrens und des TDx-FLM-Tests zur Erfassung der kindlichen Lungenreife in utero

Der TDx-Fetale-Lungenreife (FLM)-Test zur Bestimmung des Surfactant/Albumin-Quotienten wurde mit der Bestimmung des Lecithin/Sphingomyelin-Quotienten aus dem Fruchtwasser retrospektiv im Hinblick auf die Fähigkeit verglichen, ein Respiratory-Distress-Syndrom (RDS) beim Neu-, insbesondere Frühgeborenen vorherzusagen. Beide Verfahren können nach den vorliegenden Daten nicht optimal zwischen der „lungenunreifen“, postpartal ein RDS entwickelnden Population und der „lungenreifen“, postpartal atemsuffizienten Population unterscheiden. Der TDx-FLM-Test scheint nach ROC-Analyse diese Aufgabe aber eher bewältigen zu können als das L/S-Verfahren, welches eine deutliche Differenzierungsschwäche zeigt. Die klinische Wertigkeit dieses Tests ist deshalb zu relativieren. Die Anwendung eines einzigen allgemeingültigen Grenzwertes ist nicht möglich. Der angewandte Grenzwert sollte an die klinische Situation, d.h. an das mütterliche und kindliche Risiko, angepaßt werden: In einer „Low-risk“-Situation bieten sich die Grenzwerte 2,6 für das L/S-Verfahren und 28 für den TDx-FLM-Test an. In einer „High-risk“-Situation sollte nach klinischen Erfordernissen individuell entschieden werden. Der bisher für das L/S-Verfahren häufig angewandte Quotient 2 ist als Grenzwert nach der ROC-Analyse wegen seiner deutlichen Differenzierungsschwäche nur mit Vorsicht anzuwenden. Der Zusammenhang der Testergebnisse des TDx-FLM-Tests und des L/S-Verfahrens ist zu Beginn des dritten Trimenons etwa von der 28. SSW bis zur 32. SSW nur schwach, nimmt im weiteren Verlauf der Schwangerschaft jedoch deutlich zu. Während bei den L/S-Werten zu Beginn des dritten Trimenons ein Anstieg der Werte über der Zeit nachweisbar ist, verändern sich die TDx-Werte kaum. Als Konsequenz ergibt sich, daß das L/S-Verfahren in dieser Phase der Schwangerschaft zur Überwachung der Lungenreife doch besser geeignet zu sein scheint als der TDx-FLM-Test. Eine Kombination der beiden Testverfahren etwa ab der 32./33. SSW könnte eine verbesserte Überwachung der fetalen Lungenreifung ermöglichen.

Visual assessment of urethrovesical junction mobility.

The aim of the study was to compare visual assessment of anterior vaginal wall descent with the Q-tip test in evaluating urethrovesical junction mobility. One hundred and eleven patients with prolapse and/or urinary incontinence were examined in the supine lithotomy position with an empty bladder. Maximum straining Q-tip tests and maximum descent of the anterior vaginal wall were measured. Using each centimeter of descent as a cutoff value, the sensitivities, specificities and positive and negative predictive values were compared to those of the Q-tip test. As the cut-off points were moved distally, specificity increased at the expense of sensitivity. There was no single cut-off point that provided adequate sensitivity and specificity to be clinically useful to replace the Q-tip test. It was concluded that visual assessment of anterior vaginal wall descent does not provide diagnostic accuracy and acceptable sensitivity and specificity to determine urethrovesical junction mobility. Other methods should be employed to assess support.

A modified ROC analysis for the selection of cut-off values and the definition of intermediate results of serodiagnostic tests

A total number of 50 sera from clinically confirmed cases of canine Borrelia (B.) burgdorferi infection and 44 negative control sera were tested with a B. burgdorferi specific antibody ELISA. The data were submitted to the ‘two-graph receiver operating characteristic’ (TG-ROC) analysis which is a plot of the test sensitivity (Se) and specificity (Sp) against the threshold (cut-off) value assuming the latter to be an independent variable. Thus, in contrast to the conventional ROC analysis, valid pairs of Se and Sp can be read for pre-assigned threshold values directly from the TG-ROC plots. A cut-off that realises equal test parameters (Se = Sp = θ 0 (theta-zero)) can be obtained as the intersection point of the two graphs. Since the value for θ 0 is below a preselected accuracy level (95% or 90%), two cut-off values are selected that represent the bounds of an ‘intermediate range’ (IR). IR can be considered as a ‘borderline’ range for the clinical interpretation of test results. The proportion of the measurement range (MR) that gives unambiguous test results can be expressed using IR as the ‘valid range proportion’ ( VRP = (MR - IR) MR) . VRP and θ 0 are useful parameters for test comparison since they do not depend upon the selection of a single cut-off point. In addition, the selection of cut-off values is supported by graphical displays of efficiency, Youden's index and likelihood ratios which can be considered as functions of the pre-assigned cut-off value. TG-ROC was derived as a user-defined template for a commercially available spreadsheet programme (MS-EXCEL, Microsoft).

Power Analysis of Cutoff-Based Randomized Clinical Trials

A cutoff-based randomized clinical trial couples cutoff-based assignment on an appropriate covariate with random assignment to help balance ethical and scientific concerns in certain situations. A statistical power algorithm based on the Fisher Z method is developed that is particular to and inclusive of cutoff-based random clinical trials and the single cutoff-point (regression-discontinuity) design, which has no randomization. This article quantifies power and sample size estimates for varying levels of randomization and cutoff-based assignment. Although more randomization engenders greater statistical power, less randomization requires a much larger increase in sample size for small treatment effects.

Terminal digit preference, random error, and bias in routine clinical measurement of blood pressure

We examined the presence, magnitude, and consequences of systematic and random errors caused by terminal digit preference in the measurement of highest systolic blood pressure during prenatal visits in 28,841 non-referred pregnant women who delivered between 1 January 1982 and 31 March 1990. In the overall distribution of terminal digit readings, 78% were read to 0, 15% to even digits other than 0, 5% to 5, and only 2% to odd digits other than 5. This preference for 0's was consistent across the entire distribution of blood pressure and for a variety of maternal characteristics.The relative frequency of the cutoff value of 140 mmHg (i.e. the percentage of readings on 140 mmHg) within the range containing the value (i.e. 138–142 mmHg) was similar to the relative frequency of other multiples of 0. This was true whether the comparison was made in the overall study sample, or in a pre-selected low-risk subgroup or high-risk subgroup, indicating no systematic bias. On the other hand, a strong tendency to read blood pressure values to the nearest 0 had a marked effect on the classification of hypertension. Changing the definition of hypertension from ⩾/140 mmHg to > 140 mmHg produced a reduction in prevalence of hypertension from 25.9 to 13.3% in the overall study sample, from 15.4 to 6.3% in the low-risk subgroup, and from 43.3 to 25.3% in the high-risk subgroup.Epidemiologic studies that compare prevalences of hypertension in different populations based on routine clinical measurement of blood pressure and a single cutoff point should assess the consequences of terminal digit preference in defining hypertension. The relative frequency and changing cutoff point approach might be helpful in evaluating the existence and consequences of systematic bias and random error caused by terminal digit preference in other routine clinical and laboratory measurements as well.

PREDICTIVE VALUE OF GLASGOW COMA SCORE FOR AWAKENING AFTER OUT-OF-HOSPITAL CARDIAC ARREST

The Glasgow coma score (GCS) during days 1-6 after cardiac arrest was used to predict neurological outcome in 360 resuscitated victims of out-of-hospital cardiac arrest. A predictive rule based on the best GCS of 216 patients resuscitated in 1983-84 (prediction group) was constructed, and its predictive power was tested on 133 patients treated in 1985 (test group). Neurological outcome was correctly predicted 2 days after cardiac arrest in 80% of the prediction group, with a best GCS of 10 or above and 4 or below as cutoff points. For patients with a best GCS of 5-9, prediction of outcome was possible 6 days after cardiac arrest, with a best GCS of 8 during the first 6 days as the single cutoff point. The rule was then validated in the test group: the sensitivity was 96%; the specificity 86%; the negative predictive value 97%; and the positive predictive value 77%. These data suggest that this simple GCS-based rule can be helpful in predicting outcome in patients resuscitated after out-of-hospital cardiac arrest, but confirmation of these data is required in a prospective study in a larger number of patients.

Predictors of rural practice location.

Attitudes toward the urban environment and place of origin were found to be the best predictors of an optometrist's practice location. When urbanism attitude and origin were scaled and placed in an equation to predict practice location, identification of an optometrist's practice location as rural or urban was highly accurate. Most important, scores on the equation were predictive of optometry students' future practice location. A single cutoff point on the equation correctly identified 79 percent of students who entered a rural or isolated small city practice and 81 percent of those who entered urban practice. The findings imply that optometry students most likely to enter rural practice can be objectively identified early in their training. If certain factors affecting choice of practice location are common to all health professions, the predictive equation presented here may be useful in the selection of students for rural practice in medicine.

Identifying the Potential Rural Optometrist

Rural optometrists were found to differ from urban optometrists in background, environmental attitude, and interest patterns. Attitude toward the urban environment and place of origin were the best predictors of an optometrist's practice location. When "urbanism" and "origin" were scaled and placed in a multiple regression equation to predict practice location, identification of an optometrist's location as rural or urban was highly accurate. Most importantly, scores on the equation were predictive of optometry students' future practice locations. A single cut-off point on the equation correctly identified 79% of students who entered rural or isolated small city practice and 81% of those who entered urban practice. The findings suggest that optometry students most likely to enter rural (or indeed urban) practice can be objectively identified early in, or even prior to, training. Such identification may assist educators in selecting and training optometrists who will deliver vision care to people in areas of greatest need.