Likelihood ratios with confidence: sample size estimation for diagnostic test studies

Confidence intervals are important summary measures that provide useful information from clinical investigations, especially when comparing data from different populations or sites. Studies of a diagnostic test should include both point estimates and confidence intervals for the tests' sensitivity and specificity. Equally important measures of a test's efficiency are likelihood ratios at each test outcome level. We present a method for calculating likelihood ratio confidence intervals for tests that have positive or negative results, tests with non-positive/non-negative results, and tests reported on an ordinal outcome scale. In addition, we demonstrate a sample size estimation procedure for diagnostic test studies based on the desired likelihood ratio confidence interval. The renewed interest in confidence intervals in the medical literature is important, and should be extended to studies analyzing diagnostic tests.     

A comparison of low-dose and normal-dose gadobutrol in MR renography and renal angiography.

OBJECTIVE: It has been advocated that a reduced injection volume with highly concentrated (1 M) contrast material can produce a sharper bolus peak and an increased intravascular first-pass gadolinium concentration when compared with the use of a lower concentration (0.5 M). A higher concentration would also cause a reduction in dose. The purpose of our study was to test the use of a low dose (0.05 mmol/kg) of gadobutrol in magnetic resonance renography and angiography and compare the findings with a dose of 0.1 mmol/kg. MATERIALS AND METHODS: One-hundred-thirty-four patients referred for magnetic resonance angiography for suspected renovascular disease participated in the study. Contrast enhanced MR renography and angiography were performed after administration of a bolus of 0.1 mmol/kg or 0.05 mmol/kg gadobutrol in randomized patients. The relative signal intensity-time curves of the aorta, peripheral cortex and parenchyma, were obtained. Two radiologists evaluated the angiographic images and evaluated the quality of angiography. RESULTS: The signal intensity with a low dose of gadobutrol was significantly lower in early phases, in the peripheral cortex (for 36, 54, 72 and 90 seconds), the parenchyma (for 36, 54, 72 seconds) and the aorta (for 18, 36, 54, 72 seconds). The decreases in the early phase obtained with a low dose of gadobutrol caused blunter time intensity curves. The difference in the quality scores of the readers for the angiographic images for the use of the two different doses was not statistically significant (p > 0.05). CONCLUSION: A lower dose of gadobutrol can be used for MR renal angiography, but for MR renography the normal dose should be used.     

Microvascular temporalis fascia transfer for penile girth enhancement.

The authors report a 44-year-old man with inadequate penile girth that caused psychological problems. Using microvascular temporalis fascia transfer, they achieved satisfactory penile girth enhancement based on reliable vascularity in a single stage.     

A Bayesian method for evaluating medical test operating characteristics when some patients' conditions fail to be diagnosed by the reference standard

The evaluation of a diagnostic test when the reference standard fails to establish a diagnosis in some patients is a common and difficult analytical problem. Conventional operating characteristics, derived from a 2 x 2 matrix, require that tests have only positive or negative results, and that disease status be designated definitively as present or absent. Results can be displayed in a 2 x 3 matrix, with an additional column for undiagnosed patients, when it is not possible always to ascertain the disease status definitively. The authors approach this problem using a Bayesian method for evaluating the 2 x 3 matrix in which test operating characteristics are described by a joint probability density function. They show that one can derive this joint probability density function of sensitivity and specificity empirically by applying a sampling algorithm. The three-dimensional histogram resulting from this sampling procedure approximates the true joint probability density function for sensitivity and specificity. Using a clinical example, the authors illustrate the method and demonstrate that the joint probability density function for sensitivity and specificity can be influenced by assumptions used to interpret test results in undiagnosed patients. This Bayesian method represents a flexible and practical solution to the problem of evaluating test sensitivity and specificity when the study group includes patients whose disease could not be diagnosed by the reference standard.     

Improving the clinical examination for a low ankle-brachial index

We sought to determine clinical examination features that predict an abnormal ankle-brachial index (ABI). Eleven United States and Canadian university-affiliated practices participated. Patients over age 55 (n=218) presenting for an outpatient appointment in a general medical clinic. We excluded patients with amputations or acute leg pain. A standard clinical examination was performed consisting of historical features and physical examination findings with Doppler ausculation. The most efficient findings were a. presence of only one Doppler-auscultated posterior tibial artery component [LR=7.0; (95% CI 4.4, 11.6)], and b. absence of a palpable pulse [LR=4.6; (95% CI 3.2, 6.6)]. We derived a score based on the number of auscultated components, grade of palpated pulse, and history of myocardial infarction (LR_score<6=7.8; LR_score≥6=0.2; c index=0.93). Clinicians required a median 2.5 min to collect the clinical information and derive the score (interquartile range 1.8 to 3.6 min), versus 8.5 min for the ABI (interquartile range 7.4 to 9.4 min). Palpation and Doppler auscultation of the posterior tibial artery, combined with knowledge of prior myocardial infarctions, were the most effective and efficient findings for patients in general medical clinics. A score based on these findings appears promising as a screening tool for a low ABI.     

Infantile neuroaxonal dystrophy: diagnosis by skin biopsy.

A child who shows progressive motor and mental deterioration after the first year of life, who has pyramidal signs, marked muscle hypotonia, but no seizures, suggests to have infantile neuroaxonal dystrophy (INAD). Beyond the age of two years, the EEG also entails characteristic findings. Diagnosis may be obtained by an ultrastructural examination of biopsied skin. The respective clinical and morphological findings are recorded and illustrated from four patients in this report.     

Factors influencing mortality in spontaneous gastric tumour perforations

Spontaneous perforation of gastric cancer is a serious complication with a very high incidence of mortality. In order to evaluate the prognostic factors influencing mortality in patients with gastric tumour perforations and to clarify the optimal surgical treatment, the records of patients at one centre during a 5-year period were evaluated retrospectively. Between 1995 and 2000, 14 patients with perforated gastric cancer were operated on in the Emergency Surgical Unit of a Turkish Hospital. This figure represents 3% of all the patients with gastric cancer who were treated during the same period. The hospital mortality was 36% in patients with perforations. The duration of symptoms suggesting perforation and the presence of pre-operative shock were predictive factors of mortality. It was concluded that those patients with pre-operative shock and delayed diagnosis should be treated with extra caution to decrease mortality. Perforation and peritonitis must be treated initially and elective radical surgery delayed.     

Lens superoxide dismutase and catalase activities in diabetic cataract

OBJECTIVE: Biochemical evidence suggests that the oxidative damage of the lens proteins is involved in the genesis of senile cataract and the development of diabetes-related pathologic changes such as the formation of cataracts. In particular, lens proteins are subject to extensive oxidative modification. Oxidative damage either decreases the antioxidant capacity or decreased antioxidant capacity results in oxidative damage. The purpose of this study was to analyze the activities of the antioxidant enzymes such as Cu,Zn Superoxide Dismutase (Cu,Zn-SOD) and catalase in the cataractous lenses of the type 2 diabetic group and cataractous lenses of the senile group. METHOD: Eighteen diabetic cataractous lenses and twenty six senile cataractous lenses were studied. Cu,Zn-SOD activity was measured in lenses by enzymatic method and catalase activity was measured by colorimetric method. RESULTS: Cu,Zn-SOD levels were significantly lower in the diabetic cataractous lenses than senile cataractous lenses (respectively 8.052 +/- 0.818, 18.216 +/- 4.217 microg/g prot. p < 0.05). Similarly, catalase levels were significantly lower in the diabetic cataractous lenses than senile cataractous lenses (respectively 0.326 +/- 0.134, 0.665 +/- 0.322 kU/g prot. p < 0.001). CONCLUSION: The results of the present study indicate that the antioxidant capacity in the diabetic cataractous lenses were decreased and this result suggests a role of antioxidant enzymes in the genesis of diabetic cataracts.