Comparing diagnostic tests: trials in people with discordant test results

Diagnostic tests are traditionally compared for accuracy against a gold standard but can also be compared prospectively in a trial. A conventional trial comparing two tests would randomize each participant to a testing strategy, but a more efficient alternative is to give both tests to all participants and follow up those with discordant results. Participants could be randomized before or after testing. The statistical analysis of such a trial has not previously been described. We investigated two estimates of the risk difference for a binary outcome: one based on analysing outcomes as if from a conventional trial and one combining estimates of different parameters in the manner of a decision analysis. We show that the trial estimate and decision analysis estimate are both unbiased and derive approximate formulae for their standard errors. By using the decision analysis estimate (but not the trial estimate), the same precision can be achieved by randomizing before testing as by randomizing after. To avoid destroying equipoise, and to allow consenting and randomizing to be carried out at the same visit, we recommend randomizing before testing. Giving both tests to all participants means fewer need to be recruited: in one example from the literature, the proposed design was nearly four times more efficient in this sense than a conventional trial design. Copyright © 2012 John Wiley & Sons, Ltd.     

Benefits of Swimming in Asthma: Effect of a Session of Swimming Lessons on Symptoms and PFTs with Review of the Literature

A study involving eight children with moderate persistent asthma was undertaken to determine whether standard swimming lessons improved symptoms and pulmonary function tests (PFTs) in asthmatic children. Five children ages 7–12 years old with moderate persistent asthma were randomized to a swimming lesson group (5- to 6-week session) and three to a control group. Both groups completed pre- and poststudy period PFTs and symptom questionnaires. Swimming lessons did not produce a significant change in asthma symptoms or PFTs. Review of previous literature found that swimming has been shown to have definite benefits in improving cardiorespiratory fitness in asthmatic children. Swimming has been shown to be less asthmogenic than other forms of exercise. Some studies have also shown improvement in asthma symptoms in children participating in exercise programs.     

Effect of Azelastine Nasal Spray on Histamine-and Allergen-Induced Skin Wheal Response in Patients with Allergic Rhinitis

Effect of azelastine nasal spray on histamine-and allergen-induced skin test response in patients suffering with allergic rhinitis was evaluated. Baseline cutaneous response to histamine and 18 common allergen extracts were recorded by skin prick tests on 10 patients. The patients were then advised to take azelastine nasal spray (1 spray per nostril, twice daily; 0.28 mg/dose). This pediatric dose is reported to be effective also in adults (age ≥ 12 years) with improved tolerability as compared with usually recommended adult dose of 2 sprays per nostril twice daily. Skin tests were repeated 2 and 6 hours after single dose, as well as after 6 days of continuous treatment. We did not find any significant difference in skin wheal response with single dose and 6 days' treatment of azelastine nasal spray (p > 0.05). It is concluded that diagnostic allergen skin tests may be performed on patients undergoing azelastine nasal spray treatment (0.28 mg/dose, twice a day) during their symptomatic period.     

Intestinal Metaplasia,High-Grade Epithelial Dysplasia and Gastric Cancer

Abstract

Objective. In 1990, Lavelle and Kanagaratnam introduced Usefulness Index (UI) test for assessment of usefulness of clinical observations. Although, nonspecific abdominal pain (NSAP) is the most common diagnosis among secondary care patients with acute abdominal pain, the efficiency of UI test is rarely considered in NSAP. Methods. In an extension of the World Organisation of Gastro-Enterology Research Committee (OMGE) acute abdominal pain study, 1333 patients presenting with acute abdominal pain were included in the study. The clinical signs (n = 14) and tests (n = 3) in each patient were recorded in detail, using a predefined structured data collection sheet, and the collected data were compared with the final diagnoses of the patients. Results. The most significant clinical tests and signs of NSAP in univariate analysis were (UI = Usefulness Index and RR = risk ratio): rigidity (UI = 0.36, RR = 32.2), rebound (UI = 0.33, RR = 6.3), guarding (UI = 0.25, RR = 4.9), Murphy's positive (UI = 0.13, 8.9), bowel sounds (UI = 0.12, RR = 3.3), and renal tenderness (UI = 0.12, RR = 2.2). The sensitivity of the doctors' initial decision in detecting NSAP was 0.70 with a specificity of 0.83 and with the UI = 0.37 and RR = 11.4. Conclusion. The patients with negative test results in rigidity, rebound, guarding, Murphy's, and bowel sounds tended to be at risk for NSAP and in these patients the UI test could be an aid for clinician to differentiate NSAP from other causes of acute abdominal pain.     

Absence of Correlation Between the Spontaneously Hypertensive Rat's Exaggerated Preference for Sweet and Alcohol Drinking Solutions

We tested the hypothesis that the exaggerated preference of the spontaneously hypertensive rat of the Okamoto strain (SHR) for alcohol-containing drinking solutions is due to its exaggerated preference for the purported sweet subtaste of alcohol. To do, this we examined in SHR (and Brown Norway (BN) controls) whether preferences for alcohol and glucose-drinking solutions were correlated. No significant correlation was found between alcohol and glucose preference in either the SHR or BN. We conclude therefore that the exaggerated alcohol preference of the SHR is not due to an exaggerated preference for the purported sweet subtaste of alcohol.     

Kidney Function in Heart Failure

Objective. The purpose of this investigation was to improve a rankit ordinal model for evaluating and validating dichotomized tests in a prospective Nordic project. Material and methods. The model is based on the assumption that the S‐shaped curve of fractions of positive for increasing concentrations can be de‐convoluted to a histogram and thereby used to calculate the parameters for a ln‐Gaussian distribution. In a Nordic survey, four urine samples with known concentrations of hCG (human chorionic gonadotrophin) and nitrites were distributed to more than 2500 practitioners' offices. Results. The results are presented as parameters (geometric mean and CV) for the components urine‐hCG and urine‐nitrites, together with fractions of positive for clinical critical values (5 and 40?IU/L for hCG), for which fractions should be below 0.01 and above 0.99, respectively, and 7?µmol/L for nitrites. Furthermore, the concentration intervals of varying fractions of positive from 0.01 to 0.99 are estimated as grey zones. The parameters and grey zones for different kits are compared. No urine‐hCG kit fulfilled the low clinical criterion, whereas all fulfilled the high criterion. Seven of the eight nitrites kits had fractions of positive above 0.9 for the company confirmation limit, but varying fractions for the clinically important limit of 7?µmol/L (fractions from 0.06 to 0.83). Conclusions. The present model makes it easy to estimate parameters for the kits, and also to estimate the fractions of measured positives for specified concentrations. It is thus suited for external quality assessment as well as for manufacturers' method validation.     

Potassium,Sodium, and Chlorides in Gastrin-Stimulatrd Gastric Secretion in Man

Conversion of coagulation time (t) to relative arbitrary substance concentration of coagulation factors(II + VII + X) abbreviated c_ra) was originally made from a measuring curve corresponding to the equation log t=a_a0 + a₁ log c_ra. Three more suitable equations are presented and tested for fit: t=A₀ + A₁/c_ra; t=B₀ + B₁/c_ra + B₂/c²_ra; log t=b₀ + b₁ log c_ra + b₂ (log c_ra)². Their suitability for the Simplastin®-A and Thrombotest® methods is also investigated. The last equation yields the best fit and replaces the errorprone reading of log-log curves by a calculation suitable for routine use.     

A Menthol Loading Test for Glucuronide Synthesis Normal Values

A menthol loading test, carried out in 19 normal young men, was found to have a wide normal range, and hence to be of limited diagnostic value in cases of hyperbilirubinaemia which might be due to impaired glucuronide synthesis.     

The involvement of KATP channels in morphine‐induced antinociception and hepatic oxidative stress in acute and inflammatory pain in rats

This study investigated the role of K_ATP channels in morphine‐induced antinociception and hepatic oxidative stress in acute and inflammatory pain. The K_ATP channel modulators (K_ATP channel opener, diazoxide 100 mg/kg, p.o, and K_ATP channel blocker, glibenclamide, 3 mg/kg i.p.) were administered with morphine (80 mg/kg, i.p.). Antinociception was assessed by the tail‐flick and formalin tests in rats and measured by the area under the curve values and the maximum percent effect for 3 h. The indices of hepatic oxidative stress: glutathione, glutathione peroxidase, and malondialdehyde were then determined in the liver homogenates obtained from the treated animals. In both tests, glibenclamide antagonized morphine‐induced antinociception, whereas diazoxide augmented it in the tail‐flick test only. In the formalin test, glibenclamide alone has a significant hyperalgesic effect, whereas diazoxide decreased the number of flinches. Coadministration of glibenclamide with morphine antagonized the hepatotoxic effect of morphine in both animal models. In the tail‐flick test, glibenclamide administered alone significantly increased malondialdehyde's level. Coadministration of diazoxide with morphine increased glutathione level in the formalin test. Diazoxide administered alone exacerbated the hepatic oxidative stress in both animal models. These findings suggest a role of K_ATP channel modulators on morphine‐induced antinociception and hepatic oxidative stress. The administration of glibenclamide may prevent morphine‐induced hepatotoxicity. The effectiveness of diazoxide in the management of pain is limited due to its deleterious effect on the liver. However, the interaction of the K_ATP channel modulators with morphine depends on the differential sensitivity to the pain stimulus.