Evaluation of adrenal function using the human corticotrophin-releasing hormone test, low dose Synacthen test and 9am cortisol level in children and adolescents with central adrenal insufficiency.

BACKGROUND: The insulin tolerance test (ITT) has become less popular in paediatrics because of the risks associated with hypoglycaemia. Human corticotrophin-releasing hormone (hCRH) test results correlate with the ITT and may be an acceptable method to test for central adrenal insufficiency (CAI). Simpler tests, such as the low dose Synacthen test (LDST) and 9am cortisol, have also been proposed. OBJECTIVE: To compare the ability of the hCRH test, LDST, 9am cortisol level and 24-h cortisol profiles to diagnose CAI in a paediatric population. DESIGN AND SETTING: A cross-sectional study in a tertiary paediatric endocrine clinic. PARTICIPANTS: Thirty-one children and adolescents (aged 2.3-18.3 years) with CAI risk factors had an hCRH test, LDST, 9am cortisol and 24-h cortisol profile performed. RESULTS: Of 23 patients with confirmed CAI (hCRH peak cortisol < 400 nmol/), 19 failed the LDST (peak cortisol < 267 nmol/l, i.e. 10th percentile for controls). Nineteen would have failed based on the 10th percentile cut point for 9am cortisol (< 140 nmol/l). Using receiver operating characteristic (ROC) curve coordinates, a 9am cortisol < 108 nmol/l was sensitive (83%) and specific (99%) for CAI. The 9am cortisol levels measured on two occasions were repeatable (94%) and correlated (r = 0.83, P = 0.01). All eight adrenally sufficient patients (hCRH peak cortisol > or = 400 nmol/l) passed the LDST. Seven had normal 9am cortisol (> or = 140 nmol/l). The 24-h cortisol area under the curve (AUC) for these patients was within the 10th-90th percentiles for control subjects' AUC. The peak cortisol to hCRH and LDST were correlated (r = 0.88, P = 0.01), with no difference between the peaks (mean difference -5.3 nmol/l, P = 0.69). CONCLUSIONS: In children with CAI risk factors, the diagnosis can be made if unstressed 9am cortisol is < 108 nmol/l. As cortisol levels > 381 nmol/l are highly suggestive of normal hypothalamic-pituitary-adrenal (HPA) function, stimulation testing need only be performed if 9am cortisol is 108-381 nmol/l. The LDST should be interpreted cautiously because mild CAI may be missed. When stimulation results are marginal, 24-h cortisol profiles can provide reassurance of normal cortisol status.

Advantages of the nested case-control design in diagnostic research.

BACKGROUND: Despite its benefits, it is uncommon to apply the nested case-control design in diagnostic research. We aim to show advantages of this design for diagnostic accuracy studies. METHODS: We used data from a full cross-sectional diagnostic study comprising a cohort of 1295 consecutive patients who were selected on their suspicion of having deep vein thrombosis (DVT). We draw nested case-control samples from the full study population with case:control ratios of 1:1, 1:2, 1:3 and 1:4 (per ratio 100 samples were taken). We calculated diagnostic accuracy estimates for two tests that are used to detect DVT in clinical practice. RESULTS: Estimates of diagnostic accuracy in the nested case-control samples were very similar to those in the full study population. For example, for each case:control ratio, the positive predictive value of the D-dimer test was 0.30 in the full study population and 0.30 in the nested case-control samples (median of the 100 samples). As expected, variability of the estimates decreased with increasing sample size. CONCLUSION: Our findings support the view that the nested case-control study is a valid and efficient design for diagnostic studies and should also be (re)appraised in current guidelines on diagnostic accuracy research.

Impact of minimally invasive surgery on the pediatric surgical profession.

We conducted a survey among pediatric surgeons to examine the impact of the advent of minimally invasive surgery (MIS) on the pediatric surgical profession with respect to job satisfaction and training challenges. An invitation to participate in a web-based questionnaire was sent out to 306 pediatric surgeons. Apart from demographic details and training recommendations, parameters relevant to job satisfaction, including patient interaction, peer pressure, ethical considerations, academic progress, ability to train residents, and financial remuneration, were studied. The response rate was 38.2%. Working in a unit performing MIS was identified by 71% of respondents as the most effective and feasible modality of training in MIS. Inability to get away from a busy practice was the most common reason cited for inability to acquire MIS training. The overall responses to the job satisfaction parameters showed a positive trend in the current MIS era for patient interaction, ethical considerations, academic progress, and training residents, with a negative trend for peer pressure and financial remuneration. The enthusiastic minimally invasive surgeons (EMIS) were defined as those having more than 5 years of MIS experience and also performing more than 10% of their work using MIS. Of the 113 responses analyzed, 67 belonged to the EMIS category. Those belonging to the EMIS group were less likely to feel inadequate in training their residents, in meeting the felt needs of the patients, or to complain about peer pressure. They were more likely to consider MIS to be as relevant and beneficial in children as in adults. Embracing MIS, as represented by the EMIS group, correlated with an overall greater job satisfaction.

Distraction from randomization in diagnostic research.

The ultimate goal of medical care, including diagnostic testing, is to improve patient outcome. Accordingly, it has been advocated widely that when establishing a test's diagnostic accuracy, the impact of the test on patient outcome subsequently must be quantified. When studying patient outcome in medical research, the use of randomized comparisons comes into perspective. In our view, randomized studies often are not necessary to validly estimate the effect of the diagnostic test on patient outcome. Results of cross-sectional diagnostic studies, combined with results from therapeutic studies, often will suffice.

Genetic programming outperformed multivariable logistic regression in diagnosing pulmonary embolism.

OBJECTIVE: Genetic programming is a search method that can be used to solve complex associations between large numbers of variables. It has been used, for example, for myoelectrical signal recognition, but its value for medical prediction as in diagnostic and prognostic settings, has not been documented. STUDY DESIGN AND SETTING: We compared genetic programming and the commonly used logistic regression technique in the development of a prediction model using empirical data from a study on diagnosis of pulmonary embolism. Using part (67%) of the data, we developed and internally validated (using bootstrapping techniques) a diagnostic prediction model by genetic programming and by logistic regression, and compared both on their predictive ability in the remaining data (validation set). RESULTS: In the validation set, the area under the ROC curve of the genetic programming model was significantly larger (0.73; 95%CI: 0.64-0.82) than that of the logistic regression model (0.68; 0.59-0.77). The calibration of both models was similar, indicating a similar amount of overoptimism. CONCLUSION: Although the interpretation of a genetic programming model is less intuitive and this is the first empirical study quantifying its value for medical prediction, genetic programming seems a promising technique to develop prediction rules for diagnostic and prognostic purposes.

Walking exercise in patients with intermittent claudication. Experience in routine clinical practice.

BACKGROUND: In patients with intermittent claudication, exercise in the form of walking is effective in reducing pain and maximising achievable walking distance. However, data are lacking on the implementation of walking exercise in these patients. AIMS: To explore the current behaviour and views of patients with intermittent claudication towards taking walking exercise. DESIGN OF STUDY: Postal questionnaire and focus group meetings. SETTING: Two academic general practice networks (Utrecht and Maastricht Universities) in The Netherlands. METHOD: Three hundred and seventy-five patients with intermittent claudication, selected from the files of general practitioners participating in two academic general practice networks, were sent a postal questionnaire; 216 (58%) were returned. Nine of these responders also attended a focus group meeting. RESULTS: Seventy per cent (151/216) of the patients reported having received advice about walking exercise. If specified, the advice given most often recommended walking in the local neighbourhood (56%, 84/151). Fifty-two per cent (113/216) of all patients actually performed walking exercise and only 32%of them received any kind of supervision. Among the barriers for taking walking exercise, 'comorbidity', 'lack of (specific) advice' and 'lack of supervision' were often mentioned. Among the stimuli to start and continue walking, 'following the doctor's advice', 'relief of complaints' and 'a better general condition' were often mentioned by patients. CONCLUSIONS: Walking exercise was not carried out by almost half of patients with intermittent claudication in this study. Lack of specific advice and supervision were found to be important barriers to taking walking exercise.

Advances in diagnostics for microbial agents: can clinical validation keep pace with the technical promises?

New technologies are revolutionizing diagnostic microbiology, but implementation of methodological advances in test evaluation has been extraordinarily slow. Published reports frequently fail to clearly distinguish between studies of analytical accuracy and those of clinical diagnostic performance. We argue that the evaluation of sensitivity and specificity, while necessary and occasionally problematic, is often inadequate to define the appropriate role of a new diagnostic test. To determine whether a test adds additional (incremental) value to the diagnostic information already available to the clinician, evaluation studies with a multivariable approach may also be needed. The impact of a test on patient outcome is best measured by a randomized controlled trial, but this may be unnecessary in certain well-defined situations. To improve the quality of published test evaluations close collaboration between clinicians, clinical microbiologists, and epidemiologists, as well as insistence by journal editors on the use of established reporting standards are essential.

Validating and updating a prediction rule for neurological sequelae after childhood bacterial meningitis.

Recently, a prediction rule for developing neurological sequelae after childhood bacterial meningitis was developed on a small derivation set. Before implementing in practice a prediction rule must first be tested in new patients (external validation). Our aim was to study the external validity of this rule and, if necessary, to update the rule. The prediction rule was tested on newly available data (validation set) by assessing the rule's calibration and discrimination. We updated the prediction rule by adding extra predictors and re-estimating the regression coefficients of the original predictors in the combined datasets. The rule showed poor agreement between predicted risks and observed frequencies. The ROC area was 0.65 (95% CI 0.57-0.72), which was statistically significantly lower than in the derivation set (0.87 (0.78-0.96)), p-value<0.01. The updated prediction rule showed adequate performance in the combined data sets; the ROC area was 0.77 (95% CI 0.72-0.82). Further study of the generalizability of this updated rule may stimulate application in clinical practice.