The contribution of serum cortisone and glucocorticoid metabolites to detrimental bone health in patients receiving hydrocortisone therapy

Background Glucocorticoid therapy is the most common cause of iatrogenic osteoporosis. Less is known regarding the effect of glucocorticoids when used as replacement therapy on bone remodelling in patients with adrenal insufficiency. Enhanced intracellular conversion of inactive cortisone to active cortisol, by 11 beta-hydroxysteroid dehydrogenase type 1(11β-HSD1) and other enzymes leading to alterations in glucocorticoid metabolism, may contribute to a deleterious effect on bone health in this patient group. Methods Study design: An open crossover prospective study randomizing ten hypopituitary men, with severe ACTH deficiency, to three commonly used hydrocortisone dose regimens. Measurements: Following 6 weeks of each regimen, patients underwent 24-h serum cortisol/cortisone sampling, measurement of bone turnover markers, and a 24-h urine collection for measurement of urinary steroid metabolites by gas chromatography-mass spectrometry (GC-MS). Serum cortisone and cortisol were analysed by liquid chromatography-mass spectrometry (LC-MS). Results Dose-related and circadian variations in serum cortisone were seen to parallel those for cortisol, indicating conversion of ingested hydrocortisone to cortisone. The median area under the curve (AUC) of serum cortisone was significantly higher in patients on dose A (20 mg/10 mg) [670.5 (IQR 621–809.2)] compared to those on dose C (10 mg/5 mg) [562.8 (IQR 520.1–619.6), p = 0.01]. A negative correlation was observed between serum cortisone and bone formation markers, OC [1–49] (r = − 0.42, p = 0.03), and PINP (r = − 0.49, p = 0.01). There was a negative correlation between the AUC of night-time serum cortisone levels with the bone formation marker, OC [1–49] (r = − 0.41, p = 0.03) but there were no significant correlations between day-time serum cortisone or cortisol with bone turnover markers. There was a negative correlation between total urinary cortisol metabolites and the bone formation markers, PINP (r = − 0.39, p = 0.04), and OC [1–49] (r = − 0.35, p = 0.06). Conclusion Serum cortisol and cortisone and total urinary corticosteroid metabolites are negatively associated with bone turnover markers in patients receiving replacement doses of hydrocortisone, with nocturnal glucocorticoid exposure having a potentially greater influence on bone turnover. Trial registration Irish Medicines Board Clinical Trial Number – CT900/459/1 and EudraCT Number – 2007-005018-37. Registration date: 07-09-2007

Empirical Tests for Evaluation of Multirate Filter Bank Parameters

Empirical tests have been developed for evaluating the numerical properties of multirate M-band filter banks represented as N matrices of filter coe#cients. Each test returns a numerically observed estimate ofa1 M vector parameter in which the m element corresponds to the m filter band. These vector valued parameters can be readily converted to scalar valued parameters for comparison of filter bank performance or optimization of filter bank design. However, they are intended primarily for the characterization and verification of filter banks. By characterizing the numerical performance of analytic or algorithmic designs, these tests facilitate the experimental verification of theoretical specifications

ICAR: endoscopic skull‐base surgery

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Cross‐sectional study on patients' understanding and views of the informed consent procedure of a secondary stroke prevention trial

Background and purpose Improving understanding of study contents and procedures might enhance recruitment into studies and retention during follow-up. However, data in stroke patients on understanding of the informed consent (IC) procedure are sparse. Methods We conducted a cross-sectional study among ischemic stroke patients taking part in the IC procedure of an ongoing cluster-randomized secondary prevention trial. All aspects of the IC procedure were assessed in an interview using a standardized 20-item questionnaire. Responses were collected within 72 h after the IC procedure and analyzed quantitatively and qualitatively. Participants were also asked their main reasons for participation. Results A total of 146 stroke patients (65 ± 12 years old, 38% female) were enrolled. On average, patients recalled 66.4% (95% confidence interval = 65.2%–67.5%) of the content of the IC procedure. Most patients understood that participation was voluntary (99.3%) and that they had the right to withdraw consent (97.1%); 79.1% of the patients recalled the study duration and 56.1% the goal. Only 40.3% could clearly state a benefit of participation, and 28.8% knew their group allocation. Younger age, higher graduation, and allocation to the intervention group were associated with better understanding. Of all patients, 53% exclusively stated a personal and 22% an altruistic reason for participation. Conclusions Whereas understanding of patient rights was high, many patients were unable to recall other important aspects of study content and procedures. Increased attention to older and less educated patients may help to enhance understanding in this patient population. Actual recruitment and retention benefit of an improved IC procedure remains to be tested in a randomized trial