New insights into the antimicrobial mechanisms of copper touch surfaces

Survival of pathogens on touch surfaces contributes to increasing incidence and spread of antibiotic resistance and infection in hospitals. One way to address this could be to use biocidal surfaces in conjunction with improved cleaning regimes. Exposure to moist copper alloy surfaces, to simulate fomite contamination, resulted in a rapid kill of significant bacterial, viral and fungal pathogens. We now report studies on dry surfaces with a range of pathogens to elucidate the antimicrobial mechanism

Management of incidental adrenal tumours.

An incidental adrenal tumour, described in this article as an “adrenal incidentaloma,” is an adrenal mass discovered during imaging that was not performed for suspected adrenal disease. These are being detected more frequently in an ageing population through the increased use of computed tomography (eg, computed tomography urogram, or colonoscopy) and magnetic resonance imaging (MRI) scans with enhanced resolution. This article highlights the management of adrenal incidentalomas, collating recommendations from international guidelines, and is aimed at non-specialists

Relaxation and Guided Imagery Significantly Reduces Androgen Levels and Distress in Polycystic Ovary Syndrome: Pilot Study

AIM: Women with polycystic ovary syndrome (PCOS) often have elevated levels of the androgen testosterone, and are at increased risk of anxiety and depression. This study aimed to use psychological relaxation with guided imagery to decrease androgen levels and improve mood in PCOS. METHODS: Repeated-measures. Thirteen women with PCOS underwent six weekly treatment sessions, and a follow-up session, of calming breathing, muscle relaxation, and guided imagery. The main outcome measures were mood and quality of life (QoL) – assessed using validated questionnaires – and hormones, which were assayed in serum using tandem mass spectrometry. RESULTS: There was a small but statistically significant reduction in DHEAS from before to after Week 1 (p <.044) and from before to after Week 6 (p <.001). From before to after Week 6 there were also small but statistically significant reductions in androstenedione (p <.010) and cortisol (p <.003). From Week 1 to Week 6 there was a significant reduction in anxiety (p <.037). There was a significant improvement in depression from Week 1 to Week 6 (p <.034) and from Week 1 to follow-up (p <.011). There were no significant changes in free or total testosterone, nor in QoL. CONCLUSIONS: This is the first study to use a relaxation programme to reduce adrenal androgens in PCOS

Bioavailability of oral hydrocortisone corrected for binding proteins and measured by LC-MS/MS using serum cortisol and salivary cortisone

Context: The assessment absolute bioavailability of oral hydrocortisone is complicated by its saturable binding to cortisol binding globulin (CBG). Previous assessment of bioavailability used a cortisol radioimmunoassay which has cross reactivity with other steroids. Salivary cortisone is a measure of free cortisol and LC-MS/MS is the gold standard method for measuring steroids. We here report the absolute bioavailability of hydrocortisone calculated using serum cortisol and salivary cortisone measured by LC-MS/MS. Methods: 14 healthy male dexamethasone suppressed volunteers were administered 20 mg hydrocortisone either intravenously or orally by tablet. Samples of serum and saliva were taken and measured for cortisol and cortisone by LC-MS/MS. Serum cortisol was corrected for saturable binding using published data and pharmacokinetic parameters derived using the program WinNonlin. Results: The mean (95% CI) bioavailability of oral hydrocortisone calculated from serum cortisol, unbound serum cortisol and salivary cortisone was 1.00 (0.89-1.14); 0.88 (0.75-1.05); and 0.93 (0.83-1.05), respectively. Conclusion: The data confirm that, after oral administration, hydrocortisone is completely absorbed. The data derived from serum cortisol corrected for protein binding, and that from salivary cortisone, are similar supporting the concept that salivary cortisone reflects serum free cortisol levels and that salivary cortisone can be used as a non-invasive method for measuring the pharmacokinetics of hydrocortisone

Real world evidence supports waking salivary cortisone as a screening test for adrenal insufficiency

Objective Worldwide, adults and children are at risk of adrenal insufficiency largely due to infectious diseases and adrenal suppression from use of anti-inflammatory glucocorticoids. Home waking salivary cortisone is an accurate screening test for adrenal insufficiency, it has potential to reduce costs, and patients prefer it to the adrenocorticotropin (ACTH) (synacthen) stimulation test. We carried out a service evaluation of home waking salivary cortisone in clinical care to identify implementation barriers. Design, Patients and Measurements Service evaluation in a centre where 212 patients referred for adrenal insufficiency had a waking salivary cortisone. Problems encountered during testing were recorded and patient feedback, via focus groups, collected. Results From all patients providing a waking salivary cortisone 55% had a normal test, 23% adrenal suppression, and 22% an equivocal result requiring a clinical centre ACTH stimulation test. The median (interquartile range [IQR]) for the time of the saliva sample was 07:40 (07:00–08:40). The median (IQR) days between collection and (i) delivery to local laboratory was 1 (0.25–2) day; (ii) reporting by local laboratory was 13 (11–18) days. Patients considered the test is “easy to do” and preferred it to the inpatient ACTH stimulation test. The principal challenge to clinical implementation was results reporting to clinicians due to delays at the local laboratory. Conclusions This service evaluation provides real-world evidence that home waking salivary cortisone is an effective, practical screening test for adrenal insufficiency. It identified key barriers to testing implementation that need to be addressed when introducing the test to a health service

An oral lipidic native testosterone formulation that is absorbed independent of food

Context There is no licensed oral native testosterone (NT) because of challenges in the formulation. Licensed oral formulations of the ester, testosterone undecanoate (TU), require a meal for absorption and generate supraphysiological dihydrotestosterone (DHT) levels. Objective To develop an oral NT formulation. Design and methods A lipid-based formulation of native testosterone filled into soft-gelatin capsules at 40 mg per capsule was designed with 2 years of stability at ambient temperature. Pharmacokinetic comparison studies of this oral lipidic NT formulation to oral TU were conducted in dogs and hypogonadal men. Results In dogs, 40 mg NT was well absorbed under fasted conditions whereas 40 mg TU required a high-fat meal: for NT, the mean fed/fasted AUC ratio was 1.63 and for TU 7.05. In hypogonadal men, fed and fasted NT had similar pharmacokinetics: Cmax mean 26.5 vs 30.4 nmol/L (769 vs 882 ng/dL), AUC0–10 h 87 vs 88.6 h nmol/L. NT (fed state) showed a testosterone AUC increase of 45% between 120 and 200 mg, and NT 200 mg gave a similar mean AUC0–10 h to TU 80 mg: 87 vs 64.8 h nmol/L. Serum TU levels were variable and on a molar basis were ~ten-fold higher than serum testosterone levels after TU 80 mg fed. The DHT: testosterone AUC0–10 h ratio was more physiological for NT than TU being 0.19 vs 0.36. There were no emerging safety concerns with NT. Conclusion This novel oral lipidic native testosterone formulation has potential advantages over oral TU of dosing independently of food and a lower risk of supraphysiological DHT levels. Significance statement There is no licensed oral testosterone because of challenges in formulation, and the oral formulations of the ester, testosterone undecanoate, require a fatty meal for absorption and generate supraphysiological dihydrotestosterone levels. We have overcome the design challenges and formulated an oral native testosterone that can be taken with or without food and provides physiological levels of testosterone and dihydrotestosterone in hypogonadal men. This formulation, DITEST, has the potential advantage of being oral for patients who do not tolerate injections and less risk of adverse events that might theoretically be associated with elevated dihydrotestosterone levels. Future studies will need to define the dosing regimen for replacement in hypogonadal men

Pharmacodynamic studies of nasal tetracosactide with salivary glucocorticoids for a non-invasive Short Synacthen Test

Context: The Short Synacthen Test (SST) is the gold standard for diagnosing adrenal insufficiency. It requires invasive administration of Synacthen, venous sampling and is resource-intensive. Objective: To develop a nasally administered SST, with salivary glucocorticoids measurement, to assess the adrenal response. Design: We conducted five studies: four open-label, sequence-randomised, crossover, pharmacodynamic studies testing six doses/formulations and a repeatability study. Additionally, pharmacokinetic analysis was undertaken using our chosen formulation, 500 µg tetracosactide with mucoadhesive chitosan, Nasacthin003, in our paediatric study. Setting: Adult and children’s Clinical Research Facilities. Participants: 36 healthy adult males and 24 healthy children. Intervention: We administered all six nasal formulations using a CE marked atomisation device. The intravenous comparators were 250 µg or 1 µg SST. Main Outcome Measures: We analysed paired blood and saliva samples for plasma cortisol and salivary cortisol and cortisone. Results: The addition of chitosan to tetracosactide and dose escalation increased peak cortisol response (p=0·01 and 0·001 respectively). The bioavailability of Nasacthin003 was 14·3%. There was no significant difference in plasma cortisol at 60 minutes between 500 µg Nasacthin003 and 250 µg intravenous Synacthen (p=0.17). The repeatability coefficient at 60 minutes was 105 nmol/l for intravenous Synacthen and for salivary cortisol and cortisone was 10·3 and 21·1 nmol/L respectively. The glucocorticoid response in children was indistinguishable from that of adults. Conclusions: Nasal administration of Nasacthin003 generates equivalent plasma cortisol values to the 250 µg intravenous SST and, with measurement at 60 minutes of salivary cortisol or cortisone, provides a non-invasive test for adrenal insufficiency

The carnivorous feeding behavior of early Homo at HWK EE, Bed II, Olduvai Gorge, Tanzania

The regular consumption of large mammal carcasses, as evidenced by butchery marks on fossils recovered from Early Stone Age archaeological sites, roughly coincides with the appearance of Homo habilis. However, the significance of this niche expansion cannot be appreciated without an understanding of hominin feeding behavior and their ecological interactions with mammalian carnivores. The Olduvai Geochronology and Archaeology Project (OGAP) has recovered a large and well-preserved fossil assemblage from the HWK EE site, which was deposited just prior to the first appearance of Acheulean technology at Olduvai Gorge and likely represents one of the last H. habilis sites at Olduvai. This taphonomic analysis of the larger mammal fossil assemblage excavated from HWK EE shows evidence of multiple occupations over a long period of time, suggesting the site offered resources that were attractive to hominins. There was a water source indicated by the presence of fish, crocodiles, and hippos, and there was possible tree cover in an otherwise open habitat. The site preserves several stratigraphic intervals with large fossil and artifact assemblages within two of these intervals. Feeding traces on bone surfaces suggest hominins at the site obtained substantial amounts of flesh and marrow, particularly from smaller size group 1-2 carcasses, and exploited a wide range of taxa, including megafauna. A strong carnivore signal suggests hominins scavenged much of their animal foods during the two main stratigraphic intervals. In the later interval, lower carnivore tooth mark and hammerstone percussion mark frequencies, in addition to high epiphyseal to shaft fragment ratios, suggest hominins and carnivores did not fully exploit bone marrow and grease, which may have been acquired from nutritionally-stressed animals that died during a dry period at Olduvai. The diversity of fauna that preserve evidence of butchery suggests that the HWK EE hominins were opportunistic in their acquisition of carcass foods