11β-HSD1 inhibition in men mitigates prednisolone-induced adverse effects in a proof-of-concept randomised double-blind placebo-controlled trial

Glucocorticoids prescribed to limit inflammation, have significant adverse effects. As 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) regenerates active glucocorticoid, we investigated whether 11β-HSD1 inhibition with AZD4017 could mitigate adverse glucocorticoid effects without compromising their anti-inflammatory actions. We conducted a proof-of-concept, randomized, double-blind, placebo-controlled study at Research Unit, Churchill Hospital, Oxford, UK (NCT03111810). 32 healthy male volunteers were randomized to AZD4017 or placebo, alongside prednisolone treatment. Although the primary endpoint of the study (change in glucose disposal during a two-step hyperinsulinemic, normoglycemic clamp) wasn’t met, hepatic insulin sensitivity worsened in the placebo-treated but not in the AZD4017-treated group. Protective effects of AZD4017 on markers of lipid metabolism and bone turnover were observed. Night-time blood pressure was higher in the placebo-treated but not in the AZD4017-treated group. Urinary (5aTHF+THF)/THE ratio was lower in the AZD4017-treated but remained the same in the placebo-treated group. Most anti-inflammatory actions of prednisolone persisted with AZD4017 co-treatment. Four adverse events were reported with AZD4017 and no serious adverse events. Here we show that co-administration of AZD4017 with prednisolone in men is a potential strategy to limit adverse glucocorticoid effects

A global horizon scan of the future impacts of robotics and autonomous systems on urban ecosystems

Technology is transforming societies worldwide. A major innovation is the emergence of robotics and autonomous systems (RAS), which have the potential to revolutionize cities for both people and nature. Nonetheless, the opportunities and challenges associated with RAS for urban ecosystems have yet to be considered systematically. Here, we report the findings of an online horizon scan involving 170 expert participants from 35 countries. We conclude that RAS are likely to transform land use, transport systems and human–nature interactions. The prioritized opportunities were primarily centred on the deployment of RAS for the monitoring and management of biodiversity and ecosystems. Fewer challenges were prioritized. Those that were emphasized concerns surrounding waste from unrecovered RAS, and the quality and interpretation of RAS-collected data. Although the future impacts of RAS for urban ecosystems are difficult to predict, examining potentially important developments early is essential if we are to avoid detrimental consequences but fully realize the benefits

The Improving Global Health fellowship: a qualitative analysis of innovative leadership development for NHS healthcare professionals

Abstract Background The importance of leadership development in the early stages of careers in the NHS has been highlighted in recent years and many programmes have been implemented which seek to develop leadership skills in healthcare professionals. The Improving Global Health (IGH) Fellowship scheme is one such programme, it provides a unique leadership development opportunity through an overseas placement with a focus on quality improvement work. This evaluation examines the impact of completing an IGH Fellowship on the career and leadership development of participants, who are referred to as Fellows. Methods Fellows who had returned from overseas placement between August 2008 and February 2015 were invited to complete an anonymised online questionnaire, which collected information on: demographic details, motivations for applying to the programme, leadership development and the impact of the IGH Fellowship on their career. Fifteen semi-structured interviews were conducted to further explore the impact of the programme on Fellows’ leadership development and career progression. Interview transcripts were manually coded and underwent thematic content analysis. Results The questionnaire had a 67% (74/111) response rate. The number of fellows who self-identified as a leader more than doubled on completion of the IGH Fellowship (24/74 pre-fellowship versus 58/74 post-fellowship). 74% (55/74) reported that the IGH Fellowship had an impact upon their career, 35 of which reported that the impact was “substantial”. The themes that emerged from the interviews revealed a personal development cycle that consolidated the fellows’ interests and values whilst enhancing their self-efficacy and subsequently impacted positively upon their career choices. Three interviewees expressed frustration at the lack of opportunity to utilise their new skills on returning to the United Kingdom (UK). Conclusions The IGH Fellowship successfully empowered healthcare professionals to self-identify as leaders. Of the 45/74 respondents who commented on the impact of the IGH Fellowship on their career, 41/45 comments were positive. The fellows described a process of experiential learning, reflection and evolving cultural intelligence, which consolidated their interests and values. The resultant increase in self-efficacy empowered these returned fellows in their choice of career

The Health of the Nation Outcome Scales for Children and Adolescents in an adolescent in-patient sample

The primary aims of the study were to examine the reliability and validity of the Health of the Nation Outcome Scales for Children and Adolescents (HoNOSCA) in a sample of adolescents requiring medium to long-term in-patient psychiatric treatment and to examine the association between HoNOSCA scores and age, gender and length of treatment.A multidisciplinary team completed the HoNOSCA for 51 adolescent patients at intake and at 3- and 6-months following admission to the unit.The study provided support for the test-retest reliability, concurrent and convergent validity, but not the internal reliability, of the HoNOSCA. Total HoNOSCA scores at intake were similar to those found in adolescent outpatient samples, although there were some differences at the level of individual items. Similarly, while the total HoNOSCA score showed some sensitivity to change, using the total HoNOSCA score obscured important changes in specific domains of functioning over the course of admission.The HoNOSCA was found to be a valid measure of global functioning at intake, thereby supporting its use in an adolescent psychiatric unit. However, focusing on individual items, rather than total score, appears more useful in evaluating the impact of inpatient psychiatric treatment on adolescents

11β-HSD1 inhibition in men mitigates prednisolone-induced adverse effects in a proof-of-concept randomised double-blind placebo-controlled trial

Glucocorticoids prescribed to limit inflammation, have significant adverse effects. As 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) regenerates active glucocorticoid, we investigated whether 11β-HSD1 inhibition with AZD4017 could mitigate adverse glucocorticoid effects without compromising their anti-inflammatory actions. We conducted a proof-of-concept, randomized, double-blind, placebo-controlled study at Research Unit, Churchill Hospital, Oxford, UK (NCT03111810). 32 healthy male volunteers were randomized to AZD4017 or placebo, alongside prednisolone treatment. Although the primary endpoint of the study (change in glucose disposal during a two-step hyperinsulinemic, normoglycemic clamp) wasn’t met, hepatic insulin sensitivity worsened in the placebo-treated but not in the AZD4017-treated group. Protective effects of AZD4017 on markers of lipid metabolism and bone turnover were observed. Night-time blood pressure was higher in the placebo-treated but not in the AZD4017-treated group. Urinary (5aTHF+THF)/THE ratio was lower in the AZD4017-treated but remained the same in the placebo-treated group. Most anti-inflammatory actions of prednisolone persisted with AZD4017 co-treatment. Four adverse events were reported with AZD4017 and no serious adverse events. Here we show that co-administration of AZD4017 with prednisolone in men is a potential strategy to limit adverse glucocorticoid effects

Time to Peak Glucose and Peak C-Peptide During the Progression to Type 1 Diabetes in the Diabetes Prevention Trial and TrialNet Cohorts

OBJECTIVE To assess the progression of type 1 diabetes using time to peak glucose or C-peptide during oral glucose tolerance tests (OGTTs) in autoantibody-positive relatives of people with type 1 diabetes. RESEARCH DESIGN AND METHODS We examined 2-h OGTTs of participants in the Diabetes Prevention Trial Type 1 (DPT-1) and TrialNet Pathway to Prevention (PTP) studies. We included 706 DPT-1 participants (mean ± SD age, 13.84 ± 9.53 years; BMI Z-score, 0.33 ± 1.07; 56.1% male) and 3,720 PTP participants (age, 16.01 ± 12.33 years; BMI Z-score, 0.66 ± 1.3; 49.7% male). Log-rank testing and Cox regression analyses with adjustments (age, sex, race, BMI Z-score, HOMA-insulin resistance, and peak glucose/C-peptide levels, respectively) were performed. RESULTS In each of DPT-1 and PTP, higher 5-year diabetes progression risk was seen in those with time to peak glucose >30 min and time to peak C-peptide >60 min (P < 0.001 for all groups), before and after adjustments. In models examining strength of association with diabetes development, associations were greater for time to peak C-peptide versus peak C-peptide value (DPT-1: χ2 = 25.76 vs. χ2 = 8.62; PTP: χ2 = 149.19 vs. χ2 = 79.98; all P < 0.001). Changes in the percentage of individuals with delayed glucose and/or C-peptide peaks were noted over time. CONCLUSIONS In two independent at-risk populations, we show that those with delayed OGTT peak times for glucose or C-peptide are at higher risk of diabetes development within 5 years, independent of peak levels. Moreover, time to peak C-peptide appears more predictive than the peak level, suggesting its potential use as a specific biomarker for diabetes progression