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Background: The introduction of adalimumab in the management of hidradenitis suppurativa (HS) raises questions regarding the cost-efficacy of treatment. Objectives: To explore cost-efficacy of treatment with anti-tumour necrosis factor (TNF) agents in a real-world cohort. Methods: Patients with Hurley stage II and III HS with ≥ 1 year of follow-up and at least three visits per year from September 2003 to December 2016 were analysed. Patient visits were divided into two categories – visits for treatment with agents blocking TNF or visits for other therapies. The cost of exacerbations was calculated based on the cost of items provided in current price lists or by the national health insurance agency in cases of hospitalization. Effectiveness of anti-TNF agents was calculated by assessing containment of exacerbations. The primary study end point was the cost-savings achieved using anti-TNF agents. Results: Overall, 1211 patient visits for 250 patients were analysed. Total containment of exacerbations was found in 25·1% of visits involving other therapies and in 63·4% of visits involving anti-TNF agents. The cost-savings per patient visit for patients receiving anti-TNF agents vs. other therapies was €178·92. The odds ratio for the total containment of exacerbations among patients with Hurley stage II and III was 4·86 and 6·03, respectively (P = 0·466). Treatment with anti-TNF agents was an independent variable affecting annual cost as shown by two-way analysis of variance. In Hurley stage III HS, mean annual cost was €8309·60 under other therapies compared with €3264·20 using anti-TNF agents (P = 0·004). Conclusions: Treatment with anti-TNF agents achieves significant cost–benefit through containment of HS exacerbations. The efficacy of anti-TNF agents was similar for both disease stages. © 2018 British Association of Dermatologists

With the prevalence of global project-focused organisations, project management is emerging as a vital conduit of innovation within such companies. This study aims to provide a detailed meta-analytic insight into contemporary project management trends, with a particular focus on complexity of innovative projects. Trends in project management literature were analysed from 1975 to 2015. Findings from the analysis highlight the importance of strategic alignment, agility, competencies development and risk management for successful project implementation. By exploring inherent dynamics enabling/constraining practitioners to deliver projects successfully in complex, uncertain environments helps reveal factors influencing their ability to collaborate and realise innovative potential. The analysis also highlights a lack of standardisation in project management practices, which hinders the effective dealing with innovative complexity. Overall the study contributes to further our understanding of managing complex projects.

With the prevalence of global project-focused organisations, project management is emerging as a vital conduit of innovation within such companies. This study aims to provide a detailed meta-analytic insight into contemporary project management trends, with a particular focus on complexity of innovative projects. Trends in project management literature were analysed from 1975 to 2015. Findings from the analysis highlight the importance of strategic alignment, agility, competencies development and risk management for successful project implementation. By exploring inherent dynamics enabling/constraining practitioners to deliver projects successfully in complex, uncertain environments helps reveal factors influencing their ability to collaborate and realise innovative potential. The analysis also highlights a lack of standardisation in project management practices, which hinders the effective dealing with innovative complexity. Overall the study contributes to further our understanding of managing complex projects.

Many industrialised nations have changing demographic profiles, as increased longevity and decreased birth rates lead to an ageing population. This presents significant challenges for workforces, as older employees retire and there are insufficient numbers of younger employees to take their place. This leads to skills shortages, and strong competition for those who are available. This paper considers these issues in the context of Queensland, the third largest state of Australia. The Queensland Government is addressing the issues for all industries in the state, primarily through a Skills Plan and an Experience Pays Awareness Strategy. As the largest employer in the state, the Queensland Government has commenced implementing the Experience Pays Awareness Strategy within its own workforce. The approach touches on many facets of HRM. The HRM policy framework and tools are examined for their potential to support increased participation of older employees. A range of issues are addressed for older workers, including their competence and health and safety issues. Issues for managers include addressing myths and subtle discrimination against older workers, as well as managing cross-generational workforce. Other strategies and methods are targeted at cultural factors, such as the expectations of older workers, and the myths and discrimination against older workers. Yet other strategies are aimed at organisational issues such retention of knowledge and succession planning.

Inactivating PROP1 gene alterations are responsible for over 50% of familial combined pituitary hormone deficiency cases. Pituitary enlargement followed by regression and subnormal pituitary size has been documented in a number of PROP1 deficient patients. Data derived from PROP1 deficient mice (Ames dwarfs) have revealed some of the underlying cellular mechanisms. Nevertheless, long-term magnetic resonance imaging (MRI) findings in two PROP1 deficient patients suggest the evolution of pituitary pathology as more complex and persistent than previously described. Patient A had enlarged pituitary gland (pituitary height: 9-10 mm), demonstrated by serial MRI carried out from age 5 to 8.5 yr, small pituitary gland (4 mm) at age 10 yr and pituitary enlargement (111 mm) at age 19 yr. Patient B had a pituitary gland of normal size at age 7 yr (5 mm), whereas at age 14.3 and 16.3 yr, an enlarged pituitary gland was disclosed (10 and 11 mm, respectively). Both series of events are suggestive of a persistent pathophysiological mechanism in the pituitary gland of patients with PROP1 gene defects. Therefore, long-term pituitary follow-up by MRI in such patients may be necessary even in the case of a small or normal pituitary gland. It must be noted that current data from the Ames dwarf mouse cannot fully explain the observed pituitary size fluctuation.

Pituitary morphology in patients with Prop1 gene mutations varies. Most patients demonstrate a normal or small pituitary gland. Occasionally, pituitary enlargement of undetermined origin has also been detected. In the present study we use long-term magnetic resonance imagingfindings to characterize the morphological abnormalities of the pituitary gland in 15 patients (aged 2.5-45 yr) with combined pituitary hormone deficiency caused by Prop1 gene mutations (GA296del/GA296del in seven, GA296del/A150del in two, A150del/A150del in five, and GA296del/R73H in one patient) and attempt to uncover the origin and nature of the pituitary enlargement. Small pituitary gland was detected in seven patients (25.2 +/- 14.4 yr of age), normal pituitary size in three patients (10.2 +/- 5.8 yr of age), and pituitary enlargement in five patients (6.5 +/- 2.7 yr of age). The pituitary enlargement consisted of a nonenhancing mass lesion interposed between the normally enhancing anterior lobe and the neurohypophysis. The pituitary stalk was displaced anteriorly, whereas the neurohypophysis was orthotopic, displaying a normal signal. Spontaneous regression of the mass lesion with normalization of the pituitary stalk position was observed in three patients. Our data indicate that although a small pituitary gland is usually observed in older subjects, a significant number of young patients with Prop1 gene mutations demonstrate pituitary enlargement with subsequent regression. The distinct magnetic resonance imaging characteristics of the pituitary enlargement in our patients in conjunction with pertinent data from Prop1-deficient mice suggest that the mass causing the pituitary enlargement most likely originates from the intermediate lobe.

Objective: To identify the genetic defect in a neonate presented with prolonged jaundice and central hypothyroidism. Design: Central hypothyroidism was detected in a neonate initially examined for prolonged jaundice, and levothyroxine therapy was initiated. Direct sequencing of the Prop1 gene was carried out and pituitary function and morphology were evaluated using hormonal testing and magnetic resonance imaging (MRI) respectively. Methods: Dynamic hormonal testing was carried out using established methodologies. Hormones were determined by RIA or chemiluminescence immunoassays. Genomic analysis of the Prop1 gene was performed by direct sequencing. MRI protocol: sagittal spin echo T2-weighted scans 2500/90 (TR/TE). plain and contrast-enhanced sagittal and coronal spin echo T1-weighted scans 500/20 (TR/TE). Results: Low thyroid hormones (coupled with lack of TSH rise), low GH, normal cortisol and normal prolactin values were detected. Direct sequencing revealed the presence of two mutations in the Prop1 gene: GA296del and Q83X. The 083X was further confirmed by PvuII restriction digestion and represented a novel Prop1 gene mutation. which was not detected in 100 controls tested. Pituitary enlargement was detected, with respect to normal-for-age controls. Conclusions: (i) The Q83X mutation extends the spectrum of Prop1 gene mutations: (ii) central hypothyroidism in a neonate might constitute the initial sign of Prop1 gene defect; (iii) the patient is the youngest individual with Prop1 gene defect and pituitary enlargement presented to date; and (iv) early detection of Prop1 gene mutations facilitates genetic counseling and ensures prompt management of the anticipated hormonal insufficiencies.