Reliability of functional outcome measures in adults with neurofibromatosis 1

Objectives: To determine intra-rater and inter-rater reliability of functional outcome measures in adults with neurofibromatosis 1 (NF1) and to ascertain how closely objective and subjective measures align. Methods: Forty-nine ambulant adults with NF1 aged 16 years and over were included in this observational study. Median age 31 years (range 16-66), 29 females, 20 males. Participants were video-recorded or photographed performing four functional outcome measures. Four raters from the Neurofibromatosis centre multi-disciplinary team independently scored the measures to determine inter-rater reliability. One rater scored the measures a second time on a separate occasion to determine intra-rater reliability. The measures evaluated were the functional reach, timed up and go, ten metre walk and a modified nine-hole peg tests. Participants also completed a disease specific quality of life questionnaire (INF1-QOL). Results: Inter-rater reliability and intra-rater reliability scores (intra-class coefficient, ICC) were similar for each outcome measure. Excellent rater agreement (ICC r ≥ 0.9) was found for the functional reach, timed up and go and the 10 metre walk tests. Rater agreement was good for the modified 9-hole peg test; ICC r= 0.75 for intra-rater reliability and 0.76 for inter-rater reliability. The timed up and go and the 10 metre walk tests correlated highly with perceived mobility challenges in the quality of life questionnaire (INF1-QOL). Conclusions: The functional reach, timed up and go and 10 metre walk tests are potentially useful outcome measures for monitoring NF1 treatment and will be assessed for validity and reliability in future multi-centre studies

Free-of-charge medicine schemes in the NHS: A local and regional drug and therapeutic committee's experience

INTRODUCTION: Free-of-charge (FoC) medicine schemes are increasingly available and allow access to investigational treatments outside clinical trials or in advance of licensing or NHS commissioning. METHODS: We retrospectively reviewed FoC medicine schemes evaluated between 2013 and 2019 by a single NHS trust and a regional drug and therapeutics committee (DTC). The details of each locally reviewed FoC scheme, and any nationally available Medicines and Healthcare products Regulatory Agency Early Access to Medicines Scheme (MHRA EAMS) in the same period, were recorded and categorised. RESULTS: Most FoC schemes (95%) allowed access to medicines intended to address an unmet clinical need. Over 7 years, 90% were company-FoC schemes and 10% were MHRA EAMS that were locally reviewed. Phase 3 clinical trial data were available for 44% of FoC schemes, 37% had phase 2 data and 19% were supported only by phase 1 data, retrospective observational studies or preclinical data. Utilisation of company-FoC schemes increased on average by 50% per year, while MHRA EAMS schemes showed little growth. CONCLUSION: Company-FoC medicine schemes are increasingly common. This may indicate a preference for pharmaceutical companies to independently co-ordinate schemes. Motivations for company-FoC schemes remain unclear and many provide access to treatments that are yet to be evaluated in appropriately conducted clinical trials, and whose efficacy and risk of harm remain uncertain. There is no standardisation of this practice and there is no regulatory oversight. Moreover, no standardised data collection framework is in place that could demonstrate the utility of such programmes in addressing unmet clinical need or to allow generation of further evidence

The Cam-type Deformity of the Proximal Femur Arises in Childhood in Response to Vigorous Sporting Activity

Background: The prevalence of a cam-type deformity in athletes and its association with vigorous sports activities during and after the growth period is unknown. Questions/purposes: We therefore compared the prevalence and occurrence of a cam-type deformity by MRI in athletes during childhood and adolescence with an age-matched control group. Patients and Methods: We retrospectively reviewed 72 hips in 37 male basketball players with a mean age of 17.6years (range, 9-25years) and 76 asymptomatic hips of 38 age-matched volunteers who had not participated in sporting activities at a high level. Results: Eleven (15%) of the 72 hips in the athletes were painful and had positive anterior impingement tests on physical examination. Internal rotation of the hip averaged 30.1° (range, 15°-45°) in the control group compared with only 18.9° (range, 0°-45°) in the athletes. The maximum value of the alpha angle throughout the anterosuperior head segment was larger in the athletes (average, 60.5°±9°), compared with the control group (47.4°±4°). These differences became more pronounced after closure of the capital growth plate. Overall, the athletes had a 10-fold increased likelihood of having an alpha angle greater than 55° at least at one measurement position. Conclusions: Our observations suggest a high intensity of sports activity during adolescence is associated with a substantial increase in the risk of cam-type impingement. These patients also may be at increased risk of subsequent development of secondary coxarthrosis. Level of Evidence: Level II, diagnostic study. See the Guidelines for Authors for a complete description of levels of evidenc

Human Resource Management of US multinationals in Germany and the UK.

This research examines human resource management (HRM) in subsidiaries of US multinational firms (MNCs) operating in the UK and Germany. Together with parallel studies in Ireland and Spain it explores the potential tensions resulting from a transfer of US-type human resource (HR) policies to Europe. Whilst we expected that the liberal market British economy would not provide a major challenge for the transfer of US practices, we foresaw that the more densely institutionalized German business system would constitute a more serious barrier to transfer. This report is based on case studies of four large US MNCs. In all four firms we conducted interviews in the British and German subsidiaries, as well as the US and/or European headquarters, with HR managers, line managers and non-managerial employees. For three substantive issues – diversity management, employee participation and pay – as well as for the processual issue of ‘centralization–decentralization’ this report analyses whether the four US MNCs studied have global policies, how these are transferred to Europe and the extent to which they have to be adapted to the British and German contexts. Our findings support previous research which suggests that HR policies in US MNCs are not only relatively standardised, but also build on US domestic policies. However, the mechanisms of transfer appear to have changed. Whereas in the past, written guidelines, the transfer of home-country employees and extensive reporting seem to have been the major mechanisms employed to ensure that global policies were applied, today HR information systems, regional European headquarters and international teams of HR managers seem to play a more important role. Over the last decade, national subsidiaries in both countries have lost autonomy in HR decision-making. However, this has not been primarily in the form of recentralization towards headquarters, but rather towards the regional level and/or business unit. Turning to substantive issues, as expected, the German institutional environment represents a stronger challenge for US MNCs than the British one. Of particular importance is codetermination which affects all four firms and which in at least three of them exerts pressure on local management to adjust global polices to local conditions. However, in most cases the observed deviations were only marginal. Similarly, the German system of multi-employer bargaining does not constitute a major hurdle for US MNCs seeking to apply global practices. Although in general German host-country pressures were stronger than those in the UK, we found that UK management was able to use its role of interpreter of the local environment to force some adaptation of global policies, particularly in the substantive area of diversity management, suggesting that the extent to which local adaptation occurs is not entirely dependent on the strength of employment-relations institutions in the host country. Regarding practical implications, our research points firmly to the limits of global policies. With their knowledge of the local context subsidiary-level managers can and should have some freedom to adapt global policies to the local context. At least in Germany they have an additional role, as they have to manage a complex institutional environment. The system of collective bargaining and codetermination fosters collective HR policies that are often incompatible with the more individualistic global policies pursued by US MNCs. Nevertheless, as the case studies show, US MNCs are able to manage these institutions in such a way that the need for adaptation is minimized. This process of institutional arbitrage tends to be performed by local managers with a deep knowledge of the hostenvironment

Immobilisation of glycosidases from commercial preparation on magnetic beads: Part 2: Aroma enhancement in wine using immobilised glycosidases

Most of the terpenes in wines are conjugated to various sugars, representing a significant reservoir of aromatic precursors. To promote the release of these terpenes, certain enzymes, such as β-glucosidase, α-arabinosidase and α-rhamnosidase, are necessary. A simple and cost-effective procedure for the immobilisation of multiple glycosidase activities (β-D-glucopyranosidase, α-L-arabinofuranosidase, α-L-rhamnopyranosidase and β-D-xylopyranosidase) from commercial Aspergillus niger preparation onto magnetic beads as carriers was developed as reported in Part 1 (Ferner et al. 2016).The aim of this work was to analyse a possible application of this immobilised biocatalyst due to its well-known advantages over soluble enzyme preparations – that is, control of the reaction process and preparation of enzyme-free products. Volatile compounds were analysed by gas chromatography (mass spectrometric detection). After the treatment of the model wine with different glycosides and white wine with immobilised glycosidases, the amount of free terpenes was significantly increased with respect to that of the control wine.The results of this study are of considerable interest for possible future applications of immobilised enzymes in the wine-making industry

Evaluation of quality of life in adults with neurofibromatosis 1 (NF1) using the Impact of NF1 on Quality Of Life (INF1-QOL) questionnaire

Background Neurofibromatosis 1 (NF1) is an inherited, multi-system, tumour suppressor disorder with variable complications that cause psychological distress and social isolation. The study aim was to develop and validate a disease-specific questionnaire to measure quality of life (QOL) in NF1 that is suitable both as an assessment tool in clinical practice and in clinical trials of novel therapy. Methods The Impact of NF1 on Quality of Life (INF1-QOL) questionnaire was developed by a literature search for common terms, focus group (n=6), semi-structured interviews (n=21), initial drafts (n =50) and final 14 item questionnaire (n=50). Bivariate correlations between items, exploratory factor analysis, correlations with severity and EuroQol were employed. Results INF1-QOL showed good internal reliability (Cronbach’s alpha 0.87), mean total INF1-QOL score was 8.64 (SD 6.3), median 7.00, range 0-30 (possible range 0-42); no significant correlations with age or gender. The mean total EuroQol score was 7.38 (SD 2.87), median 6.5, mean global EuroQol score was 76.34 (SD 16.56), median 80. Total INF1-QOL score correlated with total EuroQol r=0.82, p<0.0001. The highest impact on QOL was moderate or severe problems with anxiety and depression (32%) and negative effects of NF1 on role and outlook on life (42%). The mean inter-relater reliability for grading of clinical severity scores was 0.71 (range 0.65-0.79), and intra-class correlation was 0.92. The mean clinical severity score was 1.95 (SD 0.65) correlating r=0.34 with total INF1-QOL score p<0.05 and correlated 0.37 with total EuroQol score p<0.01. The clinical severity score was mild in 17 (34%), moderate in 16 (32%) and 17 (34%) individuals had severe disease. Conclusions INF1-QOL is a validated, reliable disease specific questionnaire that is easy and quick to complete. Role and outlook on life and anxiety and depression have the highest impact on QOL indicating the variability, severity and unpredictability of NF1. INFI-QOL correlates moderately with clinical severity. The moderate relationship between INF1-QOL and physician rated severity emphasizes the difference between clinical and patient perception. INFI-QOL will be useful in individual patient assessment and as an outcome measure for clinical trials

Advancing understanding on industrial relations in multinational companies: key research challenges and the INTREPID contribution

peer-reviewedThis paper has three principal aims. It firstly provides some theoretical background on the key current research issues and challenges in regard to industrial relations in multinational companies. It then presents a concise review of scholarship to date on industrial relations in multinational companies using INTREPID (Investigation of Transnationals Employment Practices: an International Database) data. Finally, the paper identifies some of the main industrial relations issues that remain to be addressed, in effect charting a form of research agenda for future work using the INTREPID data, with particular focus on the potential contribution from ‘late joiners’ to the INTREPID project.ACCEPTEDpeer-reviewe

Contested resources: unions, employers, and the adoption of new work practices in US and UK telecommunications

The pattern of adoption of high-performance work practices has been explained in terms of strategic contingency and in terms of union presence. We compare the post-deregulation/privatization changes in work practice at AT&T, Bell Atlantic and British Telecom. On the basis of these cases, we argue that the choice of new work practices should be understood as a consequence not only of the company's resources or changes in its environment, nor of a simple union presence, but also as a consequence of the practices' effects on union power, the nature of the union's engagement, and the union's strategic choices