Global games and general claims: locating the contribution of Kristensen and Zeitlin.

This is a pre-copy-editing, author-produced PDF of an article accepted for publication in Socio-Economic Review following peer review. The definitive publisher-authenticated version Ferner, A.M. (2008) Global games and general claims: locating the contribution of Kristensen and Zeitlin. Socio-Economic Review, 6 (2) pp. 379-384. is available online at: http://dx.doi.org/doi:10.1093/ser/mwn00

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

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

The dynamics of central control and subsidiary autonomy in the management of human resources: case study evidence from US MNCs in the UK

This article revisits a central question in the debates on the management of multinationals: the balance between centralized policy-making and subsidiary autonomy. It does so through data from a series of case studies on the management of human resources in American multinationals in the UK. Two strands of debate are confronted. The first is the literature on differences between multinationals of different national origins which has shown that US companies tend to be more centralized, standardized, and formalized in their management of human resources. It is argued that the literature has provided unconvincing explanations of this pattern, failing to link it to distinctive features of the American business system in which US multinationals are embedded. The second strand is the wider debate on the balance between centralization and decentralization in multinationals. It is argued that the literature neglects important features of this balance: the contingent oscillation between centralized and decentralized modes of operation and (relatedly) the way in which the balance is negotiated by organizational actors through micro-political processes whereby the external structural constraints on the company are defined and interpreted. In such negotiation, actors’ leverage often derives from exploiting differences between the national business systems in which the multinational operates

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

A systematic review and meta-analysis of thiazide-induced hyponatraemia: time to reconsider electrolyte monitoring regimens after thiazide initiation?

Aims: Hyponatraemia is one of the major adverse effects of thiazide and thiazide-like diuretics and the leading cause of drug-induced hyponatraemia requiring hospital admission. We sought to review and analyze all published cases of this important condition. Methods: Ovid Medline, Embase, Web of Science and PubMed electronic databases were searched to identify all relevant articles published before October 2013. A proportions meta-analysis was undertaken. Results: One hundred and two articles were identified of which 49 were single patient case reports. Meta-analysis showed that mean age was 75 (95% CI 73, 77) years, 79% were women (95% CI 74, 82) and mean body mass index was 25 (95% CI 20, 30) kg m−2. Presentation with thiazide-induced hyponatraemia occurred a mean of 19 (95% CI 8, 30) days after starting treatment, with mean trough serum sodium concentration of 116 (95% CI 113, 120) mm and serum potassium of 3.3 (95% CI 3.0, 3.5) mm. Mean urinary sodium concentration was 64 mm (95% CI 47, 81). The most frequently reported drugs were hydrochlorothiazide, indapamide and bendroflumethiazide. Conclusions: Patients with thiazide-induced hyponatraemia were characterized by advanced age, female gender, inappropriate saliuresis and mild hypokalaemia. Low BMI was not found to be a significant risk factor, despite previous suggestions. The time from thiazide initiation to presentation with hyponatraemia suggests that the recommended practice of performing a single investigation of serum biochemistry 7–14 days after thiazide initiation may be insufficient or suboptimal. Further larger and more systematic studies of thiazide-induced hyponatraemia are required

A systematic review and meta-analysis of thiazide-induced hyponatraemia: time to reconsider electrolyte monitoring regimens after thiazide initiation?

Aims: Hyponatraemia is one of the major adverse effects of thiazide and thiazide-like diuretics and the leading cause of drug-induced hyponatraemia requiring hospital admission. We sought to review and analyze all published cases of this important condition. Methods: Ovid Medline, Embase, Web of Science and PubMed electronic databases were searched to identify all relevant articles published before October 2013. A proportions meta-analysis was undertaken. Results: One hundred and two articles were identified of which 49 were single patient case reports. Meta-analysis showed that mean age was 75 (95% CI 73, 77) years, 79% were women (95% CI 74, 82) and mean body mass index was 25 (95% CI 20, 30) kg m−2. Presentation with thiazide-induced hyponatraemia occurred a mean of 19 (95% CI 8, 30) days after starting treatment, with mean trough serum sodium concentration of 116 (95% CI 113, 120) mm and serum potassium of 3.3 (95% CI 3.0, 3.5) mm. Mean urinary sodium concentration was 64 mm (95% CI 47, 81). The most frequently reported drugs were hydrochlorothiazide, indapamide and bendroflumethiazide. Conclusions: Patients with thiazide-induced hyponatraemia were characterized by advanced age, female gender, inappropriate saliuresis and mild hypokalaemia. Low BMI was not found to be a significant risk factor, despite previous suggestions. The time from thiazide initiation to presentation with hyponatraemia suggests that the recommended practice of performing a single investigation of serum biochemistry 7–14 days after thiazide initiation may be insufficient or suboptimal. Further larger and more systematic studies of thiazide-induced hyponatraemia are required

Clinical presentation and prognostic indicators in 100 adults and children with neurofibromatosis 1 associated non-optic pathway brain gliomas

Type 1 Neurofibromatosis (NF1) is a common autosomal dominant condition, with a major impact on the nervous system, eye, bone, and skin, and a predisposition to malignancy. At present it is not possible to predict clinically or on imaging, whether a brain tumour will remain indolent or undergo high-grade change. There are no consensus guidelines on the follow-up of non-optic pathway glioma (non-OPG) tumours in NF1. One hundred patients from the National NF1 Service with generalised NF1 and a diagnosis of non-OPG glioma were followed up for a median time of 63 months after glioma detection. Forty-two patients underwent surgical intervention. Ninety-one percent (38) of those requiring surgery did so within 5 years of diagnosis of glioma. Serial neuroimaging was undertaken in 88 patients. In 66 (75%), the lesion on the scan was stable or had improved at follow-up. High-grade lesions were present in five patients and were strongly associated with tumours in the thalamus (p = 0.001). Five patients died during follow-up. The diagnosis of high-grade glioma had a HR of 99.7 (95% CI 11.1-898.9, p < 000.1) on multivariate Cox regression to evaluate predictive factors related to death. In our cohort of 100 patients with NF1, we have shown that tumours in the thalamus are more likely to be associated with radiological progression, high-grade tumours, and surgical intervention. As a result of this finding, heightened surveillance with more frequent imaging should be considered in thalamic involvement. We have also demonstrated that over 40% of patients underwent surgery, and did so within 5 years of tumour diagnosis. Serial imaging should be undertaken for at the very least, 5 years from tumour detection

Scottish and Newcastle antiemetic pre-treatment for paracetamol poisoning study (SNAP)

BACKGROUND: Paracetamol (acetaminophen) poisoning remains the commonest cause of acute liver injury in Europe and North America. The intravenous (IV) N-acetylcysteine (NAC) regimen introduced in the 1970s has continued effectively unchanged. This involves 3 different infusion regimens (dose and time) lasting over 20 hours. The same weight-related dose of NAC is used irrespective of paracetamol dose. Complications include frequent nausea and vomiting, anaphylactoid reactions and dosing errors. We designed a randomised controlled study investigating the efficacy of antiemetic pre-treatment (ondansetron) using standard NAC and a modified, shorter, regimen. METHODS/DESIGN: We designed a double-blind trial using a 2 × 2 factorial design involving four parallel groups. Pre-treatment with ondansetron 4 mg IV was compared against placebo on nausea and vomiting following the standard (20.25 h) regimen, or a novel 12 h NAC regimen in paracetamol poisoning. Each delivered 300 mg/kg bodyweight NAC. Randomisation was stratified on: paracetamol dose, perceived risk factors, and time to presentation. The primary outcome was the incidence of nausea and vomiting following NAC. In addition the frequency of anaphylactoid reactions and end of treatment liver function documented. Where clinically necessary further doses of NAC were administered as per standard UK protocols at the end of the first antidote course. DISCUSSION: This study is primarily designed to test the efficacy of prophylactic anti-emetic therapy with ondansetron, but is the first attempt to formally examine new methods of administering IV NAC in paracetamol overdose. We anticipate, from volunteer studies, that nausea and vomiting will be less frequent with the new NAC regimen. In addition as anaphylactoid response appears related to plasma concentrations of both NAC and paracetamol anaphylactoid reactions should be less likely. This study is not powered to assess the relative efficacy of the two NAC regimens, however it will give useful information to power future studies. As the first formal randomised clinical trial in this patient group in over 30 years this study will also provide information to support further studies in patients in paracetamol overdose, particularly, when linked with modern novel biomarkers of liver damage, patients at different toxicity risk. TRIAL REGISTRATION: EudraCT number 2009-017800-10, ClinicalTrials.gov IdentifierNCT0105027