Challenges to sovereign ambitions: forces of convergence and divergence within the global pharmaceutical sector and the UK's withdrawal from the European Union.

This paper maps key regulatory, governance and legal challenges associated with the UK's withdrawal from the European Union (EU) in terms of convergent and divergent pressures within the global pharmaceutical sector. These include (i) convergent regulatory pressures associated with the European framework for pre-market licensing; (ii) convergent and divergent industry pressures with regard to drug discovery and manufacturing; and (iii) divergent and convergent market pressures associated with the supply, pricing and assessment of medicines. The UK's sovereign ambitions risk a loss of influence over the licensing and surveillance of pharmaceuticals under convergent regulatory and industry pressures to engage in unilateral participation in the European regime. Further, they also risk a loss of influence over processes for pricing and assessing the effectiveness of new treatment regimens under divergent market pressures from larger pharmaceutical markets outside the EU, notably the United States.

Mapping research activity on mental health disorders in Europe: study protocol for the Mapping_NCD project.

BACKGROUND: Mental health disorders (MHDs) constitute a large and growing disease burden in Europe, although they typically receive less attention and research funding than other non-communicable diseases (NCDs). This study protocol describes a methodology for the mapping of MHD research in Europe as part of Mapping_NCD, a 2-year project funded by the European Commission which seeks to map European research funding and impact for five NCDs in order to identify potential gaps, overlaps, synergies and opportunities, and to develop evidence-based policies for future research. METHODS: The project aims to develop a multi-focal view of the MHD research landscape across the 28 European Union Member States, plus Iceland, Norway and Switzerland, through a survey of European funding entities, analysis of research initiatives undertaken in the public, voluntary/not-for-profit and commercial sectors, and expert interviews to contextualize the gathered data. The impact of MHD research will be explored using bibliometric analyses of scientific publications, clinical guidelines and newspaper stories reporting on research initiatives. Finally, these research inputs and outputs will be considered in light of various metrics that have been proposed to inform priorities for the allocation of research funds, including burden of disease, treatment gaps and cost of illness. DISCUSSION: Given the growing burden of MHDs, a clear and broad view of the current state of MHD research is needed to ensure that limited resources are directed to evidence-based priority areas. MHDs pose a particular challenge in mapping the research landscape due to their complex nature, high co-morbidity and varying diagnostic criteria. Undertaking such an effort across 31 countries is further challenged by differences in data collection, healthcare systems, reimbursement rates and clinical practices, as well as cultural and socioeconomic diversity. Using multiple methods to explore the spectrum of MHD research funding activity across Europe, this project aims to develop a broad, high-level perspective to inform priority setting for future research.

European Non-Communicable Respiratory Disease Research, 2002-13: Bibliometric Study of Outputs and Funding.

This study was conducted in order to map European research in chronic respiratory diseases (CRDs). It was intended to assist the European Commission and other research funders to identify gaps and overlaps in their portfolios, and to suggest ways in which they could improve the effectiveness of their support and increase the impact of the research on patient care and on the reduction of the incidence of the CRDs. Articles and reviews were identified in the Web of Science on research in six non-communicable respiratory diseases that were published in 2002-13 from 31 European countries. They represented only 0.8% of biomedical research output but these diseases accounted for 4.7% of the European disease burden, as measured by Disability-Adjusted Life Years (DALYs), so the sub-field is seriously under-researched. Europe is prominent in the sub-field and published 56% of the world total, with the UK the most productive and publishing more than France and Italy, the next two countries, combined. Asthma and Chronic Obstructive Pulmonary Disease (COPD) were the diseases with the most publications and the highest citation rates. They also received the most funding, with around two acknowledgments per paper (in 2009-13), whereas cystic fibrosis and emphysema averaged only one. Just over 37% of papers had no specific funding and depended on institutional support from universities and hospitals.

Magnetic resonance imaging features of vascular leiomyoma of the ankle.

Vascular leiomyoma is a benign soft tissue tumour with a predilection for middle-aged women. It is most often seen in the extremities, particularly in the lower leg. The typical lesion is a small, slow-growing subcutaneous nodule. These tumours are often unexpected or preoperatively confused with other soft tissue tumours including low-grade sarcomas, leading to wide surgical excision. This may partly be due to the relatively few studies delineating the characteristic imaging features of this entity. Here, the imaging findings of a case of vascular leiomyoma in the ankle are presented. Literature review of the magnetic resonance imaging findings of published reports and series of vascular leiomyomas of the extremities is also performed.

A regulatory governance perspective on health technology assessment (HTA) in France: the contextual mediation of common functional pressures.

The new regulatory governance perspective has introduced several insights to the study of health technology assessment (HTA): it has broadened the scope for the analysis of HTA; it has provided a more sophisticated account of national diversity and the potential for cross-border policy learning; and, it has dissolved the distinction between HTA assessment and appraisal processes. In this paper, we undertake a qualitative study of the French process for HTA with a view to introducing a fourth insight: that the emergence and continuing function of national agencies for HTA follows a broadly evolutionary pattern in which contextual factors play an important mediating role. We demonstrate that the French process for HTA is characterised by distinctive institutions, processes and evidential requirements. Consistent with the mediating role of this divergent policy context, we argue that even initiatives for the harmonisation of national approaches to HTA are likely to meet with divergent national policy responses.

A regulatory governance perspective on Health Technology Assessment (HTA) in Sweden.

Independent regulatory agencies (IRAs) for Health Technology Assessment (HTA) are a key means by which national governments have responded to the challenge of ensuring equitable public access to a new range of medicines and treatment options within the context of limited national budgets for healthcare. In this paper, we apply a regulatory governance frame to the study of the Swedish process for HTA. Based on qualitative interviews with key institutional stakeholders, we suggest that the major challenge for Swedish IRAs for HTA is successfully communicating nationally produced research outputs to the regional authorities responsible for the delivery of health services. We conclude that a regulatory governance approach to the analysis of national processes for HTA has the capacity to draw attention to a new range of challenges and issues which have direct relevance to improving the conduct of HTA within national regulatory spaces.

Regulatory space and the contextual mediation of common functional pressures: analyzing the factors that led to the German Efficiency Frontier approach.

There are no automatic links between the functional advantages and pressures associated with delegation to independent agencies for Health Technology Assessment (HTA) and their emergence in national regulatory spaces. We argue that the rise of these organizations is mediated by contextual factors, which must be explained. Accordingly, we analyze the German 'regulatory space' for health policy decision-making, identifying contextual factors relevant to the adoption of the Efficiency Frontier approach. Based on qualitative interviews with key stakeholders, we argue that the development of the Efficiency Frontier can be associated with cultural reluctance to frame healthcare prioritization decisions around cost based valuations of human health and related doubts about the validity of metrics for human health gain. Based on this finding, we conclude that the delegation of authority to independent HTA agencies follows a broadly evolutionary pattern, in which contextual factors allow for significant variation in institutional and methodological responses to the functional pressures and advantages leading to their establishment.

Predictive factors and radiological features of radiation-induced cranial nerve palsy in patients with nasopharyngeal carcinoma following radical radiotherapy.

OBJECTIVES: To identify the key predictive factors of radiation-induced cranial nerve palsy in patients with nasopharyngeal carcinoma (NPC). METHOD AND MATERIALS: From November 1998 to December 2007, all consecutive patients with newly diagnosed NPC who were curatively treated with radiotherapy and subsequently developed radiation-induced cranial nerve palsy (RICNP) were included in our study. Patients with cranial nerve palsy due to disease recurrence were excluded. Their records were retrospectively reviewed. RESULTS: Amongst 965 patients with NPC treated with radical radiotherapy, 41 developed new cranial nerve palsy. After exclusion of 5 patients with cranial nerve palsy due to recurrence, 36 (3.7%) developed RICNP. The median follow-up was 8.9 years (range, 3.2-11.3 years). Ten of the 36 patients had cranial nerve palsy at presentation. Twenty-seven patients had single cranial nerve palsy and 9 patients had multiple cranial nerve palsy. The most commonly involved cranial nerve was cranial nerve XII, with 30 patients having palsy of cranial nerve XII and 6 of them having bilateral cranial nerve XII palsies. Magnetic resonance imaging features of radiation-induced hypoglossal nerve palsy were demonstrated in our study. Multivariate analysis revealed that cranial nerve palsy at presentation was an independent prognostic factor for the development of RICNP. Other factors including T staging, N staging, gender, age, radiotherapy technique and the use of chemotherapy have no significant relationship with the risk of developing RICNP. CONCLUSION: RICNP in patients with NPC is not a rare complication, and cranial nerve palsy at presentation is an important prognostic factor.

Combined percutaneous and endoscopic approach in management of dropped gallstones following laparoscopic cholecystectomy.

Dropped gallstones due to accidental perforation of gallbladder wall during laparoscopic cholecystectomy are often encountered. However, dropped gallstones as nidus of infection with subsequent abscess formation is a rare complication of laparoscopic cholecystectomy (0.3%). Most of the reported cases of complicated dropped stones required open surgical drainage. Minimally invasive measures were less frequently employed. We report a case of dropped gallstones that were removed endoscopically through a percutaneous drainage tract.

Outcome of corneal transplantation: can a prioritisation system predict outcome?

BACKGROUND: In 1995 a prioritisation system for patients waiting for corneal transplantation surgery was adopted in British Columbia. In 1997 a routine outcome assessment programme was adopted. The authors sought to determine the outcomes of corneal transplant surgery in the province of British Columbia and to evaluate if they were associated with waiting list prioritisation. METHODS: Since May 1997 all patients who receive a corneal transplant are enrolled in the Eye Bank of British Columbia (EBBC) outcome assessment programme. Each patient fills out a visual function assessment (VFA) questionnaire before and 12 months after surgery. Data on visual acuity, pain, demographics, and other ocular complications are collected from both patients and surgeons before and after operation. RESULTS: 269 patients were enrolled in the programme between May 1997 and April 1998. 12 month follow up showed that visual acuity improved in 69.9% of patients, while it remained the same in 20.8%, and got worse in 5.9%. Overall, at follow up 16.6% of patients had intermittent pain and 5.0% had constant pain. 78.6% of patients who experienced intermittent or constant pain before surgery reported no pain at follow up. Visual function improved in 72.4% of patients, remained the same in 4.1%, and worsened in 23.5%. 88% of patients improved in at least one of the three outcome categories. Patients who had the greatest improvement had been assigned the highest priority for surgery. The 11% of patients who did not improve in any of the three categories (visual acuity, pain, or visual function) were more likely to have a preoperative visual acuity better than 20/60, most likely to have old trauma or Fuchs' dystrophy as their primary diagnosis, and to have had fewer points in the EBBC priority scoring system. CONCLUSION: The finding that patients who had a high preoperative priority score were more likely to have a good outcome suggests that the priority system was accurately identifying patients at greatest need for surgery. These findings also suggest that outcome from corneal transplant surgery is best measured as a combination of clinical indices and patient derived indices. A routine outcome assessment programme and prioritisation system can assist surgeons and eye banks in better case selection and in anticipating both objective and subjective improvement following surgery.

The combined effects of plasma and hydrogel coating on adhesion of Staphylococcus epidermidis and Staphylococcus aureus to polyurethane catheters.

The adhesion of three Staphylococcus epidermidis and three S aureus clinical isolates, to uncoated and hydrogel-coated polyurethane catheters was tested, following pretreatment of catheters with human plasma. Plasma significantly decreased the adhesion of S. epidermidis strains to uncoated polyurethane catheters, but had no significant effect on the adhesion to hydrogel-coated catheters. The influence of plasma on adhesion of S. aureus strains to catheters was strain dependent. Plasma significantly increased the adhesion of one strain (SA6) to uncoated catheters. For two other strains (SA3 and SA14) plasma produced no clear effect on their adhesion to uncoated catheters; adhesion values for each strain showed either a small but significant increase or a replicate-dependent increase or decrease. However, plasma significantly increased the adhesion of all S. aureus strains to hydrogel-coated polyurethane catheters. Overall, with the exception of one batch culture of S. epidermidis strain SE3 tested, attachment to plasma-treated hydrogel coated catheters was statistically significantly lower, by up to 85%, than attachment to plasma-treated uncoated catheters for both S. epidermidis and S. aureus.

Adhesion of staphylococci to polyurethane and hydrogel-coated polyurethane catheters assayed by an improved radiolabelling technique.

Adhesion of Staphylococcus epidermidis NCTC 11047 to the external surface of polyurethane catheters was quantified by a radiolabelling assay. Maximum adhesion was achieved with an initial cell concentration of 3 x 10(8)/ml after incubation for 120 min. The assay was tested for reproducibility by analysis of variance. Adhesion of clinical strains of S. epidermidis and S. aureus to uncoated polyurethane and hydrogel (Hydromer)-coated polyurethane catheters was compared. Hydrogel coating significantly reduced adhesion for both S. epidermidis and S. aureus (mean percentage reduction 71% for S. epidermidis, 69% for S. aureus). Clinical isolates were also tested for adhesion to polystyrene by a modified microtitration well adhesion assay; there was no correlation between staphylococcal adhesion to polyurethane catheters and adhesion to polystyrene. Cell surface hydrophobicity values varied widely for both species. Positive correlations were found between cell surface hydrophobicity and adhesion to polystyrene and uncoated polyurethane catheters for S. epidermidis but not for S. aureus.