In this Editorial, I would like to provide our readers with a brief mid-year update about our activities and efforts to bring together researchers working on intercellular signaling proteins at international meetings. The roots emerged about 20 years ago in the discovery of three genes originally designated cyr61, ctgf, and nov. The proteins encoded by these genes were first proposed to constitute a family of proteins (CCN) which now comprises 6 members (CCN1, CCN2, CCN3, CCN4-6) including the wisp proteins. These proteins were recognized to share a striking structural organization and a high degree of identity although they exhibited quite distinct biological properties. After historical considerations regarding the reasons for using the CCN acronym, and how the ICCNS publishing landscape that drove the ICCNS from Cell Communication and Signaling to the Journal of Cell Communication and Signaling, this short update will focus on the 7th edition of the International Workshop on the CCN family of genes to be held in Nice, Oct 16–19, 2013.
CCN proteins; CCN1; CCN2; CCN3 CCN4; CCN5; CCN6; ctfg; cyr61; nov; wisp; nwCCN; ICCNS; JCCS
Adults remember faces of threatening over non-threatening individuals. This memory advantage could be indicative of a system rooted deeply in cognitive evolution to track and remember individuals who have been harmful in the past and therefore might be harmful again. Conversely, adults may have learned through experience that it pays to be vigilant. In the present research, we investigated whether attention to threatening individuals is privileged in young children’s face memory. In Experiment 1, preschool-age children showed a face recognition memory advantage for individuals who were said to have committed harmful rather than helpful actions. In a further experiment, children did not selectively remember individuals who were described as the recipients of these actions, suggesting that the memory enhancement was produced by threat rather than negative valence. Together, these findings provide evidence for an early-developing system for remembering threatening individuals, consistent with an evolutionary account of its origins.
Objective: : In 2002 a new protocol was introduced based on the Canadian CT rules. Before this the Royal College of Surgeons "Galasko" report guidelines had been followed. This study evaluates the effects of the protocol and discusses the impact of the implementation of the NICE head injury guidelines—also based on the Canadian CT rules.
Methods: A "before and after" study was undertaken, using data from accident and emergency cards and hospital notes of adult patients with head injuries presenting to the emergency department over seven months in 2001 and nine months in 2002. The two groups were compared to see how rates of computed tomography (CT), admission for observation, discharge, and skull radiography had changed after introduction of the protocol.
Results: : Head CT rates in patients with minor head injuries (MHI) increased significantly from 47 of 330 (14%) to 58 of 267 (20%) (p<0.05). There were also significantly increased rates of admission for observation, from 111 (34%) to 119 (45%). Skull radiography rates fell considerably from 33% of all patients with head injuries in 2001 to 1.6% in 2002, without any adverse effect.
Conclusions: This study shows that it is possible to replace the current practice in the UK of risk stratification of adult MHI based on skull radiography, with slightly modified versions of the Canadian CT rule/NICE guidelines. This will result in a large reduction in skull radiography and will be associated with modest increases in CT and admissions rates. If introduction of the NICE guideline is to be realistic, the study suggests that it will not be cost neutral.
Health information technology (IT) is widely endorsed as a way to improve key health care outcomes, particularly patient safety. Applying a human factors approach, this paper models more explicitly how health IT might improve or worsen outcomes. The human factors model specifies that health IT transforms the work system, which transforms the process of care, which in turn transforms the outcome of care. This study reports on transformations of the medication administration process that resulted from the implementation of one type of IT: bar coded medication administration (BCMA). Registered nurses at two large pediatric hospitals in the US participated in a survey administered before and after one of the hospitals implemented BCMA. Nurses’ perceptions of the administration process changed at the hospital that implemented BCMA, whereas perceptions of nurses at the control hospital did not. BCMA appeared to improve the safety of the processes of matching medications to the medication administration record and checking patient identification. The accuracy, usefulness, and consistency of checking patient identification improved as well. In contrast, nurses’ perceptions of the usefulness, time efficiency, and ease of the documentation process decreased post-BCMA. Discussion of survey findings is supplemented by observations and interviews at the hospital that implemented BCMA. By considering the way that IT transforms the work system and the work process a practitioner can better predict the kind of outcomes that the IT might produce. More importantly, the practitioner can achieve or prevent outcomes of interest by using design and redesign aimed at controlling work system and process transformations.
health information technology; bar coded medication administration; process change; patient safety; human factors engineering
To assess how long the UK's National Institute for Health and Clinical Excellence's (NICE) Technology Appraisal Programme has taken to produce guidance and to determine independent predictors of time to guidance.
Retrospective time to event (survival) analysis.
Technology Appraisal guidance produced by NICE.
All appraisals referred to NICE by February 2010 were included, except those referred prior to 2001 and a number that were suspended.
Duration from the start of an appraisal (when the scope document was released) until publication of guidance.
Single Technology Appraisals (STAs) were published significantly faster than Multiple Technology Appraisals (MTAs) with median durations of 48.0 (IQR; 44.3–75.4) and 74.0 (IQR; 60.9–114.0) weeks, respectively (p <0.0001). Median time to publication exceeded published process timelines, even after adjusting for appeals. Results from the modelling suggest that STAs published guidance significantly faster than MTAs after adjusting for other covariates (by 36.2 weeks (95% CI −46.05 to −26.42 weeks)) and that appeals against provisional guidance significantly increased the time to publication (by 42.83 weeks (95% CI 35.50 to 50.17 weeks)). There was no evidence that STAs of cancer-related technologies took longer to complete compared with STAs of other technologies after adjusting for potentially confounding variables and only weak evidence suggesting that the time to produce guidance is increasing each year (by 1.40 weeks (95% CI −0.35 to 2.94 weeks)).
The results from this study suggest that the STA process has resulted in significantly faster guidance compared with the MTA process irrespective of the topic, but that these gains are lost if appeals are made against provisional guidance. While NICE processes continue to evolve over time, a trade-off might be that decisions take longer but at present there is no evidence of a significant increase in duration.
Health Economics; Public Health; Statistics & Research Methods
The NIsin-Controlled gene Expression system NICE of Lactococcus lactis is one of the most widespread used expression systems of Gram-positive bacteria. It is used in more than 100 laboratories for laboratory-scale gene expression experiments. However, L. lactis is also a micro-organism with a large biotechnological potential. Therefore, the aim of this study was to test whether protein production in L. lactis using the NICE system can also effectively be performed at the industrial-scale of fermentation.
Lysostaphin, an antibacterial protein (mainly against Staphylococcus aureus) from S. simulans biovar. Staphylolyticus, was used as a model system. Food-grade lysostaphin expression constructs in L. lactis were grown at 1L-, 300-L and 3000-L scale and induced with nisin for lysostaphin production. The induction process was equally effective at all scales and yields of about 100 mg/L were obtained. Up-scaling was easy and required no specific effort. Furthermore, we describe a simple and effective way of downstream processing to obtain a highly purified lysostaphin, which has been used for clinical phase I trials.
This is the first example that shows that nisin-regulated gene expression in L. lactis can be used at industrial scale to produce large amounts of a target protein, such as lysostaphin. Downstream processing was simple and in a few steps produced a highly purified and active enzyme.
Brain tumours account for <2% of all primary neoplasms but are responsible for 7% of the years of life lost from cancer before age 70 years. The latest survival trends for patients with CNS malignancies have remained largely static. The objective of this study was to evaluate the change in practice as a result of implementing the Improving Outcomes Guidance from the UK National Institute for Health and Clinical Excellence (NICE).
Patients were identified from the local cancer registry and hospital databases. We compared time from diagnosis to treatment, proportion of patients discussed at multidisciplinary team (MDT) meetings, treatment received, length of inpatient stay and survival. Inpatient and imaging costs were also estimated.
Service reconfiguration and implementation of NICE guidance resulted in significantly more patients being discussed by the MDT—increased from 66 to 87%, reduced emergency admission in favour of elective surgery, reduced median hospital stay from 8 to 4.5 days, increased use of post-operative MRI from 17 to 91% facilitating early discharge and treatment planning, and reduced cost of inpatient stay from £2096 in 2006 to £1316 in 2009. Patients treated with optimal surgery followed by radiotherapy with concomitant and adjuvant temozolomide achieved outcomes comparable to those reported in clinical trials: median overall survival 18 months (2-year survival 35%).
Advancing the management of neuro-oncology patients by moving from an emergency-based system of patient referral and management to a more planned elective outpatient-based pattern of care improves patient experience and has the potential to deliver better outcomes and research opportunities.
glioblastoma; management; surgery; radiotherapy; chemotherapy; NICE guidance
Background: Previous surveys of children's diabetes service provision in the UK have shown gradual improvements but continuing deficiencies.
Aim: To determine whether further improvements in services have occurred.
Methods: A questionnaire was mailed to all paediatricians in the UK identified as providing care for children and adolescents with diabetes. Responses were compared with results of three previous surveys, and with recommendations in the Diabetes NSF and the NICE type 1 diabetes guidelines.
Results: Replies were received from 187 consultant paediatricians in 169 centres looking after children; 89% expressed a special interest in diabetes, 98% saw children in a designated diabetic clinic, and 95% clinics now have more than 40 patients. In 98% of the clinics there was a specialist nurse (82% now children's trained), but 61% clinics had a nurse:patient ratio <1:100; 39% of clinics did not have a paediatric dietician and in 78% there was no access to psychology/psychiatry services in clinics. Glycated haemoglobin was measured routinely at clinics in 86%, annual screening for retinopathy performed in 80%, and microalbuminuria in 83%. All centres now have local protocols for ketoacidosis, but not for children undergoing surgery (90%) or severe hypoglycaemia (74%). Mean clinic HbA1c levels were significantly lower in the clinics run by specialists (8.9%) than generalists (9.4%). There have been incremental improvements over the last 14 years since the surveys began, but only two clinics met all the 10 previously published recommendations on standards of care.
Conclusions: The survey shows continuing improvements in organisational structure of services for children with diabetes but serious deficiencies remain. Publication and dissemination of the results of the previous surveys may have been associated with these improvements and similar recurrent service review may be applicable to services for other chronic childhood conditions.
Harris' reply to our defence of the National Institute for Clinical Excellence's (NICE) current cost‐effectiveness procedures contains two further errors. First, he wrongly draws a conclusion from the fact that NICE does not and cannot evaluate all possible uses of healthcare resources at any one time and generally cannot know which National Health Service (NHS) activities would be displaced or which groups of patients would have to forgo health benefits: the inference is that no estimate is or can be made by NICE of the benefits to be forgone. This is a non‐sequitur. Second, he asserts that it is a flaw at the heart of the use of quality‐adjusted life years (QALYs) as an outcome measure that comparisons between people need to be made. Such comparisons do indeed have to be made, but this is not a consequence of the choice of any particular outcome measure, be it the QALY or anything else.
The Improving Access to Psychological Therapies (IAPT) programme is a large-scale initiative that aims to greatly increase the availability of NICE recommended psychological treatment for depression and anxiety disorders within the National Health Service in England. This article describes the background to the programme, the arguments on which it is based, the therapist training scheme, the clinical service model, and a summary of progress to date. At mid-point in a national roll-out of the programme progress is generally in line with expectation, and a large number of people who would not otherwise have had the opportunity to receive evidence-based psychological treatment have accessed, and benefited from, the new IAPT services. Planned future developments and challenges for the programme are briefly described.
In the past 5 years, a convergence of studies has resulted in a broad
appreciation in the cancer research community that reprogramming of cellular
metabolism may be more central to cancer than appreciated in the past 30 years.
The re-emergence of cancer metabolism stems in part from discoveries that a
number of common oncogenes and tumor suppressor genes more directly control cell
metabolism than previously thought. In addition, a number of what would
previously have been called “card-carrying” metabolic enzymes have
been identified as human tumor suppressors or oncogenes, causally mutated in a
variety of human cancers. This growing appreciation of the role of altered cell
metabolism has led to further investigation into the rate-limiting proteins
involved in different aspects of the unique metabolism of tumor cells. Targeting
cancer metabolism with drugs requires a therapeutic window in which tumor cells,
compared to normal tissues, have a greater dependence on specific metabolic
enzymes. Themes that have emerged in the past decade of developing
oncogene-targeted cancer therapeutics suggest that tumors with distinct
oncogenic lesions are likely to require drugs that target distinct metabolic
pathways. Ultimately, the hope is that detailed knowledge of oncogene and tumor
suppressor gene functions and their effects on metabolism will lead to drug
combinations that will be far more effective in treating cancers.
Long-term sickness absence and incapacity benefits (disability pension) rates have increased across industrialised countries. Effective measures are needed to support return to work. The recommendations of this guidance were informed by the most appropriate available evidence of effectiveness and cost-effectiveness. Public health evidence was provided by research using a variety of study designs that attempted to determine the outcome of a particular intervention by evaluating status before and after the intervention had been effected, and was not limited to randomised control trials. Where the evidence base was depleted or underdeveloped, expert witnesses were called to give their opinion on the best available evidence and emerging interventions. The process enabled challenge and contestability from stakeholder groups at different points as the guidance was developed. Forty-five heterogeneous studies were included in the review of interventions to reduce long-term sickness absence and transitions from short-term to long-term absence (mainly covering the former and also mainly examining musculoskeletal conditions). The analysis of evidence was restricted to descriptive synthesis. Three general themes emerged from an analysis of the studies that were more likely to report positive results: early interventions; multidisciplinary approaches; and interventions with a workplace component. Two further reviews were undertaken, one on interventions to reduce the re-occurrence of sickness absence, which identified seven studies on lower back pain, and concluded that early intervention and direct workplace input are important factors. The final evidence review focused on six studies of interventions for those in receipt of incapacity benefit. The evidence was that work-focused interviews coupled with access to tailored support are effective and cost-effective interventions. Practitioners should consider the impact of interventions and management options on work ability for patients of working age. Work ability should be considered a key outcome for future intervention studies.
evidence-based medicine; guideline; sick leave; sick leave, cost; work capacity evaluation
Background: NICE guidelines for the management of head injury were published in June 2003. Their recommendations differ markedly from previous guidelines published by the Royal College of Surgeons (RCS). In place of skull radiography and admission, computed tomography (CT) is advocated. The impact of these guidelines on service provision in the UK is unknown.
Methods: Data on all clinical correlates of children presenting with any severity of head injury was collected in three hospitals in the northwest of England. The current skull radiograph (SXR), CT scan, and admission rates were determined. The rates of SXR, CT scan, and admission that should have occurred when following either the RCS or NICE guidelines were then determined.
Results: Data from 10 965 patients who attended three hospitals between February 2000 and August 2002 was studied. Twenty five per cent of patients received a SXR, 0.9% a CT scan, and 3.7% were admitted. Strict adherence to the RCS guidelines would have resulted in a 50% SXR rate, a 1.6% CT scan rate, and a 7.1% admission rate. Adherence to NICE guidelines would result in a 0.3% SXR rate, an 8.7% CT scan rate, and a 1.4% admission rate, although the CT rate would drop to 6.3% if vomiting three or more times in the under 12s was used instead of more than one vomit.
Conclusions: The new NICE guidelines do not increase the workload caused by patients attending with head injury but they move their management from the observation ward to the radiology department.
Hyperglycemia is associated with increased mortality in critically ill patients. Randomized trials of intensive insulin therapy have reported inconsistent effects on mortality and increased rates of severe hypoglycemia. We conducted a meta-analysis to update the totality of evidence regarding the influence of intensive insulin therapy compared with conventional insulin therapy on mortality and severe hypoglycemia in the intensive care unit (ICU).
We conducted searches of electronic databases, abstracts from scientific conferences and bibliographies of relevant articles. We included published randomized controlled trials conducted in the ICU that directly compared intensive insulin therapy with conventional glucose management and that documented mortality. We included in our meta-analysis the data from the recent NICE-SUGAR (Normoglycemia in Intensive Care Evaluation — Survival Using Glucose Algorithm Regulation) study.
We included 26 trials involving a total of 13 567 patients in our meta-analysis. Among the 26 trials that reported mortality, the pooled relative risk (RR) of death with intensive insulin therapy compared with conventional therapy was 0.93 (95% confidence interval [CI] 0.83–1.04). Among the 14 trials that reported hypoglycemia, the pooled RR with intensive insulin therapy was 6.0 (95% CI 4.5–8.0). The ICU setting was a contributing factor, with patients in surgical ICUs appearing to benefit from intensive insulin therapy (RR 0.63, 95% CI 0.44–0.91); patients in the other ICU settings did not (medical ICU: RR 1.0, 95% CI 0.78–1.28; mixed ICU: RR 0.99, 95% CI 0.86–1.12). The different targets of intensive insulin therapy (glucose level ≤ 6.1 mmol/L v. ≤ 8.3 mmol/L) did not influence either mortality or risk of hypoglycemia.
Intensive insulin therapy significantly increased the risk of hypoglycemia and conferred no overall mortality benefit among critically ill patients. However, this therapy may be beneficial to patients admitted to a surgical ICU.
Over the past 30 years, fetal movement counts have been recommended to women in the second half of pregnancy as a way of monitoring fetal wellbeing and providing an early warning of fetal distress. However, guidance from the National Institute of Clinical Excellence (NICE) recommends abandoning this. Evidence is reviewed to show that the chance of preventing physical damage to the fetus is indeed low. The activity of monitoring movements has been favoured by the majority of women. The new NICE guidance is useful to clarify professional understanding of the limitation of counting fetal movements, but women who notice decreased movements will still need referral for human factors.
fetal movement; maternal welfare; perinatal care
Mortality from coronary heart disease has been falling in the UK since the 1970s, but remains higher than in most other Western countries. Most patients receive some treatment for secondary prevention after myocardial infarction, but not all patients are offered the most effective secondary prevention package. The recently published NICE guideline for secondary prevention in patients after myocardial infarction, summarised in this article, makes clear recommendations for management of patients after myocardial infarction, based on best available evidence. The guidelines update the 2001 NICE guideline, and have expanded and emphasised the recommendations for physical activity, dietary and other lifestyle changes, and cardiac rehabilitation, and updated the recommendations for drug therapy.
The National Institute for Health and clinical Excellence (NICE) depression guideline (2004) and the updated Quality and Outcomes Framework (QOF) ( 2006) in general practice have introduced the concepts of screening severity assessment, for example using the Patient Health Questionnaire 9 (PHQ-9), and ‘stepped care’ for depression.
To explore primary care practitioner perspectives on the clinical utility of the NICE guideline and the impact of the QOF on diagnosis and management of depression in routine practice.
Design and setting
Qualitative study using focus groups from four multidisciplinary practice teams with diverse populations in south Yorkshire.
Four focus groups were conducted, using a topic guide and audiotaping. There were 38 participants: GPs, nurses, doctors in training, mental health workers, and a manager. Data analysis was iterative and thematic.
The NICE guideline, with its embedded principles of holism and evidence-based practice, was viewed positively but its impact was compromised by resource and practitioner barriers to implementation. The perceived imposition of the screening questions and severity assessments (PHQ-9) with no responsive training had required practitioners to work hard to minimise negative impacts on their work, for example: constantly adapting consultations to tick boxes; avoiding triggering open displays of distress without the time to offer appropriate care; positively managing how their patients were labelled. Further confusion was experienced around the evolving content of psychological interventions for depression.
Organisational barriers to the implementation of the NICE guideline and the limited scope of the QOF highlight the need for policy makers to work more effectively with the complex realities of general practice in order to systematically improve the quality and delivery of ‘managed’ care for depression.
depression; primary health care; qualitative
Background. Multidisciplinary team (MDT) working in oncology aims to improve outcomes for patients with cancer. One role is to ensure the implementation of best practice and National Institute for Health and Clinical Excellence (NICE) guidance. In this study, we have assessed the role of MDT in implementing the TA121 appraisal of the use of carmustine wafers in high grade gliomas. Methods. 296 patients with high-grade glioma suitable for maximal resection were recruited from 17 Neurosurgical Centres. The number of patients treated with carmustine wafers and reasons for not using this were recorded. Complications at 48 hours post-operatively and at 6 weeks post-radiotherapy were recorded. Results. 94/296 (32%) of suitable patients received carmustine wafers. In 55% of cases carmustine was not used due to either surgeon preference or a lack of an MDT decision. There was no increased complication rate with carmustine use at either 48 hours post-surgery or at 6 weeks post radiotherapy. Use of carmustine wafers did not decrease access to and use of chemoradiotherapy. Conclusions. One third of patients suitable for carmustine wafers received them. Their use was neither associated with more frequent complications, nor decreased use of chemoradiotherapy. Implementation of NICE TA121 Guidance is extremely variable in different MDTs across the United Kingdom.
Brain neoplasms; implementing NICE guidance; carmustine wafers; improving outcomes guidance
National Institute for Health and Clinical Excellence (NICE) clinical guidelines and subsequent NICE issued ‘recommendation reminders’ advocate discontinuing two fertility procedures and caesarean sections in women with hepatitis. We assess whether NICE guidance in 2004 and recommendation reminders were associated with a change in the rate of clinical procedures performed.
Routine inpatient Hospital Episode Statistics (HES) data were extracted from the HES database for 1st April 1998 to 31st March 2010 using OPCS procedure codes for varicocele operations in infertile men, endometrial biopsies in infertile women and caesarean sections in women with hepatitis B or C. We used Joinpoint regression to identify points in time when the trend in procedure rates changed markedly, to identify any influence of the release of NICE guidance.
Between 1998-2010, planned caesarean sections in women with and without hepatitis B or C increased yearly (annual percentage change (APC) 4.9%, 95% CI 2.1% to 7.7%) in women with hepatitis, compared with women without (APC 4.0% [95% CI 2.7% to 5.3%] up to 2001, APC -0.6% [95% CI -2.8% to 1.8%] up to 2004 and 1.3% [95% CI 0.8% to 1.8%] up to 2010). In infertile women under 40 years of age, endometrial biopsies for investigation of infertility increased, APC 6.0% (95% CI 3.6% to 8.4%) up to 2003, APC 1.5% (95% CI -4.3% to 7.7%) to 2007 followed by APC 12.8% (95% CI 1.0% to 26.0%) to 2010. Varicocele procedures remained relatively static between 1998 and 2010 (APC -0.5%, 95% CI -2.3% to 1.3%).
There was no decline in use of the three studied procedures, contrary to NICE guidance, and no change in uptake associated with the timing of NICE guidance or recommendation reminders. ‘Do not do’ recommendation reminders may be ineffective at improving clinical practice or achieving disinvestment.
NICE; Clinical guidelines; Fertility; Caesarean
To determine how hypnosis and empathic attention during percutaneous tumor treatments affect pain, anxiety, drug use, and adverse events.
For their tumor embolization or radiofrequency ablation 201 patients were randomized to receive standard care, empathic attention with defined behaviors displayed by an additional provider, or self-hypnotic relaxation including the defined empathic attention behaviours. All had local anesthetic and access to intravenous medication. Main outcome measures were: Pain and anxiety, assessed every 15 min by patient self-report; medication use with 50μg fentanyl or 1 mg midazolam = 1 unit; adverse events, defined as occurrences requiring extra medical attention including systolic blood pressure fluctuations >50mm Hg and surpassing 180 mm Hg or falling below 105 mm Hg, vaso-vagal episodes; cardiac events, and respiratory impairment.
Hypnosis patients experienced significantly less pain and anxiety than standard care and empathy patients at several time intervals and received significantly less median drug units (mean 2.00, interquartile range (IQR)1-4) than standard (mean 3.00; IQR 1.5-5.0; p = 0.0147) and empathy group patients (mean 3.50, IQR; 2.0-5.9; p = 0.0026). 31 of 65 (48%) patients in the empathy group had adverse events, significantly more than those in the hypnosis (8/66 (12%); p=0.0001) and standard care groups (18/70 (26%); p=0.0118).
Procedural hypnosis including empathic attention reduces pain, anxiety, and medication use. Conversely, empathic approaches which provide an external focus of attention and do not enhance patients’ self-coping can result in more adverse events. These findings should have major implications for the education of procedural personnel.
Systems Factorial Technology is a powerful framework for investigating the fundamental properties of human information processing such as architecture (i.e., serial or parallel processing) and capacity (how processing efficiency is affected by increased workload). The Survivor Interaction Contrast (SIC) and the Capacity Coefficient are effective measures in determining these underlying properties, based on response-time data. Each of the different architectures, under the assumption of independent processing, predicts a specific form of the SIC along with some range of capacity. In this study, we explored SIC predictions of discrete-state (Markov process) and continuous-state (Linear Dynamic) models that allow for certain types of cross-channel interaction. The interaction can be facilitatory or inhibitory: one channel can either facilitate, or slow down processing in its counterpart. Despite the relative generality of these models, the combination of the architecture-oriented plus the capacity oriented analyses provide for precise identification of the underlying system.
Parallel; Interactive; Processing; Survivor Interaction Contrast; Capacity; Response Time
To demonstrate that sensory and emotional states play an important role in moral processing, previous research has induced physical disgust in various sensory modalities (visual, tactile, gustatory, and olfactory modalities, among others) and measured its effects on moral judgment. To further assess the strength of the connection between embodied states and morality, we investigated whether the directionality of the effect could be reversed by exposing participants to different types of moral events prior to rating the same neutral tasting beverage. As expected, reading about moral transgressions, moral virtues, or control events resulted in inducing gustatory disgust, delight, or neutral taste experiences, respectively. Results are discussed in terms of the relation between embodied cognition and processing abstract conceptual representations.
The goal of antiepileptic treatment is to achieve seizure freedom or seizure control. The aim of this paper is to review the evidence for the use of lacosamide for adjunctive treatment of refractory focal seizures with or without secondary generalization, within the scope of the 2012 update of the Clinical Guideline published by the National Institute for Health and Clinical Excellence (NICE).
Clinical evidence for the use of lacosamide and other antiepileptic drugs (AEDs) was systematically reviewed, evaluated, and presented to the Guideline Development Group. Only randomized clinical trials were included. Outcomes of clinical efficacy (seizure freedom, 50% reduction in seizure frequency, time to first seizure, time to 12-month remission, treatment withdrawal, and time to treatment withdrawal), experience of adverse events, and cognitive and quality of life outcomes were reviewed. A decision model was built to weigh the clinical benefits of each adjunctive AED, measured by seizure control and seizure reduction, compared with the harm from adverse events, as measured by withdrawals from treatment due to adverse events.
Lacosamide was included as part of the recommended AEDS to be used in tertiary epilepsy centers. The evidence review showed that more participants who received lacosamide as an adjunctive treatment had at least a 50% reduction in seizure frequency compared with those taking placebo. However, more participants on lacosamide were found to experience adverse events and withdrawal from treatment compared with those on placebo. The cost-effectiveness analysis showed that compared with placebo, the benefits gained from adjunctive lacosamide were modest and uncertain, whereas the costs were significantly high. Compared with other AEDs licensed for adjunctive therapy in focal seizures, lacosamide was associated with fewer quality-adjusted life years and higher costs. Therefore, the Guideline Development Group noted that the balance of benefit and harm needs to be carefully monitored in all patients.
focal seizures; anti-epileptic drug; adjunctive therapy; clinical guideline
There is growing interest internationally in linking reimbursement decisions with recommendations for further research. In the UK, the National Institute for Health and Clinical Excellence (NICE) can issue guidance to approve the routine use of a health intervention, reject routine use or recommend use within a research programme. These latter recommendations have restricted use to ‘only in research’ (OIR) or have recommended further research alongside routine use (‘approval with research’ or AWR). However, it is not currently clear when such recommendations are likely to be made.
This study aims to identify NICE technology appraisals where OIR or AWR recommendations were made and to examine the key considerations that led to those decisions.
Draft and final guidance including OIR/AWR recommendations were identified. The documents were reviewed to establish the characteristics of the technology appraisal, the cost effectiveness of the technologies, the key considerations that led to the recommendations and the types of research required.
In total, 29 final and 31 draft guidance documents included OIR/AWR recommendations up to January 2010. Overall, 86 % of final guidance included OIR recommendations. Of these, the majority were for technologies considered to be cost ineffective (83 %) and the majority of final guidance (66 %) specified the need for further evidence on relative effectiveness. The use of OIR/AWR recommendations is decreasing over time and they have rarely been used in appraisals conducted through the single technology appraisal process.
NICE has used its ability to recommend technologies within research programmes, although predominantly within the multiple technology appraisal process. OIR recommendations have been most frequently issued for technologies considered cost ineffective and the most frequently cited consideration is uncertainty related to relative effectiveness. Key considerations cited for most AWR recommendations and some OIR recommendations included a need for further evidence on long-term outcomes and adverse effects of treatment.
Electronic supplementary material
The online version of this article (doi:10.1007/s40273-012-0013-6) contains supplementary material, which is available to authorized users.