Unmet supportive care needs, health status and minimum costs in survivors of malignant melanoma.

We explored the relationship between unmet care needs, health status, health utility and costs in people treated for melanoma via a cross-sectional follow-up survey (N = 455) 3 months to 5 years after complete resection of stage I-III cutaneous malignant melanoma. 51% (n = 232) had unmet care needs. This group had higher mean resource use, estimated conservatively (£28 vs. £10 per person) and worse overall health. Mean health-related utility index (AQoL6D) was 0.763 (95% CI 0.74; 0.79) in those with self-reported unmet need vs. 0.903 (0.89; 0.92) in those with no unmet need. Melanoma survivors with unmet need had worse outcomes in terms of anxiety (HADS 6.86 vs. 4.29), depression (HADS 4.29 vs. 2.01), overall quality of life (QoL: FACT-M 84.2 vs. 96.5). Higher resource use was associated with younger age (rs  = -.29, p < .001), older school-leaving age (rs  = .21, p < .001), reduced health utility (rs  = -.14, p = .005), higher anxiety (rs  = .22, p < .001), higher depression (rs  = .16, p = .001) and lower QoL (overall rs  = -.24, p < .001; melanoma QoL rs  = -.20, p < .001; surgery QoL rs  = -.19, p < .001). Lower health outcomes indicate increased service use, suggesting that interventions to address unmet need and improve health outcomes may reduce health costs. Integrated clinical and economic evaluations of interventions that target unmet need in melanoma survivors are required.

A (five-)level playing field for mental health conditions?: exploratory analysis of EQ-5D-5L-derived utility values.

PURPOSE: Economic evaluations of mental health interventions often measure health benefit in terms of utility values derived from the EQ-5D. For the five-level version of the EQ-5D, there are two methods of estimating utility [crosswalk and stated preference (5L-SP)]. This paper explores potential impacts for researchers and decision-makers when comparing utility values derived from either method in the specific context of mental health. METHODS: Baseline EQ-5D-5L data from three large randomised controlled trials of interventions for mental health conditions were analysed. Utility values were generated using each method. Mean utility values were compared using a series of t tests on pooled data and subgroups. Scenario analyses explored potential impacts on cost-effectiveness decisions. RESULTS: EQ-5D data were available for 1399 participants. The mean utility value for each trial was approximately 0.08 higher when estimated using the 5L-SP approach compared to crosswalk (p < 0.0001). The difference was greatest among people reporting extreme anxiety/depression (mean utility 5L-SP 0.309, crosswalk 0.084; difference = 0.225; p < 0.0001). Identical improvements in health status were associated with higher costs to gain one QALY with the 5L-SP approach; this is more pronounced when improvements are across all domains compared to improvements on the anxiety/depression domain only. CONCLUSIONS: The two approaches produce significantly different utility values in people with mental health conditions. Resulting differences in cost per QALY estimates suggest that thresholds of cost-effectiveness may also need to be reviewed. Researchers and decision-makers should exercise caution when comparing or synthesising data from trials of mental health interventions using different utility estimation approaches.

Cost-effectiveness of structured group psychoeducation versus unstructured group support for bipolar disorder: Results from a multi-centre pragmatic randomised controlled trial.

BACKGROUND: Bipolar disorder (BD) costs the English economy an estimated £5.2billion/year, largely through incomplete recovery. This analysis estimated the cost-effectiveness of group psychoeducation (PEd), versus group peer support (PS), for treating BD. METHODS: A 96-week pragmatic randomised controlled trial (RCT), conducted in NHS primary care. The primary analysis compared PEd with PS, using multiple imputed datasets for missing values. An economic model was used to compare PEd with treatment as usual (TAU). The perspective was Health and Personal Social Services. RESULTS: Participants receiving PEd (n=153) used more (costly) health-related resources than PS (n=151) (net cost per person £1098 (95% CI, £252-£1943)), with a quality-adjusted life year (QALY) gain of 0.023 (95% CI, 0.001-0.056). The cost per QALY gained was £47,739. PEd may be cost-effective (versus PS) if decision makers are willing to pay at least £37,500 per QALY gained. PEd costs £10,765 more than PS to avoid one relapse. The economic model indicates that PEd may be cost-effective versus TAU if it reduces the probability of relapse (by 15%) or reduces the probability of and increases time to relapse (by 10%). LIMITATIONS: Participants were generally inconsistent in attending treatment sessions and low numbers had complete cost/QALY data. Factors contributing to pervasive uncertainty of the results are discussed. CONCLUSIONS: This is the first economic evaluation of PEd versus PS in a pragmatic trial. PEd is associated with a modest improvement in health status and higher costs than PS. There is a high level of uncertainty in the data and results.

Psoriasis treatment and management - a systematic review of full economic evaluations.

BACKGROUND: Psoriasis frequently requires lifetime control and current therapies vary significantly in price. High-quality economic evaluations are necessary to determine if higher-cost treatments are value for money. OBJECTIVES: This review aims to identify the cost-effectiveness of psoriasis care (whether more expensive interventions are associated with savings in health care and psoriasis management and/or improve patients' health); assess the level of uncertainty and transferability of this evidence to policy and practice; and, identify future research needs. METHODS: Searches of electronic databases Embase, MEDLINE and NHS EED for full economic evaluations were conducted in January 2012 (updated April 2014). Included articles were screened, selected and critically appraised using predefined inclusion criteria and data extraction forms: 1355 articles were identified; 37 papers reporting 71 comparisons met the inclusion criteria. Treatments evaluated were systemic (n = 45), topical (n = 22), phototherapies (n = 14) and combination (n = 4). RESULTS: Despite a significant number of recent economic evaluations, the cost-effectiveness of all therapies remains unclear. This uncertainty arises from a diversity in settings, perspective and design. Economic evaluations were constrained by limited availability of high-quality short- and long-term head-to-head comparisons of the effectiveness, safety and adherence of different interventions. CONCLUSIONS: The economic evidence is dominated by comparisons of interventions to placebo, with implicit comparisons of different therapies. There is a lack of evaluations of service model innovations to deliver complex packages of care for psoriasis. Primary and secondary integrated clinical and economic research is needed to address the limitations and to identify patient preferences and barriers/facilitators to treatment.

How to recognise and treat peripheral nervous system vasculitis.

Peripheral neuropathy can be the first and only manifestation of necrotising primary immune-mediated vasculitis which, carries a high mortality. A clear idea of how to both recognise and treat peripheral nervous system vasculitis is important. We provide a practical approach to immediate and longer term treatment protocols.

The comparative responsiveness of the EQ-5D and SF-6D to change in patients with inflammatory arthritis.

PURPOSE: Comparative evidence regarding the responsiveness of the EQ-5D and SF-6D in arthritis patients is conflicting and insufficient across the range of disease severity. We examined the comparative responsiveness of the EQ-5D and SF-6D in cohorts of patients with early inflammatory disease through to severe rheumatoid arthritis (RA). METHODS: Responsiveness was tested using the effect size (ES) and standardised response mean (SRM). Correlation of change in EQ-5D and SF-6D with disease specific measures was tested using Pearson correlations and the Steiger's Z test. Treatment response and self-reported change were used as anchors of important change. RESULTS: The EQ-5D was more responsive to deterioration (ES ratio (EQ-5D/SF-6D): 1.6-3.0) and the SF-6D more responsive to improvement (ES ratio (SF-6D/EQ-5D): 1.1-1.8) in health. The SF-6D did not respond well to deterioration in patients with established severe RA (ES and SRM 0.08). The EQ-5D provided larger absolute mean change estimates but with greater variance compared to the SF-6D. CONCLUSIONS: The comparative responsiveness of the EQ-5D and SF-6D differs according to the direction of change. The level of mean change of the EQ-5D relative to the SF-6D has implications for cost-effectiveness analysis. Use of the SF-6D in patients with severe progressive disease may be inappropriate.

Science into policy: preparing for pandemic influenza.

Authoratative government pandemic preparedness requires an evidence-based approach. The scientific advisory process that has informed the current UK pandemic preparedness plans is described. The final endorsed scientific papers are now publicly available.

Cost-effectiveness of first- v. second-generation antipsychotic drugs: results from a randomised controlled trial in schizophrenia responding poorly to previous therapy.

BACKGROUND: There are claims that the extra costs of atypical (second-generation) antipsychotic drugs over conventional (first-generation) drugs are offset by improved health-related quality of life. AIMS: To determine the relative costs and value of treatment with conventional or atypical antipsychotics in people with schizophrenia. METHOD: Cost-effectiveness acceptability analysis integrated clinical and economic randomised controlled trial data of conventional and atypical antipsychotics in routine practice. RESULTS: Conventional antipsychotics had lower costs and higher quality-adjusted life-years (QALYs) than atypical antipsychotics and were more than 50% likely to be cost-effective. CONCLUSIONS: The primary and sensitivity analyses indicated that conventional antipsychotics may be cost-saving and associated with a gain in QALYs compared with atypical antipsychotics.

Array comparative genomic hybridization for diagnosis of developmental delay: an exploratory cost-consequences analysis.

A major application of array comparative genomic hybridization (aCGH) is to define a specific cause in children with undiagnosed learning and developmental disability (LDD). Medical notes for 46 consecutive patients selected for aCGH analysis by clinical dysmorphologists were abstracted for clinical investigations related to LDD and a cost-consequences analysis was performed. aCGH analysis was completed in 36 cases and five diagnostic chromosomal anomalies were identified (13.8%). The number of investigations undertaken on each child varied. With aCGH estimated to cost 590 British Pound per case, if aCGH had been undertaken after negative standard initial tests for LDD investigation, the additional cost would be 2399 British Pound per positive case. If the cost of aCGH was reduced to 256 British Pound per case (approximately 350 Euro), aCGH becomes cost neutral. All chromosomal anomalies detected by aCGH had a de Vries score of > or =5. If aCGH had only been used for individuals with a score of > or =5, the sensitivity increased to 21.7% yielding a cost of 1087 British Pound per positive case identified. Pre-selection of cases for aCGH based on de Vries criteria has a major economic impact on introducing aCGH into clinical practice. Prospective studies are required to explore the long-term costs and consequences of aCGH and identify when aCGH may provide the most benefit at least cost.

Generalisability in economic evaluation studies in healthcare: a review and case studies.

OBJECTIVES: To review, and to develop further, the methods used to assess and to increase the generalisability of economic evaluation studies. DATA SOURCES: Electronic databases. REVIEW METHODS: Methodological studies relating to economic evaluation in healthcare were searched. This included electronic searches of a range of databases, including PREMEDLINE, MEDLINE, EMBASE and EconLit, and manual searches of key journals. The case studies of a decision analytic model involved highlighting specific features of previously published economic studies related to generalisability and location-related variability. The case-study involving the secondary analysis of cost-effectiveness analyses was based on the secondary analysis of three economic studies using data from randomised trials. RESULTS: The factor most frequently cited as generating variability in economic results between locations was the unit costs associated with particular resources. In the context of studies based on the analysis of patient-level data, regression analysis has been advocated as a means of looking at variability in economic results across locations. These methods have generally accepted that some components of resource use and outcomes are exchangeable across locations. Recent studies have also explored, in cost-effectiveness analysis, the use of tests of heterogeneity similar to those used in clinical evaluation in trials. The decision analytic model has been the main means by which cost-effectiveness has been adapted from trial to non-trial locations. Most models have focused on changes to the cost side of the analysis, but it is clear that the effectiveness side may also need to be adapted between locations. There have been weaknesses in some aspects of the reporting in applied cost-effectiveness studies. These may limit decision-makers' ability to judge the relevance of a study to their specific situations. The case study demonstrated the potential value of multilevel modelling (MLM). Where clustering exists by location (e.g. centre or country), MLM can facilitate correct estimates of the uncertainty in cost-effectiveness results, and also a means of estimating location-specific cost-effectiveness. The review of applied economic studies based on decision analytic models showed that few studies were explicit about their target decision-maker(s)/jurisdictions. The studies in the review generally made more effort to ensure that their cost inputs were specific to their target jurisdiction than their effectiveness parameters. Standard sensitivity analysis was the main way of dealing with uncertainty in the models, although few studies looked explicitly at variability between locations. The modelling case study illustrated how effectiveness and cost data can be made location-specific. In particular, on the effectiveness side, the example showed the separation of location-specific baseline events and pooled estimates of relative treatment effect, where the latter are assumed exchangeable across locations. CONCLUSIONS: A large number of factors are mentioned in the literature that might be expected to generate variation in the cost-effectiveness of healthcare interventions across locations. Several papers have demonstrated differences in the volume and cost of resource use between locations, but few studies have looked at variability in outcomes. In applied trial-based cost-effectiveness studies, few studies provide sufficient evidence for decision-makers to establish the relevance or to adjust the results of the study to their location of interest. Very few studies utilised statistical methods formally to assess the variability in results between locations. In applied economic studies based on decision models, most studies either stated their target decision-maker/jurisdiction or provided sufficient information from which this could be inferred. There was a greater tendency to ensure that cost inputs were specific to the target jurisdiction than clinical parameters. Methods to assess generalisability and variability in economic evaluation studies have been discussed extensively in the literature relating to both trial-based and modelling studies. Regression-based methods are likely to offer a systematic approach to quantifying variability in patient-level data. In particular, MLM has the potential to facilitate estimates of cost-effectiveness, which both reflect the variation in costs and outcomes between locations and also enable the consistency of cost-effectiveness estimates between locations to be assessed directly. Decision analytic models will retain an important role in adapting the results of cost-effectiveness studies between locations. Recommendations for further research include: the development of methods of evidence synthesis which model the exchangeability of data across locations and allow for the additional uncertainty in this process; assessment of alternative approaches to specifying multilevel models to the analysis of cost-effectiveness data alongside multilocation randomised trials; identification of a range of appropriate covariates relating to locations (e.g. hospitals) in multilevel models; and further assessment of the role of econometric methods (e.g. selection models) for cost-effectiveness analysis alongside observational datasets, and to increase the generalisability of randomised trials.

Clinical and economic choices in anaesthesia for day surgery: a prospective randomised controlled trial.

We compared the cost-effectiveness of general anaesthetic agents in adult and paediatric day surgery populations. We randomly assigned 1063 adult and 322 paediatric elective patients to one of four (adult) or two (paediatric) anaesthesia groups. Total costs were calculated from individual patient resource use to 7 days post discharge. Incremental cost-effectiveness ratios were expressed as cost per episode of postoperative nausea and vomiting (PONV) avoided. In adults, variable secondary care costs were higher for propofol induction and propofol maintenance (propofol/propofol; p < 0.01) than other groups and lower in propofol induction and isoflurane maintenance (propofol/isoflurane; p < 0.01). In both studies, predischarge PONV was higher if sevoflurane/sevoflurane (p < 0.01) was used compared with use of propofol for induction. In both studies, there was no difference in postdischarge outcomes at Day 7. Sevoflurane/sevoflurane was more costly with higher PONV rates in both studies. In adults, the cost per extra episode of PONV avoided was pound 296 (propofol/propofol vs. propofol/ sevoflurane) and pound 333 (propofol/sevoflurane vs. propofol/isoflurane).

Separation of visibly-excited fluorescent components in fingerprint residue by thin-layer chromatography.

The use of lasers for the detection of fingermarks is widespread in the forensic field. Despite this, and the fact that many studies have been conducted into the composition of fingermark residue, the components responsible for the inherent visible fluorescence remain unidentified. Traditionally compositional studies have been performed on sweat, sebum, or skin surface washes, none of which are truly representative of the situation when a fingerprint is deposited on a surface. In this paper thin-layer chromatography (TLC) has been performed on sebum-rich fingermarks laid directly onto TLC plates and an argon ion laser used to visualize the separated components. It has been found to be a robust and reproducible method for studying the fluorescent components in fingermark residue and is considered to be more realistic than other methods of sample preparation as it eliminates the chances of extraneous matter being extracted from the skin surface. Investigations into the nature of the separated compounds have also been made and the results are reported.

A new visibly-excited fluorescent component in latent fingerprint residue induced by gaseous electrical discharge.

A technique that exposes fingerprint residue to a gaseous electrical discharge in nitrogen followed by treatment with ammonium hydrogen carbonate vapors to produce fluorescence is investigated. Particular attention is made to fluorescence observed via laser illumination at 514 nm. Insight into the nature of the fluorescent components is achieved through the use of thin-layer chromatography (TLC) of fingerprint residue. Results reported indicate the fluorescence observed is from previously non-fluorescent fractions of the fingerprint residue, and TLC results point towards lipid derivatives as a possible source of the fluorescence.

Economic evaluation of enoxaparin as postdischarge prophylaxis for deep vein thrombosis (DVT) in elective hip surgery.

OBJECTIVES: Clinical trials indicate enoxaparin thromboprophylaxis (Clexane) can be effective and safe when used in an outpatient setting and that extending the length of thromboprophylaxis with enoxaparin to the postdischarge period may be more effective than inpatient thromboprophylaxis alone. This may increase the cost of thromboprophylaxis. The objective of the study was to estimate the expected cost-effectiveness of using enoxaparin for hospital admission only vs. enoxaparin for hospital admission and for 21 days postdischarge. METHODS: Decision analysis was used to combine probability, resource use and unit cost data, using the framework of cost-effectiveness analysis. The model used a societal perspective to estimate the expected costs of treatment and outcomes to patients undergoing orthopedic surgery for elective hip replacement. Incremental cost-effectiveness ratios were calculated to provide estimates of the cost per life gained, cost per year life year gained and cost per quality-adjusted life year gained with extended use of enoxaparin thromboprophylaxis. RESULTS: There was an expected cost per quality-adjusted life year gained of pounds 5732 associated with extended enoxaparin thromboprophylaxis. The results were sensitive to the percentage of patients who could administer enoxaparin injections at home, the rate of DVT associated with standard enoxaparin thromboprophylaxis and the rate of PE associated with standard and extended enoxaparin thromboprophylaxis. CONCLUSIONS: The analyses indicated that in most cases extended enoxaparin thromboprophylaxis resulted in increased costs for health care services. In all cases, extended thromboprophylaxis with enoxaparin was associated with improved survival and life-years gained.

Solid-State 13C Nuclear Magnetic Resonance Characterization of Cellulose in the Cell Walls of Arabidopsis thaliana Leaves.

Solid-state 13C nuclear magnetic resonance was used to characterize the molecular ordering of cellulose in a cell-wall preparation containing mostly primary walls obtained from the leaves of Arabidopsis thaliana. Proton and 13C spin relaxation time constants showed that the cellulose was in a crystalline rather than a paracrystalline state or amorphous state. Cellulose chains were distributed between the interiors (40%) and surfaces (60%) of crystallites, which is consistent with crystallite cross-sectional dimensions of about 3 nm. Digital resolution enhancement revealed signals indicative of triclinic and monoclinic crystalline forms of cellulose mixed in similar proportions. Of the five nuclear spin relaxation processes used, proton rotating-frame relaxation provided the clearest distinction between cellulose and other cell-wall components for purposes of editing solid-state 13C nuclear magnetic resonance spectra.

Economics and schizophrenia: the real cost.

The total direct cost of treating schizophrenia in the UK is 397 million pounds, or 1.6% of the total health care budget. Hospital-based and community-based residential care accounts for nearly three-quarters of these costs, while drugs account for only 5%. A conservative estimate of the indirect annual costs of lost production is in the region of 1.7 billion pounds. The heterogeneity of the disease and its outcome means that average treatment costs per person with schizophrenia should be treated with caution; 97% of direct costs are incurred by less than half the patients. Therefore, treatments which reduce the dependence and disability of those most severely affected by schizophrenia are likely to have a large effect on the total cost of the disease to society and may therefore be cost-effective, even though they appear expensive initially.

Assessment of costs and benefits of drug therapy for treatment-resistant schizophrenia in the United Kingdom.

An analysis was conducted on the basis of available data to assess the economic consequences of clozapine therapy for people with moderate to severe schizophrenia in long-stay institutions or staffed group homes, with a view to providing an estimate of the likely costs and benefits of the drug. Data from a cost-effectiveness study conducted in the US, supplemented by other literature sources, were used to construct a clinical decision tree for likely clinical outcomes for such patients. A panel of UK psychiatrists provided consensus on how these patients would have been managed in the UK. The costs associated with each patient outcome were estimated, and a sensitivity analysis performed to test the assumptions made. For the patients themselves, clozapine would lead to a net gain of 5.87 years of life with no disability or only mild disability. The base case analysis showed that the direct costs of using clozapine were 91 pounds less per annum (or 1333 pounds per lifetime) than for standard neuroleptic therapy, when the effect on all health-care resources was taken into account. In addition, the sensitivity analysis showed that clozapine would be cost-saving or cost-neutral under many different assumptions. A prospective health economic study with clozapine in the management of schizophrenia would be desirable to confirm these results.