What Is the Magnitude and Long-term Economic Cost of Care of the British Military Afghanistan Amputee Cohort?

Background Personal protection equipment, improved early medical care, and rapid extraction of the casualty have resulted in more injured service members who served in Afghanistan surviving after severe military trauma. Many of those who survive the initial trauma are faced with complex wounds such as multiple amputations. Although costs of care can be high, they have not been well quantified before. This is required to budget for the needs of the injured beyond their service in the armed forces. Question/purposes The purposes of this study were (1) to quantify and describe the extent and nature of traumatic amputations of British service personnel from Afghanistan; and (2) to calculate an estimate of the projected long-term cost of this cohort. Methods A four-stage methodology was used: (1) systematic literature search of previous studies of amputee care cost; (2) retrospective analysis of the UK Joint Theatre Trauma and prosthetic database; (3) Markov economic algorithm for healthcare cost and sensitivity analysis of results; and (4) statistical cost comparison between our cohort and the identified literature. Results From 2003 to 2014, 265 casualties sustained 416 amputations. The average number of limbs lost per casualty was 1.6. The most common type of amputation was a transfemoral amputation (153 patients); the next most common amputation type was unilateral transtibial (143 patients). Using a Markov model of healthcare economics, it is estimated that the total 40-year cost of the UK Afghanistan lower limb amputee cohort is £288 million (USD 444 million); this figure estimates cost of trauma care, rehabilitation, and prosthetic costs. A sensitivity analysis on our model demonstrated a potential ± 6.19% variation in costs. Conclusions The conflict in Afghanistan resulted in high numbers of complex injuries. Our findings suggest that a long-term facility to budget for veterans’ health care is necessary

Development and validation of a gene expression test to identify hard-to-heal chronic venous leg ulcers

Background: Chronic venous leg ulcers pose a significant burden to healthcare systems, and predicting wound healing is challenging. The aim of this study was to develop a genetic test to evaluate the propensity of a chronic ulcer to heal. Methods: Sequential refinement and testing of a gene expression signature was conducted using three distinct cohorts of human wound tissue. The expression of candidate genes was screened using a cohort of acute and chronic wound tissue and normal skin with quantitative transcript analysis. Genes showing significant expression differences were combined and examined, using receiver operating characteristic (ROC) curve analysis, in a controlled prospective study of patients with venous leg ulcers. A refined gene signature was evaluated using a prospective, blinded study of consecutive patients with venous ulcers. Results: The initial gene signature, comprising 25 genes, could identify the outcome (healing versus non‐healing) of chronic venous leg ulcers (area under the curve (AUC) 0·84, 95 per cent c.i. 0·73 to 0·94). Subsequent refinement resulted in a final 14‐gene signature (WD14), which performed equally well (AUC 0·88, 0·80 to 0·97). When examined in a prospective blinded study, the WD14 signature could also identify wounds likely to demonstrate signs of healing (AUC 0·73, 0·62 to 0·84). Conclusion: A gene signature can identify people with chronic venous leg ulcers that are unlikely to heal

Multi-label classification using ensembles of pruned sets

This paper presents a Pruned Sets method (PS) for multi-label classification. It is centred on the concept of treating sets of labels as single labels. This allows the classification process to inherently take into account correlations between labels. By pruning these sets, PS focuses only on the most important correlations, which reduces complexity and improves accuracy. By combining pruned sets in an ensemble scheme (EPS), new label sets can be formed to adapt to irregular or complex data. The results from experimental evaluation on a variety of multi-label datasets show that [E]PS can achieve better performance and train much faster than other multi-label methods

Determination of caspase-3 activation fails to predict chemosensitivity in primary acute myeloid leukemia blasts

BACKGROUND: Ex-vivo chemosensitivity tests that measure cell death induction may predict treatment outcome and, therefore, represent a powerful instrument for clinical decision making in cancer therapy. Such tests are, however, work intensive and, in the case of the DiSC-assay, require at least four days. Induction of apoptosis is the mode of action of anticancer drugs and should, therefore, result in the induction of caspase activation in cells targeted by anticancer therapy. METHODS: To determine, whether caspase activation can predict the chemosensitivity, we investigated enzyme activation of caspase-3, a key executioner caspase and correlated these data with chemosensitivity profiles of acute myeloid leukemia (AML) blasts. RESULTS: There was, however, no correlation between the ex-vivo chemosensitivity assessed by measuring the overall rates of cell death by use of the DiSC-assay and caspase-3 activation. CONCLUSION: Thus, despite a significant reduction of duration of the assay from four to one day, induction of apoptosis evaluated by capase-3 activity does not seem to be a valid surrogate marker for chemosensitivity

CASPER plus (CollAborative care in Screen-Positive EldeRs with major depressive disorder): study protocol for a randomised controlled trial

Background: Depression accounts for the greatest disease burden of all mental health disorders, contributes heavily to healthcare costs, and by 2020 is set to become the second largest cause of global disability. Although 10% to 16% of people aged 65 years and over are likely to experience depressive symptoms, the condition is under-diagnosed and often inadequately treated in primary care. Later-life depression is associated with chronic illness and disability, cognitive impairment and social isolation. With a progressively ageing population it becomes increasingly important to refine strategies to identity and manage depression in older people. Currently, management may be limited to the prescription of antidepressants where there may be poor concordance; older people may lack awareness of psychosocial interventions and general practitioners may neglect to offer this treatment option. Methods/design: CASPER Plus is a multi-centre, randomised controlled trial of a collaborative care intervention for individuals aged 65 years and over experiencing moderate to severe depression. Selected practices in the North of England identify potentially eligible patients and invite them to participate in the study. A diagnostic interview is carried out and participants with major depressive disorder are randomised to either collaborative care or usual care. The recruitment target is 450 participants. The intervention, behavioural activation and medication management in a collaborative care framework, has been adapted to meet the complex needs of older people. It is delivered over eight to 10 weekly sessions by a case manager liaising with general practitioners. The trial aims to evaluate the clinical and cost effectiveness of collaborative care in addition to usual GP care versus usual GP care alone. The primary clinical outcome, depression severity, will be measured with the Patient Health Questionnaire-9 (PHQ-9) at baseline, 4, 12 and 18 months. Cost effectiveness analysis will assess health-related quality of life using the SF-12 and EQ-5D and will examine cost-consequences of collaborative care. A qualitative process evaluation will be undertaken to explore acceptability, gauge the extent to which the intervention is implemented and to explore sustainability beyond the clinical trial. Discussion: Results will add to existing evidence and a positive outcome may lead to the commissioning of this model of service in primary care. Trial registration: ISRCTN45842879 (24 July 2012)