Complete cytogenetic response and major molecular response as surrogate outcomes for overall survival in first-line treatment of chronic myelogenous leukemia: A case study for technology appraisal on the basis of surrogate outcomes evidence

Objectives In 2012, the National Institute for Health and Care Excellence assessed dasatinib, nilotinib, and standard-dose imatinib as first-line treatment of chronic phase chronic myelogenous leukemia (CML). Licensing of these alternative treatments was based on randomized controlled trials assessing complete cytogenetic response (CCyR) and major molecular response (MMR) at 12 months as primary end points. We use this case study to illustrate the validation of CCyR and MMR as surrogate outcomes for overall survival in CML and how this evidence was used to inform National Institute for Health and Care Excellence’s recommendation on the public funding of these first-line treatments for CML. Methods We undertook a systematic review and meta-analysis to quantify the association between CCyR and MMR at 12 months and overall survival in patients with chronic phase CML. We estimated life expectancy by extrapolating long-term survival from the weighted overall survival stratified according to the achievement of CCyR and MMR. Results Five studies provided data on the observational association between CCyR or MMR and overall survival. Based on the pooled association between CCyR and MMR and overall survival, our modeling showed comparable predicted mean duration of survival (21–23 years) following first-line treatment with imatinib, dasatinib, or nilotinib. Conclusions This case study illustrates the consideration of surrogate outcome evidence in health technology assessment. Although it is often recommended that the acceptance of surrogate outcomes be based on randomized controlled trial data demonstrating an association between the treatment effect on both the surrogate outcome and the final outcome, this case study shows that policymakers may be willing to accept a lower level of evidence (i.e., observational association).

When did you last predict a good idea? Exploring the case of assessing creativity through learning outcomes

It has been noted elsewhere that an idea is acknowledged to be creative if it is novel, or surprising and adaptive. So how does that fit with education's desire to measure student performance against fixed, consistent and predicted learning outcomes? This study explores practical measures and theoretical constructs that address the dearth of teaching, learning and assessment strategies to enhance creative capacity in enterprise and entrepreneurship education. It is argued that inappropriate assessment strategies can be significant inhibitors of the creativity of students and teachers. Referring to the broader discipline of 'design', as defined by Bruce and Besant (2002) – the application of human creativity to a purpose – both broad employer satisfaction with education and fast growing economic success are found (DCMS, 2014). As predictable assessment outcomes equal predictable students, these understandings can inform educators who wish to map and develop enhanced creative endeavours such as opportunity recognition, communication and innovation.

Integrating urban ecosystem sustainability assessment into policy-making: Insights from the Gold Coast City

This paper introduces a policy-making support tool called ‘Micro-level Urban ecosystem Sustainability IndeX (MUSIX)’. The index serves as a sustainability assessment model that monitors six aspects of urban ecosystems, hydrology, ecology, pollution, location, design, and efficiency based on parcel-scale indicators. This index is applied in a case study investigation in the Gold Coast City, Queensland, Australia. The outcomes reveal that there are major environmental problems caused by increased impervious surfaces from growing urban development in the study area. The findings suggest that increased impervious surfaces are linked to increased surface runoff, car dependency, transport-related pollution, poor public transport accessibility, and unsustainable built environment. This paper presents how the MUSIX outputs can be used to guide policy-making through the evaluation of existing policies.

Outcomes of ruptured abdominal aortic aneurysm

Ruptured abdominal aortic aneurysm (RAAA) is a life-threatening event, and without operative treatment the patient will die. The overall mortality can be as high as 80-90%; thus repair of RAAA should be attempted whenever feasible. The quality of life (QoL) has become an increasingly important outcome measure in vascular surgery. Aim of the study was to evaluate outcomes of RAAA and to find out predictors of mortality. In Helsinki and Uusimaa district 626 patients were identified to have RAAA in 1996-2004. Altogether 352 of them were admitted to Helsinki University Central Hospital (HUCH). Based on Finnvasc Registry, 836 RAAA patients underwent repair of RAAA in 1991-1999. The 30-day operative mortality, hospital and population-based mortality were assessed, and the effect of regional centralisation and improving in-hospital quality on the outcome of RAAA. QoL was evaluated by a RAND-36 questionnaire of survivors of RAAA. Quality-adjusted life years (QALYs), which measure length and QoL, were calculated using the EQ-5D index and estimation of life expectancy. The predictors of outcome after RAAA were assessed at admission and 48 hours after repair of RAAA. The 30-day operative mortality rate was 38% in HUCH and 44% nationwide, whereas the hospital mortality was 45% in HUCH. Population-based mortality was 69% in 1996-2004 and 56% in 2003-2004. After organisational changes were undertaken, the mortality decreased significantly at all levels. Among the survivors, the QoL was almost equal when compared with norms of age- and sex-matched controls; only physical functioning was slightly impaired. Successful repair of RAAA gave a mean of 4.1 (0-30.9) QALYs for all RAAA patients, although non-survivors were included. The preoperative Glasgow Aneurysm Score was an independent predictor of 30-day operative mortality after RAAA, and it also predicted the outcome at 48- hours for initial survivors of repair of RAAA. A high Glasgow Aneurysm Score and high age were associated with low numbers of QALYs to be achieved. Organ dysfunction measured by the Sequential Organ Failure Assessment (SOFA) score at 48 hours after repair of RAAA was the strongest predictor of death. In conclusion surgery of RAAA is a life-saving and cost-effective procedure. The centralisation of vascular emergencies improved the outcome of RAAA patients. The survivors had a good QoL after RAAA. Predictive models can be used on individual level only to provide supplementary information for clinical decision-making due to their moderate discriminatory value. These results support an active operation policy, as there is no reliable measure to predict the outcome after RAAA.

Evaluation of collaborative assessment of work integrated learning

The international trend towards an increasingly standards-based approach to higher education and the resultant focus on the assurance of learning in tertiary programs have generated a strong emphasis on the assessment of outcomes across the higher education sector. In legal education, curriculum reform is highly prevalent internationally as a result of various reviews of legal education. As legal education focuses more on the attainment of a broader set of outcomes encompassing soft skills, capabilities and attributes, more authentic assessment will need to be developed appropriate to this new environment, meaning that modes of assessment with strong application in real-life settings should be preferred.

Human health risk assessment of heavy metals in urban stormwater

Toxic chemical pollutants such as heavy metals (HMs) are commonly present in urban stormwater. These pollutants can pose a significant risk to human health and hence a significant barrier for urban stormwater reuse. The primary aim of this study was to develop an approach for quantitatively assessing the risk to human health due to the presence of HMs in stormwater. This approach will lead to informed decision making in relation to risk management of urban stormwater reuse, enabling efficient implementation of appropriate treatment strategies. In this study, risks to human health from heavy metals were assessed as hazard index (HI) and quantified as a function of traffic and land use related parameters. Traffic and land use are the primary factors influencing heavy metal loads in the urban environment. The risks posed by heavy metals associated with total solids and fine solids (<150µm) were considered to represent the maximum and minimum risk levels, respectively. The study outcomes confirmed that Cr, Mn and Pb pose the highest risks, although these elements are generally present in low concentrations. The study also found that even though the presence of a single heavy metal does not pose a significant risk, the presence of multiple heavy metals could be detrimental to human health. These findings suggest that stormwater guidelines should consider the combined risk from multiple heavy metals rather than the threshold concentration of an individual species. Furthermore, it was found that risk to human health from heavy metals in stormwater is significantly influenced by traffic volume and the risk associated with stormwater from industrial areas is generally higher than that from commercial and residential areas.

A cultural assessment of family dispute resolution: Findings about cultural appropriateness from the evaluation of a family relationship centre

The cultural appropriateness of human service processes is a major factor in determining the effectiveness of their delivery. Sensitivity to issues of culture is particularly critical in dealing with family disputes, which are generally highly emotive and require difficult decisions to be made regarding children, material assets and ongoing relationships. In this article we draw on findings from an evaluation of the Family Relationship Centre at Broadmeadows (FRCB) to offer some insights into and suggestions about managing cultural matters in the current practice of family dispute resolution (FDR) in Australia. The brief for the original research was to evaluate the cultural appropriateness of FDR services offered to culturally and linguistically diverse (CALD) communities living within the FRCB’s catchment area, specifically members of the Lebanese, Turkish and Iraqi communities. The conclusions of the evaluations were substantially positive. The work of the Centre was found to illustrate many aspects of best practice but also raised questions worthy of future exploration. The current article reports on overall cultural appropriateness, particularly identifying barriers which may inhibit access and how acculturation may play a role in reducing perception of barriers. An earlier article reported on access, retention and outcomes for these CALD groups (Akin Ojelabi et al., 2011).

Non-small cell lung cancer : studies on pathogenesis, tumour targeting and treatment outcomes

Lung cancer accounts for more cancer-related deaths than any other cancer. In Finland, five-year survival ranges from 8% to 13%. The main risk factor for lung cancer is long-term cigarette smoking, but its carcinogenesis requires several other factors. The aim of the present study was to 1) evaluate post-operative quality of life, 2) compare clinical outcomes between minimally invasive and conventional open surgery, 3) evaluate the role of oxidative stress in the carcinogenesis of non-small lung cancer (NSCLC), and 4) to identify and characterise targeted agents for therapeutic and diagnostic use in surgery. For study I, pneumonectomy patients replied to 15D quality of life and baseline dyspnea questionnaires. Study III involved a prospective quality of life assessment using the 15D questionnaire after lobectomy or bi-lobectomy. Study IV was a retrospective comparison of clinical outcomes between 212 patients treated with open thoracotomy and 116 patients who underwent a minimally invasive technique. Study II measured parameters of oxidative metabolism (myeloperoxidase activity, glutathione content and NADPH oxidase activity) and DNA adducts. Study V employed the phage display method and identified a core motif for homing peptides. This method served in cell-binding, cell-localisation, and biodistribution studies. Following both pneumonectomy and lobectomy, NSCLC patients showed significantly decreased long-term quality of life. No significant correlation was noted between post-operative quality of life and pre-operative pulmonary function tests. Women suffered more from increased dyspnea after pneumonectomy which was absent after lobectomy or bi-lobectomy. Patients treated with video-assisted thoracoscopy showed significantly decreased morbidity and shorter periods of hospitalization than did open surgery patients. This improvement was achieved even though the VATS patients were older and suffered more comorbid conditions and poorer pulmonary function. No significant differences in survival were noted between these two groups. An increase in NADPH oxidase activity was noted in tumour samples of both adenocarcinoma and squamous cell carcinoma. This increase was independent from myeloperoxidase activity. Elevated glutathione content was noted in tumour tissue, especially in adenocarcinoma. After panning the clinical tumour samples with the phage display method, an amino acid sequence of ARRPKLD, the Thx, was chosen for further analysis. This method proved selective of tumour tissue in both in vitro and in vivo cell-binding assay, and biodistribution showed tumour accumulation. Because of the significantly reduced quality of life following pneumonectomy, other operative strategies should be implemented as an alternative (e.g. sleeve-lobectomy). To treat this disease, implementation of a minimally invasive surgical technique is safe, and the results showed decreased morbidity and a shorter period of hospitalisation than with thoracotomy. This technique may facilitate operative treatment of elderly patients with comorbid conditions who might otherwise be considered inoperable. Simultaneous exposure to oxidative stress and altered redox states indicates the important role of oxidative stress in the pathogenesis and malignant transformation of NSCLC. The studies showed with great specificity and with favourable biodistribution that Thx peptide is specific to NSCLC tumours. Thx thus shows promise in imaging, targeted therapy, and monitoring of treatment response.

Dynamics of rural energy access in India: An assessment

India's rural energy challenges are formidable with the presence of majority energy poor. In 2005, out of a rural population of 809 million, 364 million lacked access to electricity and 726 million to modern cooking fuels. This indicates low effectiveness of government policies and programs of the past, and need for a more effective approach to bridge this gap. However, before the government can address this challenge, it is essential that it gain a deeper insight into prevailing status of energy access and reasons for such outcomes. Toward this, we perform a critical analysis of the dynamics of energy access status with respect to time, income and regions, and present the results as possible indicators of effectiveness of policies/programmes. Results indicate that energy deprivations are highest for poorest households with 93% depending on biomass for cooking and 62% lacking access to electricity. The annual growth rates in expansion in energy access are gradually declining from double digit growth rates experienced 10 years back to just around 4% in recent years. Regional variations indicate, on an average, cooking access levels were 5.3 times higher in top five states compared to bottom five states whereas this ratio was 3.4 for electricity access. (C) 2011 Elsevier Ltd. All rights reserved.

An assessment of development options in the longline fishery

The principal objective of this study is to evaluate the benefits that accrue to the national economies as a result of different longline operational models and licensing regimes, computed, for comparability reasons, on a per tonne basis. The primary source for the derivation of these per tonne returns was individual fisheries enterprises currently operating in the sector in the countries chosen for this study. In each case, the company disclosed to the consultant detailed financial, operational and marketing data which has enabled the findings to be based upon actual empirical data, rather than assumptions or interpretations of current practice and benefit outcomes. Data obtained related principally to the 2005 calendar year. [36pp.]

Impact of depressive symptoms on subjective well-being: the importance of patient-reported outcomes in schizophrenia

Objective: The subjective experience of psychotic patients toward treatment is a key factor in medication adherence, quality of life, and clinical outcome. The aim of this study was to assess the subjective well-being in patients with schizophrenia and to examine its relationship with the presence and severity of depressive symptoms. Methods: A multicenter, cross-sectional study was conducted with clinically stable outpatients diagnosed with schizophrenia. The Subjective Well-Being under Neuroleptic Scale - short version (SWN-K) and the Calgary Depression Scale for Schizophrenia (CDSS) were used to gather information on well-being and the presence and severity of depressive symptoms, respectively. Spearman's rank correlation was used to assess the associations between the SWN-K total score, its five subscales, and the CDSS total score. Discriminative validity was evaluated against that criterion by analysing the area under the curve (AUC). Results: Ninety-seven patients were included in the study. Mean age was 35 years (standard deviation = 10) and 72% were male. Both the total SWN-K scale and its five subscales correlated inversely and significantly with the CDSS total score (P < 0.0001). The highest correlation was observed for the total SWN-K (Spearman's rank order correlation [ rho] = -0.59), being the other correlations: mental functioning (-0.47), social integration (-0.46), emotional regulation (-0.51), physical functioning (-0.48), and self-control (-0.41). A total of 33 patients (34%) were classified as depressed. Total SWN-K showed the highest AUC when discriminating between depressive severity levels (0.84), followed by emotional regulation (0.80), social integration (0.78), physical functioning and self-control (0.77), and mental functioning (0.73). Total SWN-K and its five subscales showed a significant linear trend against CDSS severity levels (P < 0.001). Conclusion: The presence of moderate to severe depressive symptoms was relatively high, and correlated inversely with patients' subjective well-being. Routine assessment of patient-reported measures in patients with schizophrenia might reduce potential discrepancy between patient and physician assessment, increase therapeutic alliance, and improve outcome.

Smoked marine fish from Western Region, Ghana: a value chain assessment

The value chain analysis of ths report focused on smoked marine fish- overwhelmingly the most important fish product originating in Western Region, Ghana. Smoked fish from Western Region is mainly destined for the domestic market where demand is very strong. Small quantities of smoked fish are destined for markets in Togo, Benin and Nigeria. The underlying objective of the fisheries value chain analysis is to identify opportunities for growth in the fisheries value chain, with an emphasis on those opportunities that have the potential to generate significant additional livelihoods, particularly at the level of the fishing communities and for low-income groups. The results from the value chain analysis will be used to identify pilot interventions to promote those livelihood outcomes. The main focus for the study is smoked fish (major species/product forms) destined for domestic markets. However, work will also be undertaken on the fresh fish trade and frozen fish to find out more about the significance of these value chains.

Subclinical Depressive Symptoms and Continued Cannabis Use: Predictors of Negative Outcomes in First Episode Psychosis

Background Although depressive symptoms in first episode psychosis have been associated with cannabis abuse, their influence on the long-term functional course of FEP patients who abuse cannabis is unknown. The aims of the study were to examine the influence of subclinical depressive symptoms on the long-term outcome in first episode-psychosis patients who were cannabis users and to assess the influence of these subclinical depressive symptoms on the ability to quit cannabis use. Methods 64 FEP patients who were cannabis users at baseline were followed-up for 5 years. Two groups were defined: (a) patients with subclinical depressive symptoms at least once during follow-up (DPG), and (b) patients without subclinical depressive symptoms during follow-up (NDPG). Psychotic symptoms were measured using the Positive and Negative Syndrome Scale (PANSS), depressive symptoms using the Hamilton Depression Rating Scale (HDRS)-17, and psychosocial functioning was assessed using the Global Assessment of Functioning (GAF). A linear mixed-effects model was used to analyze the combined influence of cannabis use and subclinical depressive symptomatology on the clinical outcome. Results Subclinical depressive symptoms were associated with continued abuse of cannabis during follow-up (beta=4.45; 95% confidence interval [CI]: 1.78 to 11.17; P=.001) and with worse functioning (beta=-5.50; 95% CI: -9.02 to -0.33; P=.009). Conclusions Subclinical depressive symptoms and continued cannabis abuse during follow-up could be predictors of negative outcomes in FEP patients.

Estuarine use assessment: trial project in Casco Bay, Maine

The National Centers for Coastal Ocean Science (NCCOS) of the National Oceanic and Atmospheric Administration (NOAA) is interested in developing a project to determine the health of estuaries based on the stated or desired uses of society. An estuarine use assessment could complement the National Coastal Assessment, which tracks coastal and estuarine health through a series of environmental indicators. These indicators are used to assign a “score” to each coastal region, with some indicators reflecting the ability of the region to support desired uses such as fishing and swimming. An estuarine use assessment could also provide valuable information to resource managers and other decision-makers as they face decisions about the optimal and most sustainable mix of activities in an estuary. An initial step of an estuarine use assessment would be to define and quantify the desired societal uses of the estuary. Society includes residents living near the estuary or industries relying on the estuary, seasonal residents and tourists that use the estuary on a more limited basis, and the public at-large that may use or value the estuary indirectly. The desired uses may include discrete, visible uses such as swimming, recreational or commercial fishing, and navigation. They also may extend to broader, more intangible uses such as maintaining ecological functions or aesthetic appeal. National legislation such as the Estuary Restoration Act, which promotes and funds the restoration of estuaries in the U.S., reflects the public’s desire for estuaries to retain their ecological structures and functions. This report summarizes a project carried out in 2003 that attempted to quantify the desired human uses of a specific estuary in Maine and to determine current measures of success used by coastal managers in Maine to track the ability of the estuary to support desired uses. Casco Bay was chosen as the spatial embayment for which to delineate uses, and nutrient enrichment was selected as the parameter for confirming assumptions about current measures of outcomes related to uses. The report highlights some of the challenges to completing an estuarine use assessment and offers general recommendations for addressing these challenges.

Prioritizing county-level well-being: Moving toward assessment of Gulf Coast counties impacted by the Deepwater Horizon Industrial Disaster

To develop a portfolio of indicators and measures that could best measure changes in the social, economic, environmental and health dimensions of well-being in coastal counties we convened a group of experts March 8-9, 2011 in Charleston, SC, U.S.A. The region of interest was of the northern Gulf of Mexico, specifically, those coastal counties most impacted during the explosion and subsequent oil spill from the Macondo Prospect wellhead during the summer of 2010. Over the course of the two-day workshop participants moved through presentations and facilitated sessions to identify and prioritize potential indicators and measures deemed most valuable for capturing changes in well-being related to changes in or disruption of ecosystem services. The experts reached consensus on a list of indicators that are now being operationalized by NOAA researchers. The ultimate goal of this research project is to determine whether a meaningful set of social and economic indicators can be developed to document changes in well-being that occur as a result of changes in ecosystem services. The outcomes and outputs from the workshop that is the subject of this report helped us to identify high-quality indicators useful for measuring well-being.