Reinforcing the ‘diminished’ subject? The implications of the ‘vulnerability zeitgeist’ for well-being in educational settings

Pessimistic discourses about crises in youth and children's well-being, mental health and vulnerability permeate English educational policy and practice. These generate vague and slippery elisions of wellbeing and mental health, and the related rise of an ad hoc, confusing market of psycho-emotional interventions promoted by new types of 'pay-experts'. Revisiting earlier arguments that these developments depict a ‘diminished’ human subject, we propose that the incoherent state of policy, much research and practice in this area warrants robust challenge and critique. In particular, more precision about key concepts of social and emotional learning, mental health and wellbeing, a reining in of universal programmes, and serious interest in the types of curriculum that can offer richer, more meaningful alternatives to developing wellbeing in educational settings

A cost-effectiveness analysis of condom distribution programmes for the prevention of sexually transmitted infections in England

Background Prevention of sexually transmitted infection (STI) incidence in England is a high priority, particularly among young people, men who have sex with men (MSM) and black ethnic minorities. An economic evaluation of condom distribution programmes (CDPs) to reduce STI transmission is presented. Methods An economic model using a Bernoulli process estimated the number of people acquiring an STI as a function of its prevalence, transmission rate, condom use, condom failure rate and number of sexual contacts. Models were developed for young people (13–24 years), black ethnic minorities, MSM and the general English population. Effectiveness evidence came from a recent systematic review. For young people, a CDP was modelled (relative risk for condom use=1.23), along with an exploratory analysis of the impact on unintended pregnancies. For other populations, threshold analyses were used to identify the combination of costs and effect size required to make a programme cost-effective. Results The base case predicted that CDP for all young people in England could avert 5123 STI cases per annum, with an incremental cost–effectiveness ratio of £17 411. In addition, it could avert 118 pregnancies and 82 abortions and save £333 000 in associated costs. Schemes for black ethnic minorities and MSM could also be cost-effective even with relatively high costs and small effect sizes. Conclusion CDPs for young people are likely to be cost-effective or cost-saving. CDPs for other high-risk populations may also be cost-effective if they can increase condom use, since high HIV prevalence in these groups imposes a considerable health and cost burden

A model of transformational learning for early childhood community-based workers: Sajag training for responsive caregiving

A global goal for early childhood education and care is to ensure universal, “quality” provision that reaches all children. Achieving this goal requires a well-prepared workforce that is equipped to adapt to and deliver early childhood programs across the vastly diverse contexts and communities where children are growing up around the world. Yet currently there is a severe shortage of early childhood workers, particularly in “low resource” and complex communities. Evidence to support appropriate training for such workers is also lacking. In response, this paper presents findings from a case study of a large-scale training program for community-based early childhood workers in central-east India. A total of 650 community-based Village Communicators were trained to deliver a responsive caregiving package to parents of young children. Data collected over 3 months highlight how the unique contextually grounded, caring and reflexive approach to training resulted in profound personal and professional change among training participants. The findings are of significance in informing policy and practice associated with global goals for early childhood. First, they challenge the technical, programmatic approaches to training that are commonly adopted for preparing this workforce. Second, they evidence the potentially transformative, long-term impact of person-centered approaches to training that facilitate knowledge-sharing to understand local needs and attitudes. Third, they provide insight into ways in which training programs can support enhanced local relevance and effectiveness of early childhood services implemented for children and families across diverse contexts

An updated systematic review of studies mapping (or cross walking) measures of health related-quality of life to generic preference-based measures to generate utility values

Background Mapping is an increasingly common method used to predict instrument-specific preference-based health-state utility values (HSUVs) from data obtained from another health-related quality of life (HRQoL) measure. There have been several methodological developments in this area since a previous review up to 2007. Objective To provide an updated review of all mapping studies that map from HRQoL measures to target generic preference-based measures (EQ-5D measures, SF-6D, HUI measures, QWB, AQoL measures, 15D/16D/17D, CHU-9D) published from January 2007 to October 2018. Data sources A systematic review of English language articles using a variety of approaches: searching electronic and utilities databases, citation searching, targeted journal and website searches. Study selection Full papers of studies that mapped from one health measure to a target preference-based measure using formal statistical regression techniques. Data extraction Undertaken by four authors using predefined data fields including measures, data used, econometric models and assessment of predictive ability. Results There were 180 papers with 233 mapping functions in total. Mapping functions were generated to obtain EQ-5D-3L/EQ-5D-5L-EQ-5D-Y (n = 147), SF-6D (n = 45), AQoL-4D/AQoL-8D (n = 12), HUI2/HUI3 (n = 13), 15D (n = 8) CHU-9D (n = 4) and QWB-SA (n = 4) HSUVs. A large number of different regression methods were used with ordinary least squares (OLS) still being the most common approach (used ≥ 75% times within each preference-based measure). The majority of studies assessed the predictive ability of the mapping functions using mean absolute or root mean squared errors (n = 192, 82%), but this was lower when considering errors across different categories of severity (n = 92, 39%) and plots of predictions (n = 120, 52%). Conclusions The last 10 years has seen a substantial increase in the number of mapping studies and some evidence of advancement in methods with consideration of models beyond OLS and greater reporting of predictive ability of mapping functions

Adalimumab for Treating Moderate-to-Severe Hidradenitis Suppurativa: An Evidence Review Group Perspective of a NICE Single Technology Appraisal

As part of its single technology appraisal (STA) process, the UK National Institute for Health and Care Excellence (NICE) invited the manufacturer of adalimumab (AbbVie) to submit evidence on the clinical effectiveness and cost effectiveness of adalimumab for the treatment of moderate-to-severe hidradenitis suppurativa (HS). The appraisal assessed adalimumab as monotherapy in adult patients with an inadequate response to conventional systemic HS therapy. The School of Health and Related Research Technology Appraisal Group was commissioned to act as the independent Evidence Review Group (ERG). The ERG produced a critical review of the evidence for the clinical effectiveness and cost effectiveness of the technology based on the company’s submission to NICE. The evidence was mainly derived from three randomised controlled trials comparing adalimumab with placebo in adults with moderate-to-severe HS. The clinical-effectiveness review found that significantly more patients achieved a clinical response in the adalimumab groups than in the control groups but that the treatment effect varied between trials and there was uncertainty regarding its impact on a range of other relevant outcomes as well as long-term efficacy. The company’s submitted Markov model assessed the incremental cost effectiveness of adalimumab versus standard care for the treatment of HS from the perspective of the UK NHS and Personal Social Services (PSS) over a lifetime horizon. The original submitted model, including a patient access scheme (PAS), suggested that the incremental cost-effectiveness ratio (ICER) for adalimumab versus standard care was expected to be £16,162 per quality-adjusted life-year (QALY) gained. Following a critique of the model, the ERG’s preferred base case, which corrected programming errors and structural problems surrounding discontinuation rules and incorporated a lower unit cost for HS surgery, resulted in a probabilistic ICER of £29,725 per QALY gained. Based on additional analyses undertaken by the company and the ERG following the publication of the appraisal consultation document (ACD), the Appraisal Committee concluded that the maximum possible ICER for adalimumab compared with supportive care was between £28,500 and £33,200 per QALY gained but was likely to be lower. The Appraisal Committee recommended adalimumab (with the PAS) for the treatment of active moderate-to-severe HS in adults whose disease has not responded to conventional systemic therapy

Ponatinib for Treating Chronic Myeloid Leukaemia: An Evidence Review Group Perspective of a NICE Single Technology Appraisal

As part of its single technology appraisal process, the National Institute for Health and Care Excellence (NICE) invited the company that manufactures ponatinib (Inclusig®; Incyte Corporation) to submit evidence for the clinical and cost effectiveness for previously treated chronic myeloid leukaemia (CML) and Philadelphia-chromosome-positive acute lymphoblastic leukaemia (Ph+ ALL). This paper focusses on the three phases of CML: the chronic phase (CP), the accelerated phase (AP) and the blast crisis phase (BP). The School of Health and Related Research Technology Appraisal Group at the University of Sheffield was commissioned to act as the independent Evidence Review Group (ERG). This article presents the critical review of the company's submission by the ERG and the outcome of the NICE guidance. Clinical evidence for ponatinib was derived from a phase II, industry-sponsored, single-arm, open-label, multicentre, non-comparative study. Despite the limited evidence and potential for biases, this study demonstrated that ponatinib was likely to be an effective treatment (in terms of major cytogenetic response and major haematological response) with an acceptable safety profile for patients with CML. Given the absence of any head-to-head studies comparing ponatinib with other relevant comparators, the company undertook a matching-adjusted indirect comparison (MAIC) of ponatinib with bosutinib. The approach was only used for patients with CP-CML because comprehensive data were not available for the AP- or BP-CML groups to allow the matching technique to be used. Despite the uncertainty about the MAIC approach, ponatinib was considered likely to offer advantages over bosutinib in the third-line setting, particularly for complete cytogenetic response. The company developed two health economic models to assess the cost effectiveness of ponatinib for the treatment of patients in CP-CML or in advanced CML (AP- or BP-CML, which were modelled separately). The company did not adequately explore the uncertainty in the survivor functions. As a result, the ERG believed the uncertainty in the decision problem was underestimated. Exploratory analyses undertaken by the ERG produced the following results for ponatinib. In CP-CML, from £18,246 to £27,667 per quality-adjusted life-year (QALY) gained compared with best supportive care (BSC), from £19,680 to £37,381 per QALY gained compared with bosutinib and from £18,279 per QALY gained to dominated compared with allogeneic stem cell transplant (allo-SCT). In AP-CML, the cost per QALY gained for ponatinib ranged from £7123 to £17,625 compared with BSC, and from dominating to £61,896 per QALY gained compared with allo-SCT. In BP-CML, the cost effectiveness of ponatinib ranged from £5033 per QALY gained to dominated compared with allo-SCT, although it was likely to be at the more favourable end of this range, and dominant in all scenarios compared with BSC. The NICE appraisal committee concluded that ponatinib is a cost-effective use of NHS resources in the considered population, subject to the company providing the agreed discount in the Patient Access Scheme

Neurovascular unit dysfunction with blood-brain barrier hyperpermeability contributes to major depressive disorder: a review of clinical and experimental evidence

About one-third of people with major depressive disorder (MDD) fail at least two antidepressant drug trials at 1 year. Together with clinical and experimental evidence indicating that the pathophysiology of MDD is multifactorial, this observation underscores the importance of elucidating mechanisms beyond monoaminergic dysregulation that can contribute to the genesis and persistence of MDD. Oxidative stress and neuroinflammation are mechanistically linked to the presence of neurovascular dysfunction with blood-brain barrier (BBB) hyperpermeability in selected neurological disorders, such as stroke, epilepsy, multiple sclerosis, traumatic brain injury, and Alzheimer’s disease. In contrast to other major psychiatric disorders, MDD is frequently comorbid with such neurological disorders and constitutes an independent risk factor for morbidity and mortality in disorders characterized by vascular endothelial dysfunction (cardiovascular disease and diabetes mellitus). Oxidative stress and neuroinflammation are implicated in the neurobiology of MDD. More recent evidence links neurovascular dysfunction with BBB hyperpermeability to MDD without neurological comorbidity. We review this emerging literature and present a theoretical integration between these abnormalities to those involving oxidative stress and neuroinflammation in MDD. We discuss our hypothesis that alterations in endothelial nitric oxide levels and endothelial nitric oxide synthase uncoupling are central mechanistic links in this regard. Understanding the contribution of neurovascular dysfunction with BBB hyperpermeability to the pathophysiology of MDD may help to identify novel therapeutic and preventative approaches

A Model of Transformational Learning for Early Childhood Community-based Workers: Sajag Training for Responsive Caregiving

AbstractA global goal for early childhood education and care is to ensure universal, “quality” provision that reaches all children. Achieving this goal requires a well-prepared workforce that is equipped to adapt to and deliver early childhood programs across the vastly diverse contexts and communities where children are growing up around the world. Yet currently there is a severe shortage of early childhood workers, particularly in “low resource” and complex communities. Evidence to support appropriate training for such workers is also lacking. In response, this paper presents findings from a case study of a large-scale training program for community-based early childhood workers in central-east India. A total of 650 community-based Village Communicators were trained to deliver a responsive caregiving package to parents of young children. Data collected over 3 months highlight how the unique contextually grounded, caring and reflexive approach to training resulted in profound personal and professional change among training participants. The findings are of significance in informing policy and practice associated with global goals for early childhood. First, they challenge the technical, programmatic approaches to training that are commonly adopted for preparing this workforce. Second, they evidence the potentially transformative, long-term impact of person-centered approaches to training that facilitate knowledge-sharing to understand local needs and attitudes. Third, they provide insight into ways in which training programs can support enhanced local relevance and effectiveness of early childhood services implemented for children and families across diverse contexts.</jats:p