A Phase II Trial of Bevacizumab in Patients with Recurrent/Progressive Solid Tumor Brain Metastases That Have Progressed Following Whole-Brain Radiation Therapy.

Patients with solid tumor brain metastases that progress after whole-brain radiation have limited options. This prospective trial investigated the efficacy, safety, and tolerability of bevacizumab as salvage therapy in this population. Eligible patients received bevacizumab 10 mg/kg intravenously every 2 weeks until progression. The primary endpoint was radiologic response using Response Assessment in Neuro-Oncology (RANO) criteria. The secondary endpoints were progression-free survival (PFS), overall survival (OS), duration of response, and safety. Quality of life (QOL) was studied using the Functional Assessment of Cancer Therapy-Brain (FACT-Br) scale. Twenty-seven patients were enrolled, with twenty-four having evaluable data for response. The majority of histologies (n = 21, 78%) were breast cancer. The remaining histologies were non-small-cell lung cancer (n = 4, 15%), neuroendocrine cancer (n = 1, 3%), and papillary fallopian serous adenocarcinoma (n = 1, 3%). Eighteen patients had radiologic response, with two patients demonstrating partial response (8.33%) and sixteen patients demonstrating stable disease (66.7%). The median duration of response was 203 days. PFS at 6 months was 46%, median PFS was 5.3 m, and median OS was 9.5 m. Treatment was well tolerated, with six patients experiencing grade 3 lymphopenia and hypertension. There was one grade 3 thromboembolism. QOL was not negatively impacted. Bevacizumab is a safe and feasible salvage treatment with durable response and favorable overall survival for patients with progressive brain metastases after whole-brain radiation.

Identifying core global mental health professional competencies: A multi-sectoral perspective.

Concerned with sustainably alleviating mental distress and promoting the right to health worldwide, global mental health (GMH) is practised across various contexts spanning the humanitarian-development-peace nexus. The inherently intersectoral and multidisciplinary nature of GMH calls for competency frameworks and training programmes that embody diversity, decolonisation and multiprofessionalism. Existing competency frameworks have failed to capture the multi-sectoral, inter-professional nature of contemporary GMH practice. In response to these needs, a qualitative content analysis of relevant job advertisements was conducted to distil a comprehensive set of professional competencies in contemporary GMH practice. Approximately 200 distinct skills and competencies were extracted from 70 job advertisements and organised into four meta-dimensions: 'skills', 'sector', 'self' and 'subject'. The first known systematic attempt at a multi-sectoral GMH competency framework, it offers a springboard for exploring vital yet overlooked professional competencies such as resilience, self-reflection, political skills and entrepreneurialism. On this basis, recommendations for building a competent, agile and effective GMH workforce with diversified and future-proof skillsets are proposed. The framework can also inform inter-professional training and curriculum design, and capacity-building initiatives aimed at early-career professional development, particularly in low- and middle-income settings.

Using Interactive 3D Visualisations in Neuropsychiatric Education.

Obsessive compulsive disorder (OCD) is a neuropsychiatric disorder with a global prevalence of 2-3%. OCD can have an enormous impact on the lives of those with the disorder, with some studies suggesting suicidal ideation is present in over 50% of individuals with OCD, and other data showing a significant number of individuals attempt suicide. It is therefore important that individuals with OCD receive the best possible treatment. A greater understanding of the underlying pathophysiology of neuropsychiatric disorders among professionals and future clinicians can lead to improved treatment. However, data suggests that many students and clinicians experience "neurophobia", a lack of knowledge or confidence in cases involving the nervous system. In addition, research suggests that the relationship many students have with neurological conditions deteriorates over time, and can persist into practice.If individuals living with conditions such as OCD are to receive the best possible treatment, it is crucial that those administering care are equipped with a thorough understanding of such disorders. While research has shown that the use of interactive 3D models can improve anatomy education and more specifically neurology education, the efficacy of using of such models to engage with neuropsychiatric conditions, specifically OCD, has not been assessed. This study seeks to address this gap.In this study an interactive application for Android devices was designed using standardised software engineering methods in order to improve neuropsychiatry literacy by empowering self-pace learning through interactive 3D visualisations and animations of the neural circuitry involved in OCD. A pilot test and a usability assessment were conducted among five postgraduate life science students. Findings relating to user experience were promising, and pre-test vs. post-test evaluation suggested encouraging outcomes regarding the effectiveness of the application in improving the knowledge and understanding of OCD. In short, this study suggests that interactive 3D visualisations can improve neuropsychiatry education. For this reason, more efforts should be made to construct similar applications in order to ensure patients always receive the best possible care. Fig. 2.1 A diagrammatic representation of the CSTC circuit, based on a similar diagram by Robertson et al. (2017).

Designing new UK-WHO growth charts: implications for health staff use and understanding of charts and growth monitoring.

New pre-school UK charts have been produced incorporating the new World Health Organization growth standards based on healthy breastfed infants. This paper describes the process by which the charts and evidence-based instructions were designed and evaluated, and what it revealed about professional understanding of charts and growth monitoring. A multidisciplinary expert group drew on existing literature, new data analyses and parent focus groups as well as two series of chart-plotting workshops for health staff. The first series explored possible design features and general chart understanding. The second evaluated an advanced prototype with instructions, using plotting and interpretation of three separate scenarios on the old charts, compared with the new charts. The first plotting workshops (46 participants) allowed decisions to be made about the exact chart format, but it also revealed widespread confusion about use of adjustment for gestation and the plotting of birthweight. In the second series (78 participants), high levels of plotting inaccuracy were identified on both chart formats, with 64% of respondents making at least one major mistake. Significant neonatal weight loss was poorly recognized. While most participants recognized abnormal and normal growth patterns, 13-20% did not. Many respondents had never received any formal training in chart use. Growth charts are complex clinical tools that are, at present, poorly understood and inconsistently used. The importance of clear guidelines and formal training has now been recognized and translated into supporting educational materials (free to download at http://www.growthcharts.rcpch.ac.uk).

Policy and practice in the management of postnatal depression in Scotland.

To investigate current policy and practice in postnatal depression in Scotland and to consider how effectively guidelines were addressed. A questionnaire survey of all National Health Service Boards in Scotland between September 2003 and February 2004 to determine what written policies for postnatal depression were in place as at September 2003. This was followed by a questionnaire survey of a representative sample of general practices in Scotland to determine the routine procedures in use for managing postnatal depression in general practice primary care teams. NHS Boards and general practices in Scotland, UK. Forty-seven per cent of policies and 68% of General Practices had implemented the majority of the Scottish Intercollegiate Guidelines Network 60 evidence based recommendations. Practices were more likely than NHS Boards to have addressed a higher percentage of the recommendations (p < 0.05). Practices were more likely to implement antenatal screening for a history of puerperal psychosis if they were within NHS Boards that recommend this as routine practice. Practices within NHS Boards that had in-patient facilities for mother and baby admissions were more likely to identify these services as a treatment option than in the areas where the NHS Boards indicated the facilities were unavailable. Board guidance did not relate significantly to the likelihood of practices following the other evidence-based recommendations. Minimum standards represented by the SIGN 60 evidence-based recommendations were mostly followed in both policy and practice. If Board policy followed guidelines, the guidelines were more likely to be implemented at primary care level.

Gauging acceptance of a hepatitis C test by family planning clinic attendees in Glasgow, UK.

BACKGROUND: In the UK, pregnant women are not offered and recommended a hepatitis C virus (HCV) test because no effective intervention to prevent vertical transmission of HCV exists following conception. Mother-to-child transmission of HCV could, however, be reduced if infected women planning to have children underwent a course of therapy prior to conception. OBJECTIVE: To determine what proportion of female family planning clinic (FPC) attendees would hypothetically accept an HCV test if they were offered it and to identify the factors associated with such a decision. METHODS: Opportunistic sampling was used to recruit 1000 women attending FPCs in Glasgow during 2002/2003. Participants were asked to self-complete a brief questionnaire about HCV and testing. RESULTS: Of 964 participants, 62% reported that they would accept an HCV test if it was offered in the family planning setting and 24% indicated that they were undecided. Only 4% of women reported that they would be offended if offered an HCV test. The highest rates of hypothetical acceptance of an HCV test were reported among those who had ever injected drugs (88%) and those who felt that they were at risk of being infected with HCV (84%). Women who were single [adjusted odds ratio (OR) 1.4, 95% CI 1.1-1.8] and who were of non-white ethnic origin (adjusted OR 2.5, 95% CI 1.0-6.2) were also significantly more inclined to hypothetically accept an HCV test. CONCLUSION: Selective HCV testing to those women at high risk of HCV infection should be encouraged in the family planning setting.

Mismatched antigen prepares gamma delta T cells for suppression of airway hyperresponsiveness.

Gammadelta T cells suppress airway hyperresponsiveness (AHR) induced in allergen-challenged mice but it is not clear whether the suppression is allergen specific. The AHR-suppressive cells express TCR-Vgamma4. To test whether the suppressive function must be induced, we adoptively transferred purified Vgamma4(+) cells into gammadelta T cell-deficient and OVA-sensitized and -challenged recipients (B6.TCR-Vgamma4(-/-)/6(-/-)) and measured the effect on AHR. Vgamma4(+) gammadelta T cells isolated from naive donors were not AHR-suppressive, but Vgamma4(+) cells from OVA-stimulated donors suppressed AHR. Suppressive Vgamma4(+) cells could be isolated from lung and spleen. Their induction in the spleen required sensitization and challenge. In the lung, their function was induced by airway challenge alone. Induction of the suppressors was associated with their activation but it did not alter their ability to accumulate in the lung. Vgamma4(+) gammadelta T cells preferentially express Vdelta4 and -5 but their AHR-suppressive function was not dependent on these Vdeltas. Donor sensitization and challenge not only with OVA but also with two unrelated allergens (ragweed and BSA) induced Vgamma4(+) cells capable of suppressing AHR in the OVA-hyperresponsive recipients, but the process of sensitization and challenge alone (adjuvant and saline only) was not sufficient to induce suppressor function, and LPS as a component of the allergen was not essential. We conclude that AHR-suppressive Vgamma4(+) gammadelta T cells require induction. They are induced by allergen stimulation, but AHR suppression by these cells does not require their restimulation with the same allergen.

Different potentials of gamma delta T cell subsets in regulating airway responsiveness: V gamma 1+ cells, but not V gamma 4+ cells, promote airway hyperreactivity, Th2 cytokines, and airway inflammation.

Allergic airway inflammation and hyperreactivity are modulated by gammadelta T cells, but different experimental parameters can influence the effects observed. For example, in sensitized C57BL/6 and BALB/c mice, transient depletion of all TCR-delta(+) cells just before airway challenge resulted in airway hyperresponsiveness (AHR), but caused hyporesponsiveness when initiated before i.p. sensitization. Vgamma4(+) gammadelta T cells strongly suppressed AHR; their depletion relieved suppression when initiated before challenge, but not before sensitization, and they suppressed AHR when transferred before challenge into sensitized TCR-Vgamma4(-/-)/6(-/-) mice. In contrast, Vgamma1(+) gammadelta T cells enhanced AHR and airway inflammation. In normal mice (C57BL/6 and BALB/c), enhancement of AHR was abrogated only when these cells were depleted before sensitization, but not before challenge, and with regard to airway inflammation, this effect was limited to C57BL/6 mice. However, Vgamma1(+) gammadelta T cells enhanced AHR when transferred before challenge into sensitized B6.TCR-delta(-/-) mice. In this study Vgamma1(+) cells also increased levels of Th2 cytokines in the airways and, to a lesser extent, lung eosinophil numbers. Thus, Vgamma4(+) cells suppress AHR, and Vgamma1(+) cells enhance AHR and airway inflammation under defined experimental conditions. These findings show how gammadelta T cells can be both inhibitors and enhancers of AHR and airway inflammation, and they provide further support for the hypothesis that TCR expression and function cosegregate in gammadelta T cells.