A Phase I Dose Escalation Trial of Gemcitabine with Radiotherapy for Breast Cancer in the Treatment of Unresectable Chest Wall Recurrences

The purpose of this study was to determine the maximum tolerated dose (MTD) of gemcitabine when given concurrently with standard radiotherapy for the treatment of chest wall recurrences, and to compare actuarial rates of local-regional control with those achieved in historical controls. Patients with unresectable chest wall recurrences were enrolled in a phase I trial of concurrent gemcitabine and radiotherapy. Gemcitabine was increased at 150 mg/m 2 /week increments, starting at 300 mg/m 2 /week. Radiotherapy was delivered to the chest wall and regional nodes to a total of 60 to 70 Gy in 2 Gy daily fractions. Treatment toxicity was assessed and a comparison of treatment outcome was performed between study patients and historical groups treated with either radiotherapy alone or excision followed by radiotherapy. The dose-limiting toxicities of neutropenia and thrombocytopenia occurred at the second planned dose of 450 mg/m 2 /week after accrual of only six patients, resulting in a MTD of 300 mg/m 2 /week. Myelosuppression and skin desquamation were commonly observed. Actuarial rates of local-regional control were 100%, 50%, and 90% at 2 years for the gemcitabine with radiotherapy, radiotherapy alone, and excision followed by radiotherapy groups, respectively ( p  = 0.105). The difference among the Kaplan–Meier curves for overall local-regional control was statistically significant at p  = 0.007 in favor of combined gemcitabine and radiotherapy. The MTD of gemcitabine is 300 mg/m 2 /week when gemcitabine is delivered concurrently with radiotherapy for unresectable chest wall failures. This novel approach suggests excellent local-regional control when compared to historical controls. A phase II trial is warranted. Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75565/1/j.1075-122X.2004.21305.x.pd

Prognostic Factors in 77 Curative Chest Wall Resections for Isolated Breast Cancer Recurrence

Background: Full-thickness chest wall resection (CWR) is the preferred treatment for breast cancer (BC) patients with extensive isolated locoregional recurrence. It remains a challenge to select patients that will benefit most from this treatment. The aim of this study was to define prognostic factors in patients who undergo CWR with curative intent. Methods: BC patients who underwent a CWR with curative intent for recurrence of disease between 1986 and 2006 were included in this retrospective study. Twenty-two factors were studied in a univariate analyses, and multivariate stepwise Cox regression analyses was performed. Results: Seventy-seven patients were included in this study. The 5-year overall survival was 25%. There was one postoperative death. Univariate analyses showed that three prognostic factors were significantly correlated with OS and disease-free survival: (1) interval between primary treatment and CWR (P = .02 and .004, respectively), (2) chemotherapy for recurrence (P = .05 and .05, respectively), and (3) resection specimen smaller than 150 cm2(P = .03 and .009, respectively). An interval lasting >10 years between primary treatment and CWR remained statistically significantly correlated with better overall survival and disease-free survival after multivariate analyses. Conclusions: CWR is a safe treatment in patients who have isolated extensive BC recurrence. The best survival outcome was seen in patients after a disease-free interval of >10 years. Existing data show that adjuvant radiotherapy and adjuvant hormone therapy for estrogen-positive tumors improves overall survival. Neoadjuvant chemotherapy may be considered in individual patients

Control of hyperglycaemia in paediatric intensive care (CHiP): study protocol.

BACKGROUND: There is increasing evidence that tight blood glucose (BG) control improves outcomes in critically ill adults. Children show similar hyperglycaemic responses to surgery or critical illness. However it is not known whether tight control will benefit children given maturational differences and different disease spectrum. METHODS/DESIGN: The study is an randomised open trial with two parallel groups to assess whether, for children undergoing intensive care in the UK aged <or= 16 years who are ventilated, have an arterial line in-situ and are receiving vasoactive support following injury, major surgery or in association with critical illness in whom it is anticipated such treatment will be required to continue for at least 12 hours, tight control will increase the numbers of days alive and free of mechanical ventilation at 30 days, and lead to improvement in a range of complications associated with intensive care treatment and be cost effective. Children in the tight control group will receive insulin by intravenous infusion titrated to maintain BG between 4 and 7.0 mmol/l. Children in the control group will be treated according to a standard current approach to BG management. Children will be followed up to determine vital status and healthcare resources usage between discharge and 12 months post-randomisation. Information regarding overall health status, global neurological outcome, attention and behavioural status will be sought from a subgroup with traumatic brain injury (TBI). A difference of 2 days in the number of ventilator-free days within the first 30 days post-randomisation is considered clinically important. Conservatively assuming a standard deviation of a week across both trial arms, a type I error of 1% (2-sided test), and allowing for non-compliance, a total sample size of 1000 patients would have 90% power to detect this difference. To detect effect differences between cardiac and non-cardiac patients, a target sample size of 1500 is required. An economic evaluation will assess whether the costs of achieving tight BG control are justified by subsequent reductions in hospitalisation costs. DISCUSSION: The relevance of tight glycaemic control in this population needs to be assessed formally before being accepted into standard practice

Outcome prediction with a social cognitive battery: a multicenter longitudinal study

The interest in social cognition in schizophrenia is justified by the relationship between deficits in these skills and negative functional outcomes. Although assessment batteries have already been described, there is no consensus about which measures are useful in predicting patient functioning or quality of life (QoL). We investigated a set of five measures of recognition of facial emotions, theory of mind (ToM), and empathy in a cohort of 143 patients with schizophrenia or schizoaffective disorder at inclusion and, amongst whom 79 were reassessed 1 year later. The distribution was satisfactory for the TREF (Facial Emotion Recognition Task), V-SIR (Versailles-Situational Intention Reading), and QCAE (Questionnaire of Cognitive and Affective Empathy). Internal consistency was satisfactory for the TREF, V-SIR, V-Comics (Versailles Intention Attribution Task), and QCAE. Sensitivity to change was acceptable for the TREF. The TREF and V-SIR showed a cross-sectional relationship with functioning beyond the clinical symptoms of schizophrenia but not beyond neurocognition. Moreover, the TREF and V-SIR at inclusion could not predict functioning one year later, whereas most neurocognitive and clinical dimensions at inclusion could. Finally, only affective QCAE showed a significant cross-sectional, but not longitudinal, association with QoL. In conclusion, the TREF had satisfactory psychometric properties and showed a cross-sectional, but not longitudinal, association with objective outcome measures, thus appearing to be reliable in clinical practice and research. The V-SIR also showed promising psychometric properties, despite a possible weakness to detect change. However, these measures should be interpreted within the context of the good predictive power of the neurocognitive and clinical status on the outcome.Sorbonne Universités à Paris pour l'Enseignement et la RechercheFondaMental-Cohorte

Blended Learning and Sustainable Development

The concept of blended learning has its origins in the 1960’s when new options for technology-mediated education became available to complement conventional approaches to face-to-face teaching in higher education and other contexts. In HE institutions, blended learning has now become so widespread that many regard it as the “new normal” in describing HE approaches to teaching and learning. However, the ubiquity of the blended learning concept in HE is problematic for establishing a common understanding of the concept, which is essential for identifying how it contributes to sustainable development. Blended learning may be defined as the design of learning experiences that draw on a combination of face-face, distance, or online delivery methods, learning technologies, delivery multimedia, and pedagogical methodologies to achieve a mix of learning outcomes in educational or training contexts. Blended learning designs can support sustainable development, including the social, economic, and environmental dimensions of sustainability and protect global environmental resources to meet the needs of the present and future generations. This chapter first examines the various conceptualisations of blended learning in HE teaching and learning systems, and then proceeds to examine contemporary understanding of how HE blended learning provision contributes or might contribute to sustainable development and to the Sustainable Development Goals (SDGs)