This book is open access under a CC BY 4.0 license. It constitutes a unique source of knowledge and guidance for all healthcare workers who care for patients with sepsis and septic shock in ...resource-limited settings. More than eighty percent of the worldwide deaths related to sepsis occur in resource-limited settings in low and middle-income countries. Current international sepsis guidelines cannot be implemented without adaptations towards these settings, mainly because of the difference in local resources and a different spectrum of infectious diseases causing sepsis. This prompted members of the Global Intensive Care working group of the European Society of Intensive Care Medicine (ESICM) and the Mahidol-Oxford Tropical Medicine Research Unit (MORU, Bangkok, Thailand) - among which the Editors – to develop with an international group of experts a comprehensive set of recommendations for the management of sepsis in resource-limited settings. Recommendations are based on both current scientific evidence and clinical experience of clinicians working in resource-limited settings. The book includes an overview chapter outlining the current challenges and future directions of sepsis management as well as general recommendations on the structure and organization of intensive care services in resource-limited settings. Specific recommendations on the recognition and management of patients with sepsis and septic shock in these settings are grouped into seven chapters. The book provides evidence-based practical guidance for doctors in low and middle income countries treating patients with sepsis, and highlights areas for further research and discussion.
Summary Background Over half of childhood intracranial ependymomas occur in children younger than 5 years. As an adjuvant treatment, radiotherapy can be effective, but has the potential to damage the ...child's developing nervous system at a crucial time—with a resultant reduction in IQ and cognitive impairment, endocrinopathy, and risk of second malignancy. We aimed to assess the role of a primary chemotherapy strategy in avoiding or delaying radiotherapy in children younger than 3 years with intracranial ependymoma. Methods Between December, 1992, and April, 2003, we enrolled 89 children with ependymoma who were aged 3 years or younger at diagnosis, of whom nine had metastatic disease on pre-operative imaging. After maximal surgical resection, children received alternating blocks of myelosuppressive and non-myelosuppressive chemotherapy every 14 days for an intended duration of 1 year. Radiotherapy was withheld unless local imaging (ie, from the child's treatment centre) showed progressive disease. Findings 50 of the 80 patients with non-metastatic disease progressed, 34 of whom were irradiated for progression. The 5-year cumulative incidence of freedom from radiotherapy for the 80 non-metastatic patients was 42% (95% CI 32–53). With a median follow-up of 6 years (range 1·5–11·3), overall survival for the non-metastatic patients at 3 years was 79·3% (95% CI 68·5–86·8) and at 5 years 63·4% (51·2–73·4). The corresponding values for event-free survival were 47·6% (36·2–58·1) and 41·8% (30·7–52·6). There was no significant difference in event-free or overall survival between complete and incomplete surgical resection, nor did survival differ according to histological grade, age at diagnosis, or site of disease. In 47 of 59 (80%) patients who progressed, relapse resulted from local control only. The median time to progression for the 59 patients who progressed was 1·6 years (range 0·1–10·2 years). The median age at irradiation of the whole group was 3·6 years (range 1·5–11·9). For the 80 non-metastatic patients, the 23 who achieved the highest relative dose intensity of chemotherapy had the highest post-chemotherapy 5-year overall survival of 76% (95% CI 46·6–91·2), compared with 52% (33·3–68·1) for the 32 patients who achieved the lowest relative dose intensity of chemotherapy. Interpretation This protocol avoided or delayed radiotherapy in a substantial proportion of children younger than 3 years without compromising survival. These results suggest, therefore, that primary chemotherapy strategies have an important role in the treatment of very young children with intracranial ependymoma.
Permeability of tumor vasculature can be a major barrier to successful drug delivery, particularly for high molecular weight agents such as monoclonal antibodies and their diagnostic or therapeutic ...conjugates. In this study, changes in permeability of SCCVII tumor vessels after radiation treatment were evaluated by dynamic magnetic resonance imaging as a function of time after irradiation using a generation-8 polyamidoamine dendrimer (G8-Gd-D)-based magnetic resonance imaging contrast agent shown previously to be confined to tumor blood vessels. Tumor irradiation consisted of either single doses (2-15 Gy) or various daily fractionated doses (5 days). A single radiation dose of 15 Gy resulted in significant transient image enhancement of the tumor tissue with a maximum occurring between 7 and 24 hours after radiation treatment. No observable enhancement was recorded for fractionated radiation doses. Use of dynamic magnetic resonance imaging coupled with G8-Gd-D provides an exquisite methodology capable of defining the timing of enhanced permeability of macromolecules in tumors after irradiation. Such information might be applied to optimize the efficacy of subsequent or concurrent therapies including radiolabeled antibodies or other anticancer agents in combination with external beam therapies.
Adoption of precision agriculture technology has received considerable attention, but abandonment has received little. This paper identifies factors motivating adoption and abandonment of precision ...soil sampling in cotton. Younger producers who farmed more cotton area, owned more of their cropland, planted more non-cotton area, or used a computer were more likely to adopt precision soil sampling. Those with more cotton area or who owned livestock were more likely to abandon, while those who used precision soil sampling longer, or used variable-rate fertilizer application were less likely to abandon precision soil sampling.
Abstract Background Pilocytic astrocytomas (PA) are common childhood brain tumours whose management and prognosis vary widely depending on location.1 H magnetic resonance spectroscopy (MRS) measures ...biochemistry in vivo and shows promise for characterising brain tumours and aiding management. Methods Single voxel MRS (1.5 Tesla, TE 30 ms, TR 1500 ms) was performed on 27 children with PAs. Cases were designated ‘progressors’ if tumour progression led to their clinical management plan being altered. Results Prior to treatment, supratentorial tumours had significantly higher myo-inositol ( p < 0.01, t -test) and glutamate plus glutamine ( p = 0.02, t -test) than cerebellar tumours. Optic pathway or thalamic tumours that progressed had a significantly ( p = 0.04, t -test) lower myo-inositol at initial MRS than those with stable disease. Myo-inositol levels decreased significantly in progressors between the initial and subsequent MRS ( p = 0.03, paired t -test). Changes in myo-inositol occurred before clinical and radiological progression. Conclusions MRS identifies differences with anatomical location in PAs and yields potential non-invasive biomarkers of prognosis.
If circumference is at a higher centile than weight, and particularly if it is increasing from the centile recorded at birth, early assessment is needed to review neurodevelopment and consider other ...diagnoses such as hydrocephalus or tumour. 2 This measurement should be repeated at follow-up. (25 September.) 2 Wilne S, Coller K, Collier J, Kennedy C, Grundy R, Walker D. The diagnosis of brain tumours in children: a guideline to assist healthcare professionals in the assessment of children who may have a brain tumour.
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