226 research outputs found
Evaluation of children's centres in England (ECCE) : strand 1: first survey of children's centre leaders in the most deprived areas
This report is the first output from the Evaluation of Children's Centres in England (ECCE), a six year study commissioned by the Department for Education and undertaken by NatCen Social Research, the University of Oxford and Frontier Economics. The aim of ECCE is to provide an in-depth understanding of children's centre services, including their effectiveness in relation to different management and delivery approaches and the cost of delivering different types of services. The aim of Strand 1 is to profile children’s centres in the most disadvantaged areas, providing estimates on different aspects of provision with which to select centres for subsequent stages of the evaluation and to explore different models of provision. The findings below relate to 500 children's centres that are representative of all phase 1 and 2 centres (i.e. those in the 30percent most deprived areas).</p
Findings from a pilot randomised trial of an asthma internet self-management intervention (RAISIN)
<b>Objective </b>To evaluate the feasibility of a phase 3
randomised controlled trial (RCT) of a website (Living
Well with Asthma) to support self-management.<p></p>
<b>Design and setting</b> Phase 2, parallel group, RCT,
participants recruited from 20 general practices across
Glasgow, UK. Randomisation through automated voice
response, after baseline data collection, to website
access for minimum 12 weeks or usual care.<p></p>
<b>Participants </b>Adults (age≥16 years) with physician
diagnosed, symptomatic asthma (Asthma Control
Questionnaire (ACQ) score ≥1). People with unstable
asthma or other lung disease were excluded.<p></p>
<b>Intervention</b> Living Well with Asthma’ is a desktop/
laptop compatible interactive website designed with
input from asthma/ behaviour change specialists, and
adults with asthma. It aims to support optimal
medication management, promote use of action plans,
encourage attendance at asthma reviews and increase
physical activity.<p></p>
<b>Outcome measures</b> Primary outcomes were
recruitment/retention, website use, ACQ and mini-
Asthma Quality of Life Questionnaire (AQLQ).
Secondary outcomes included patient activation,
prescribing, adherence, spirometry, lung inflammation
and health service contacts after 12 weeks. Blinding
postrandomisation was not possible.<p></p>
<b>Results </b>Recruitment target met. 51 participants
randomised (25 intervention group). Age range
16–78 years; 75% female; 28% from most deprived
quintile. 45/51 (88%; 20 intervention group) followed
up. 19 (76% of the intervention group) used the
website, for a mean of 18 min (range 0–49). 17 went
beyond the 2 ‘core’ modules. Median number of logins
was 1 (IQR 1–2, range 0–7). No significant difference
in the prespecified primary efficacy measures of ACQ
scores (−0.36; 95% CI −0.96 to 0.23; p=0.225), and
mini-AQLQ scores (0.38; −0.13 to 0.89; p=0.136). No
adverse events.<p></p>
<b>Conclusions</b> Recruitment and retention confirmed
feasibility; trends to improved outcomes suggest use of
Living Well with Asthma may improve self-management
in adults with asthma and merits further development
followed by investigation in a phase 3 trial
Evaluation of children’s centres in England (ECCE). Strand 1: First survey of children’s centre leaders in the most deprived areas
This is the final version of the report. Available from the Department for Education via the link in this record.The evaluation of children’s centres in England (ECCE) is a 6-year study commissioned by the Department for Education (DfE) and undertaken by NatCen Social Research, the University of Oxford and Frontier Economics.
The aim of this report is to profile children’s centres in the most disadvantaged areas, providing estimates on different aspects of provision and to explore different models of provision. The profile covers all main aspects of provision including management, staff, services, users and finance and involves nearly 500 children’s centres, representative of all phase 1 and 2 centres in the most disadvantaged area
An Integrated Disease/Pharmacokinetic/Pharmacodynamic Model Suggests Improved Interleukin-21 Regimens Validated Prospectively for Mouse Solid Cancers
Interleukin (IL)-21 is an attractive antitumor agent with potent immunomodulatory functions. Yet thus far, the cytokine has yielded only partial responses in solid cancer patients, and conditions for beneficial IL-21 immunotherapy remain elusive. The current work aims to identify clinically-relevant IL-21 regimens with enhanced efficacy, based on mathematical modeling of long-term antitumor responses. For this purpose, pharmacokinetic (PK) and pharmacodynamic (PD) data were acquired from a preclinical study applying systemic IL-21 therapy in murine solid cancers. We developed an integrated disease/PK/PD model for the IL-21 anticancer response, and calibrated it using selected “training” data. The accuracy of the model was verified retrospectively under diverse IL-21 treatment settings, by comparing its predictions to independent “validation” data in melanoma and renal cell carcinoma-challenged mice (R2>0.90). Simulations of the verified model surfaced important therapeutic insights: (1) Fractionating the standard daily regimen (50 µg/dose) into a twice daily schedule (25 µg/dose) is advantageous, yielding a significantly lower tumor mass (45% decrease); (2) A low-dose (12 µg/day) regimen exerts a response similar to that obtained under the 50 µg/day treatment, suggestive of an equally efficacious dose with potentially reduced toxicity. Subsequent experiments in melanoma-bearing mice corroborated both of these predictions with high precision (R2>0.89), thus validating the model also prospectively in vivo. Thus, the confirmed PK/PD model rationalizes IL-21 therapy, and pinpoints improved clinically-feasible treatment schedules. Our analysis demonstrates the value of employing mathematical modeling and in silico-guided design of solid tumor immunotherapy in the clinic
Left common carotid artery arising from the brachiocephalic trunk: a case report
An abnormal origin of the left common carotid artery from the initial portion of the brachiocephalic trunk was found in the superior mediastinum in a 81-year-old Caucasian male cadaver during dissection practice. We report on the exact morphology of that variant that is appeared in an incidence of 0,2% in the literature. We discuss the relative literature and pay attention on the significance of such a variation for clinicians in its recognition and protection
Predicting Outcomes of Prostate Cancer Immunotherapy by Personalized Mathematical Models
Therapeutic vaccination against disseminated prostate cancer (PCa) is partially effective in some PCa patients. We hypothesized that the efficacy of treatment will be enhanced by individualized vaccination regimens tailored by simple mathematical models.We developed a general mathematical model encompassing the basic interactions of a vaccine, immune system and PCa cells, and validated it by the results of a clinical trial testing an allogeneic PCa whole-cell vaccine. For model validation in the absence of any other pertinent marker, we used the clinically measured changes in prostate-specific antigen (PSA) levels as a correlate of tumor burden. Up to 26 PSA levels measured per patient were divided into each patient's training set and his validation set. The training set, used for model personalization, contained the patient's initial sequence of PSA levels; the validation set contained his subsequent PSA data points. Personalized models were simulated to predict changes in tumor burden and PSA levels and predictions were compared to the validation set. The model accurately predicted PSA levels over the entire measured period in 12 of the 15 vaccination-responsive patients (the coefficient of determination between the predicted and observed PSA values was R(2) = 0.972). The model could not account for the inconsistent changes in PSA levels in 3 of the 15 responsive patients at the end of treatment. Each validated personalized model was simulated under many hypothetical immunotherapy protocols to suggest alternative vaccination regimens. Personalized regimens predicted to enhance the effects of therapy differed among the patients.Using a few initial measurements, we constructed robust patient-specific models of PCa immunotherapy, which were retrospectively validated by clinical trial results. Our results emphasize the potential value and feasibility of individualized model-suggested immunotherapy protocols
The Local Optima Level in Chemotherapy Schedule Optimisation
In this paper a multi-drug Chemotherapy Schedule Optimisation Problem (CSOP) is subject to Local Optima Network (LON) analysis. LONs capture global patterns in fitness landscapes. CSOPs have not previously been subject to fitness landscape analysis. We fill this gap: LONs are constructed and studied for meaningful structure. The CSOP formulation presents novel challenges and questions for the LON model because there are infeasible regions in the fitness landscape and an unknown global optimum; it also brings a topic from healthcare to LON analysis. Two LON Construction algorithms are proposed for sampling CSOP fitness landscapes: a Markov-Chain Construction Algorithm and a Hybrid Construction Algorithm. The results provide new insight into LONs of highly-constrained spaces, and into the proficiency of search operators on the CSOP. Iterated Local Search and Memetic Search, which are the foundations for the LON algorithms, are found to markedly out-perform a Genetic Algorithm from the literature
Damage to the Superficial Peroneal Nerve in Operative Treatment of Fibula Fractures: Straight to the Bone? Case Report and Review of the Literature
Ankle fractures are a significant part of the lower extremity trauma seen in the emergency department. Neurologic complications of ankle fracture surgery are infrequently described but account for significant morbidity. The risk of nerve injury is increased for the Blair and Botte type B pattern of the intermediate cutaneous dorsal nerve branch, crossing the distal fibula from posterior to anterior (at 5 to 7 cm from malleolar tip). This pattern is present in about 10% to 15% of patients. Injuries to the superficial peroneal nerve and its branches negatively influence the outcome. Early recognition and protection might reduce the incidence of superficial peroneal nerve injuries during open reduction and internal fixation of lateral malleolus fractures. We describe 2 surgically treated ankle fractures with superficial peroneal nerve branch (intermediate cutaneous dorsal nerve) involvement and review the current literature
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