Day and night home closed-loop insulin delivery in adults with type 1 diabetes: three-center randomized crossover study.

OBJECTIVE: To evaluate the feasibility of day and night closed-loop insulin delivery in adults with type 1 diabetes under free-living conditions. RESEARCH DESIGN AND METHODS: Seventeen adults with type 1 diabetes on insulin pump therapy (means ± SD age 34 ± 9 years, HbA1c 7.6 ± 0.8%, and duration of diabetes 19 ± 9 years) participated in an open-label multinational three-center crossover study. In a random order, participants underwent two 8-day periods (first day at the clinical research facility followed by 7 days at home) of sensor-augmented insulin pump therapy (SAP) or automated closed-loop insulin delivery. The primary end point was the time when sensor glucose was in target range between 3.9 and 10.0 mmol/L during the 7-day home phase. RESULTS: During the home phase, the percentage of time when glucose was in target range was significantly higher during closed-loop compared with SAP (median 75% [interquartile range 61-79] vs. 62% [53-70], P = 0.005). Mean glucose (8.1 vs. 8.8 mmol/L, P = 0.027) and time spent above target (P = 0.013) were lower during closed loop, while time spent below target was comparable (P = 0.339). Increased time in target was observed during both daytime (P = 0.017) and nighttime (P = 0.013). CONCLUSIONS: Compared with SAP, 1 week of closed-loop insulin delivery at home reduces mean glucose and increases time in target without increasing the risk of hypoglycemia in adults with relatively well-controlled type 1 diabetes.This is the author accepted manuscript. The final version can be found published here: http://care.diabetesjournals.org/content/37/7/1931.abstract

Evaluation of the current knowledge limitations in breast cancer research: a gap analysis

BACKGROUND A gap analysis was conducted to determine which areas of breast cancer research, if targeted by researchers and funding bodies, could produce the greatest impact on patients. METHODS Fifty-six Breast Cancer Campaign grant holders and prominent UK breast cancer researchers participated in a gap analysis of current breast cancer research. Before, during and following the meeting, groups in seven key research areas participated in cycles of presentation, literature review and discussion. Summary papers were prepared by each group and collated into this position paper highlighting the research gaps, with recommendations for action. RESULTS Gaps were identified in all seven themes. General barriers to progress were lack of financial and practical resources, and poor collaboration between disciplines. Critical gaps in each theme included: (1) genetics (knowledge of genetic changes, their effects and interactions); (2) initiation of breast cancer (how developmental signalling pathways cause ductal elongation and branching at the cellular level and influence stem cell dynamics, and how their disruption initiates tumour formation); (3) progression of breast cancer (deciphering the intracellular and extracellular regulators of early progression, tumour growth, angiogenesis and metastasis); (4) therapies and targets (understanding who develops advanced disease); (5) disease markers (incorporating intelligent trial design into all studies to ensure new treatments are tested in patient groups stratified using biomarkers); (6) prevention (strategies to prevent oestrogen-receptor negative tumours and the long-term effects of chemoprevention for oestrogen-receptor positive tumours); (7) psychosocial aspects of cancer (the use of appropriate psychosocial interventions, and the personal impact of all stages of the disease among patients from a range of ethnic and demographic backgrounds). CONCLUSION Through recommendations to address these gaps with future research, the long-term benefits to patients will include: better estimation of risk in families with breast cancer and strategies to reduce risk; better prediction of drug response and patient prognosis; improved tailoring of treatments to patient subgroups and development of new therapeutic approaches; earlier initiation of treatment; more effective use of resources for screening populations; and an enhanced experience for people with or at risk of breast cancer and their families. The challenge to funding bodies and researchers in all disciplines is to focus on these gaps and to drive advances in knowledge into improvements in patient care

Day and night closed-loop control in adults with type 1 diabetes: a comparison of two closed-loop algorithms driving continuous subcutaneous insulin infusion versus patient self-management.

OBJECTIVE: To compare two validated closed-loop (CL) algorithms versus patient self-control with CSII in terms of glycemic control. RESEARCH DESIGN AND METHODS: This study was a multicenter, randomized, three-way crossover, open-label trial in 48 patients with type 1 diabetes mellitus for at least 6 months, treated with continuous subcutaneous insulin infusion. Blood glucose was controlled for 23 h by the algorithm of the Universities of Pavia and Padova with a Safety Supervision Module developed at the Universities of Virginia and California at Santa Barbara (international artificial pancreas [iAP]), by the algorithm of University of Cambridge (CAM), or by patients themselves in open loop (OL) during three hospital admissions including meals and exercise. The main analysis was on an intention-to-treat basis. Main outcome measures included time spent in target (glucose levels between 3.9 and 8.0 mmol/L or between 3.9 and 10.0 mmol/L after meals). RESULTS: Time spent in the target range was similar in CL and OL: 62.6% for OL, 59.2% for iAP, and 58.3% for CAM. While mean glucose level was significantly lower in OL (7.19, 8.15, and 8.26 mmol/L, respectively) (overall P = 0.001), percentage of time spent in hypoglycemia (<3.9 mmol/L) was almost threefold reduced during CL (6.4%, 2.1%, and 2.0%) (overall P = 0.001) with less time ≤2.8 mmol/L (overall P = 0.038). There were no significant differences in outcomes between algorithms. CONCLUSIONS: Both CAM and iAP algorithms provide safe glycemic control

Characterization of Equine Chronic Tendon Lesions in Low- and High-Field Magnetic Resonance Imaging

In equine medicine, experience regarding MRI of chronic tendon lesions is limited, and evidence on the suitability of different sequences in 3 T high-field MRI is scarce. Therefore, macroscopically healthy and altered tendons were examined by histology and in 0.27 T low- and 3 T high-field MRI, focusing on T1-weighted (T1w) sequences to visualize chronic lesions. In high-field MRI, tendons were positioned parallel (horizontal) and perpendicular (vertical) to the magnetic field, acknowledging the possible impact of the magic angle effect. The images were evaluated qualitatively and signal intensities were measured for quantitative analysis. Qualitative evaluation was consistent with the quantitative results, yet there were differences in lesion detection between the sequences. The low-field T1w GRE sequence and high-field T1w FLASH sequence with vertically positioned tendons displayed all tendon lesions. However, the horizontally scanned high-field T1w SE sequence failed to detect chronic tendon lesions. The agreement regarding tendon signal intensities was higher between high-field sequences scanned in the same orientation (horizontal or vertical) than between the same types of sequence (SE or FLASH), demonstrating the impact of tendon positioning. Vertical scanning was superior for diagnosis of the tendon lesions, suggesting that the magic angle effect plays a major role in detecting chronic tendon disease

10PRT/0496: Oxford Community Treatment Order Evaluation Trial (OCTET): a single-outcome randomised controlled trial of compulsory outpatient treatment in psychosis (ISRCTN73110773)

Background: different forms of compulsory supervision and treatment of outpatients with severe mental illness have developed internationally in the wake of widespread deinstitutionalisation. Community Treatment Orders (CTOs) for patients with psychiatric illness became available in 2008 as a treatment option in England and Wales under the amended Mental Health Act 2007. There is no convincing experimental evidence for the efficacy of compulsory outpatient treatment, so current clinical guidance and decision making is not based on firm evidence. Section 17 leave remains a lawful option for supervision of patients in the community.Aims: OCTET is designed as a single-outcome randomised trial to test the hypothesis that CTOs reduce readmissions to hospital in patients compared with patients not subject to CTOs. Design and population: patients will be randomised on a 1:1 basis to a CTO or section 17 leave. Outcome data will be collected from patients’ interviews and medical notes at baseline, and at 6 and 12 months. Eligible patients are those considered suitable for CTO by their clinical team, diagnosed with psychosis, aged 18-65 years, and not subject to any other legal restrictions. Outcomes: the single primary outcome is rate of readmission to hospital in a 12-month follow-up. Secondary outcomes are: number of days in psychiatric hospital, time to readmission, engagement with clinical services and loss to care, adherence to prescribed medication, satisfaction with services, and clinical and social outcomes. Sample size: the proposed sample size is 300, based on the North Carolina trial, the only rigorous randomised trial of compulsory outpatient treatment published. That study found a difference of 16% in the proportion readmitted to psychiatric hospital between the two groups. Assuming similar rates of readmission in our control group (48%), we require 288 patients to detect a similar difference with a significance level of 5% and power of 80%. Attrition is anticipated to be negligible because primary outcome data are available from medical records. Analysis plan: analysis will be on an intention-to-treat basis. The primary analysis will be a test of the difference in the proportion of patients readmitted during follow-up between the two groups. If the data can be transformed into a normal distribution, a t test will be used to compare the difference between the two groups. If normality cannot be achieved, Wilcoxon's rank-sum test will be used. Two-sided significance tests will be used. If the proportion of patients with missing data for the primary outcome exceeds 20% in either group, a sensitivity analysis will be done<br/

Solute and particle retention in the digestive tract of the Phillip's dikdik (Madoqua saltiana phillipsi), a very small browsing ruminant: Biological and methodological implications

Morphological characteristics of the forestomach, as well as reports of a natural diet that mostly excludes monocots, suggest that dikdiks (Madoqua spp.), among smallest extant ruminants, should have a ‘moosetype’ forestomach physiology characterised by a low degree of selective particle retention. We tested this assumption in a series of feeding experiments with 12 adult Phillip's dikdiks (Madoqua saltiana phillipsi) on three different intake levels per animal, using cobalt-EDTA as a solute marker and a ‘conventional’ chromiummordanted fibre (b2 mm; mean particle size 0.63 mm) marker for the particle phase. Body mass had no influence on retention measurements, whereas food intake level clearly had. Drinking water intake was not related to the retention of the solute marker. In contrast to our expectations, the particle marker was retained distinctively longer than the solute marker. Comparisons with results in larger ruminants and with faecal particle sizes measured in dikdiks suggested that in these small animals, the chosen particle marker was above the critical size threshold, above which particle delay in the forestomach is not only due to selective particle retention (as compared to fluids), but additionally due to the ruminal particle sorting mechanism that retains particles above this threshold longer than particles below this threshold. A second study with a similar marker of a lower mean particle size (0.17 mm, which is below the faecal particle size reported for dikdiks) resulted in particle and fluid retention patterns similar to those documented in other ‘moose-type’ ruminants. Nevertheless, even this smaller particle marker yielded retention times that were longer than those predicted by allometric equations based on quarter-power scaling, providing further support for observations that small ruminants generally achieve longer retention times and higher digestive efficiencies than expected based on their body size