A 24-Week, Randomized, Treat-to-Target Trial Comparing Initiation of Insulin Glargine Once-Daily With Insulin Detemir Twice-Daily in Patients With Type 2 Diabetes Inadequately Controlled on Oral Glucose-Lowering Drugs

OBJECTIVE - To determine whether glargine is noninferior to detemir regarding the percentage of patients reaching A1C <7% without symptomatic hypoglycemia <= 3.1 mmol/l. RESEARCH DESIGN AND METHODS - In this 24-week trial, 973 insulin-naive type 2 diabetic patients on stable oral glucose-lowering drugs with A1CS. 7.0-10.5% were randomized to glargine once daily or detemir twice daily. Insulin doses were systematically titrated. RESULTS - 27.5 and 25.6% of patients reached the primary outcome with glargine and detemir, respectively, demonstrating the noninferiority of glargine. Improvements in A1C were -1.46 +/- 1.09% for glargine and -1.54 +/- 1.11% for detemir (P = 0.149), with similar proportions of patients achieving A1C <7% (P = 0.254) but more detemir-treated patients reaching A1C <6.5% (P = 0.017). Hypoglycemia risk was similar. Weight gain was higher for glargine (difference: 0.77 kg, P <0.001). Glargine doses were lower than detemir doses: 43.5 +/- 129.0 vs. 76.5 +/- 50.5 units/day (P <0.001). CONCLUSIONS - In insulin-naive type 2 diabetic patients, glargine reached similar control as detemir, with more weight gain, but required significantly lower dose

Contact frequency determines outcome of basal insulin initiation trials in type 2 diabetes

Aims/hypothesis The aim of the present study was to investigate whether predetermined contact frequency with the study teamand endpoint insulin dose are associated with study outcomes in basal insulin initiation trials in type 2 diabetes. Methods A systematic Medline search was performed. Using data from the selected studies, contact frequency was plotted against HbA(1c) reduction and endpoint insulin dose. The importance of face-to-face vs telephone contact was also analysed. Insulin dose was plotted against HbA(1c) reduction, hypoglycaemia rate and weight gain. To investigate non-specific study effects, the relationship between contact frequency and HbA(1c) was also assessed in dipeptidyl peptidase-4 (DPP-4) inhibitor trials. Results The reduction in HbA(1c) was highly correlated with contact frequency and endpoint insulin dose (r(2)=0.751, p<0.001 and r(2)=0.433, p=0.008, respectively). However, after adjusting for contact frequency, the relationship between insulin dose and HbA(1c) reduction was no longer significant (p=0.270). The frequency of both clinical and telephone contacts were independent predictors of HbA(1c) improvement (p=0.010 and p<0.001, respectively). We found no dose response relationship between end-of-study insulin dose and hypoglycaemia or weight gain. In DPP-4 inhibitor studies, contact frequency was not positively associated with HbA(1c). Conclusions/interpretation The frequency of contact with the study team is highly correlated with the improvement in HbA(1c) achieved in basal insulin initiation trials in type 2 diabetic patients. This has important implications for trial design and interpretation, as well as for clinical car

Food Price Shocks and the Political Economy of Global Agricultural and Development Policy

The recent spikes of global food prices induced a rapid increase in mass media coverage, public policy attention, and donor funding for food security and for agriculture and rural poverty. This has occurred while the shift from low to high food prices has induced a shift in (demographic or social) location of the hunger and poverty effects, but the total number of undernourished and poor people has declined over the same period. We suggest that the observed pattern can be explained by the presence of a global urban bias on agriculture and food policy in developing countries, and we discuss whether this global urban bias may actually benefit poor farmers. We argue that the food price spikes have succeeded where others have failed in the past: to move the problems of poor and hungry farmers to the top of the policy agenda and to induce development and donor strategies to help them

Business process variant analysis based on mutual fingerprints of event logs

Comparing business process variants using event logs is a common use case in process mining. Existing techniques for process variant analysis detect statistically-significant differences between variants at the level of individual entities (such as process activities) and their relationships (e.g. directly-follows relations between activities). This may lead to a proliferation of differences due to the low level of granularity in which such differences are captured. This paper presents a novel approach to detect statistically-significant differences between variants at the level of entire process traces (i.e. sequences of directly-follows relations). The cornerstone of this approach is a technique to learn a directly-follows graph called mutual fingerprint from the event logs of the two variants. A mutual fingerprint is a lossless encoding of a set of traces and their duration using discrete wavelet transformation. This structure facilitates the understanding of statistical differences along the control-flow and performance dimensions. The approach has been evaluated using real-life event logs against two baselines. The results show that at a trace level, the baselines cannot always reveal the differences discovered by our approach, or can detect spurious differences.This research is partly funded by the Australian Research Council (DP180102839) and Spanish funds MINECO and FEDER (TIN2017-86727-C2-1-R).Peer ReviewedPostprint (author's final draft

Polar and hydrogen-bonding effects of alcohols on the emission spectrum of styrene-triethylamine system

The emission spectra of styrene (ST)-triethylamine (TEA) systems were measured under steady-state illumination conditions in some THF-protic solvent mixtures. The fluorescence spectrum of the ST-TEA system in THF consists of two bands (band A at 304 nm (fluorescence of ST) and band B at 460 nm (emission from an exciplex)). The intensity of band A increased and that of band B decreased with increasing amounts of protic solvents in THF-protic solvent mixtures. The increase in the intensity of band A was explained by the decrease in the concentration of free amine owing to the hydrogen-bonding interaction (or protonation) between TEA and protic solvents. The decrease in the intensity of band B was considered to be caused by the decrease in the concentration of free amine on the addition of protic solvents and the enhanced conversion of the exciplex to an ion pair with increasing solvent polarity. The polar effect was expressed as a function of the relative permittivity of the solution.</p

Physical activity to improve cognition in older adults: can physical activity programs enriched with cognitive challenges enhance the effects? A systematic review and meta-analysis

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Intrathecal treatment of neoplastic meningitis due to breast cancer with a slow-release formulation of cytarabine

DepoCyte is a slow-release formulation of cytarabine designed for intrathecal administration. The goal of this multi-centre cohort study was to determine the safety and efficacy of DepoCyte for the intrathecal treatment of neoplastic meningitis due to breast cancer. DepoCyte 50 mg was injected once every 2 weeks for one month of induction therapy; responding patients were treated with an additional 3 months of consolidation therapy. All patients had metastatic breast cancer and a positive CSF cytology or neurologic findings characteristic of neoplastic meningitis. The median number of DepoCyte doses was 3, and 85% of patients completed the planned 1 month induction. Median follow up is currently 19 months. The primary endpoint was response, defined as conversion of the CSF cytology from positive to negative at all sites known to be positive, and the absence of neurologic progression at the time the cytologic conversion was documented. The response rate among the 43 evaluable patients was 28% (CI 95%: 14–41%); the intent-to-treat response rate was 21% (CI 95%: 12–34%). Median time to neurologic progression was 49 days (range 1–515(+)); median survival was 88 days (range 1–515(+)), and 1 year survival is projected to be 19%. The major adverse events were headache and arachnoiditis. When drug-related, these were largely of low grade, transient and reversible. Headache occurred on 11% of cycles; 90% were grade 1 or 2. Arachnoiditis occurred on 19% of cycles; 88% were grade 1 or 2. DepoCyte demonstrated activity in neoplastic meningitis due to breast cancer that is comparable to results reported with conventional intrathecal agents. However, this activity was achieved with one fourth as many intrathecal injections as typically required in conventional therapy. The every 2 week dose schedule is a major advantage for both patients and physicians. © 2001 Cancer Research Campaign http://www.bjcancer.co