Dapagliflozin add-on to metformin in type 2 diabetes inadequately controlled with metformin:a randomized, double-blind, placebo-controlled 102-week trial

Background: Management of type 2 diabetes with metformin often does not provide adequate glycemic control, thereby necessitating add-on treatment. In a 24-week clinical trial, dapagliflozin, an investigational sodium glucose cotransporter 2 inhibitor, improved glycemic control in patients inadequately controlled with metformin. The present study is an extension that was undertaken to evaluate dapagliflozin as long-term therapy in this population.Methods: This was a long-term extension (total 102 weeks) of a 24-week phase 3, multicenter, randomized, placebo-controlled, double-blind, parallel-group trial. Patients were randomly assigned (1:1:1:1) to blinded daily treatment (placebo, or dapagliflozin 2.5 to 5, or 10 mg) plus open-label metformin (=1,500 mg). The previously published primary endpoint was change from baseline in glycated hemoglobin (HbA1c) at 24 weeks. This paper reports the follow-up to week 102, with analysis of covariance model performed at 24 weeks with last observation carried forward; a repeated measures analysis was utilized to evaluate changes from baseline in HbA1c, fasting plasma glucose (FPG), and weight.Results: A total of 546 patients were randomized to 1 of the 4 treatments. The completion rate for the 78-week double-blind extension period was lower for the placebo group (63.5%) than for the dapagliflozin groups (68.3% to 79.8%). At week 102, mean changes from baseline HbA1c (8.06%) were +0.02% for placebo compared with -0.48% (P = 0.0008), -0.58% (P

Behind the scenes:a week in the life of a Senior Pro-Vice Chancellor

Helen Higson graduated from Cambridge University in 1982 and followed this up with an MSc with the Open University and a PhD at Birkbeck College London. She started working in HE at Southampton University and has spent the last 25 years at Aston University. Her roles there have been various, starting as PA to the Pro-Vice-Chancellor External Relations and spending 20 years with Aston Business School. Helen was awarded a Personal Chair in Higher Education Learning and Management in 2008 and is currently Senior Pro-Vice-Chancellor, with responsibility for International Relations, Employability, Schools Liaison, Registry and Planning. Helen was awarded an AUA Fellowship in 2010 and an OBE in the 2011 New Year Honours list.

Novel glucagon-like peptide-1 (GLP-1) analog (Val8)GLP-1 results in significant improvements of glucose tolerance and pancreatic β-cell function after 3-week daily administration in obese diabetic (ob/ob) mice

This study evaluates the antidiabetic potential of an enzyme-resistant analog, (Val8)GLP-1. The effects of daily administration of a novel dipeptidyl peptidase IV-resistant glucagon-like peptide-1 (GLP-1) analog, (Val8)GLP-1, on glucose tolerance and pancreatic β-cell function were examined in obese-diabetic (ob/ob) mice. Acute intraperitoneal administration of (Val8)GLP-1 (6.25-25 nmol/kg) with glucose increased the insulin response and reduced the glycemic excursion in a dose-dependent manner. The effects of (Val8)GLP-1 were greater and longer lasting than native GLP-1. Once-daily subcutaneous administration of (Val8)GLP-1 (25 nmol/kg) for 21 days reduced plasma glucose concentrations, increased plasma insulin, and reduced body weight more than native GLP-1 without a significant change in daily food intake. Furthermore, (Val8)GLP-1 improved glucose tolerance, reduced the glycemic excursion after feeding, increased the plasma insulin response to glucose and feeding, and improved insulin sensitivity. These effects were consistently greater with (Val8)GLP-1 than with native GLP-1, and both peptides retained or increased their acute efficacy compared with initial administration. (Val8)GLP-1 treatment increased average islet area 1.2-fold without changing the number of islets, resulting in an increased number of larger islets. These data demonstrate that (Val8)GLP-1 is more effective and longer acting than native GLP-1 in obese-diabetic ob/ob mice.

Efficacy and safety of dapagliflozin monotherapy in people with Type 2 diabetes:a randomized double-blind placebo-controlled 102-week trial

Aims: To assess initial pharmacotherapy of Type 2 diabetes with the sodium-glucose cotransporter-2 inhibitor dapagliflozin. Methods: This double-blind, placebo-controlled trial, randomly allocated people with Type 2 diabetes aged 18-77 years and inadequate glycaemic control on diet and exercise [HbA1c 53-86 mmol/mol (7.0-10.0%)] to receive placebo (n = 75) or dapagliflozin monotherapy 2.5 mg (n = 65), 5 mg (n = 64) or 10 mg (n = 70) once daily in the morning. After 24 weeks, low-dose double-blind metformin 500 mg/day was added to the placebo group regimen (placebo+low-dose metformin group). Changes in HbA1c level, fasting plasma glucose and body weight, as well as adverse events, were assessed over 102 weeks. Results: Of the 274 participants randomized, 167 completed the study (60.9%). At 102 weeks, significant differences vs placebo+low-dose metformin with dapagliflozin 5 and 10 mg were observed for HbA1c (-5.8 mmol/mol [-0.53%], P = 0.018; and -4.8 mmol/mol [-0.44%], P = 0.048), respectively); and for FPG (-0.69 mmol/L, P = 0.044; and -1.12 mmol/l, P = 0.001, respectively). For body weight, the difference between the dapagliflozin 10-mg group and the placebo+low-dose metformin group was significant (-2.60 kg; P = 0.016). Hypoglycaemic events were uncommon, with rates of 5.3% for placebo+low-dose metformin group and 0-4.6% for the dapagliflozin groups. Genital infections and urinary tract infections were more common in the dapagliflozin groups than in the placebo+low-dose metformin group. Conclusions: Dapagliflozin as monotherapy in treatment-naïve people with early Type 2 diabetes improved glycaemic control and reduced weight without increasing hypoglycaemia over 102 weeks. Dapagliflozin may provide an alternative initial pharmacotherapy in such people.

Lymphocyte peroxiredoxin-2 levels are depleted one week after ultra-endurance exercise

Peroxiredoxin-2 (PRDX-2) belongs to a family of thiol containing proteins and is important for antioxidant defense, redox signaling and cell function. This study examined whether lymphocyte PRDX-2 levels are altered over one month following ultra-endurance exercise. Nine middle-aged men participated in a 145 mile ultra-endurance running race event. Blood drawing was undertaken immediately before, upon completion/retirement, and at one, seven and twenty eight-days following the race. PRDX-2 levels were examined at each time-point, for all participants (n=9) by reducing SDS-PAGE and western blotting. Further analysis using non-reducing SDS-PAGE and western blotting was undertaken in a sub-group of men who completed the race (n = 4) to investigate PRDX-2 oligomeric state (indicative of oxidation state). Ultra-endurance exercise caused a significant alteration in lymphocyte PRDX-2 levels (F(4,32) 3.409, p=0.020, η2 =0.299): seven-days after the race PRDX-2 levels fell by 70% (p=0.013) and at twenty eight-days after the race returned to near-normal levels. PRDX-2 dimers (intracellular reduced PRDX-2 monomers) in three of the four participants, who finished the race, were increased upon race completion. Furthermore, PRDX-2 monomers (intracellular over-oxidized PRDX-2 monomers) in two of these four participants were present upon race completion, but absent seven-days after the race. This study found that PRDX-2 levels in lymphocytes were reduced below normal levels seven-days after an ultra-endurance running race. We suggest that excessive reactive oxygen species production, induced by ultra-endurance exercise may, in part, explain the depletion of lymphocyte PRDX-2 by triggering its turnover after oxidation.

Evaluation of a six-week professional education curriculum designed to retain registered psychiatric nurses

During the past few years there has been a drastic shortage of registered nurses in the field. The shortage appears to have affected the field of psychiatric mental health nursing most intensely. The psychiatric nursing shortage is a multifaceted problem grounded in decreasing federal funds for advanced clinical training, inadequate undergraduate psychiatric experiences, lack of a well prepared articulate role model, the integrated curriculum and the confusion and blurring associated with the roles and functions of the psychiatric mental health nurse.^ This dissertation will describe the current nursing shortage; the decline in enrollment to nursing programs; the history of psychiatric nursing as a discipline; the shortage of psychiatric mental health nurses; factors contributing to the psychiatric nursing shortage and a plan for a solution to the nursing shortage in psychiatry.^ The paper focuses on an evaluation conducted on an internship curriculum designed to facilitate effective nursing care in the treatment of clients who exhibit emotional problems. The purpose of this study was to attract and retain nurses to employment opportunities in four Hospital Corporation of America (HCA) facilities, using a six week internship program.^ The study will yield an analysis of the effect of combining psychodynamic principles and knowledge with skills in the clinical area. The demands of educational practice have been merged with the discipline of psychiatric nursing in the development of this curriculum. ^

Effectiveness of peer counseling on high school students who failed two or more classes in a nine week quarter

The purpose of this study was to examine the effectiveness of peer counseling on high school students who have previously failed two or more classes in a nine week quarter.^ This study was constructed by comparing students who previously failed and were subsequently given peer counseling with a matched group of students who failed and did not receive peer counseling.^ To test the proposed research question, 324 students from a large urban school system were randomly chosen from a computer generated list of students who failed courses, matched on variables of number of classes failed, grade level and gender. One student from each matched pair was randomly placed in either the experimental or control group. 162 students from Group 1 (experimental) were assigned a peer counselor with their pair assigned to Group 2 (control). Group 1 received peer counseling at least 4 times during the third nine week academic quarter (Quarter 3) while Group 2 did not.^ The Grade Point Averages (GPA) for all students were collected both at the end of Quarter 2 and Quarter 3, at which time peer counseling was terminated. GPA's were also collected nine weeks after counseling was terminated.^ Results were determined by multiple regression, analysis of covariance and t-test. A level of significance was set at.05. There was significant increase in the GPA's of those counseled students immediately after peer counseling and also nine weeks after counseling was terminated, while the group not receiving peer counseling showed no increase. It was noted that there were significantly more school drop-outs from the non-counseled group than the counseled group. The number of classes failed, high school attended, grade level and gender were not found to be significant.^ The conclusion from this study was that peer counseling does impact significantly on the GPA's of students experiencing academic failure. Recommendations from this study were to implement and expand peer counseling programs with more failing students, continue counseling for longer than one quarter, include students in drop-out programs and students from different socio-economic and racial backgrounds, and conduct subsequent evaluation. ^

Searching for the Holy Grail of International Education: Feedback from Hospitality Management Study Abroad Participants

This article reports on a study done among hospitality management students who participated in study abroad programs between January 2001 and May 2003. The participants in the study were both incoming students to the US and outgoing students from the US. The study investigates, among other things, why they had decided to study abroad, why they had selected a particular institution, how their home institution compared to the partner institution abroad, and what they perceived to be the benefits and relevance of their international experiences. It was found that respondents were generally very positive about the study abroad experience. Some interesting differences of opinion were found when the perceptions of the incoming students were compared to those of the outgoing students. The results of this study may be of particular interest to hospitality management administrators and faculty who create and administer international exchange programs.

Elementary music and classroom teachers' time -use: A comparison by grade level, time of day, and day of the week

This study investigated time-use of elementary music teachers and elementary classroom teachers to determine: (1) whether there was a relationship between grade level, time of day, and day of the week and teachers' time-use in teaching, monitoring, and non-curricular, and (2) whether ethnicity, training, and years of experience affect teacher time-use. Sixty-nine music teachers and 55 classroom teachers participated. ^ A MANOVA was used to examine the hypothesized relationship. ANOVA results were significant for time spent teaching, monitoring, and non-curricular. An independent t test revealed a significance difference (t (302) = 5.20, p < .001) between the two groups of teachers. A significant difference was found for teaching, t (302) = 5.20, p < .001: music teachers spent more time actively teaching than did classroom teachers. There was a significant difference for monitoring (t (302) = 13.62, p < .001): classroom teachers allocated more time to monitoring than did music teachers. A significant difference was also found for non-curricular (t (302) = 7.03, p < .001): music teachers spent more time in this category of activities than did classroom teachers. ^ Analyses of the activities subsumed under the major categories indicated significant differences between elementary music teachers and elementary classroom teachers, overall, in subject matter (p < .001), discussion (p < .05), school-wide activities (p < .001), seatwork (p < .001), giving directions (p < .001), changing activities (p < .001), lunch (p < .05), planning (p < .001) and interruption (p < .001). Analyses of the relationship and ethnicity, training, degree, experience indicated significant difference for main effect, ethnicity (F(2, 116) = 4.22, p < .017). Time-use for black non-Hispanic teachers was higher than time-use for those who were Hispanic and white non-Hispanic. ^ Analyses of time-use by grade showed no increase for either group as grade level increased. A statistically significant Wilks Lambda ( F (1,294) = .917 p < .013) was found for the independent variable day of the week. ANOVA indicated that elementary classroom teachers monitored more on Thursdays and Fridays: music teachers allocated more time to non-curricular activities on Fridays. ^

Elementary music and classroom teachers' time-use: a comparison by grade level, time of day, and day of the week

This study investigated time-use of elementary music teachers and elementary classroom teachers to determine: (1) whether there was a relationship between grade level, time of day, and day of the week and teachers' time-use in teaching, monitoring, and non-curricular, and (2) whether ethnicity, training, and years of experience affect teacher time-use. Sixty-nine music teachers and 55 classroom teachers participated. A MANOVA was used to examine the hypothesized relationship. ANOVA results were significant for time spent teaching, monitoring, and non-curricular. An independent t test revealed a significance difference (t (302) = 5.20, p Analyses of the activities subsumed under the major categories indicated significant differences between elementary music teachers and elementary classroom teachers, overall, in subject matter ( p teachers was higher than time-use for those who were Hispanic and white non-Hispanic. Analyses of time-use by grade showed no increase for either group as grade level increased. A statistically significant Wilks Lambda ( F (1,294) = .917 p < .013 ) was found for the independent variable day of the week. ANOVA indicated that elementary classroom teachers monitored more on Thursdays and Fridays: music teachers allocated more time to non-curricular activities on Fridays.

Mafteaḥ leshon ha-ḳodesh, That is the Key of the Holy Tongue : Wherein is contained, First the Hebrue Grammer (in a manner) word for word out of P. Martinius : Englished for the benefit of those that (being ignorant in the Latine) are desirous to learne the holy tongue

by John Udall ; Carefully corrected, and many faults amended which were found both in the Latine and English copies By a Jew Rabine