Saxagliptin in combination with Metformin or Sulfonylurea achieved HbA1c goals

Diabetes affects over 1.2 million people in Australia. Saxagliptin (SAXA) is a potent, selective dipeptidyl peptidase-4 (DPP-4) inhibitor. Three 24-week phase 3 studies assessed efficacy and safety of SAXA as add-on to Metformin (MET), as initial combination therapy with MET, or as add-on to the sulfonylurea (SU) glyburide (GLY) in patients (pts) with type 2 diabetes (T2D) and inadequate glycaemic control. In the add-on to MET study, 743 pts inadequately controlled on MET alone (HbA1c 7.0%–10.0%; mean baseline (BL) HbA1c 8.0%; mean T2D duration 6.5 yrs) were randomised to SAXA or placebo (PBO) with ongoing dose of MET. In the initial combination study, 1306 drug naïve pts (HbA1c8.0%–12.0%; mean BL HbA1c 9.5%; mean T2D duration 1.7 yrs) were randomised to SAXA + MET, SAXA + PBO, or MET + PBO. In the add-on to SU study, 768 pts inadequately controlled on SU alone (HbA 1c7.5%–10.0%; mean BL HbA1c 8.4%; mean T2D duration 6.9 yrs) were randomised to SAXA or uptitrated GLY + PBO in addition to open-label GLY. Efficacy analyses used ANCOVA model. The proportion of patients reaching HbA1c goals used Fisher exact test. HbA1c goals were predefined for each study. In all three studies, statistically significantly greater proportions of SAXA-treated pts achieved HbA1c goals of <7.0% and ≤6.5% vs. control at 24 wks (Table). Twice as many pts treated with SAXA added to MET or GLY achieved the HbA1c goal of <7% and ≤6.5% relative to control at 24 wks. For all three studies, the frequency of adverse events (AEs) was generally similar for SAXA vs. control (Table). SAXA 5 mg + MET as either add-on or initial combination therapy, and SAXA 5 mg + SU significantly improved glycaemic control, was well tolerated and achieved predefined HbA1c goals vs. control in more patients

G-protein signaling: back to the future

Heterotrimeric G-proteins are intracellular partners of G-protein-coupled receptors (GPCRs). GPCRs act on inactive Gα·GDP/Gβγ heterotrimers to promote GDP release and GTP binding, resulting in liberation of Gα from Gβγ. Gα·GTP and Gβγ target effectors including adenylyl cyclases, phospholipases and ion channels. Signaling is terminated by intrinsic GTPase activity of Gα and heterotrimer reformation — a cycle accelerated by ‘regulators of G-protein signaling’ (RGS proteins). Recent studies have identified several unconventional G-protein signaling pathways that diverge from this standard model. Whereas phospholipase C (PLC) β is activated by Gαq and Gβγ, novel PLC isoforms are regulated by both heterotrimeric and Ras-superfamily G-proteins. An Arabidopsis protein has been discovered containing both GPCR and RGS domains within the same protein. Most surprisingly, a receptor-independent Gα nucleotide cycle that regulates cell division has been delineated in both Caenorhabditis elegans and Drosophila melanogaster. Here, we revisit classical heterotrimeric G-protein signaling and explore these new, non-canonical G-protein signaling pathways

A Triple Test for Behavioral Economics Models and Public Health Policy

We propose a triple test to evaluate the usefulness of behavioral economics models for public health policy. Test 1 is whether the model provides reasonably new insights. Test 2 is on whether these have been properly applied to policy settings. Test 3 is whether they are corroborated by evidence. Where a test is not passed, this may point to directions for needed further research. We exemplify by considering the cases of social interactions models, self-control models and, in relation to health message framing, prospect theory; out of these, only a correctly applied prospect theory fully passes the tests at present

Outcomes in Patients with Degenerative vs. Non-Degenerative Meniscus Tears

Meniscus tears are the second most common orthopedic injury of the knee with an incidence of 12% to 14% and a prevalence of 61 cases per 100,000 persons.2,3 Physical therapy (PT) is a standard of care for these patients post-meniscectomy, but research is conflicting on the benefits and the most appropriate outcome measures to use when assessing activity levels in these patients. The main purpose of this dissertation was to explore 5 performance-based outcome measure (single-limb single hop test for distance (SLHT), single-limb crossover hop test for distance (CHT), Edgren side step test (ESST), Illinois agility test (IAT), and stair measure test (SMT)), 3 of which were recommended by the clinical practice guidelines (CPGs) for meniscal lesions, in order to provide information on the reliability and validity of these measures for patients after meniscectomy. A secondary purpose of this dissertation was to identify the differences in outcomes between patients with degenerative meniscus tears and non-degenerative meniscus tear by investigating recovery post-arthroscopic partial meniscectomy. A convenience sample of patients who underwent an arthroscopic partial meniscectomy were recruited from the University of Miami Hospital sports medicine clinic. Subjects were categorized into one of two groups based on whether their meniscus tear was degenerative or not. Subjects were treated by one of five physical therapists. The rehabilitation protocol consisted of 45 minutes to 1 hour of PT 2-3x/week for a total of 8 weeks. A general protocol was followed for the first 4 weeks of rehabilitation and an individualized protocol was incorporated into the final 4 weeks of rehabilitation. Assessments were performed at initial PT evaluation (week 0), at four weeks post-meniscectomy (week 4), and 8 weeks post-meniscectomy (week 8). Comparisons were made in terms of impairments, activity limitations, and participation restrictions using both patient-reported outcomes (IKDC, Tegner) and performance-based outcomes. This work provides information on the reliability and validity of 5 activity level performance-based outcome measures for patients after arthroscopic partial meniscectomy. Additionally, it discusses the importance of making sure these outcome measures are appropriate to the population of patients being examined. Because there are two different subpopulations of patients with meniscus tears, patients with degenerative meniscus tear and patients with non-degenerative meniscus tears, different activity level outcome measures should be considered when studying and treating these different types of patients with meniscus tears. Finally, this work demonstrates similar patterns of recovery in patients with degenerative and non-degenerative meniscus tears. Both groups nearly recover to their pre-morbid level of activity after 8-weeks of PT

Using the Stress Response Along an Elevational Gradient to Understand Habitat Suitability of the Southern Gray-cheeked Salamander, Plethodon metcalfi

Over the next 100 years, global mean temperatures are expected to warm. With warming climates, some environments may become unsuitable for an organism, resulting in local extinctions. Currently, nearly 50% of amphibians are threatened by habitat destruction, pollution, disease, and overexploitation. To make matters worse, warming temperatures may push more amphibians closer to extinction. However, many organisms can respond to rapidly changing conditions by changing their physiology. The stress response is a common mechanism that organisms use to allocate energy towards life-sustaining processes in response to changing environmental conditions. Here, we leveraged the natural changes in temperature and humidity that occur along an elevational gradient to determine how stress varies upon exposure to changing environmental conditions. We conducted a reciprocal transplant study at low, mid, and high areas within the elevational range of the Southern gray-cheeked salamander (Plethodon metcalfi) in a balanced experimental design. The relative level of stress between treatments was measured using neutrophil:lymphocyte ratio (N:L) from blood samples. Data suggests that mass and elevation contribute to salamander stress responses and may indicate that high elevation sites provide the most suitable habitat for Southern gray-cheeked salamanders

Skin resistance values across taxa

Skin resistance values across tax