Oral diabetes medication monotherapy and short-term mortality in individuals with type 2 diabetes and coronary artery disease

Objective To determine whether sulfonylurea use, compared with non-sulfonylurea oral diabetes medication use, was associated with 2-year mortality in individuals with well-controlled diabetes and coronary artery disease (CAD). Research design and methods We studied 5352 US veterans with type 2 diabetes, obstructive CAD on coronary angiography, hemoglobin A1c ≤7.5% at the time of catheterization, and taking zero or one oral diabetes medication (categorized as no medications, non-sulfonylurea medication, or sulfonylurea). We estimated the association between medication category and 2-year mortality using inverse probability of treatment-weighted (IPW) standardized mortality differences and IPW multivariable Cox proportional hazards regression. Results 49%, 35%, and 16% of the participants were on no diabetes medications, non-sulfonylurea medications, and sulfonylureas, respectively. In individuals on no medications, non-sulfonylurea medications, and sulfonylureas, the unadjusted mortality rates were 6.6%, 5.2%, and 11.9%, respectively, and the IPW-standardized mortality rates were 5.9%, 6.5%, and 9.7%, respectively. The standardized absolute 2-year mortality difference between non-sulfonylurea and sulfonylurea groups was 3.2% (95% CI 0.7 to 5.7) (p=0.01). In Cox proportional hazards models, the point estimate suggested that sulfonylurea use might be associated with greater hazard of mortality than non-sulfonylurea medication use, but this finding was not statistically significant (HR 1.38 (95% CI 1.00 to 1.93), p=0.05). We did not observe significant mortality differences between individuals on no diabetes medications and non-sulfonylurea users. Conclusions Sulfonylurea use was common (nearly one-third of those taking medications) and was associated with increased 2-year mortality in individuals with obstructive CAD. The significance of the association between sulfonylurea use and mortality was attenuated in fully adjusted survival models. Caution with sulfonylurea use may be warranted for patients with well-controlled diabetes and CAD, and metformin or newer diabetes medications with cardiovascular safety data could be considered as alternatives when individualizing therapy

The comparative effectiveness and efficiency of cognitive behaviour therapy and generic counselling in the treatment of depression: evidence from the 2(nd) UK National Audit of psychological therapies.

BACKGROUND: Cognitive Behaviour Therapy (CBT) is the front-line psychological intervention for step 3 within UK psychological therapy services. Counselling is recommended only when other interventions have failed and its effectiveness has been questioned. METHOD: A secondary data analysis was conducted of data collected from 33,243 patients across 103 Improving Access to Psychological Therapies (IAPT) services as part of the second round of the National Audit of Psychological Therapies (NAPT). Initial analysis considered levels of pre-post therapy effect sizes (ESs) and reliable improvement (RI) and reliable and clinically significant improvement (RCSI). Multilevel modelling was used to model predictors of outcome, namely patient pre-post change on PHQ-9 scores at last therapy session. RESULTS: Counselling received more referrals from patients experiencing moderate to severe depression than CBT. For patients scoring above the clinical cut-off on the PHQ-9 at intake, the pre-post ES (95% CI) for CBT was 1.59 (1.58, 1.62) with 46.6% making RCSI criteria and for counselling the pre-post ES was 1.55 (1.52, 1.59) with 44.3% of patients meeting RCSI criteria. Multilevel modelling revealed a significant site effect of 1.8%, while therapy type was not a predictor of outcome. A significant interaction was found between the number of sessions attended and therapy type, with patients attending fewer sessions on average for counselling [M = 7.5 (5.54) sessions and a median (IQR) of 6 (3-10)] than CBT [M = 8.9 (6.34) sessions and a median (IQR) of 7 (4-12)]. Only where patients had 18 or 20 sessions was CBT significantly more effective than counselling, with recovery rates (95% CIs) of 62.2% (57.1, 66.9) and 62.4% (56.5, 68.0) respectively, compared with 44.4% (32.7, 56.6) and 42.6% (30.0, 55.9) for counselling. Counselling was significantly more effective at two sessions with a recovery rate of 34.9% (31.9, 37.9) compared with 22.2% (20.5, 24.0) for CBT. CONCLUSIONS: Outcomes for counselling and CBT in the treatment of depression were comparable. Research efforts should focus on factors other than therapy type that may influence outcomes, namely the inherent variability between services, and adopt multilevel modelling as the given analytic approach in order to capture the naturally nested nature of the implementation and delivery of psychological therapies. It is of concern that half of all patients, regardless of type of intervention, did not show reliable improvement

Transforming the effectiveness and equity of a psychological therapy service: a case study in the English NHS talking therapies program

To work with a psychological therapies service to implement a recovery plan, as required by a government body, aimed at improving patient outcomes (effectiveness) and decreasing practitioner variability (equity). A case-study utilizing components of a learning health system, including nationally mandated patient outcome data, comprising three 18-month phases: (1) retrospective baseline; (2) improving patient outcomes (management-led); and (3) reducing practitioner variability (clinician-led). Primary analyses focused on 35 practitioners (NPR = 35) who were constant across the three phases and their patients in each phase (NPA = 930, 1226, 1217, respectively). Reliable improvement rates determined patient outcomes and multilevel modeling yielded practitioner effects. To test generalizability, results were compared to the whole practitioner sample for each phase: (1) NPR = 81, NPA = 1982; (2) NPR = 80, NPA = 2227; (3) NPR = 74, NPA = 2267. Ethical approval was granted by the Health Research Authority. Patient outcomes improved in successive phases for both the core and whole practitioner samples with the largest impact occurring in the management-led intervention. Practitioner variability decreased in successive phases in both the core and whole practitioner samples except in the management-led intervention of the whole sample. Compared with the management-led intervention, the practitioner-led intervention yielded a decrease in practitioner effect exceeding 60% in the core sample and approaching 50% in the whole sample. The implementation of multiple components of a learning health system can lead to improvements in both the effectiveness and equity of a psychological therapy service

Acid-Labile Traceless Click Linker for Protein Transduction

Intracellular delivery of active proteins presents an interesting approach in research and therapy. We created a protein transduction shuttle based on a new traceless click linker that combines the advantages of click reactions with implementation of reversible pH-sensitive bonds. The azidomethyl-methylmaleic anhydride (AzMMMan) linker was found compatible with different click chemistries, demonstrated in bioreversible protein modification with dyes, polyethylene glycol, or a transduction carrier. Linkages were stable at physiological pH but reversible at the mild acidic pH of endosomes or lysosomes. We show that pH-reversible attachment of a defined endosome-destabilizing three-arm oligo(ethane amino)amide carrier generates an effective shuttle for protein delivery. The cargo protein nlsEGFP, when coupled via the traceless AzMMMan linker, experiences efficient cellular uptake and endosomal escape into the cytosol, followed by import into the nucleus. In contrast, irreversible linkage to the same shuttle hampers nuclear delivery of nlsEGFP which after uptake remains trapped in the cytosol. Successful intracellular delivery of bioactive ß-galactosidase as a model enzyme was also demonstrated using the pH-controlled shuttle system

Osteocytes and mechanical loading: The Wnt connection

Bone adapts to the mechanical forces that it experiences. Orthodontic tooth movement harnesses the cell‐ and tissue‐level properties of mechanotransduction to achieve alignment and reorganization of the dentition. However, the mechanisms of action that permit bone resorption and formation in response to loads placed on the teeth are incompletely elucidated, though several mechanisms have been identified. Wnt/Lrp5 signalling in osteocytes is a key pathway that modulates bone tissue's response to load. Numerous mouse models that harbour knock‐in, knockout and transgenic/overexpression alleles targeting genes related to Wnt signalling point to the necessity of Wnt/Lrp5, and its localization to osteocytes, for proper mechanotransduction in bone. Alveolar bone is rich in osteocytes and is a highly mechanoresponsive tissue in which components of the canonical Wnt signalling cascade have been identified. As Wnt‐based agents become clinically available in the next several years, the major challenge that lies ahead will be to gain a more complete understanding of Wnt biology in alveolar bone so that improved/expedited tooth movement becomes a possibility

Analytic results for Gaussian wave packets in four model systems: II. Autocorrelation functions

The autocorrelation function, A(t), measures the overlap (in Hilbert space) of a time-dependent quantum mechanical wave function, psi(x,t), with its initial value, psi(x,0). It finds extensive use in the theoretical analysis and experimental measurement of such phenomena as quantum wave packet revivals. We evaluate explicit expressions for the autocorrelation function for time-dependent Gaussian solutions of the Schrodinger equation corresponding to the cases of a free particle, a particle undergoing uniform acceleration, a particle in a harmonic oscillator potential, and a system corresponding to an unstable equilibrium (the so-called `inverted' oscillator.) We emphasize the importance of momentum-space methods where such calculations are often more straightforwardly realized, as well as stressing their role in providing complementary information to results obtained using position-space wavefunctions.Comment: 18 pages, RevTeX, to appear in Found. Phys. Lett, Vol. 17, Dec. 200

Investigating the social value of the Ripon rivers flood alleviation scheme

This paper argues for an approach to flood alleviation design that considers the need not only for technical knowledge, but also a social perspective. It is predicted that more intense rainfall and rising sea levels will result in a greater number of people vulnerable to flood events. Flood alleviation design in the UK is often focused upon technical and cost-effective solutions, and consideration of social impact is seen as secondary. This paper examines how the social value of a UK flood alleviation scheme is perceived and discussed, by the local community and by those responsible for the design of the scheme, and exposes differences in perceptions both between and within these two groups. It recommends a future approach in which an understanding of the social value of a flood alleviation scheme is first co-produced with the community affected, enabling the design of a socially acceptable and successful project.The research presented in this paper is part of a larger study. The research is conducted with the aid of funding from an Engineering and Physical Sciences Research Council (EPSRC) iCASE doctoral award. Ove Arup and Partners also provide sponsorship as part of the award.This is the final version of the article. It first appeared from Wiley via http://dx.doi.org/10.1111/jfr3.1217

Eikonal analysis of Coulomb distortion in quasi-elastic electron scattering

An eikonal expansion is used to provide systematic corrections to the eikonal approximation through order $1/k^2$, where $k$ is the wave number. Electron wave functions are obtained for the Dirac equation with a Coulomb potential. They are used to investigate distorted-wave matrix elements for quasi-elastic electron scattering from a nucleus. A form of effective-momentum approximation is obtained using trajectory-dependent eikonal phases and focusing factors. Fixing the Coulomb distortion effects at the center of the nucleus, the often-used ema approximation is recovered. Comparisons of these approximations are made with full calculations using the electron eikonal wave functions. The ema results are found to agree well with the full calculations.Comment: 12 pages, 6 Postscript figure

Weak localization of light by cold atoms: the impact of quantum internal structure

Since the work of Anderson on localization, interference effects for the propagation of a wave in the presence of disorder have been extensively studied, as exemplified in coherent backscattering (CBS) of light. In the multiple scattering of light by a disordered sample of thermal atoms, interference effects are usually washed out by the fast atomic motion. This is no longer true for cold atoms where CBS has recently been observed. However, the internal structure of the atoms strongly influences the interference properties. In this paper, we consider light scattering by an atomic dipole transition with arbitrary degeneracy and study its impact on coherent backscattering. We show that the interference contrast is strongly reduced. Assuming a uniform statistical distribution over internal degrees of freedom, we compute analytically the single and double scattering contributions to the intensity in the weak localization regime. The so-called ladder and crossed diagrams are generalized to the case of atoms and permit to calculate enhancement factors and backscattering intensity profiles for polarized light and any closed atomic dipole transition.Comment: 22 pages Revtex, 9 figures, to appear in PR

Tuba and Euphonium

Program listing performers and works performed