A randomized, controlled trial of 3.0 mg of liraglutide in weight management

BACKGROUND Obesity is a chronic disease with serious health consequences, but weight loss is difficult to maintain through lifestyle intervention alone. Liraglutide, a glucagonlike peptide-1 analogue, has been shown to have potential benefit for weight management at a once-daily dose of 3.0 mg, injected subcutaneously. METHODS We conducted a 56-week, double-blind trial involving 3731 patients who did not have type 2 diabetes and who had a body-mass index (BMI; the weight in kilograms divided by the square of the height in meters) of at least 30 or a BMI of at least 27 if they had treated or untreated dyslipidemia or hypertension. We randomly assigned patients in a 2:1 ratio to receive once-daily subcutaneous injections of liraglutide at a dose of 3.0 mg (2487 patients) or placebo (1244 patients); both groups received counseling on lifestyle modification. The coprimary end points were the change in body weight and the proportions of patients losing at least 5% and more than 10% of their initial body weight. RESULTS At baseline, the mean (±SD) age of the patients was 45.1±12.0 years, the mean weight was 106.2±21.4 kg, and the mean BMI was 38.3±6.4; a total of 78.5% of the patients were women and 61.2% had prediabetes. At week 56, patients in the liraglutide group had lost a mean of 8.4±7.3 kg of body weight, and those in the placebo group had lost a mean of 2.8±6.5 kg (a difference of -5.6 kg; 95% confidence interval, -6.0 to -5.1; P<0.001, with last-observation-carried-forward imputation). A total of 63.2% of the patients in the liraglutide group as compared with 27.1% in the placebo group lost at least 5% of their body weight (P<0.001), and 33.1% and 10.6%, respectively, lost more than 10% of their body weight (P<0.001). The most frequently reported adverse events with liraglutide were mild or moderate nausea and diarrhea. Serious events occurred in 6.2% of the patients in the liraglutide group and in 5.0% of the patients in the placebo group. CONCLUSIONS In this study, 3.0 mg of liraglutide, as an adjunct to diet and exercise, was associated with reduced body weight and improved metabolic control. (Funded by Novo Nordisk; SCALE Obesity and Prediabetes NN8022-1839 ClinicalTrials.gov number, NCT01272219.)

Resident Front Office Experience: A Systems-Based Practice Activity

doi;10.3885/meo.2008.T000012

Resident Front Office Experience: A Systems-Based Practice Activity

Purpose: We set out to create and evaluate a systems-based practice experience designed to introduceresidents to front office responsibilities and stimulate suggestions for front office improvements.Methods: On two occasions in 2002 and 2006, each resident in the Obstetrics and Gynecology Department was trained by a front office staff member for one day. The residents completed pre- and post-experience surveys, answered open-ended questions about their experience, and volunteeredsuggestions for improving the front office staff, and were evaluated by their precepting staff member.Results: All but two of 23 particpating residents participated enthusiastically. These residents perceived experiencing the staff as vital to the success of the practice, reported an increased sense of appreciation for the training of staff personnel, and were evaluated favorably.Conclusion: This program gave our residents an appreciation for the training and responsibilities of pivotal office staff and an opportunity to suggest improvements. This program also satisfied ACGME resident education requirements regarding systems-based practice.Keywords: resident education, front office, systems-based practic

Molecular features of the copper binding sites in the octarepeat domain of the prion protein.

Recent evidence suggests that the prion protein (PrP) is a copper binding protein. The N-terminal region of human PrP contains four sequential copies of the highly conserved octarepeat sequence PHGGGWGQ spanning residues 60-91. This region selectively binds Cu2+ in vivo. In a previous study using peptide design, EPR, and CD spectroscopy, we showed that the HGGGW segment within each octarepeat comprises the fundamental Cu2+ binding unit [Aronoff-Spencer et al. (2000) Biochemistry 40, 13760-13771]. Here we present the first atomic resolution view of the copper binding site within an octarepeat. The crystal structure of HGGGW in a complex with Cu2+ reveals equatorial coordination by the histidine imidazole, two deprotonated glycine amides, and a glycine carbonyl, along with an axial water bridging to the Trp indole. Companion S-band EPR, X-band ESEEM, and HYSCORE experiments performed on a library of 15N-labeled peptides indicate that the structure of the copper binding site in HGGGW and PHGGGWGQ in solution is consistent with that of the crystal structure. Moreover, EPR performed on PrP(23-28, 57-91) and an 15N-labeled analogue demonstrates that the identified structure is maintained in the full PrP octarepeat domain. It has been shown that copper stimulates PrP endocytosis. The identified Gly-Cu linkage is unstable below pH approximately 6.5 and thus suggests a pH-dependent molecular mechanism by which PrP detects Cu2+ in the extracellular matrix or releases PrP-bound Cu2+ within the endosome. The structure also reveals an unusual complementary interaction between copper-structured HGGGW units that may facilitate molecular recognition between prion proteins, thereby suggesting a mechanism for transmembrane signaling and perhaps conversion to the pathogenic form

Family Structure and Ownership Transition as “Polar Opposites”: An Emotional Embeddedness Perspective

Family firms provide a fertile ground to study emotions as a source of contradiction. The interplay of a firm and an owner family exerts influence on strategic decisions in a way that differs from decision-making in non-family firms, such as ownership transition choices. I apply an emotional embeddedness perspective to explain ownership transition choices, which contradict the prevailing instrumental logic in management research. Repeated interactions between actors with different roles in a family firm shape the quality of the family's structure and its effect on important strategic outcomes. The interplay of family structure and emotional embeddedness can lead to ownership transition choices that contradict an instrumental logic of action. Although family structure might be conducive to internal ownership transition, this choice is not always the preferred option because of intervening conditions and the application of alternative principles of action. Researchers in the field of contradiction studies should probe into situations in the management context, in which circumstances may favour the application of an instrumental logic but actually lead to unexpected choices and outcomes. This would enhance our understanding of contingencies that foster alternative action principles in economic action and interaction