A Randomized Trial Investigating the Pharmacokinetics,Pharmacodynamics, and Safety of Subcutaneous Semaglutide Once-Weekly in Healthy Male Japanese and Caucasian Subjects

Introduction

Semaglutide is a glucagon-like peptide-1 analogue for once-weekly subcutaneous treatment of type 2 diabetes. This trial compared the pharmacokinetics, pharmacodynamics, and safety of semaglutide in Japanese and Caucasian subjects.

Methods

In this single-center, double-blind, parallel-group, 13-week trial, 44 healthy male subjects (22 Japanese, 22 Caucasian) were randomized within each race to semaglutide 0.5 mg (n = 8), 1.0 mg (n = 8), placebo 0.5 mg (n = 3) or 1.0 mg (n = 3). The primary endpoint was semaglutide exposure at steady state [area under the curve (AUC_0–168h)].

Results

Steady-state exposure of semaglutide was similar for both populations: AUC_0–168h estimated race ratio (ERR), Japanese/Caucasian: 0.5 mg, 1.06; 1.0 mg, 0.99; maximum concentration (C_max) ERR: 0.5 mg, 1.06; 1.0 mg, 1.02. Exposure after the first dose (0.25 mg) was slightly higher in Japanese versus Caucasian subjects (AUC_0–168h ERR 1.11; C_max ERR 1.14). Dose-dependent increases in AUC_0–168h and C_max occurred in both populations. Accumulation was as expected, based on the half-life (t_1/2, ~ 1 week) and dosing interval of semaglutide. Significant body weight reductions were observed with semaglutide 0.5 mg and 1.0 mg in Japanese (both p ≤ 0.05) and Caucasian (both p ≤ 0.05) subjects versus placebo. No new safety issues were identified.

Conclusions

The pharmacokinetic, pharmacodynamic, and safety profiles of semaglutide were similar in Japanese and Caucasian subjects, suggesting that no dose adjustment is required for the clinical use of semaglutide in Japanese subjects.

Funding

Novo Nordisk A/S, Denmark.

Trial registration

ClinicalTrials.gov identifier NCT02146079. Japanese trial registration number JapicCTI-142550.

     

Identifying Opportunities to Improve Pain Among Patients With Serious Illness

Context

Pain is a common and distressing symptom. Pain management is a core competency for palliative care (PC) teams.

The changing role of residential intervention

ABSTRACT

The role of therapeutic residential care (TRC) is changing. In fact, this article reframes the terminology of TRC and uses “residential interventions” to more accurately reflect that residential programs provide time-limited “intervention” and treatment efforts must connect and extend to families and communities. Such changes are being compelled by necessity and innovation. Necessity is demanding evidence, data, and durable positive outcomes for this expensive intervention. Innovation is transforming basic service delivery through meaningful inclusion of youth and families and effective collaboration with community-based organizations. Service elements that confound this changing role are being reconsidered, including reductions in length of stay, a focus on long-term permanency, and the location of the actual intervention from program-centric practice to interventions in the home and community.     

Tree-in-bud sign

Abdominal Radiology -     

Development and initial evaluation of an instrument to assess physiotherapists’ clinical reasoning focused on clients’ behavior change

Background and Aim: A systematically developed and evaluated instrument is needed to support investigations of physiotherapists’ clinical reasoning integrated with the process of clients’ behavior change. This study’s aim was to develop an instrument to assess physiotherapy students’ and physiotherapists’ clinical reasoning focused on clients’ activity-related behavior and behavior change, and initiate its evaluation, including feasibility and content validity. Methods: The study was conducted in three phases: 1) determination of instrument structure and item generation, based on a model, guidelines for assessing clinical reasoning, and existing measures; 2) cognitive interviews with five physiotherapy students to evaluate item understanding and feasibility; and 3) a Delphi process with 18 experts to evaluate content relevance. Results: Phase 1 resulted in an instrument with four domains: Physiotherapist; Input from client; Functional behavioral analysis; and Strategies for behavior change. The instrument consists of case scenarios followed by items in which key features are identified, prioritized, or interpreted. Phase 2 resulted in revisions of problems and approval of feasibility. Phase 3 demonstrated high level of consensus regarding the instrument’s content relevance. Conclusions: This feasible and content-validated instrument shows potential for use in investigations of physiotherapy students’ and physiotherapists’ clinical reasoning, however continued development and testing are needed.     

Rehabilitation after total joint replacement: a scoping study

Purpose: The evidence supporting rehabilitation after joint replacement, while vast, is of variable quality making it difficult for clinicians to apply the best evidence to their practice. We aimed to map key issues for rehabilitation following joint replacement, highlighting potential avenues for new research.

Materials and methods: We conducted a scoping study including research published between January 2013 and December 2016, evaluating effectiveness of rehabilitation following hip and knee total joint replacement. We reviewed this work in the context of outcomes described from previously published research.

Results: Thirty individual studies and seven systematic reviews were included, with most research examining the effectiveness of physiotherapy-based exercise rehabilitation after total knee replacement using randomized control trial methods. Rehabilitation after hip and knee replacement whether carried out at the clinic or monitored at home, appears beneficial but type, intensity and duration of interventions were not consistently associated with outcomes. The burden of comorbidities rather than specific rehabilitation approach may better predict rehabilitation outcome. Monitoring of recovery and therapeutic attention appear important but little is known about optimal levels and methods required to maximize outcomes.

Conclusions: More work exploring the role of comorbidities and key components of therapeutic attention and the therapy relationship, using a wider range of study methods may help to advance the field.

• Implications for Rehabilitation

• Physiotherapy-based exercise rehabilitation after total hip replacement and total knee replacement, whether carried out at the clinic or monitored at home, appears beneficial.

• Type, intensity, and duration of interventions do not appear consistently associated with outcomes.

• Monitoring a patient’s recovery appears to be an important component. The available research provides limited guidance regarding optimal levels of monitoring needed to achieve gains following hip and knee replacement and more work is required to clarify these aspects.

• The burden of comorbidities appears to better predict outcomes regardless of rehabilitation approach.

     

Treatment of Dural Carotid-Cavernous Fistulas via the Medial Ophthalmic Vein

Aim: To present a novel approach to treatment of dural carotid-cavernous fistulas via the medial ophthalmic vein.

Design: Retrospective case series.

Material and Methods: In this retrospective case series, we present 2 patients (3 eyes) with Type C dural CCFs, who had failed cannulation via the conventional transfemoral route and the transorbital superior ophthalmic vein approach. They subsequently underwent CCF occlusion via an anterior orbital approach through the medial ophthalmic veins, at the Department of Ophthalmology, National University Hospital Singapore. CCF occlusion was confirmed intraoperatively using angiography. Both patients were evaluated postoperatively for best-corrected visual acuity and resolution of clinical signs and symptoms.

Results: Successful occlusion of CCFs via the medial ophthalmic veins were achieved in all three orbits, with excellent visual and cosmetic outcomes postoperatively.

Conclusion: Dural CCFs may potentially lead to severe visual dysfunction and should be diagnosed and treated promptly. When all venous routes have been exhausted, the transorbital approach via the medial ophthalmic vein remains an excellent and viable alternative to access the fistula. Close cooperation between the orbital, anesthetic and radiological teams is essential in ensuring success of the operation.