Improved compactly computable objective measures for predicting the acceptiability of speech communications systems

Issued as Monthly status reports [1-7], and Final report, Project no. E-21-61

Selecting GLP-1 agonists in the management of type 2 diabetes: differential pharmacology and therapeutic benefits of liraglutide and exenatide

Failure of secretion of the incretin hormone glucagon-like peptide-1 (GLP-1) plays a prominent role in type 2 diabetes, and restoration of GLP-1 action is an important therapeutic objective. Although the short duration of action of GLP-1 renders it unsuited to therapeutic use, 2 long-acting GLP-1 receptor agonists, exenatide and liraglutide, represent a significant advance in treatment. In controlled trials, both produce short-term glucose-lowering effects, with the reduction in hemoglobin A1c of up to 1.3%. These responses are often superior to those observed with additional oral agents. However, unlike sulfonylureas, thiazolidinediones, or insulin, all of which lead to significant weight gain, GLP-1 receptor agonists uniquely result in long-term weight loss of around 5 kg, and higher doses may enhance this further. Reduction in blood pressure of 2–7 mm Hg also has been observed. Both drugs produce transient mild gastrointestinal side effects; although mild hypoglycemia can occur, this is usually in combination with other hypoglycemic therapies. However, serious hypoglycemia and acute pancreatitis are rare. The once-daily dosage of liraglutide makes it more convenient than twice-daily dosage of prandial exenatide, and a superior glucose-lowering effect was observed in the only head-to-head comparison reported so far. Besides cost, these considerations currently favor liraglutide over exenatide. Further studies are needed to confirm long-term safety, and most importantly, that short-term benefits translate into long-term reductions of diabetes-related cardiovascular events and other complications

Assessment of the quality of online patient information resources for patients considering parastomal hernia treatment

Aim: The aim was to examine the quality of online patient information resources for patients considering parastomal hernia treatment.Methods: A Google search was conducted using lay search terms for patient facing sources on parastomal hernia. The quality of the content was assessed using the validated DISCERN instrument. Readability of written content was established using the Flesch–Kincaid score. Sources were also assessed against the essential content and process standards from the National Institute for Health and Care Excellence (NICE) framework for shared decision making support tools. Content analysis was also undertaken to explore what the sources covered and to identify any commonalities across the content.Results: Fourteen sources were identified and assessed using the identified tools. The mean Flesch–Kincaid reading ease score was 43.61, suggesting that the information was difficult to read. The overall quality of the identified sources was low based on the pooled analysis of the DISCERN and Flesch–Kincaid scores, and when assessed against the criteria in the NICE standards framework for shared decision making tools. Content analysis identified eight categories encompassing 59 codes, which highlighted considerable variation between sources.Conclusions: The current information available to patients considering parastomal hernia treatment is of low quality and often does not contain enough information on treatment options for patients to be able to make an informed decision about the best treatment for them. There is a need for high-quality information, ideally co-produced with patients, to provide patients with the necessary information to allow them to make informed decisions about their treatment options when faced with a symptomatic parastomal hernia

Induced frailty and acute sarcopenia are overlapping consequences of hospitalisation in older adults

OBJECTIVES: To determine the effects of hospitalisation upon frailty and sarcopenia. METHODS: Prospective cohort study at single UK hospital including adults ≥70 years-old admitted for elective colorectal surgery, emergency abdominal surgery, or acute infections. Serial assessments for frailty (Fried, Frailty Index, Clinical Frailty Scale [CFS]), and sarcopenia (handgrip strength, ultrasound quadriceps and/or bioelectrical impedance analysis, and gait speed and/or Short Physical Performance Battery) were conducted at baseline, 7 days post-admission/post-operatively, and 13 weeks post-admission/post-operatively. RESULTS: Eighty participants were included (mean age 79.2, 38.8% females). Frailty prevalence by all criteria at baseline was higher among medical compared to surgical participants. Median and estimated marginal CFS values and Fried frailty prevalence increased after 7 days, with rates returning towards baseline at 13 weeks. Sarcopenia incidence amongst those who did not have sarcopenia at baseline was 20.0%. However, some participants demonstrated improvements in sarcopenia status, and overall sarcopenia prevalence did not change. There was significant overlap between diagnoses with 37.3% meeting criteria for all four diagnoses at 7 days. CONCLUSIONS: Induced frailty and acute sarcopenia are overlapping conditions affecting older adults during hospitalisation. Rates of frailty returned towards baseline at 13 weeks, suggesting that induced frailty is reversible

Multi-arm multi-stage (MAMS) randomised selection designs:Impact of treatment selection rules on the operating characteristics

Background: Multi-arm multi-stage (MAMS) randomised trial designs have been proposed to evaluate multiple research questions in the confirmatory setting. In designs with several interventions, such as the 8-arm 3-stage ROSSINI-2 trial for preventing surgical wound infection, there are likely to be strict limits on the number of individuals that can be recruited or the funds available to support the protocol. These limitations may mean that not all research treatments can continue to accrue the required sample size for the definitive analysis of the primary outcome measure at the final stage. In these cases, an additional treatment selection rule can be applied at the early stages of the trial to restrict the maximum number of research arms that can progress to the subsequent stage(s).This article provides guidelines on how to implement treatment selection within the MAMS framework. It explores the impact of treatment selection rules, interim lack-of-benefit stopping boundaries and the timing of treatment selection on the operating characteristics of the MAMS selection design.Methods: We outline the steps to design a MAMS selection trial. Extensive simulation studies are used to explore the maximum/expected sample sizes, familywise type I error rate (FWER), and overall power of the design under both binding and non-binding interim stopping boundaries for lack-of-benefit.Results: Pre-specification of a treatment selection rule reduces the maximum sample size by approximately 25% in our simulations. The familywise type I error rate of a MAMS selection design is smaller than that of the standard MAMS design with similar design specifications without the additional treatment selection rule. In designs with strict selection rules - for example, when only one research arm is selected from 7 arms - the final stage significance levels can be relaxed for the primary analyses to ensure that the overall type I error for the trial is not underspent. When conducting treatment selection from several treatment arms, it is important to select a large enough subset of research arms (that is, more than one research arm) at early stages to maintain the overall power at the pre-specified level.Conclusions: Multi-arm multi-stage selection designs gain efficiency over the standard MAMS design by reducing the overall sample size. Diligent pre-specification of the treatment selection rule, final stage significance level and interim stopping boundaries for lack-of-benefit are key to controlling the operating characteristics of a MAMS selection design. We provide guidance on these design features to ensure control of the operating characteristics

Baseline Nutritional Status and In-Hospital Step Count are Associated with Muscle Quantity, Quality, and Function:Results of an Exploratory Study

This exploratory study aimed to assess associations of baseline nutritional status and in-hospital step count with muscle quantity, quality, and function. Seventy-nine participants aged ≥70 years (mean age 79.1 years, 44.3% female) were recruited (elective colorectal surgery, emergency abdominal surgery, and general medical patients with infections). Baseline nutrition (Mini Nutritional Assessment) and in-hospital step count (Fitbit Inspire devices) were assessed. Ultrasound quadriceps, bioelectrical impedance analysis, and physical function were assessed at baseline and 7 (±2) days and 13 (±1) weeks post-admission/post-operatively. Baseline nutritional status was associated with baseline rectus femoris ultrasound echogenicity (normal: 58.5, at risk: 68.5, malnourished: 81.2; p = 0.025), bilateral anterior thigh thickness (normal: 5.07 cm, at risk: 4.03 cm, malnourished: 3.05 cm; p = 0.021), and skeletal muscle mass (Sergi equation) (normal: 21.6 kg, at risk: 18.2 kg, malnourished: 12.0 kg; p = 0.007). Step count was associated with baseline patient-reported physical function (&lt;900 37.1, ≥900 44.5; p = 0.010). There was a significant interaction between nutrition, step count, and time for skeletal muscle mass (Janssen equation) (p = 0.022).</p

Baseline Nutritional Status and In-Hospital Step Count are Associated with Muscle Quantity, Quality, and Function:Results of an Exploratory Study

This exploratory study aimed to assess associations of baseline nutritional status and in-hospital step count with muscle quantity, quality, and function. Seventy-nine participants aged ≥70 years (mean age 79.1 years, 44.3% female) were recruited (elective colorectal surgery, emergency abdominal surgery, and general medical patients with infections). Baseline nutrition (Mini Nutritional Assessment) and in-hospital step count (Fitbit Inspire devices) were assessed. Ultrasound quadriceps, bioelectrical impedance analysis, and physical function were assessed at baseline and 7 (±2) days and 13 (±1) weeks post-admission/post-operatively. Baseline nutritional status was associated with baseline rectus femoris ultrasound echogenicity (normal: 58.5, at risk: 68.5, malnourished: 81.2; p = 0.025), bilateral anterior thigh thickness (normal: 5.07 cm, at risk: 4.03 cm, malnourished: 3.05 cm; p = 0.021), and skeletal muscle mass (Sergi equation) (normal: 21.6 kg, at risk: 18.2 kg, malnourished: 12.0 kg; p = 0.007). Step count was associated with baseline patient-reported physical function (&lt;900 37.1, ≥900 44.5; p = 0.010). There was a significant interaction between nutrition, step count, and time for skeletal muscle mass (Janssen equation) (p = 0.022).</p