Mealtime fast-acting insulin aspart versus insulin aspart for controlling postprandial hyperglycaemia in people with insulin-resistant Type 2 diabetes.

AIM: This post hoc analysis explored whether mealtime fast-acting insulin aspart treatment provided an advantage in postprandial plasma glucose (PPG) control vs. insulin aspart in people with Type 2 diabetes receiving high doses of bolus insulin. METHODS: A post hoc, post-randomization, subgroup analysis of a 26-week, randomized, double-blind, treat-to-target trial (onset 2) that compared mealtime fast-acting insulin aspart vs. mealtime insulin aspart, both in a basal-bolus regimen, in people with Type 2 diabetes uncontrolled on basal insulin therapy and metformin. At the end of trial, the impact of fast-acting insulin aspart and insulin aspart on PPG control was assessed with a standard liquid meal test and participants were grouped into three post-randomization subgroups: meal test bolus insulin dose ≤ 10 units per dose (n = 171), > 10-20 units per dose (n = 289) and > 20 units per dose (n = 146). RESULTS: A statistically significant treatment difference in favour of fast-acting insulin aspart vs. insulin aspart was observed for the change in PPG increment at all post-meal time points (from 1 to 4 h) for those in the > 20 units bolus insulin subgroup. There was no difference in the magnitude of change from baseline in HbA1c level between fast-acting insulin aspart and insulin aspart in any of the bolus insulin dose subgroups (data herein). CONCLUSION: Fast-acting insulin aspart may hold promise as a more effective treatment compared with insulin aspart for controlling PPG in people with insulin-resistant Type 2 diabetes.

The effect of basal-bolus therapy varies with baseline 1,5-anhydroglucitol level in people with Type 2 diabetes: a post hoc analysis.

AIMS: To investigate the impact of baseline 1,5-anhydroglucitol on the treatment effect of basal-bolus therapy in people with Type 2 diabetes. METHODS: Post hoc analysis of onset 3, an 18-week, randomized, phase 3 trial evaluating the efficacy and safety of fast-acting insulin aspart in basal-bolus therapy (n = 116) vs. basal insulin-only therapy (n = 120) in people with Type 2 diabetes. The estimated treatment difference in change from baseline in HbA1c was investigated for different cut-off values of baseline 1,5-anhydroglucitol (2, 3, 4, 5 and 6 µg/ml). RESULTS: The estimated treatment difference in change from baseline in HbA1c between basal-bolus therapy and basal insulin-only therapy was statistically significantly greater in participants with baseline 1,5-anhydroglucitol ≤3 µg/ml (n = 34) vs. >3 µg/ml (n = 198) [estimated treatment difference (95% CI): -1.53% (-2.12; -0.94) vs. -0.82% (-1.07; -0.57); P-value for interaction = 0.03]. The estimated treatment difference became more pronounced when comparing participants with 1,5-anhydroglucitol ≤2 µg/ml (n = 15) vs. >2 µg/ml (n = 217) [estimated treatment difference (95% CI): -2.26% (-3.15; -1.36) vs. -0.85% (-1.08; -0.62); P-value for interaction = 0.003]. For cut-off values ≥4 µg/ml, estimated treatment differences were numerically greater below the cut-off compared with above, although the interaction terms were not statistically significant. CONCLUSION: This analysis indicates that people with Type 2 diabetes with low 1,5-anhydroglucitol have an added treatment benefit with basal-bolus therapy compared with people with higher 1,5-anhydroglucitol. Further research is needed to clarify any clinical utility of these findings. Clinical Trials Registry No: NCT01850615.

Durability and tolerability of dapagliflozin over 52 weeks as add-on to metformin and sulphonylurea in type 2 diabetes.

AIMS: To evaluate the safety and efficacy of dapagliflozin as add-on therapy to metformin plus sulphonylurea over 52 weeks. METHODS: Patients with type 2 diabetes mellitus (T2DM) using sulphonylurea and metformin received dapagliflozin 10 mg/day or placebo added to therapy for 52 weeks (24-week randomized, double-blind period plus 28-week double-blind extension). RESULTS: A total of 219 patients were randomized 1 : 1 to dapagliflozin or placebo. Over 52 weeks, glycated haemoglobin (HbA1c) and fasting plasma glucose levels showed greater improvement from baseline with dapagliflozin (-0.8% and -1.5 mmol/l) than with placebo (-0.1% and 0.6 mmol/l). More patients achieved HbA1c <7.0% with dapagliflozin (27.3%) than with placebo (11.3%) at 52 weeks. Dapagliflozin was associated with greater reductions in body weight and systolic blood pressure (-2.9 kg and -1.0 mmHg) compared with placebo (-1.0 kg and 1.1 mmHg). Greater increases in total, LDL and HDL cholesterol and decreases in triglycerides were observed with dapagliflozin (3.4, 4.8, 6.9 and -8.0%, respectively) versus placebo (1.4, 0.9, 0.6 and 2.9%, respectively). Fewer patients were rescued for failing to reach glycaemic targets with dapagliflozin (9.3%) than with placebo (44.4%). Adverse events and serious adverse events were similar between groups (dapagliflozin: 69.7 and 6.4%; placebo: 73.4 and 7.3%). More hypoglycaemic events were observed with dapagliflozin (15.6%) than with placebo (8.3%). Genital infections were reported in more patients in the dapagliflozin (10.1%) than in the placebo group (0.9%) and urinary tract infection frequency was similar in the two groups (10.1 and 11.0%). CONCLUSION: Dapagliflozin as add-on to metformin plus a sulphonylurea was well tolerated and improvement in glycaemic control was maintained over 52 weeks.

A study comparing insulin lispro mix 25 with glargine plus lispro therapy in patients with Type 2 diabetes who have inadequate glycaemic control on oral anti-hyperglycaemic medication: results of the PARADIGM study.

AIMS: To test the hypothesis that initiation and intensification with 25% insulin lispro, 75% insulin lispro protamine suspension (LM25), is non-inferior to initiation and intensification with glargine + insulin lispro therapy on change from baseline in HbA(1c). METHODS: In this randomized, non-inferiority (margin of 0.4%), parallel, prospective, multi-country, 48-week, open-label study, patients (n = 426) with Type 2 diabetes inadequately controlled with oral anti-hyperglycaemic medications were assigned to either initiating therapy with one daily LM25 injection, progressing up to three daily injections (full analysis set n = 211; per protocol set n = 177) or initiating therapy with one daily glargine injection and progressing up to three daily insulin lispro injections (full analysis set n = 212; per protocol set n = 184). RESULTS: LM25 therapy was found to be non-inferior to glargine + insulin lispro therapy by study end (upper limit of 95% CI < 0.4), with a least-squares mean difference (95% CI) in HbA(1c) (LM25 minus glargine + insulin lispro) of -0.4 mmol/mol (95% CI -2.7 to 1.9); -0.04% (95% CI -0.25 to 0.17). No statistically significant differences between treatment groups were found in the percentage of patients achieving HbA(1c) targets or postprandial blood glucose levels. The increase in insulin dose, number of injections and weight change during the course of the study were similar in both groups. Patients in both groups experienced similar hypoglycaemia rates and safety profile. CONCLUSIONS: For patients with Type 2 diabetes inadequately controlled with oral anti-hyperglycaemic medications, glycaemic control when initiating and intensifying with LM25 therapy was found to be non-inferior to treatment with glargine + insulin lispro therapy.

Adhesive contact media--an update on graft fixation and burn scar management.

With the introduction of silicone gel in 1981, the emphasis in the treatment of burn scar management has changed from pressure to the use of contact media. A range of 'contact media' has been introduced, allowing for therapy to be individualized to the patient and the scar. Over the last few years, the introduction of 'the adhesive technique' has allowed for earlier therapy with the aim of preventing or minimizing scar hypertrophy with better short- and long-term cosmetic results. The mode of action of 'contact media' is discussed, with a suggested hypothesis and further lines of investigation.

Short-term heat acclimation training improves physical performance: a systematic review, and exploration of physiological adaptations and application for team sports.

BACKGROUND: Studies have demonstrated that longer-term heat acclimation training (≥8 heat exposures) improves physical performance. The physiological adaptations gained through short-term heat acclimation (STHA) training suggest that physical performance can be enhanced within a brief timeframe. OBJECTIVE: The aim of this systematic review was to determine if STHA training (≤7 heat exposures) can improve physical performance in healthy adults. DATA SOURCES: MEDLINE, PubMed, and SPORTDiscus™ databases were searched for available literature. STUDY SELECTION: Studies were included if they met the following criteria: STHA intervention, performance measure outcome, apparently healthy participants, adult participants (≥18 years of age), primary data, and human participants. STUDY APPRAISAL: A modified McMaster critical appraisal tool determined the level of bias in each included study. RESULTS: Eight papers met the inclusion criteria. Studies varied from having a low to a high risk of bias. The review identified aerobic-based tests of performance benefit from STHA training. Peak anaerobic power efforts have not been demonstrated to improve. LIMITATIONS: At the review level, this systematic review did not include tolerance time exercise tests; however, certain professions may be interested in this type of exercise (e.g. fire-fighters). At the outcome level, the review was limited by the moderate level of bias that exists in the field. Only two randomized controlled trials were included. Furthermore, a limited number of studies could be identified (eight), and only one of these articles focused on women participants. CONCLUSIONS: The review identified that aerobic-based tests of performance benefit from STHA training. This is possibly through a number of cardiovascular, thermoregulatory, and metabolic adaptations improving the perception of effort and fatigue through a reduction in anaerobic energy release and elevation of the anaerobic threshold. These results should be viewed with caution due to the level of available evidence, and the limited number of papers that met the inclusion criteria of the review. STHA training can be applied in the team-sport environment during a range of instances within the competitive season. A mixed high-intensity protocol may only require five sessions with a duration of 60 min to potentially improve aerobic-based performance in trained athletes.

Do people with chronic pain have impaired executive function? A meta-analytical review.

A widely held belief within the clinical community is that chronic pain is associated with cognitive impairment, despite the absence of a definitive systematic review or meta-analysis on the topic. The current systematic review and meta-analysis aimed to establish the current evidence concerning the difference in executive function between people with chronic pain and healthy controls. Six databases were searched for citations related to executive function and chronic pain from inception to June 24, 2013. Two reviewers independently assessed studies for eligibility and extracted relevant data according to the Cochrane Collaboration and Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Twenty five studies were included in the review and twenty two studies in the meta-analysis. A small to moderate impairment in executive function performance was found in people with chronic pain across cognitive components, although all studies had a high risk of bias. The current evidence suggests impairment of executive function in people with chronic pain, however, important caveats exist. First, executive function involves many cognitive components and there is no standard test for it. Second, moderators of executive function, such as medication and sleep, were seldom controlled for in studies of executive function performance.

Motor imagery in people with a history of back pain, current back pain, both, or neither.

INTRODUCTION: There is mounting evidence that cortical maps are disrupted in chronic limb pain and that these disruptions may contribute to the problem and be a viable target for treatment. Little is known as to whether this is also the case for the most common and costly chronic pain-back pain. OBJECTIVES: To investigate the effects of back pain characteristics on the performance of left/right trunk judgment tasks, a method of testing the integrity of cortical maps. METHODS: A total of 1008 volunteers completed an online left/right trunk judgment task in which they judged whether a model was rotated or laterally flexed to the left or right in a series of images. RESULTS: Participants who had back pain at the time of testing were less accurate than pain-free controls (P=0.027), as were participants who were pain free but had a history of back pain (P<0.01). However, these results were driven by an interaction such that those with current back pain and a history of back pain were less accurate (mean [95% CI]=76% [74%-78%]) than all other groups (>84% [83%-85%]). DISCUSSION: Trunk motor imagery performance is reduced in people with a history of back pain when they are in a current episode. This is consistent with disruption of cortical proprioceptive representation of the trunk in this group. On the basis of this result, we propose a conceptual model speculating a role of this measure in understanding the development of chronic back pain, a model that can be tested in future studies.

Evidence for working memory deficits in chronic pain: a systematic review and meta-analysis.

People with chronic pain commonly report impaired cognitive function. However, to date, there has been no systematic evaluation of the body of literature concerning cognitive impairment and pain. Nor have modern meta-analytical methods been used to verify and clarify the extent to which cognition may be impaired. The objective of this study was to systematically evaluate and critically appraise the literature concerning working memory function in people with chronic pain. The study was conducted along Cochrane collaboration and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement guidelines. A sensitive search strategy was designed and conducted with the help of an expert librarian using 6 databases. Twenty-four observational studies evaluating behavioural and/or physiological outcomes in a chronic pain group and a control group met the inclusion criteria. All studies had a high risk of bias, owing primarily to lack of assessor blinding to outcome. High heterogeneity within the field was found with the inclusion of 24 papers using 21 different working memory tests encompassing 9 different working memory constructs and 9 different chronic pain populations. Notwithstanding high heterogeneity, pooled results from behavioural outcomes reflected a consistent, significant moderate effect in favour of better performance by healthy controls and, with the exception of one study, pooled results from physiological outcomes reflected no evidence for an effect. Future research would benefit from the use of clearly defined constructs of working memory, as well as standardised methods of testing.

The effects of graded motor imagery and its components on chronic pain: a systematic review and meta-analysis.

UNLABELLED: Graded motor imagery (GMI) is becoming increasingly used in the treatment of chronic pain conditions. The objective of this systematic review was to synthesize all evidence concerning the effects of GMI and its constituent components on chronic pain. Systematic searches were conducted in 10 electronic databases. All randomized controlled trials (RCTs) of GMI, left/right judgment training, motor imagery, and mirror therapy used as a treatment for chronic pain were included. Methodological quality was assessed using the Cochrane risk of bias tool. Six RCTs met our inclusion criteria, and the methodological quality was generally low. No effect was seen for left/right judgment training, and conflicting results were found for motor imagery used as stand-alone techniques, but positive effects were observed for both mirror therapy and GMI. A meta-analysis of GMI versus usual physiotherapy care favored GMI in reducing pain (2 studies, n = 63; effect size, 1.06 [95% confidence interval, .41, 1.71]; heterogeneity, I(2) = 15%). Our results suggest that GMI and mirror therapy alone may be effective, although this conclusion is based on limited evidence. Further rigorous studies are needed to investigate the effects of GMI and its components on a wider chronic pain population. PERSPECTIVE: This systematic review synthesizes the evidence for GMI and its constituent components on chronic pain. This review may assist clinicians in making evidence-based decisions on managing patients with chronic pain conditions.