Health-related quality of life in relapsed/refractory multiple myeloma treated with melflufen and dexamethasone: analyses from the phase III OCEAN study.

Not available.

Impact of walk advice alone or in combination with supervised or home-based structured exercise on patient-reported physical function and generic and disease-specific health related quality of life in patients with intermittent claudication, a secondary analysis in a randomized clinical trial.

BACKGROUND: Supervised exercise is an integral part of the recommended first-line treatment for patients with intermittent claudication (IC). By reflecting the patients' perspectives, patient-reported outcome measurements provide additional knowledge to the biomedical endpoints and are important outcomes to include when evaluating exercise interventions in patients with IC. We aimed to evaluate the one-year impact of three strategies: unsupervised Nordic pole walk advice (WA), WA + six months of home-based structured exercise (HSEP) or WA + six months of hospital-based supervised exercise (SEP) on health-related quality of life and patient-reported physical function in patients with IC. METHODS: This secondary exploratory analysis of a multi-center, randomized clinical trial compared three exercise strategies. The primary outcome of the secondary analysis was the one-year change in the 36-Item Short-Form (SF-36). Secondary outcomes were three- and six-months SF-36 changes alongside three, six- and 12-months changes in the disease-specific Vascular Quality of Life instrument (VascuQoL) and the Patient-Specific Functional Scale (PSFS). The Kruskal-Wallis test with Bonferroni-adjusted post-hoc tests were used for between-group comparisons. Effect size calculations were used to describe the size of observed treatment effects, and the clinical meaningfulness of observed changes in the VascuQoL summary score at one year was studied using established minimally important difference (MID) thresholds. RESULTS: A total of 166 patients with IC, mean age: 72.1 (SD 7.4) years, 41% women, were randomized. No significant between-group differences were observed over time for the SF-36 or the PSFS scores whereas some significant between-group differences were observed in the VascuQoL domain and summary scores over time, favoring SEP and/or HSEP over WA. The observed SF-36 and VascuQoL domain and summary score effect sizes were small to moderate, and many domain score effect sizes also remained unchanged over time. A significantly higher proportion of the patients in the SEP group reached the VascuQoL summary score MID of improvement in one year. CONCLUSION: Clinically important improvements were observed in SEP using the VascuQoL, while we did not observe any significant between-group differences using the SF-36. Whereas effect sizes for the observed changes over time were generally small, a significantly higher proportion of patients in SEP reached the VascuQoL MID of improvement. TRIAL REGISTRATION: NCT02341716, January 19, 2015 (retrospectively registered).

Cost-Effectiveness of Exercise Therapy in Patients with Intermittent Claudication-A Comparison of Supervised Exercise, Home-Based Structured Exercise, and Walk Advice from the SUNFIT Trial.

Hospital-based supervised exercise (SEP) is a guideline-recommended intervention for patients with intermittent claudication (IC). However, due to the limited availability of SEP, home-based structured exercise programs (HSEP) have become increasingly popular alongside the "go home and walk" advice. We evaluated the cost-effectiveness of walk advice (WA) with Nordic pole walking vs. SEP combined with WA or HSEP combined with WA. We used data from the SUNFIT RCT (NCT02341716) to measure quality-adjusted life-years (QALYs) over a 12-month follow-up, and economic costs were obtained from a hospital cost-per-patient accounting system. Incremental cost-effectiveness ratios (ICERs) were calculated, and uncertainty was assessed using nonparametric bootstrapping. The average health-care-cost per patient was similar in the WA (EUR 1781, n = 51) and HSEP (EUR 1820, n = 48) groups but higher in the SEP group (EUR 4619, n = 50, p-value < 0.01). Mean QALYs per patient during the follow-up were similar with no statistically significant differences. The findings do not support SEP as a cost-effective treatment for IC, as it incurred significantly higher costs without providing additional health improvements over WA with or without HSEP during the one-year observation period. The analysis also suggested that HSEP may be cost-effective compared to WA, but only with a 64% probability.

The Impact of Nordic Pole Walk Advice Alone or in Combination With Exercise Strategies on Daily Physical Activity in Patients With Intermittent Claudication: A Randomized Clinical Trial.

OBJECTIVE: The impact of exercise interventions on physical activity (PA) remains undetermined in intermittent claudication, which is why it is important to include objectively measured PA as an additional endpoint. The aim of this prespecified secondary analysis of a randomized clinical trial was to investigate the impact of unsupervised Nordic pole walk advice (WA) alone or in combination with hospital-based supervised exercise (SEP) or home-based structured exercise (HSEP) on PA in patients with intermittent claudication. METHODS: In total, 166 patients with intermittent claudication (mean age = 72 [SD = 7.4] y; 41% women) were randomized to 3 intermittent claudication-treatment strategies: WA, WA + SEP, or WA + HSEP. All patients received Nordic poles and standardized WA (≥30 min, 3 times weekly). Patients randomized to HSEP and SEP accepted participation in an additional 6-months exercise program. PA was measured with an accelerometer-based activPAL3 monitor for 7 days at baseline and at 3, 6, and 12 months. PA outcomes were steps per day, time spent within a stepping cadence ≥100 steps per minute, time spent upright, number of body transitions from sitting to standing, and number of sitting bouts of >30 minutes and >60 minutes. RESULTS: At 1 year, no intergroup differences were observed in any of the PA variables, whereas significant intergroup differences were observed at 3 months regarding time spent within a stepping time cadence ≥100 steps per minute. The mean change for HSEP (2.47 [SD = 10.85] min) was significantly different from the mean change for WA (-3.20 [SD = 6.24] min). At 6 months, the number of sitting bouts (>60 min) for SEP was significantly different from WA (mean change = 0.24 [SD = 0.69] vs -0.23 [SD = 0.81]). CONCLUSION: This study indicates that the addition of 6 months of HSEP or SEP does not improve PA at 1 year, as compared to unsupervised WA alone. Factors of importance for increasing PA in patients with intermittent claudication require further investigation. IMPACT: At the 1-year follow-up, the addition of intermittent claudication-tailored additional exercise strategies did not improve daily PA in patients with intermittent claudication compared with unsupervised Nordic pole WA alone. Future studies may explore the role of behavior change techniques to increase PA in this patient group.

Effectiveness of supervised exercise, home-based exercise, or walk advice strategies on walking performance and muscle endurance in patients with intermittent claudication (SUNFIT trial): a randomized clinical trial.

AIMS: Supervised exercise is a guideline-recommended treatment in intermittent claudication (IC). Hospital-based supervised exercise programmes (SEPs) are underutilized, while home-based structured exercise programmes (HSEPs) have attracted interest. The results from HSEP in IC are inconsistent and may confer no benefit over walk advice (WA) and be less effective than SEP. The aim of the study was to compare the effectiveness of best medical treatment, including Nordic pole WA alone, or WA + SEP or WA + HSEP for patients with IC. METHODS AND RESULTS: This three-armed, multicentre randomized clinical trial enrolled patients with IC; all patients received best medical treatment including walking poles and the advice of regular Nordic pole walking (WA). For HSEP and SEP, additional exercise programmes were provided. The primarily investigated hypothesis was a non-inferiority analysis of SEP vs. HSEP regarding the 6-min walk test (6MWT) maximum distance, with a pre-defined non-inferiority margin of 50 m. Supporting outcomes included muscle endurance tests and the walking impairment questionnaire. Outcomes were assessed at baseline, 3, 6, and 12 months by a blinded evaluator. Altogether 166 patients (mean age 72 years; 59% males) were randomized. In HSEP and SEP, 24 and 26% patients, respectively, were fully exercise adherent. All three groups improved pain-free walking distance over time, but there were no significant intergroup differences. The intergroup 6MWT difference between SEP and HSEP from 0 to 12 months was -11.6 m, 95% confidence interval: -36.4 to 13.0 m (i.e. within the pre-specified non-inferiority margin). CONCLUSION: The HSEP was non-inferior to SEP in patients with IC. There were no significant differences observed between the three groups at 1 year. REGISTRATION: ClinicialTrials.gov: NCT02341716.

Patient-reported outcomes in relapsed/refractory multiple myeloma treated with melflufen plus dexamethasone: analyses from the Phase II HORIZON study.

Relapsed/refractory multiple myeloma (RRMM) is known to have a high burden of disease and complications associated with refractoriness to prior lines of therapy. Severe pain and fatigue symptoms and impairments in physical and emotional functioning have been strongly linked to reduced health-related quality of life (HRQoL) in patients with RRMM. Assessment of patient reported-outcome measures from the pivotal, Phase II HORIZON study (OP-106; NCT02963493) in patients with RRMM (n = 64) demonstrated that melphalan flufenamide (melflufen) plus dexamethasone treatment preserved HRQoL. Patients had clinically meaningful improvements, even after eight treatment cycles, in relevant scales such as global health status/QoL, physical functioning, emotional functioning, pain, and fatigue. Patients with triple-class-refractory disease (n = 50) displayed similar improvements. Patient-reported outcome deterioration was delayed for a substantial amount of time in patients who experienced a response to melflufen plus dexamethasone treatment relative to patients who did not experience a response. These findings support the notion that treatment with melflufen plus dexamethasone may sustain or improve HRQoL over time in patients with RRMM, including in patients with triple-class-refractory disease for whom outcomes are generally worse. The clinical benefits observed in patients from the HORIZON trial are encouraging and supportive of translation into real-world practice.

A population-adjusted indirect comparison of cardiovascular benefits of once-weekly subcutaneous semaglutide and dulaglutide in the treatment of patients with type 2 diabetes, with or without established cardiovascular disease.

INTRODUCTION: Cardiovascular (CV) effects of once-weekly subcutaneous (s.c.) semaglutide 0.5 and 1 mg and dulaglutide 1.5 mg are reported in their respective placebo-controlled cardiovascular outcome trials (CVOTs), SUSTAIN 6 and REWIND. There is no head-to-head CVOT comparing these treatments and heterogeneity between their CVOTs renders conventional indirect comparison inappropriate. Therefore, a matching-adjusted indirect comparison (MAIC) was performed to compare the effects of s.c. semaglutide and dulaglutide on major adverse cardiovascular events (MACE) in patients with and without established cardiovascular disease (CVD). METHODS: Individual patient data from SUSTAIN 6 were matched with aggregate data from REWIND, using a propensity score method to balance baseline effect-modifying patient characteristics. Hazard ratios (HRs) for three-point (3P) MACE (CV death, non-fatal myocardial infarction, non-fatal stroke), anchored via placebo, were then indirectly compared between balanced populations. Sensitivity analyses were performed to test the robustness of the main analysis. RESULTS: After matching, included effect modifiers were balanced. In the main analysis, s.c. semaglutide was associated with a statistically significant 35% reduction in 3P MACE versus placebo (HR, 0.65 [95% confidence interval [CI]; 0.48, 0.87]) and nonsignificantly greater reduction (26%) versus dulaglutide (HR, 0.74 [95% CI; 0.54, 1.01]). Results were supported by all sensitivity analyses. CONCLUSIONS: This study demonstrated a statistically significant lower risk of 3P MACE for s.c. semaglutide versus placebo, in a population with lower prevalence of pre-existing CVD than that in the pre-specified primary analysis in SUSTAIN 6. Reduction in 3P MACE with s.c. semaglutide was greater than with dulaglutide, although not statistically significant.

Efficacy of Once-Weekly Semaglutide vs Empagliflozin Added to Metformin in Type 2 Diabetes: Patient-Level Meta-analysis.

CONTEXT: No head-to-head trials have directly compared once-weekly (OW) semaglutide, a human glucagon-like peptide-1 analog, with empagliflozin, a sodium-glucose co-transporter-2 inhibitor, in type 2 diabetes (T2D). OBJECTIVE: We indirectly compared the efficacy of OW semaglutide 1 mg vs once-daily (OD) empagliflozin 25 mg in patients with T2D inadequately controlled on metformin monotherapy, using individual patient data (IPD) and meta-regression methodology. DESIGN, SETTING, PARTICIPANTS, AND INTERVENTIONS: IPD for patients with T2D receiving metformin monotherapy and randomized to OW semaglutide 1 mg (SUSTAIN 2, 3, 8 trials), or to OD empagliflozin 25 mg (PIONEER 2 trial) were included. Meta-regression analyses were adjusted for potential prognostic factors and effect modifiers. MAIN OUTCOME MEASURES: The primary efficacy outcomes were change from baseline to end-of-treatment (~1 year) in HbA1c (%-point) and body weight (kg). Responder outcomes and other clinically relevant efficacy measures were analyzed. RESULTS: Baseline characteristics were similar between OW semaglutide (n = 995) and empagliflozin (n = 410). Our analyses showed that OW semaglutide significantly reduced mean HbA1c and body weight vs empagliflozin (estimated treatment difference: -0.61%-point [95% confidence interval (CI): -0.72; -0.49] and -1.65 kg [95% CI: -2.22; -1.08], respectively; both P < 0.0001). Complementary analyses supported the robustness of these results. A significantly greater proportion of patients on OW semaglutide vs empagliflozin also achieved HbA1c targets and weight-loss responses. CONCLUSIONS: This indirect comparison suggests that OW semaglutide 1 mg provides superior reductions in HbA1c and body weight vs OD empagliflozin 25 mg in patients with T2D when added to metformin monotherapy.

Evaluating the Long-Term Cost-Effectiveness of Once-Weekly Semaglutide Versus Once-Daily Liraglutide for the Treatment of Type 2 Diabetes in the UK.

INTRODUCTION: Once-weekly semaglutide 1 mg is a novel glucagon-like peptide-1 receptor agonist (GLP-1 RA) for the treatment of type 2 diabetes that has demonstrated significantly greater reductions in glycated haemoglobin (HbA1c) and body weight than the GLP-1 RA once-daily liraglutide 1.2 mg in the SUSTAIN 10 trial. The present analysis aimed to evaluate the long-term cost-effectiveness of once-weekly semaglutide 1 mg versus once-daily liraglutide 1.2 mg from a UK healthcare payer perspective. METHODS: Long-term outcomes were projected using the IQVIA CORE Diabetes Model (version 9.0), with baseline characteristics and treatment effects sourced from SUSTAIN 10. Patients were assumed to initiate treatment with GLP-1 RAs and continue treatment until HbA1c exceeded 7.5%, at which point GLP-1 RAs were discontinued and basal insulin was initiated. Pharmacy costs and costs of complications were measured in 2018 pounds sterling (GBP), with future costs and outcomes discounted at 3.5% per annum. Utilities were taken from published sources. RESULTS: In the base-case analysis, once-weekly semaglutide 1 mg was associated with an increase in discounted life expectancy of 0.21 years and discounted quality-adjusted life expectancy of 0.30 quality-adjusted life-years, compared with once-daily liraglutide 1.2 mg. Clinical benefits were achieved at reduced costs, with lifetime cost savings of GBP 140 per patient with semaglutide versus liraglutide, owing to a reduction in diabetes-related complications, in particular cardiovascular disease (mean cost saving of GBP 279 per patient). Therefore, once-weekly semaglutide 1 mg was dominant compared with once-daily liraglutide 1.2 mg. The results of the sensitivity analyses were similar, demonstrating the robustness of the base-case analysis. CONCLUSIONS: Once-weekly semaglutide 1 mg is a cost-effective treatment option versus once-daily liraglutide 1.2 mg, based on the SUSTAIN 10 trial, from a UK healthcare payer perspective.

Semaglutide improves health-related quality of life versus placebo when added to standard of care in patients with type 2 diabetes at high cardiovascular risk (SUSTAIN 6).

AIM: To assess what drives change in health-related quality of life (HRQoL) in type 2 diabetes in the SUSTAIN 6 trial and identify potential mediators of the treatment effect of semaglutide on HRQoL scores. MATERIALS AND METHODS: The Short Form (SF)-36v2® questionnaire [comprising physical component summary (PCS) and mental component summary (MCS)] was used to assess changes in HRQoL from baseline to week 104, by treatment, in a prespecified analysis. This post-hoc analysis assessed change in PCS and MCS using the following factors as parameter/covariate, using descriptive statistics and linear regressions: major adverse cardiac events, hypoglycaemia, gastrointestinal adverse events, at least one episode of nausea, vomiting or diarrhoea, and change in glycated haemoglobin (HbA1c), body weight, blood pressure, heart rate and estimated glomerular filtration rate. RESULTS: Mean change in overall PCS score was +1.0 with semaglutide versus +0.4 with placebo, and +0.5 versus -0.2 for MCS. The treatment effect of semaglutide versus placebo (unadjusted estimate) was 0.7 [(95% confidence interval 0.1, 1.2); P = 0.018] on PCS and this was reduced when adjusted for change in HbA1c [0.4 (-0.2, 1.0), P = .167] and body weight [0.3 (-0.3, 0.9), P = .314]. The unadjusted treatment effect on MCS [0.7 (-0.0, 1.5), P = .054] was only reduced when adjusted for change in HbA1c [0.3 (-0.4, 1.1), P = .397]. When adjusting for all other parameters separately, the estimated effect of semaglutide on PCS and MCS qualitatively did not change. CONCLUSIONS: Semaglutide improved HRQoL versus placebo; greater improvements with semaglutide versus placebo were possibly mediated, in part, by change in HbA1c and body weight. Clinicaltrials.gov: NCT01720446 (SUSTAIN 6).

A Relative Cost of Control Analysis of Once-Weekly Semaglutide Versus Exenatide Extended-Release, Dulaglutide and Liraglutide in the UK.

INTRODUCTION: Once-weekly semaglutide 1 mg is a novel glucagon-like peptide 1 receptor agonist (GLP-1 RA) that, in the SUSTAIN clinical trials, has demonstrated greater reductions in glycated haemoglobin (HbA1c) and body weight than the other GLP-1 RAs exenatide extended-release (ER) 2 mg, dulaglutide 1.5 mg and liraglutide 1.2 mg. The aim of this analysis was to evaluate the relative cost of control of achieving treatment goals in people with type 2 diabetes (T2D) treated with once-weekly semaglutide versus exenatide ER, dulaglutide and liraglutide from a UK perspective. METHODS: Proportions of patients reaching HbA1c targets (< 7.0% and < 7.5%), weight loss targets (≥ 5% reduction in body weight) and composite endpoints (HbA1c < 7.0% without weight gain or hypoglycaemia; reduction in HbA1c of ≥ 1% and weight loss of ≥ 5%) were obtained from the SUSTAIN clinical trials. Annual per patient treatment costs were based on wholesale acquisition costs from July 2019 in the UK. Cost of control was calculated by plotting relative treatment costs against relative efficacy. RESULTS: The annual per patient cost was similar for all GLP-1 RAs. Once-weekly semaglutide was superior to exenatide ER, dulaglutide and liraglutide in bringing patients to HbA1c and weight loss targets, and to composite endpoints. When looking at the composite endpoint of HbA1c < 7.0% without weight gain or hypoglycaemia, exenatide ER, dulaglutide and liraglutide were 50.0%, 21.6% and 51.3% less efficacious in achieving this, respectively, than once-weekly semaglutide. Consequently, the efficacy-to-cost ratios for once-weekly semaglutide were superior to all comparators in bringing patients to all endpoints. CONCLUSIONS: The present study showed that once-weekly semaglutide offers superior cost of control versus exenatide ER, dulaglutide and liraglutide in terms of achieving clinically relevant, single and composite endpoints. Once-weekly semaglutide 1 mg would therefore represent good value for money in the UK setting.

Test-retest reliability, agreement, and minimal detectable change in the 6-minute walk test in patients with intermittent claudication.

OBJECTIVE: Standardized walk tests are important for objective assessment of walking distance in patients with intermittent claudication (IC). The 6-minute walk test (6MWT) has been suggested to correlate more closely than testing on a treadmill with everyday ambulatory function, but its measurement properties have hardly been studied in IC. The aim of this study was to determine the test-retest reliability, agreement, standard error of measurement (SEM), and minimal detectable change of the 6MWT in patients with IC. METHODS: This reliability and agreement study recruited 102 patients with stable IC (mean age, 72 ± 7.4 years; 43 women) from the vascular surgery outpatient clinic at Sahlgrenska University Hospital in Sweden. The patients performed the 6MWT twice, with at least 30 minutes of rest between tests. To determine test-retest reliability, the intraclass correlation coefficient was calculated. Bland-Altman plots were used to measure agreement. RESULTS: The mean walking distance in both test and retest was 397.8 m (standard deviation, 81.2 m; N = 100), and the individual walking distance varied from 175 to 600 m. Excellent test-retest reliability for the 6MWT (intraclass correlation coefficient, 0.95; 95% confidence interval, 0.9-0.97) was observed. The SEM was 16.6 m (95% confidence interval, 14.6-19.3), the SEM percentage was 4.2%, and the minimal detectable change was 46 m. Five observations (5%) were positioned outside the limits of agreement; there was a small proportional bias, and the scatter of values for differences decreased as the average values increased. CONCLUSIONS: The excellent test-retest reliability implies that it is sufficient for a patient with IC to perform the 6MWT once, at every test occasion. For the individual, an improvement or deterioration in maximum walking distance of >46 m after an intervention would be required to be 95% confident that the change is significant. Being a simple and clinically useful test, the 6MWT can be widely used to evaluate the effects of different interventions in patients with IC.

Postprandial glucose and healthcare resource use: a cross-sectional survey of adults with diabetes treated with basal-bolus insulin.

AIMS: Postprandial glucose (PPG) control is a well-known challenge for diabetes management, yet there is limited research on how PPG affects healthcare resource utilization. This study investigated the association between PPG levels and healthcare resource utilization among adults with diabetes treated with basal-bolus insulin. METHODS: A web-based, cross-sectional survey (n = 940) of adults with type 1 or type 2 diabetes and treated with basal and bolus insulins was conducted in Italy, the UK, and the US. Descriptive analyses included frequencies, cross-tabulations, and comparison of means. Incidence-rate ratios (IRR) were calculated using negative binomial regression analysis to investigate the relationship between elevated PPG and healthcare resource utilization. Models controlled for demographic characteristics, duration of diabetes, and diabetes-related complications. RESULTS: Among respondents who measured PPG regularly and reported their two highest PPG values in the past week (n = 691), the mean average highest PPG value was 11.9 mmol/L (SD = 4.0). On average, holding other variables constant at their means, a 1 mmol/L increase in PPG was associated with an increase in healthcare resource utilization related to diabetes and elevated PPG, including the expected number of healthcare provider (HCP) visits in the past 6 months (IRR [95% CI] = 1.14 [1.08-1.21], p < .001), the expected number of calls/emails to HCPs in the past 6 months (IRR [95% CI] = 1.12 [1.06-1.19], p < .001), and the expected number of overnight hospitalizations in the past year (IRR [95% CI] = 1.14 [1.07-1.23], p < .001). LIMITATIONS: The study relied on self-reported data, which may be subject to recall bias. Given the cross-sectional nature of the study, results should be interpreted with caution. CONCLUSIONS: Increased PPG levels were significantly associated with increased healthcare resource utilization among adults with diabetes. Additional education regarding PPG monitoring may help improve the day-to-day management of diabetes and reduce healthcare costs.

Timing of Insulin Injections, Adherence, and Glycemic Control in a Multinational Sample of People with Type 2 Diabetes: A Cross-Sectional Analysis.

INTRODUCTION: We investigated the association of bolus insulin dose timing with demographics, adherence, diabetes education program participation, experience with hypoglycemic events, glycemic control, and patient preference among respondents with type 2 diabetes. METHODS: Adults with type 2 diabetes from 12 countries were recruited to a Web-based self-reported patient preference survey. Adherence was measured using an adapted Morisky Medication Adherence Scale questionnaire. RESULTS: In total 1483 respondents reported using bolus insulin with 58% (n = 864) dosing bolus insulin before meals (pre-meal cohort), 354 (24%) during or after meals (post-meal cohort), and 265 (18%) before, during, or after meals (mixed cohort). The mixed cohort was excluded, thus 1218 respondents were included in the analysis. Respondent distribution across HbA1c category differed significantly depending on insulin dose timing (p = 0.0006); more respondents in the post-meal cohort (40%) had HbA1c ≥ 9% (74.9 mmol/mol) than in the pre-meal cohort (29%). The post-meal cohort was significantly more likely to report non-adherence than the pre-meal cohort (OR = 1.50, p = 0.01) and significantly more often reported participating in diabetes education programs (p < 0.05). Seventy-eight percent of all respondents reported preferring bolus insulin administrable whenever convenient. CONCLUSIONS: Approximately 24% of respondents never comply with guidelines for insulin dose timing, with higher risk of non-adherence and increased participation in diabetes care programs. Respondents dosing insulin post-meal are more likely to have poor glycemic control (HbA1c ≥ 9%, 74.9 mmol/mol). Given that many respondents had high HbA1c and were non-adherent, a treatment which satisfies patient preference for bolus insulin with flexible dose timing could be considered. FUNDING: Novo Nordisk.

Projected long-term outcomes in patients with type 1 diabetes treated with fast-acting insulin aspart vs conventional insulin aspart in the UK setting.

AIM: To assess the impact of faster aspart vs insulin aspart on long-term clinical outcomes and costs for patients with type 1 diabetes mellitus (T1DM) in the UK setting. METHODS: The QuintilesIMS CORE Diabetes Model was used to project clinical outcomes and costs over patient lifetimes in a cohort with data on baseline characteristics from the "onset 1" trial. Treatment effects were taken from the 26-week main phase of the onset 1 trial, with costs and utilities based on literature review. Future costs and clinical benefits were discounted at 3.5% annually. RESULTS: Projections indicated that faster aspart was associated with improved discounted quality-adjusted life expectancy (by 0.13 quality-adjusted life-years) vs insulin aspart. Improved clinical outcomes resulted from fewer diabetes-related complications and a delayed time to their onset with faster aspart. Faster aspart was found to be associated with reduced costs vs insulin aspart (cost savings of £1715), resulting from diabetes-related complications avoided and reduced treatment costs. CONCLUSIONS: Faster aspart was associated with improved clinical outcomes and cost savings vs insulin aspart for patients with T1DM in the UK setting.

Is there an omission effect in prosocial behavior? A laboratory experiment on passive vs. active generosity.

We investigate whether individuals are more prone to act selfishly if they can passively allow for an outcome to be implemented (omission) rather than having to make an active choice (commission). In most settings, active and passive choice alternatives differ in terms of factors such as the presence of a suggested option, costs of taking an action, and awareness. We isolate the omission effect from confounding factors in three experiments, and find no evidence that the distinction between active and passive choices has an independent effect on the propensity to implement selfish outcomes. This suggests that increased selfishness through omission, as observed in various economic choice situations, is driven by other factors than a preference for selfish omissions.

Understanding bolus insulin dose timing: the characteristics and experiences of people with diabetes who take bolus insulin.

OBJECTIVE: Despite the increased popularity of newer, fast-acting bolus insulin treatment options that allow for more flexibility in the timing of bolus insulin dosing in recent years, relatively little is known about people with diabetes who administer bolus insulin at differing times in relation to their meals. The purpose of this study was to investigate bolus insulin dose timing in relation to meals among people with type 1 (T1D) and type 2 (T2D) diabetes, as well as to better understand the characteristics and experiences of people who bolus dose at differing times. METHODS: A web-based survey of adults with T1D and T2D treated with bolus insulin therapy in Germany, the UK, and USA was conducted. RESULTS: A total of 906 respondents completed the survey (39% T1D; 61% T2D). A majority of respondents reported bolus dosing before meals in the previous week (57.0%), followed by after meals (18.9%), with meals (12.7%), and at varying times (11.5%). Compared to respondents who dosed with or after meals, those who dosed before meals were significantly less likely to experience hypoglycemia (before, 55.7%; with, 72.8%; after, 68.7%; p < .001) in the previous week. Respondents who bolus dosed before meals were significantly more likely to perceive bolus dose timing as flexible (45.5%) compared to those who dosed with (27.8%) or after (35.7%) meals (p < .001). CONCLUSION: Results show that many people with T1D and T2D dose their bolus insulin with or after meals. Key limitations of all self-report surveys include potential bias in responses and generalizability of findings. However, the study was designed to help mitigate these limitations. The findings have implications for clinicians and suggest opportunities for improving diabetes education and care.

Dielectric and other properties of polyimide aerogels containing fluorinated blocks.

The dielectric and other properties of a series of low-density polyimide block copolymer aerogels have been characterized. Two different anhydride-capped polyimide oligomers were synthesized: one from 2,2-bis(3,4-dicarboxyphenyl)hexafluoropropane dianhydride (6FDA) and 4,4'-oxidianiline (ODA) and the other from biphenyl-3,3',4,4'-tetracarboxylic dianhydride and ODA. The oligomers were combined with 1,3,5-triaminophenoxybenzene to form a block copolymer networked structure that gelled in under 1 h. The polyimide gels were supercritically dried to give aerogels with relative dielectric constants as low as 1.08. Increasing the amount of 6FDA blocks by up to 50% of the total dianhydride decreased the density of the aerogels, presumably by increasing the free volume and also by decreasing the amount of shrinkage seen upon processing, resulting in a concomitant decrease in the dielectric properties. In this study, we have also altered the density independent of fluorine substitution by changing the polymer concentration in the gelation reactions and showed that the change in dielectric due to density is the same with and without fluorine substitution. The aerogels with the lowest dielectric properties and lowest densities still had compressive moduli of 4-8 MPa (40 times higher than silica aerogels at the same density), making them suitable as low dielectric substrates for lightweight antennas for aeronautic and space applications.

Patient perspective on the management of atrial fibrillation in five European countries.

BACKGROUND: Long-term management of chronic conditions, such as atrial fibrillation (AF), require frequent interactions with the healthcare systems. The multinational EUropean Patient Survey in Atrial Fibrillation (EUPS-AF) was conducted to investigate patient satisfaction with AF management in different of five European healthcare systems at a time of changing treatment paradigms for stroke prophylaxis, prior to the advent of newer oral anticoagulants. METHODS: Adults (>18 years) were recruited at random from the total populations of France, Germany, Italy, Spain and the UK using a randomized telephone dialling system. At least 300 respondents per country reporting to have a diagnosis of AF or receiving oral anticoagulation therapy for suspected AF or to have a heart rhythm disturbance completed a structured telephone interview. RESULTS: Most respondents were satisfied with their treatment for AF over the previous 12 months, with 85.5% (n = 1289) rating their care as good or better. Suboptimal clinical practices, however, were identified in several key areas. Coordination of primary and secondary care and a lack of patient engagement and support were particular issues, especially for those patients likely to have extensive contact with their healthcare system. CONCLUSIONS: In the context of Europe-wide guidelines for management of AF, most patients with AF were satisfied with their care, but for a greater proportion of patients, some aspects are unsatisfactory. Patient-centred surveys, such as the EUPS-AF, are crucial for understanding the factors that contribute to patient satisfaction and compliance with long-term treatment for chronic conditions.

Low dielectric polyimide aerogels as substrates for lightweight patch antennas.

The dielectric properties and loss tangents of low-density polyimide aerogels have been characterized at various frequencies. Relative dielectric constants as low as 1.16 were measured for polyimide aerogels made from 2,2'-dimethylbenzidine (DMBZ) and biphenyl 3,3',4,4'-tetracarbozylic dianhydride (BPDA) cross-linked with 1,3,5-triaminophenoxybenzene (TAB). This formulation was used as the substrate to fabricate and test prototype microstrip patch antennas and benchmark against state of practice commercial antenna substrates. The polyimide aerogel antennas exhibited broader bandwidth, higher gain, and lower mass than the antennas made using commercial substrates. These are very encouraging results, which support the potential advantages of the polyimide aerogel-based antennas for aerospace applications.