Treatment effect of semaglutide 2.4 mg on health-related quality of life from STEP 1 SF-6D derived from SF-36 with Australian weights.

AIM: This study aimed to determine the comparative treatment effects of semaglutide 2.4 mg and placebo on health utility index scores [6-dimension short-form survey (SF-6D)] with Australian weights in full analysis set (FAS) and in post-hoc subgroups of the STEP 1 trial, defined according to different body mass index (BMI) cut-off points and presence of comorbidities at baseline. The study also explored the correlation between baseline BMI and SF-6D in the STEP 1 trial population. METHODS: The 36-item SF survey (SF-36) scores from STEP 1 were mapped to SF-6D health states and converted to utility index scores using an Australian valuation algorithm. The change from baseline in SF-6D utility score (95% confidence intervals) was compared between semaglutide 2.4 mg and placebo at week 68 using the mixed model for repeated measurements approach. The relationship between utility scores and BMI at baseline was assessed by multiple linear regression analyses, controlling for demographic and clinical parameters. RESULTS: The estimated mean treatment difference in SF-6D utility score favoured semaglutide 2.4 mg, and, at week 68, it was 0.057 (0.038-0.076) for the FAS. A greater treatment effect was noted in subgroups with presence of symptomatic comorbidities, i.e. 0.077 (0.027-0.128) to 0.105 (0.030-0.179) at week 68. A 1-unit increase in BMI was associated with a utility loss of 0.0075 (-0.0089 to -0.0062) for the FAS population, while controlling for demographic and clinical parameters. CONCLUSION: To our knowledge, this is the first study showing statistically significant and clinically meaningful improvements in SF-6D utility scores with weight-loss pharmacotherapy in Australia.

A Matching-adjusted Indirect Comparison of Nivolumab Plus Cabozantinib Versus Pembrolizumab Plus Axitinib in Patients with Advanced Renal Cell Carcinoma.

BACKGROUND: The comparative efficacy and health-related quality of life (HRQoL) outcomes of nivolumab plus cabozantinib versus pembrolizumab plus axitinib as first-line treatments for advanced renal cell carcinoma (aRCC) have not been assessed in head-to-head trials. OBJECTIVE: To assess the efficacy and HRQoL outcomes of nivolumab plus cabozantinib versus pembrolizumab plus axitinib. DESIGN, SETTING, AND PARTICIPANTS: Patient-level data for nivolumab plus cabozantinib from the CheckMate 9ER trial and published data for pembrolizumab plus axitinib from the KEYNOTE-426 trial were used. CheckMate 9ER data were reweighted to match the key baseline characteristics as reported in KEYNOTE-426. INTERVENTION: Nivolumab (240 mg every 2 wk) plus cabozantinib (40 mg once daily) and pembrolizumab (200 mg every 3 wk) plus axitinib (5 mg twice daily, initially). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Hazard ratios (HRs) for progression-free survival (PFS), duration of response, overall survival (OS), and deterioration in HRQoL were assessed using weighted Cox proportional-hazard models, with sunitinib as a common anchor. Objective response rates (ORRs) and changes in HRQoL scores from baseline were assessed as difference-in-differences for the two treatments relative to sunitinib. RESULTS AND LIMITATIONS: After balancing patient characteristics between the trials, nivolumab plus cabozantinib was associated with significantly improved PFS (HR [95% confidence interval {CI}] 0.70 [0.53-0.93]; p = 0.01) and a significantly decreased risk of confirmed deterioration in HRQoL (Functional Assessment of Cancer Therapy-Kidney Symptom Index-Disease-related Symptoms: HR [95% CI] 0.48 [0.34-0.69]) versus pembrolizumab plus axitinib. OS was similar between treatments (HR [95% CI] 0.99 [0.67-1.44]; p = 0.94). Nivolumab plus cabozantinib was associated with numerically greater ORRs (difference-in-difference [95% CI] 8.4% [-1.7 to 18.4]; p = 0.10) and longer duration of response (HR [95% CI] 0.79 [0.47-1.31]; p = 0.36) than pembrolizumab plus axitinib. Comparative studies using data with a longer duration of follow-up are warranted. CONCLUSIONS: Nivolumab plus cabozantinib significantly improved PFS and HRQoL compared with pembrolizumab plus axitinib as first-line treatment for aRCC. PATIENT SUMMARY: This study was conducted to indirectly compare the results of two immunotherapy-based combinations-nivolumab plus cabozantinib versus pembrolizumab plus axitinib-for patients who have not received any treatment for advanced renal cell carcinoma. Patients who received nivolumab plus cabozantinib had a significant improvement in the length of time without worsening of their disease and in their perceived physical and mental health compared with pembrolizumab plus axitinib; patients remained alive for a similar length of time from the start of either treatment. This analysis further adds to our current knowledge of the relative benefits of these two treatment regimens and will help with physician and patient treatment decisions.

Enzalutamide and Quality of Life in Biochemically Recurrent Prostate Cancer.

BACKGROUND: EMBARK, a controlled trial reported elsewhere, showed enzalutamide plus leuprolide (combination) and enzalutamide monotherapy prolonged metastasis-free survival versus placebo plus leuprolide (alone) in patients with high-risk biochemically recurrent prostate cancer. Health-related quality of life was also analyzed but not reported. METHODS: In EMBARK, patients with biochemical recurrence (prostate-specific antigen doubling time of ≤9 months) were randomly assigned (1:1:1) to combination (n=355), leuprolide-alone (n=358), or enzalutamide monotherapy (n=355). In this article we provide the patient-reported outcomes (PROs) from EMBARK at baseline and every 12 weeks until metastasis or death. The key end point was time to first and confirmed clinically meaningful deterioration (TTFD/TTCD) in pain and health-related quality of life using four PRO measures and predefined thresholds. RESULTS: At baseline, all groups had high health-related quality of life. For worst pain, the median TTFD was 19.35 months with leuprolide alone, 13.93 months with combination (hazard ratio, 1.08; 95% confidence interval [CI], 0.89 to 1.30) and 16.59 months with monotherapy (hazard ratio, 1.09; 95% CI, 0.90 to 1.31). The median TTCD was 66.27 months with leuprolide alone, 80.00 months with combination (hazard ratio, 0.82; 95% CI, 0.65 to 1.04), and 60.91 months with monotherapy (hazard ratio, 1.02; 95% CI, 0.82 to 1.28). For Functional Assessment of Cancer Therapy­Prostate total score, the median TTFD was 11.10 months with leuprolide alone, 8.31 months with combination (hazard ratio, 1.14; 95% CI, 0.95 to 1.36), and 8.38 months with monotherapy (hazard ratio, 1.17; 95% CI, 0.98 to 1.39). The median TTCD was 36.53 months with leuprolide alone, 38.77 months with combination (hazard ratio, 1.04; 95% CI, 0.85 to 1.28), and 30.55 months with monotherapy (hazard ratio, 1.16; 95% CI, 0.95 to 1.41). CONCLUSIONS: The PROs from EMBARK show that both enzalutamide combination and monotherapy versus leuprolide alone, with oncologic benefits noted above, preserved high health-related quality of life in patients with high-risk biochemical recurrence of prostate cancer. (Funded by Pfizer and Astellas Pharma; ClinicalTrials.gov number, NCT02319837.)

Glacial and postglacial sedimentary infill in Slovakian High Tatra Mts. lakes: Acoustic survey and lithological data.

The data presented in this paper are related to the research article "Sub-bottom and bathymetry sonar inspection of postglacial lacustrine infill of the alpine lakes (Tatra Mts., Slovakia)" (Dhavamani et al., 2022). An implementation of acoustic sonar protocols provided data for the interpretation of glacigene, glaciolacustrine, postglacial, mass-movement deposits, and geodynamic factors influencing the sedimentation in seven alpine and sub-alpine Tatra Mountains lakes. The field data document the survey track lines of the sonars and allow to identify the location of the geomorphologic phenomena described in (Dhavamani et al., 2022). The laboratory data obtained by micro-CT document the lithology of glaciolacustrine and postglacial lake infill and support the interpretation of sub-bottom sonar record.

Subsidies to Increase Remote Pollution?

During the last decade, Central Europe became a cynosure for the world for its unparalleled public support for renewable energy. For instance, the production of electricity from purpose-grown biomass received approximately twice the amount in subsidies as that produced from biowaste. Moreover, the guaranteed purchase price of electricity from solar panels was set approximately five times higher than that from conventional sources. This controversial environmental donation policy led to the devastation of large areas of arable land, a worsening of food availability, unprecedented market distortions, and serious threats to national budgets, among other things. Now, the first proposals to donate the purchase price of electric vehicles (and related infrastructure) from national budgets have appeared for public debate. Advocates of these ideas argue that they can solve the issue of electricity overproduction, and that electric vehicles will reduce emissions in cities. However, our analysis reveals that, as a result of previous scandals, environmental issues have become less significant to local citizens. Given that electric cars are not yet affordable for most people, in terms of local purchasing power, this action would further undermine national budgets. Furthermore, while today's electromobiles produce zero pollution when operated, their sum of emissions (i.e. global warming potential) remains much higher than that of conventional combustion engines. Therefore, we conclude that the mass usage of electromobiles could result in the unethical improvement of a city environment at the expense of marginal regions.