Combination Therapy With Glucagon-Like Peptide-1 Receptor Agonists and Sodium-Glucose Cotransporter 2 Inhibitors in Older Patients With Type 2 Diabetes: A Real-World Evidence Study

Objectives: Scientific literature about the combination of glucagon-like peptide-1 receptor agonists (GLP1ra) and sodium-glucose cotransporter 2 (SGLT2) inhibitors in older patients is scarce. We sought to assess the real-world efficacy and safety of SGLT2 inhibitors and GLP-1ra combination therapy in older patients (>65 years of age). Methods: This was an observational, prospective, multicenter study based on clinical practice. Patients were stratified according to tertiles of baseline glycated hemoglobin (A1C) levels and to treatment schedule. Results: We included 113 patients (65.5% men, mean age 70.4±8.8 years). The body mass index was 36.5 (±6.6) kg/m2. The baseline A1C level was 8.0% (±1.2%). At the 6-month follow up, we found a significant reduction in A1C levels (–1.1%; p<0.0001), body mass index (–2.1 kg/m2; p<0.00003) and systolic blood pressure (–13 mmHg; p<0.000005). Patients who had the highest baseline A1C levels (≥8.4%) showed greater improvement in A1C levels (p<0.0001), weight (p<0.0001) and quality-of-life scores (p<0.0001). The greatest reduction in A1C levels and weight was seen in patients who started both drugs simultaneously (p<0.0001). The second greatest reduction was seen when GLP-1ra was added to previous treatment with an SGLT2i (p<0.0001). Also of note was a decrease in systolic blood pressure in patients for whom an SGLT2i was added to previous GLP-1ra treatment (p<0.0001). Of the patients, 34.3% achieved the combined endpoint of A1C levels <7% and weight loss ≥5% without hypoglycemia. Conclusions: This study’s findings provide evidence of clinically meaningful reductions in A1C level, body weight and systolic blood pressure in older patients with type 2 diabetes who are taking combined regimens. The dropout and hypoglycemia rates were minimal, and treatment was tolerated well

Effectiveness of a healthy lifestyle promotion program as adjunctive teletherapy for treatment-resistant major depression during COVID 19 pandemic: A randomized clinical trial protocol

INTRODUCTION: Treatment-resistant depression (TRD) has a high prevalence and can be exacerbated by poor physical health and economic hardships, which have become common stressors during the current COVID-19 pandemic. The therapeutic approaches used to treat these patients are not always available, may be not be accepted by some patients, and often require face-to-face interactions. OBJECTIVE: The main aim of this study will be to evaluate the effectiveness of an Internet-based adjuvant lifestyle-based intervention for patients with TRD. METHODS: This will be a parallel, randomized, and controlled clinical trial. A total of 180 patients with TRD will be randomly allocated (1:1:1) to 1 of 3 groups: treatment prescribed by the mental health team and written suggestions for lifestyle changes (placebo control group); treatment prescribed by the mental health team, written suggestions for lifestyle changes, and an 8-week mindfulness-based cognitive therapy program (active control group); or treatment prescribed by the mental health team, written suggestions for lifestyle changes, and an 8-week lifestyle change promotion program (intervention group). We will perform this study during the COVID-19 pandemic, and will administer interventions by teletherapy, and contact participants by telephone calls, text messages, and/or teleconferences. We will collect patient data using questionnaires administered at baseline, immediately after the intervention, and after 6 and 12 months. The primary outcome will be score on the Beck Depression Inventory-II. The secondary outcomes will be score on the Clinical Global Impressions Scale (used to quantify and track patient progress and treatment response over time) and health-related quality of life measured using the European Quality of Life-5 Dimensions Questionnaire. DISCUSSION: Patients with TRD are especially vulnerable when face-to-face psychotherapy is unavailable. The main strength of the proposed study is the novelty of the intervention to be used as an adjuvant therapy. Our results may provide guidance for treatment of patients with TRD in future situations that require lockdown measures. CLINICALTRIALS REGISTRATION NUMBER: NCT04428099

Early biomarkers of diabetic kidney disease. A focus on albuminuria and a new combination of antidiabetic agents

Aims: We aimed to determine the efficacy and safety of sodium-glucose cotransporter type 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists to prevent worsening urinary albumin-to-creatinine ratio as an early biomarker of diabetes kidney disease. Methods: A total of 178 patients with type 2 diabetes and obesity received combination treatment with SGLT2i added to GLP1ra (n = 76), GLP1ra added to SGLT2i (n = 50) or GLP1ra plus SGLT2i from start (n = 52), according to investigators´ best clinical judgement. Major outcomes assessed at 26 weeks were changes in urine albumintocreatinine-ratio (UACR), estimated glomerular filtration rate (eGFR), glycated haemoglobin, body weight and systolic blood pressure. Results: All patients (58.6% men, mean age 61.9 ± 10.0 years) completed the study. Baseline HbA1c, weight and eGFR levels were 8.2 ± 0.9%, 109.9 ± 19 kg and 83.3 ± 19.6 mL/min/m2 , respectively. At 26 weeks, we found significant reductions in HbA1c (1.16%), weight (5.17 kg) and systolic blood pressure (8.13 mmHg). The reduction in UACR was 15.14 mg/g (95% CI 8.50-22.4) (-24.6 ± 64.7%), which was greatest in the group of patients with SGLT2i added on to GLP1ra therapy (116.7 mg/g; 95% CI: 54-296.5 mg/g; P < .001. Patients with urinary albumin-to-creatinine ratio ≥30 mg/g, showed a higher declines (63.18 mg/g [95% CI 44.5-104.99]) (-56 ± 65.9%). The greatest reduction in urinary albumin-to-creatinine ratio was obtained when SGLT2i was added to GLP1ra (116.7 mg/g). The eGFR did not significantly change along the study period. Conclusion: Our results show the beneficial effect of GLP1ra and SGLT2i combination therapy on early biomarkers of diabetes kidney disease such as albuminuria and in other significant outcomes for diabetes control

Effectiveness of an mHealth intervention combining a smartphone app and smart band on body composition in an overweight and obese population: Randomized controlled trial (EVIDENT 3 study)

Background: Mobile health (mHealth) is currently among the supporting elements that may contribute to an improvement in health markers by helping people adopt healthier lifestyles. mHealth interventions have been widely reported to achieve greater weight loss than other approaches, but their effect on body composition remains unclear. Objective: This study aimed to assess the short-term (3 months) effectiveness of a mobile app and a smart band for losing weight and changing body composition in sedentary Spanish adults who are overweight or obese. Methods: A randomized controlled, multicenter clinical trial was conducted involving the participation of 440 subjects from primary care centers, with 231 subjects in the intervention group (IG; counselling with smartphone app and smart band) and 209 in the control group (CG; counselling only). Both groups were counselled about healthy diet and physical activity. For the 3-month intervention period, the IG was trained to use a smartphone app that involved self-monitoring and tailored feedback, as well as a smart band that recorded daily physical activity (Mi Band 2, Xiaomi). Body composition was measured using the InBody 230 bioimpedance device (InBody Co., Ltd), and physical activity was measured using the International Physical Activity Questionnaire. Results: The mHealth intervention produced a greater loss of body weight (–1.97 kg, 95% CI –2.39 to –1.54) relative to standard counselling at 3 months (–1.13 kg, 95% CI –1.56 to –0.69). Comparing groups, the IG achieved a weight loss of 0.84 kg more than the CG at 3 months. The IG showed a decrease in body fat mass (BFM; –1.84 kg, 95% CI –2.48 to –1.20), percentage of body fat (PBF; –1.22%, 95% CI –1.82% to 0.62%), and BMI (–0.77 kg/m2, 95% CI –0.96 to 0.57). No significant changes were observed in any of these parameters in men; among women, there was a significant decrease in BMI in the IG compared with the CG. When subjects were grouped according to baseline BMI, the overweight group experienced a change in BFM of –1.18 kg (95% CI –2.30 to –0.06) and BMI of –0.47 kg/m2 (95% CI –0.80 to –0.13), whereas the obese group only experienced a change in BMI of –0.53 kg/m2 (95% CI –0.86 to –0.19). When the data were analyzed according to physical activity, the moderate-vigorous physical activity group showed significant changes in BFM of –1.03 kg (95% CI –1.74 to –0.33), PBF of –0.76% (95% CI –1.32% to –0.20%), and BMI of –0.5 kg/m2 (95% CI –0.83 to –0.19). Conclusions: The results from this multicenter, randomized controlled clinical trial study show that compared with standard counselling alone, adding a self-reported app and a smart band obtained beneficial results in terms of weight loss and a reduction in BFM and PBF in female subjects with a BMI less than 30 kg/m2 and a moderate-vigorous physical activity level. Nevertheless, further studies are needed to ensure that this profile benefits more than others from this intervention and to investigate modifications of this intervention to achieve a global effect

Initial results of NEXT-DEMO, a large-scale prototype of the NEXT-100 experiment

NEXT-DEMO is a large scale prototype and demonstrator of the NEXT-100 High Pressure Xenon Gas TPC, which will search for the neutrinoless double beta decay of Xe-136 using 100-150 kg of enriched xenon gas. The apparatus was built to prove the expected performance of NEXT-100, namely, energy resolution better than 1% FWHM at 2.5 MeV and event topological reconstruction. In this paper we describe the operation and initial results of the detector. A resolution of 1.7% FWHM at 511 keV (0.77% FWHM at 2.5 MeV) is obtained in the full fiducial volume of the detector. A topological analysis shows that electrons are identified by the characteristic blob energy deposit associated to the Bragg peak in 98.5% of the cases, with a rate of misidentification (two blobs) of 0.14%

Dietary Fat Intake and the Risk of Depression: The SUN Project

Emerging evidence relates some nutritional factors to depression risk. However, there is a scarcity of longitudinal assessments on this relationship

Evaluation of uncertainties in mean and extreme precipitation under climate change for northwestern Mediterranean watersheds from high-resolution Med and Euro-CORDEX ensembles

The climate change impact on mean and extreme precipitation events in the northern Mediterranean region is assessed using high-resolution EuroCORDEX and MedCORDEX simulations. The focus is made on three regions, Lez and Aude located in France, and Muga located in northeastern Spain, and eight pairs of global and regional climate models are analyzed with respect to the SAFRAN product. First the model skills are evaluated in terms of bias for the precipitation annual cycle over historical period. Then future changes in extreme precipitation, under two emission scenarios, are estimated through the computation of past/future change coefficients of quantile-ranked model precipitation outputs. Over the 1981–2010 period, the cumulative precipitation is overestimated for most models over the mountainous regions and underestimated over the coastal regions in autumn and higher-order quantile. The ensemble mean and the spread for future period remain unchanged under RCP4.5 scenario and decrease under RCP8.5 scenario. Extreme precipitation events are intensified over the three catchments with a smaller ensemble spread under RCP8.5 revealing more evident changes, especially in the later part of the 21st century

Development of Micromegas for neutrinoless double beta decay searches

International audienceThe present paper is a summary of experimental tests performed with microbulk Micromegas for application in a neutrinoless double beta decay experiment based in a xenon TPC. No critical limitation related with high pressure has been detected for Micromegas, which has been tested up to 10 bar. No significant differences have been found between low energy X-rays and high energy alpha tracks regarding ionization yield and electronic transparency of Micromegas mesh. Using 5.5 MeV alphas in argon-isobutane mixtures, values as low as 1.8% FWHM have been obtained, with possible evidence that better resolutions are achievable. These results seems independent of pressure (probed up to 4.5 bar) or gas mixture (microbulks have run in xenon without quencher). The imperative necessity of high quality gas led to start on a new TPC and MPGD dedicated lab at Zaragoza