The psychosocial burden of hidradenitis suppurativa: the patients' perspectives

We designed a qualitative study to interview 12 patients with Hidradenitis Suppurativa. This was done by means of a semistructured interview. Questions on quality of life, the impact of their skin disease on family, friends, work, intimate relationships, treatments, etc. were asked. Patients consented to be interviewed and to be video taped to facilitate the transcription of the interviews. The interviews lasted between 30 and 60 minutes and were carried out by a psychologist and a social worker. The dermatologist had previously seen the patients and filled in a form with the Hurley Stage, years of evolution and treatment..

Effect of Lifestyle Intervention in the Concentration of Adipoquines and Branched Chain Amino Acids in Subjects with High Risk of Developing Type 2 Diabetes: Feel4Diabetes Study

Introduction: The global prevalence of type 2 diabetes (T2D) is increasing rapidly, especially in low- and middle-income countries and has a high number of associated comorbidities. Plasmatic concentrations of branched chain amino acids (BCAA) and retinol-binding protein 4 (RBP4) have been shown to be elevated in T2D subjects in cross-sectional studies. However, the effect of lifestyle community-based interventions on BCAA and RBP4 concentrations has not yet been analyzed. Material and methods: The Feel4Diabetes study is a school and community-based intervention that identified 360 European families with a high risk of developing T2D according to the FINDRISC questionnaire. Families were randomized in control and intervention groups were followed-up from 2016 to 2018. In the Spanish families, the concentration of BCAA and RBP4 was determined in 266 subjects (115 control and 151 intervention group) that attended the three time-point assessments by colorimetric and ELISA reaction, respectively. Results: Baseline BCAA levels showed positive correlations with the FINDRISC score and glucose impairment (baseline glucose, insulin, and glycated hemoglobin), body mass index, and body weight. The participants receiving the community-based intervention showed a significant decrease in glycated hemoglobin and BCAA levels compared to the control group (p = 0.011 and p < 0.001, respectively). However, baseline RBP4 did not show significant correlations with anthropometric and glycemic parameters, and no significant change was observed in anthropometric parameters and RBP4 concentrations throughout the follow-up. Conclusion: A community-based intervention on lifestyle led to a significant reduction in BCAA levels regardless of weight loss. These findings suggest that this interventional approach could be promising in T2D prevention

Glucosylpolyphenols as Inhibitors of Aβ-Induced Fyn Kinase Activation and Tau Phosphorylation: Synthesis, Membrane Permeability, and Exploratory Target Assessment within the Scope of Type 2 Diabetes and Alzheimer's Disease

Despite the rapidly increasing number of patients suffering from type 2 diabetes, Alzheimer's disease, and diabetes-induced dementia, there are no disease-modifying therapies that are able to prevent or block disease progress. In this work, we investigate the potential of nature-inspired glucosylpolyphenols against relevant targets, including islet amyloid polypeptide, glucosidases, and cholinesterases. Moreover, with the premise of Fyn kinase as a paradigm-shifting target in Alzheimer's drug discovery, we explore glucosylpolyphenols as blockers of Aβ-induced Fyn kinase activation while looking into downstream effects leading to Tau hyperphosphorylation. Several compounds inhibit Aβ-induced Fyn kinase activation and decrease pTau levels at 10 μM concentration, particularly the per-O-methylated glucosylacetophloroglucinol and the 4-glucosylcatechol dibenzoate, the latter inhibiting also butyrylcholinesterase and β-glucosidase. Both compounds are nontoxic with ideal pharmacokinetic properties for further development. This work ultimately highlights the multitarget nature, fine structural tuning capacity, and valuable therapeutic significance of glucosylpolyphenols in the context of these metabolic and neurodegenerative disorders.European Commission GA 612347Fundação para a Ciência e a Tecnologia SFRH/BD/93170/2013, SFRH/BD/116614/2016, PD/BD/142847/2018, SFRH/BD/145600/2019, CEECIND/03414/2018, CEECIND/02300/2017, UIDB/00100/2020, UIDB/04046/2020, UIDB/04378/2020, IF/00780/2015Gobierno de España CTQ2016-78703-PJunta de Andalucía FQM13

Do physical activity and screen time mediate the association between European fathers' and their children's weight status? Cross-sectional data from the Feel4Diabetes-study

BACKGROUND: Most research on parenting and childhood obesity and obesity-related behaviours has focused on mothers while fathers have been underrepresented. Yet, recent literature has suggested that fathers uniquely influence their children''s lifestyle behaviours, and hence could also affect their weight status, but this has not yet been scientifically proven. Therefore, the present study aimed to determine whether the association between fathers'' weight status and their children''s weight status is mediated by fathers'' and children''s movement behaviours (i.e. physical activity (PA) and screen time (ST)). METHODS: Cross-sectional data of 899 European fathers and their children were analyzed. Fathers/male caregivers (mean age =¿43.79¿±¿5.92¿years, mean BMI =¿27.08¿±¿3.95) completed a questionnaire assessing their own and their children''s (mean age =¿8.19¿±¿0.99¿years, 50.90% boys, mean BMIzscore =¿0.44¿±¿1.07) movement behaviours. Body Mass Index (BMI, in kg/m2) was calculated based on self-reported (fathers) and objectively measured (children) height and weight. For children, BMI z-scores (SD scores) were calculated to obtain an optimal measure for their weight status. Serial mediation analyses were performed using IBM SPSS 25.0 Statistics for Windows to test whether the association between fathers'' BMI and children''s BMI is mediated by fathers'' PA and children''s PA (model 1) and fathers'' ST and children''s ST (model 2), respectively. RESULTS: The present study showed a (partial) mediation effect of fathers'' PA and children''s PA (but not father''s ST and children''s ST) on the association between fathers'' BMI and children''s BMI (model for PA; coefficient: 0.001, 95% CI: [0.0001, 0.002]; model for ST; coefficient: 0.001, 95% CI: [0.000, 0.002]). Furthermore, fathers'' movement behaviours (PA and ST) were positively associated with their children''s movement behaviours (PA and ST) (model for PA, coefficient: 0.281, SE: 0.023, p <¿0.001; model for ST, coefficient: 0.345, SE: 0.025, p¿<¿0.001). CONCLUSIONS: These findings indicate that the influence of fathers on their children''s weight status partially occurs through the association between fathers'' PA and children''s PA (but not their ST). As such, intervening by focusing on PA of fathers but preferably of both members of the father-child dyad (e.g. engaging fathers and their children in co-PA) might be a novel and potentially effective strategy for interventions aiming to prevent childhood overweight and obesity. Longitudinal studies or intervention studies confirming these findings are however warranted to make meaningful recommendations for health intervention and policy. TRIAL REGISTRATION: The Feel4Diabetes-study is registered with the clinical trials registry http://clinicaltrials.gov , ID: 643708

The effect of a cluster-randomized controlled trial on lifestyle behaviors among families at risk for developing type 2 diabetes across Europe: the Feel4Diabetes-study

Background: This study investigated the effect of the Feel4Diabetes-intervention, a 2-year multilevel intervention, on energy balance-related behaviors among European families at risk for developing type 2 diabetes. Intervention effects on self-reported physical activity, sedentary behavior and eating behaviors were investigated across and within the participating countries: Belgium, Finland, Greece, Spain, Hungary and Bulgaria. Methods: Families were recruited through schools, located in low socio-economic status areas. In total, 4484 families at risk for developing type 2 diabetes were selected using the FINDRISC-questionnaire. Parents’ and children’s energy balance-related behaviors data were collected by questionnaires at three time points (baseline, mid- and post intervention). Families assigned to the intervention group were invited to participate in a 2-year school-, community-, and family-based intervention to promote a healthier lifestyle, including counseling sessions (first intervention year) and text messages (second intervention year). Families assigned to the control group received standard care, including medical check-up results and recommendations and tips regarding a healthy lifestyle. To assess the intervention-effects, Mixed Models were conducted using the R-Package “lmer “with R v3.2. Results: Significant intervention effects were found on a certain number of families’ lifestyle behaviors. Significant favorable intervention effects were detected on parents’ water consumption and consumption of fruit and vegetables, and on children’s consumption of sweets and moderate-to-vigorous physical activity. Analyses by country revealed significant favorable intervention effects on water consumption and on moderate-to-vigorous physical activity in Belgian parents and on fruit and vegetable consumption among Belgian children, on sweets consumption among Spanish parents and children, and on moderate-to-vigorous physical activity among Finnish children. Unfavorable intervention effects were found on the consumption of soft drinks and sugar-containing juices among Hungarian children and parents, while when examining the intervention effects for the overall population and per country, 10 from the 112 investigated outcome variables were improved in the intervention group compared to the control group (9%). Conclusions: The Feel4Diabetes-intervention managed to improve a certain number of targeted lifestyle behaviors while the intervention was not effective on a large number of targeted lifestyle behaviors. The findings of the current study are encouraging, but further research is needed on how we can further improve effectiveness of lifestyle interventions to prevent type 2 diabetes in families at risk. Trial registration: The Feel4Diabetes-study is registered with the clinical trials registry http://clinicaltrials.gov, ID: 643708. © 2021, The Author(s)

Pembrolizumab as Consolidation Strategy in Patients with Multiple Myeloma: Results of the GEM-Pembresid Clinical Trial

PD1 expression in CD4+ and CD8+ T cells is increased after treatment in multiple myeloma patients with persistent disease. The GEM-Pembresid trial analyzed the efficacy and safety of pembrolizumab as consolidation in patients achieving at least very good partial response but with persistent measurable disease after first- or second-line treatment. Moreover, the characteristics of the immune system were investigated to identify potential biomarkers of response to pembrolizumab. One out of the 17 evaluable patients showed a decrease in the amount of M-protein, although a potential late effect of high-dose melphalan could not be ruled out. Fourteen adverse events were considered related to pembrolizumab, two of which (G3 diarrhea and G2 pneumonitis) prompted treatment discontinuation and all resolving without sequelae. Interestingly, pembrolizumab induced a decrease in the percentage of NK cells at cycle 3, due to the reduction of the circulating and adaptive subsets (0.615 vs. 0.43, p = 0.007; 1.12 vs. 0.86, p = 0.02). In the early progressors, a significantly lower expression of PD1 in CD8+ effector memory T cells (MFI 1327 vs. 926, p = 0.03) was observed. In conclusion, pembrolizumab used as consolidation monotherapy shows an acceptable toxicity profile but did not improve responses in this MM patient population. The trial was registered at clinicaltrials.gov with identifier NCT02636010 and with EUDRACT number 2015-003359-23.This study was funded by Fundación Ramón Areces (FRA 16/003). T.P. is supported by a grant from the AECC (INVES18043PAIN). This study received financial support from Merck Sharp & Dohme of Spain, a subsidiary of Merck & Co., Inc., Whitehouse Station, New Jersey, USA

Methodology of the health economic evaluation of the Feel4Diabetes-study

Background: The clinical and economic burden of type 2 diabetes mellitus on society is rising. Effective and efficient preventive measures may stop the increasing prevalence, given that type 2 diabetes mellitus is mainly a lifestyle-driven disease. The Feel4Diabetes-study aimed to tackle unhealthy lifestyle (unhealthy diet, lack of physical activity, sedentary behaviour, and excess weight) of families with a child in the first grades of elementary school. These schools were located in regions with a relatively low socio-economic status in Belgium, Bulgaria, Finland, Greece, Hungary and Spain. Special attention was paid to families with a high risk of developing type 2 diabetes mellitus. Methods: The aim of this paper is to describe the detailed methodology of the intervention’s cost-effectiveness analysis. Based on the health economic evaluation of the Toybox-study, both a decision analytic part and a Markov model have been designed to assess the long-term (time horizon of 70 year with one-year cycles) intervention’s value for money. Data sources used for the calculation of health state incidences, transition probabilities between health states, health state costs, and health state utilities are listed. Intervention-related costs were collected by questionnaires and diaries, and attributed to either all families or high risk families only. Conclusions: The optimal use of limited resources is pivotal. The future results of the health economic evaluation of the Feel4Diabetes-study will contribute to the efficient use of those resources.Publication of this supplement was funded by the European Union’s Horizon 2020 research and innovation programme under grant agreement n° 643708

Pembrolizumab as consolidation strategy in patients with multiple myeloma: Results of the GEM-Pembresid clinical trial

PD1 expression in CD4+ and CD8+ T cells is increased after treatment in multiple myeloma patients with persistent disease. The GEM-Pembresid trial analyzed the efficacy and safety of pembrolizumab as consolidation in patients achieving at least very good partial response but with persistent measurable disease after first- or second-line treatment. Moreover, the characteristics of the immune system were investigated to identify potential biomarkers of response to pembrolizumab. One out of the 17 evaluable patients showed a decrease in the amount of M-protein, although a potential late effect of high-dose melphalan could not be ruled out. Fourteen adverse events were considered related to pembrolizumab, two of which (G3 diarrhea and G2 pneumonitis) prompted treatment discontinuation and all resolving without sequelae. Interestingly, pembrolizumab induced a decrease in the percentage of NK cells at cycle 3, due to the reduction of the circulating and adaptive subsets (0.615 vs. 0.43, p = 0.007; 1.12 vs. 0.86, p = 0.02). In the early progressors, a significantly lower expression of PD1 in CD8+ effector memory T cells (MFI 1327 vs. 926, p = 0.03) was observed. In conclusion, pembrolizumab used as consolidation monotherapy shows an acceptable toxicity profile but did not improve responses in this MM patient population. The trial was registered at clinicaltrials.gov with identifier NCT02636010 and with EUDRACT number 2015-003359-23

Distribution and outcomes of a phenotype-based approach to guide COPD management: Results from the CHAIN cohort

Rationale: The Spanish guideline for COPD (GesEPOC) recommends COPD treatment according to four clinical phenotypes: non-exacerbator phenotype with either chronic bronchitis or emphysema (NE), asthma-COPD overlap syndrome (ACOS), frequent exacerbator phenotype with emphysema (FEE) or frequent exacerbator phenotype with chronic bronchitis (FECB). However, little is known on the distribution and outcomes of the four suggested phenotypes. Objective: We aimed to determine the distribution of these COPD phenotypes, and their relation with one-year clinical outcomes. Methods: We followed a cohort of well-characterized patients with COPD up to one-year. Baseline characteristics, health status (CAT), BODE index, rate of exacerbations and mortality up to one year of follow-up were compared between the four phenotypes. Results: Overall, 831 stable COPD patients were evaluated. They were distributed as NE, 550 (66.2%); ACOS, 125 (15.0%); FEE, 38 (4.6%); and FECB, 99 (11.9%); additionally 19 (2.3%) COPD patients with frequent exacerbations did not fulfill the criteria for neither FEE nor FECB. At baseline, there were significant differences in symptoms, FEV1 and BODE index (all p<0.05). The FECB phenotype had the highest CAT score (17.1±8.2, p<0.05 compared to the other phenotypes). Frequent exacerbator groups (FEE and FECB) were receiving more pharmacological treatment at baseline, and also experienced more exacerbations the year after (all p<0.05) with no differences in one-year mortality. Most of NE (93%) and half of exacerbators were stable after one year. Conclusions: There is an uneven distribution of COPD phenotypes in stable COPD patients, with significant differences in demographics, patient-centered outcomes and health care resources use