Integrative Clinical, Hormonal and Molecular Data associate with Invasiveness in Acromegaly: REMAH Study.

INTRODUCTION: Growth-hormone (GH)-secreting pituitary-tumors (GHomas) are the most common acromegaly cause. At diagnosis, most of them are macroadenomas, and up to 56% display cavernous sinus invasion. Biomarkers assessment associated with tumor-growth and invasion are important to optimize their management. OBJECTIVES: To identify clinical/hormonal/molecular-biomarkers associated with tumor-size and invasiveness in GHomas, and to analyze the influence of pre-treatment with somatostatin-analogs or dopamine-agonists in key molecular biomarkers expression. METHODS: Clinical/analytical/radiological-variables were evaluated in 192 patients from the REMAH-study (ambispective multicenter post-surgery study of the Spanish Society of Endocrinology and Nutrition). Expression of somatostatin/ghrelin/dopamine-systems components, and key pituitary/proliferation-markers were evaluated in GHomas after the first surgery. Univariate/multivariate regression studies were performed to identify association between variables. RESULTS: 80% of patients harbor macroadenomas (63.8% with extrasellar-growth). Associations between larger and more invasive GHomas with younger age, visual-abnormalities, higher IGF1-levels, extrasellar/suprasellar-growth and/or cavernous-sinus invasion were found. Higher GH1 and lower PRL/POMC/CGA/AVPR1B/DRD2T/DRD2L expression levels (p<0.05) were associated to tumor invasiveness. LASSO´s penalized regression identified combinations of clinical and molecular features with AUCs between 0.67-0.82. Preoperative therapy with dopamine-agonist or somatostatin-analogs did not alter the expression of any of the markers analyzed except for DRD1/AVPR1B (up-regulated with dopamine-agonist), and FSHB/CRHR1 (down-regulated with somatostatin-analogs). CONCLUSIONS: A specific combination of clinical/analytical/molecular variables was found to be associated with tumor invasiveness and growth capacity in GHomas. Pre-treatment with first-line drugs for acromegaly did not significantly modify the expression of the most relevant biomarkers in our association model. These findings provide valuable insights for risk stratification and personalized management of GHomas.

Comprehensive approach to people with type 2 diabetes. Diabetes Knowledge Area of the Spanish Society of Endocrinology and Nutrition.

OBJECTIVE: To provide practical recommendations for the comprehensive approach of people with type 2 diabetes according to evidence-based medicine. PARTICIPANTS: Members of the Diabetes Knowledge Area of the Spanish Society of Endocrinology and Nutrition. METHODS: The recommendations were formulated according to the degrees of evidence of the Standards of Medical Care in Diabetes-2022. After reviewing the available evidence and formulating recommendations by the authors of each section, several rounds of comments were developed incorporating the contributions and voting on controversial points. Finally, the final document was sent to the rest of the members of the area for review and incorporation of contributions, to finally carry out the same process with the members of the Spanish Society of Endocrinology and Nutrition Board of Directors. CONCLUSIONS: The document establishes practical recommendations based on the latest available evidence for the management of people with type 2 diabetes.

Executive summary of the consensus statement of: Clinical recommendations for sport practice in people with diabetes (RECORD Guide). Update 2021. Diabetes Mellitus Area of the Spanish Society of Endocrinology and Nutrition (SEEN).

OBJECTIVE: To guide professionals involved in the care of people with diabetes mellitus who practice sport. PARTICIPANTS: Members of the Diabetes Mellitus Working Group of the Spanish Society of Endocrinology and Nutrition. METHODS: A group of experts in each area covered by the statement carried out a bibliographic review of the available evidence for each topic, based on which recommendations were subsequently agreed upon within the Diabetes Mellitus Working Group. CONCLUSIONS: The statement provides practical recommendations for the management of diabetes mellitus during sports practice.

Realist evaluation of three programmes aimed at reducing harm and risks associated with alcohol consumption in the Nouvelle Aquitaine region of France: the ECIAE study protocol.

INTRODUCTION: In Europe, alcohol consumption is responsible for many diseases, disabilities, injuries and premature deaths. In France, alcohol consumption represents an important health burden, due to its frequency, scale and the serious damage it causes. One of the keys to addressing the problem would appear to be the adoption of harm and risk reduction approaches. In order to operationalise this strategy, the Nouvelle Aquitaine Regional Health Agency is funding three different programmes to reduce the harm and risks associated with alcohol consumption: Alcochoix, Iaca and ETP (Education Thérapeutique du Patient) Conso-repère. We are interested in understanding how, under what circumstances, through which mechanisms and for which population the different programmes work. METHODS AND ANALYSIS: The ECIAE study (a cross-evaluation of the 3 programs Iaca/Alcochoix/ ETP (Patient Therapeutic Education) is a theory-based evaluation where the realist evaluation method is used to explore effects, intervention mechanisms and the influence of context on outcomes. This realist evaluation is based on multiple case studies in two nested levels. At the first level, each centre implementing the programme will represent a case. At the second level, each programme will represent a case in which a set of activities is conducted to achieve risk reduction objectives. ETHICS AND DISSEMINATION: The project will be carried out in full compliance with existing legislation and international conventions. It was subject to analysis, including a privacy impact assessment conducted by the Data Protection Officer of the University of Bordeaux. The University of Bordeaux has ensured that all the regulatory procedures related to the ECIAE study have been carried out. The dissemination plan includes scientific papers, seminars, a report and recommendation and a public restitution. The study will provide evidence-based results to help health authorities roll out strategies to reduce risks and harm associated with alcohol use.

Realist evaluation of the impact, viability and transferability of an alcohol harm reduction support programme based on mental health recovery: the Vitae study protocol.

INTRODUCTION: Addiction is considered a chronic disease associated with a high rate of relapse as a consequence of the addictive condition. Most of the current therapeutic work focuses on the notion of relapse prevention or avoidance and the control of its determinants. Since only a small portion of patients can access alcohol addiction treatment, it is crucial to find a way to offer new support towards safe consumptions, reductions or cessations. The harm reduction (HR) approach and mental health recovery perspective offers another way to support the patient with alcohol addiction. Vitae is a realist evaluation of the impact, viability and transferability of the IACA! programme, an HR programme based on the principle of psychosocial recovery for people with alcohol use disorders. METHODS AND ANALYSIS: The Vitae study adheres to the theory-driven evaluation framework where the realist evaluation method and contribution analysis are used to explore the effects, mechanisms and influence of context on the outcomes and to develop and adjust an intervention theory. This study is a 12-month, multi-case, longitudinal descriptive pilot study using mixed methods. It is multi-centred, and carried out in 10 addiction treatment or prevention centres. In this study, outcomes are related to the evolution of alcohol use and the beneficiaries trajectory in terms of psychosocial recovery during these 12 months after the start of IACA!. The target number of participants are 100 beneficiaries and 23 professionals. ETHICS AND DISSEMINATION: This research was approved by the Committee for the Protection of Persons Ouest V n°: 21/008-3HPS and was reported to the French National Agency for the Safety of Health Products. All participants will provide consent prior to participation. The results will be reported in international peer-reviewed journals and presented at scientific and public conferences. TRIAL REGISTRATION NUMBERS: NCT04927455; ID-RCB2020-A03371-38.

Place of patient-reported outcomes & experiences measurements (PROMS/PREMS) in the assessment and pricing of Health technologies in France.

In the context of health technologies assessment, patient-reported outcome measures (PROMs) have become assessment criteria that are expected by evaluation agencies along with the other usual clinical criteria. PROMs instruments measure all aspects of patient experience in connection with their health: symptoms, activities of daily living (physical function, sleep, etc.), various aspects of health-related quality of life (QoL), compliance, global impression of change in wellbeing. PROMs are useful both as 1) a primary or secondary efficacy endpoints, and 2) a tolerability criterion to supplement vigilance data reported by clinicians. Measurement of PROMs must be subject to methodological rigor that is identical to that of other assessment criteria measured by an observer. Scales must be validated, suitable for the objective, and where possible specific to a disease. In addition to standard measures of quality of life, PROMs are taken into consideration in the assessments performed by the HAS, even if their impact on the conclusions is difficult to isolate, as assessments are multifactorial and take into account all data available with regard to the medical context. The CEPS will indirectly take into account PROMs in the fixing of the price or tariff only if they have contributed to the award of the ASA/ASMR by the ad hoc committee of the HAS. The working group has formulated three recommendations which aim to further the implementation of patient-reported outcome measures: (1) Better information for all parties involved in a dossier for technology assessment, (2) Systematization of the collection of PROMs for evaluation of health products, (3) Improved quality of dossiers thanks to the use of relevant and validated tools.

Evaluation of a knowledge translation strategy to improve policymaking and practices in health promotion and disease prevention setting in French regions: TC-REG, a realist study.

OBJECTIVE: This paper presents the results of a realist evaluation of a knowledge translation (KT) intervention implemented in the field of health promotion and disease prevention at the local level in France. DESIGN: Realist evaluation study. SETTING: The target population comprised decision-makers and field professionals working in prevention and public health services operating in regions of France (ie, ARS (Agence Régionale de Santé: regional health agency), IREPS (Instance Régionale d'Education et de Promotion de la Santé pour tous: regional organisation for health promotion and education) and their partners). PARTICIPANTS: This evaluation was based on data collected from 2 seminars, 82 interviews, 18 observations and 4 focus groups over 18 months. INTERVENTION: The TC-REG intervention aimed to increase the use of evidence in cancer prevention, health promotion and disease prevention across four geographical regions in France. The intervention combined various activities: Supporting access to and adaptation of usable evidence, strengthening professionals' skills in analysing, adopting and using policy briefs, and facilitating the use of evidence in organisations and processes. RESULTS: The collected data was used to define favourable/unfavourable contexts for the use of scientific data and mechanisms to be activated to encourage the use of scientific knowledge. From these raw results eight final refined middle-range theories were defined. Organised around the mechanisms to be activated, these middle-range theories illustrate how to activate knowledge and under what conditions. These analyses provided a basis for the production of seven operational and contextualised recommendations to develop KT to inform regional policymaking regarding health promotion and disease prevention. CONCLUSION: The results obtained from the analyses led us to formulate two perspectives of an operational nature for the benefit of those involved in prevention and health promotion.

Demographic, socioeconomic, and sociocultural factors associated with any breastfeeding in homeless mothers.

In high-income countries, breastfeeding has been shown to be positively associated with socioeconomic position. However, less is known about breastfeeding practices and their associated factors among extremely disadvantaged populations. We aimed to assess the associations of cultural origins and socioeconomic factors with any breastfeeding initiation and duration in homeless families. We analyzed data from 456 children aged 6 months to 5 years from the cross-sectional ENFAMS survey, conducted in 2013 among a random sample of homeless families in shelters in the Greater Paris area. Data were collected by bilingual interviewers in 17 languages. Four nested multivariable robust Poisson regression models were run in a hierarchical framework to determine the factors associated with breastfeeding initiation and with any breastfeeding for 6 months or more. Most of the children (86.0%) had previously been or were currently being breastfed at the time of the survey; 58.9% were fed with breast milk ≥6 months. A higher maternal age and African origin were positively associated with breastfeeding ≥6 months, although the relation to the region of origin was moderated by education level. Migration to escape war, unrest or other violence and the child's birth in France were inversely associated with breastfeeding ≥6 months. Any breastfeeding by these homeless mothers seems influenced predominantly by their cultural origin and complicated by a difficult migration trajectory. The possible influence of poor material circumstances and cumulative hardship should encourage interventions targeted at homeless mothers that emphasize social/family support with a commitment to improving the family's living conditions.

Realist evaluation of a theory-based life skills programme aiming to prevent addictive behaviours in adolescents: the ERIEAS study protocol.

INTRODUCTION: Adolescence is a sensitive life stage during which tobacco, alcohol and cannabis are used as ways to learn and adopt roles. There is a great deal of interest in substance use (SU) prevention programmes for young people that work to change representations of these products and help with mobilisation of life skills. Unfortunately, few existing programmes are evidence-based.In France, a programme called Expériences Animées (EA, Animated Experiences) has been developed, inspired by life skills development programmes that have been proven to be successful. The EA programme uses animated short movies and talks with high school and secondary school pupils about the use of psychoactive substances and addictions. By allowing life skills mobilisation and modifying representations and beliefs about SU, it is aimed at delaying initiation of use of psychoactive substances, preventing adolescents from becoming regular consumers, reducing the risks and harms related to the use of these substances and opening the way for adapted support measures.We are interested in understanding how, under what circumstances, through which mechanisms and among which adolescents the EA programme works. Therefore, we have developed the ERIEAS study ('Evaluation Réaliste de l'Intervention Expériences Animées en milieu Scolaire'; Realist Evaluation of the EA Intervention in Schools). METHODS AND ANALYSIS: EA will be conducted in 10 schools. A multi-case approach will be adopted with the aim of developing and adjusting an intervention theory. The study comes under the theory-driven evaluation framework. The investigation methodology will include four stages: (i) elaboration of a middle-range theory; (ii) data collection for validating/adjusting the theory; (iii) data analysis; and (iv) refinement and adjustment of the middle-range theory and definition of the programme's key functions. ETHICS AND DISSEMINATION: The study will provide evidence-based results to health authorities to help in the rollout of health promotion strategies in schools. It will provide knowledge about the strategic configurations most suitable for leading to life skills mobilisation and change young people's representations about SU. The project will be carried out with full respect of current relevant legislation (eg, the Charter of Fundamental Rights of the European Union) and international conventions (eg, Helsinki Declaration). It follows the relevant French legislation of the research category on interventional research protocol involving the human person. The protocol was approved by the Comité et Protection des Personnes (CPP), that is, Committee for the Protection of Persons CPP SUD-EST VI n°: AU 1525 and was reported to the Agence Française de Sécurité Sanitaire des Produits de Santé (ANSM) that is, the French National Agency for the Safety of Health Products. It is in conformity with reference methodology MR003 of Bordeaux University Hospital (CNIL n° 2 026 779 v0).Trial registration detailsThis research has been registered on ClinicalTrials.gov (No. NCT04110626).The research project is registered in the European database ID-RCB (No. 2019-A01003-54).

Splicing Machinery is Dysregulated in Pituitary Neuroendocrine Tumors and is Associated with Aggressiveness Features.

Pituitary neuroendocrine tumors (PitNETs) constitute approximately 15% of all brain tumors, and most have a sporadic origin. Recent studies suggest that altered alternative splicing and, consequently, appearance of aberrant splicing variants, is a common feature of most tumor pathologies. Moreover, spliceosome is considered an attractive therapeutic target in tumor pathologies, and the inhibition of SF3B1 (e.g., using pladienolide-B) has been shown to exert antitumor effects. Therefore, we aimed to analyze the expression levels of selected splicing-machinery components in 261 PitNETs (somatotropinomas/non-functioning PitNETS/corticotropinomas/prolactinomas) and evaluated the direct effects of pladienolide-B in cell proliferation/viability/hormone secretion in human PitNETs cell cultures and pituitary cell lines (AtT-20/GH3). Results revealed a severe dysregulation of splicing-machinery components in all the PitNET subtypes compared to normal pituitaries and a unique fingerprint of splicing-machinery components that accurately discriminate between normal and tumor tissue in each PitNET subtype. Moreover, expression of specific components was associated with key clinical parameters. Interestingly, certain components were commonly dysregulated throughout all PitNET subtypes. Finally, pladienolide-B reduced cell proliferation/viability/hormone secretion in PitNET cell cultures and cell lines. Altogether, our data demonstrate a drastic dysregulation of the splicing-machinery in PitNETs that might be associated to their tumorigenesis, paving the way to explore the use of specific splicing-machinery components as novel diagnostic/prognostic and therapeutic targets in PitNETs.

Document on a comprehensive approach to type 2 diabetes mellitus. / Documento de abordaje integral de la diabetes tipo 2.

OBJECTIVE: Treatment of type 2 diabetes mellitus (T2DM) is complex and is intended to decrease morbidity and mortality. Management should therefore include adequate diabetes education, lifestyle changes, drug treatment to achieve early blood glucose control and reduction of cardiovascular (CV) risk factors, early detection and treatment of complications, and assessment of associated comorbidities. The objective was to prepare a document including all aspects required for a comprehensive approach to T2DM. PARTICIPANTS: Members of the Diabetes Mellitus Working Group of the Spanish Society of Endocrinology. METHODS: The available evidence regarding each aspect of diabetes management (blood glucose control goals, diet and exercise, drug treatment, risk factor management and control, detection of complications, and management of frail patients) was reviewed. Recommendations were formulated based on the grades of evidence stated in the 2018 Standards of Medical Care in Diabetes. Recommendations were discussed and agreed by the working group members. CONCLUSIONS: This document is intended to provide evidence-based practical recommendations for comprehensive management of T2DM by clinical endocrinologists.

Food Insecurity in Homeless Families in the Paris Region (France): Results from the ENFAMS Survey.

The number of families living in shelters in the Paris region (France) has increased by a factor of three in 10 years. In 2013, a survey was performed on homeless families in order to characterize their living conditions, their health needs, and the developmental problems in children. This probability survey was conducted in 17 languages among 801 homeless families sheltered in emergency centers for asylum-seekers, emergency housing centers, social rehabilitation centers, and social hotels in the Paris region. Among the 772 families that provided data on food security only 14.0% were with food security, whereas 43.3% were with low food security and 9.8% with very low food security (a situation where children are also affected). Stratified multivariate robust Poisson models showed that some characteristics are associated with a higher risk of food insecurity and/or of falling into very low food security, such as residential instability, single parenthood, having more than three children, depressive symptoms, housing in social hostels, and difficult access to cheap or free food locally. Given the wealth of the Paris region, resources and programs should be concentrated on improving the living situation of this vulnerable population. It needs better detection of these families, a closer social follow-up, and an increase in food aid.

Characteristics and health of homeless families: the ENFAMS survey in the Paris region, France 2013.

BACKGROUND: The objectives were to estimate the size of homeless family population in Paris region, to describe their living conditions and health and to analyse the impact of homelessness on children's growth and development, which was never investigated in France. METHODS: A cross-sectional survey was conducted on a random sample of homeless sheltered families in 2013. Families were interviewed in 17 languages and a nurse took anthropometric measures, blood samples and collected health data from child health reports. RESULTS: The population size was estimated at 10 280 families. Half were single-parent female families and 94% were born outside France. Most families had experienced housing instability and 94% were living below the poverty line (828 euros/month). Malnutrition was a major problem: the prevalence of food insecurity was high (77% of parents and 69% of children), as well as anaemia (50% of mothers and 38% of children), overweight (38% of mothers and 22% of children) and obesity (32% of mothers and 4% of children). High rates of depressive disorders were found in 30% of homeless mothers and 20% of children had signs of possible mental health disorders. DISCUSSION: These first results highlight the important number of families among the homeless population in Paris region. Families differed from other homeless people regarding social characteristics such as birthplace, single-parent status and residential instability that are likely to influence schooling, social ties, health and access to care. These results demonstrate the need for urgent actions targeting homeless families, in terms of reducing housing instability and providing adequate care, especially for children.

[Clinical recommendations for sport practice in diabetic patients (RECORD Guide). Diabetes Mellitus Working Group of the Spanish Society of Endocrinology and Nutrition (SEEN)]. / Recomendaciones clínicas para la práctica del deporte en pacientes con diabetes mellitus (Guía RECORD). Grupo de Trabajo de Diabetes Mellitus de la Sociedad Española de Endocrinología y Nutrición (SEEN).

UNLABELLED: Sporting activity is becoming a common practice in patients with diabetes mellitus (DM). This situation requires both a preliminary medical assessment and a wide range of changes in treatment which have scarcely been addressed in medical literature. OBJECTIVE: To prepare a clinical guideline on the medical approach to patients with diabetes who practice sport regularly. METHODS: An expert panel from the Diabetes Mellitus Working Group of the Spanish Society of Endocrinology and Nutrition (SEEN) reviewed the most relevant literature in each of the sections. Based both on this review and on data from the experience of a number of athletes with DM, a number of recommendations were agreed within each section. Finally, the Working Group and representatives of the SEEN jointly discussed all these recommendations. CONCLUSION: The guideline provides recommendations ranging from medical assessment before patients with DM start to practice sport to actions during and after physical activity. Recommendations are also given on aspects such as the impact of sport on blood glucose control, training schemes, or special risk situations.

Food insecurity, a determinant of obesity? - an analysis from a population-based survey in the Paris metropolitan area, 2010.

OBJECTIVE: The relationship between food insecurity and obesity is discussed in the literature. The objective of this study was to determine whether food insecurity and obesity were associated in the Paris metropolitan area. METHODS: We used data from third wave of the Health, Inequalities and Social Ruptures (SIRS) cohort study, a longitudinal population-based, representative health and socioepidemiological survey of the general population in the Paris metropolitan area. The participants' BMI (calculated using self-reported height and weight) was analyzed as a continuous variable, and a dichotomous variable (BMI < 30 kg/m(2)/BMI ≥ 30 kg/m(2)) was constructed. Food insecurity was estimated using the Household Food Security Scale Module (HFSSM) and was treated as a trichotomous variable (food security / low food security / very low food security). Multilevel models were estimated for men and women separately. RESULTS: Obesity (BMI ≥ 30 kg/m(2)) prevalence was 10.2%. The determinant of obesity differs according to gender. After adjustment for age, income and the sociooccupational group, very low food security was associated with obesity in women (OR = 2.01, 95%CI 1.05-3.82), and women with very low food security had a higher BMI (Coef. = 1.78, 95% CI 0.24-3.31). This association, however, was not significant for men (OR = 1.84, 95%CI 0.64-5.30). CONCLUSION: In times of economic crisis, it is increasingly essential to explore and understand the pathway through which very low food security is linked to obesity.