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Elena Milanesi,1 Gina Manda,1 Maria Dobre,1 Elena Codrici,1 Ionela Victoria Neagoe,1 Bogdan Ovidiu Popescu,1– 3 Ovidiu Alexandru Bajenaru2,4 †, Luiza Spiru,2,5 Catalina Tudose,2,6 Gabriel-Ioan Prada,2,7 Eugenia Irene Davidescu,2,3 Gerard Piñol-Ripoll,8 Antonio Cuadrado1,9– 12 1“Victor Babes” National Institute of Pathology, Bucharest, 050096, Romania; 2Clinical Neurosciences, Geriatrics and Gerontology Departments, “Carol Davila” University of Medicine and Pharmacy, Bucharest, 020021, Romania; 3Neurology Department, Clinical Hospital Colentina, Bucharest, 020125, Romania; 4Neurology Department, University Emergency Hospital, Bucharest, 050098, Romania; 5The Excellence Memory Center and Longevity Medicine, “Ana Aslan” International Foundation,, Bucharest, 050064, Romania; 6Section II, “Prof. Dr. Al. Obregia” Psychiatry Clinical Hospital & the Memory Center of the Romanian Alzheimer Society, Bucharest, 041914, Romania; 7Section IV, “Ana Aslan” National Institute of Gerontology and Geriatrics, Bucharest, 011241, Romania; 8Unitat Trastons Cognitius, Hospital Universitari Santa Maria-IRBLLeida, Lleida, 25198, Spain; 9Department of Endocrine Physiology and Nervous System, Instituto de Investigaciones Biomédicas “Alberto Sols” UAM-CSIC, Madrid, 28029, Spain; 10Department of Biochemistry, Faculty of Medicine, Autonomous University of Madrid, Madrid, 28049, Spain; 11Neuroscience Section, Instituto de Investigación Sanitaria La Paz (IdiPaz), Madrid, 28046, Spain; 12Centro de Investigación Biomédica en Red Sobre Enfermedades Neurodegenerativas (CIBERNED), ISCIII, Madrid, 28031, Spain†Prof. Ovidiu A. Bajenaru passed away on 03.09.2020Correspondence: Gina Manda“Victor Babes” National Institute of Pathology, 99-101 Splaiul Independentei, Bucharest, 050096, RomaniaTel +40 744246887Fax +40 21 3194528Email gina.manda@gmail.comAntonio CuadradoInstituto de Investigaciones Biomédicas “Alberto Sols” UAM-CSIC, C/Arturo Duperier 4, Madrid, 28029, SpainTel +34 638 29 65 85Fax +34 915 85 44 01Email antonio.cuadrado@uam.esPurpose: Chronic low-grade inflammation and oxidative stress are present in most of the pathologic mechanisms underlying non-communicable diseases. Inflammation and redox biomarkers might therefore have a value in disease prognosis and therapy response. In this context, we performed a case–control study for assessing in whole blood the expression profile of inflammation and redox-related genes in elderly subjects with various comorbidities.Patients and Methods: In the blood of 130 elderly subjects with various pathologies (cardiovascular disease, hypertension, dyslipidemia including hypercholesterolemia, type 2 diabetes mellitus), kept under control by polyvalent disease-specific medication, we investigated by pathway-focused qRT-PCR a panel comprising 84 inflammation-related and 84 redox-related genes.Results: The study highlights a distinctive expression profile of genes critically involved in NF-κB-mediated inflammation and redox signaling in the blood of patients with cardiovascular disease, characterized by significant down-regulation of the genes NFKB2, NFKBIA, RELA, RELB, AKT1, IRF1, STAT1, CD40, LTA, TRAF2, PTGS1, ALOX12, DUOX1, DUOX2, MPO, GSR, TXNRD2, HSPA1A, MSRA, and PDLIM1. This gene expression profile defines the transcriptional status of blood leukocytes in stable disease under medication control, without discriminating between disease- and therapy-related changes.Conclusion: The study brings preliminary proof on a minimally invasive strategy for monitoring disease in patients with cardiovascular pathology, from the point of view of inflammation or redox dysregulation in whole blood.Keywords: aging-related diseases, cardiovascular disease, inflammation, NF-κB signaling, redox metabolism, oxidative stress

Influenza affects millions globally each year, often causing severe complications, hospitalizations, and deaths, particularly among the elderly. As the global population ages, infections will pose a growing health risk. Annual vaccination remains the most effective way to prevent influenza and its complications. After the age of 65, people suffering from chronic diseases become the majority of this population category. All the data support that most of the population over 65 years old, whose immune system goes through immunosenescence, presents multimorbidity, requiring age-appropriate anti-influenza protection. The immune response to the traditional influenza vaccine has been proven to be lower in the elderly, highlighting the need for a more immunogenic vaccine specifically tailored to the elderly population group. Therefore, high-dose (HD) influenza vaccines have demonstrated their safety and are more effective in preventing influenza and its associated complications compared to standard-dose (SD) vaccines in the elderly in the context of immunosenescence. These recommendations focus on the safety, effectiveness, and efficacy of HD influenza vaccines, adapted to the elderly and available on the Romanian market, to increase the vaccination rate and, thus, protect against influenza infection and its complications. Therefore, strategies such as increased accessibility and free immunizations, as well as ensuring that flu vaccines for the elderly are prescribed without restrictions based on the number of comorbidities, should be used., Competing Interests: The authors declare no conflicts of interest., (© 2024 The Author(s).)

Background/Objectives : Vitamin B12 deficiency can cause variable symptoms, which may be irreversible if not diagnosed and treated in a timely manner. We aimed to develop a widely accepted expert consensus to guide the practice of diagnosing and treating B12 deficiency. Methods : We conducted a scoping review of the literature published in PubMed since January 2003. Data were used to design a two-round Delphi survey to study the level of consensus among 42 experts. Results : The panelists agreed on the need for educational and organizational changes in the current medical practices for diagnosing and treating B12 deficiency. Recognition of clinical symptoms should receive the highest priority in establishing the diagnosis. There is agreement that the serum B12 concentration is useful as a screening marker and methylmalonic acid or homocysteine can support the diagnosis. Patient lifestyle, disease history, and medications can provide clues to the cause of B12 deficiency. Regardless of the cause of the deficiency, initial treatment with parenteral B12 was regarded as the first choice for patients with acute and severe manifestations of B12 deficiency. The use of high-dose oral B12 at different frequencies may be considered for long-term treatment. Prophylactic B12 supplementation should be considered for specific high-risk groups. Conclusions : There is a consensus that clinical symptoms need to receive more attention in establishing the diagnosis of B12 deficiency. B12 laboratory markers can support the diagnosis. The severity of clinical symptoms, the causes of B12 deficiency, and the treatment goals govern decisions regarding the route and dose of B12 therapy.

Introduction: Currently, surgeons deal with an older patient cohort, confronting new challenges brought by the raised life expectancy. This population is unrepresented in surgical trials; therefore, the optimal therapy is still a matter of debate. The efficacy of open versus minimal invasive management of colorectal cancer (CRC) in an elderly cohort is not clearly established. The current study assesses the minimal invasive approach in elderly patients undergoing colorectal surgery. Material and Methods: The General Surgery Department database was inquired between 2012 and 2015 using the following filters: age â?¥ 65 and rectal or colon adenocarcinoma. After applying the exclusion criteria, 975 cases were obtained: 842 underwent open surgery (OS) and 133 underwent minimal invasive surgery (MIS). A propensity score matching was performed to reduce patient selection bias. Results: After the propensity score matching, the MIS group had a shorter postoperative hospital stay than the OS group (p = 0.025). From the preoperative variables, the presence of chronic lung disease was significantly higher in the OS group (p = 0.039). The presence of chronic lung disease positively associates with the Clavien-Dindo classification (p 0.001) and with the number of days from surgery to discharge (p = 0.028). Conclusion: The chronological age alone should not be a limit to MIS granting that it showed no inferiority to the OS in terms of postoperative morbidity, correlating with lower postoperative stay in the elderly. Further prospective studies are needed to assess the outcome of MIS in elderly population., (Celsius.)

Despite the significant consequences for medical practice and public health, burnout in healthcare workers remains underestimated. Pandemic periods have increased the reactivity to stress by favoring some changes whose influence are still felt., Purpose: This study aims to identify opportune factors during pandemic periods that predispose medical personnel to burnout and the differences between medical staff which worked with COVID-19 patients and those who did not work with COVID-19 patients., Material and Methods: This is a prospective study on 199 subjects, medical staff and auxiliary staff from national health units, COVID-19 and non-COVID-19, who answered questions using the Google Forms platform about the level of stress related to the workplace and the changes produced there. All statistical analyses were conducted using IBM SPSS Statistics (Version 28)., Results: The limited equipment and disinfectant solutions from the lack of medical resources category, the fear of contracting or transmitting the infection from the fears in relation to the COVID-19 pandemic category and the lack of personal and system-level experience in combating the infection due to the lack of information on and experience with COVID-19 were the most predisposing factors for burnout. No significant differences were recorded between those on the front line and the other healthcare representatives., Conclusions: The results of this study identify the stressors generated in the pandemic context with prognostic value in the development of burnout among medical personnel. At the same time, our data draw attention to the cynicism or false-optimism stage of burnout, which can mask a real decline.

The vINCI technology represents an innovative instrument developed specifically but not exclusively for older adults by technology researchers together with a medical team specialized in geriatrics and gerontology. It was designed to be independently and effortlessly used by older adults in the comfort and safety of their own environment. It is a modular and flexible platform that can integrate a large array of various sensors and can easily adapt to specific healthcare needs. The pilot study tested sensors and standardized instruments capable of evaluating several care-related parameters and of generating personalized feedback for the user dedicated to optimizing physical activity level, social interaction, and health-related quality of life. Moreover, the system was able to detect and signal events and health-related aspects that would require medical assistance. This paper presents how the innovative vINCI technology improves quality of life in older adults. This is evidenced by the results obtained following the clinical validation of the vINCI technology by older adults admitted to the Ana Aslan National Institute of Gerontology and Geriatrics (NIGG) in Bucharest.

Background: Quality of life (QOL) is a complex concept known for being influenced by socio-demographic characteristics, individual needs, perceptions and expectations. The study investigates influences of such heterogeneous variables and aims to identify and describe subgroups of older patients who share similar response patterns for the four domains (physical health, psychological health, social relationships and environment) of World Health Organization Quality of Life instrument, Short Form (WHOQOL-BREF)., Methods: The sample used included older Romanian patients (N = 60; equal numbers of men and women; mean age was 71.95, SD = 5.98). Latent Profile Analysis (LPA) was conducted to explore quality of life profiles with the four WHOQOL-BREF domains as input variables. Differences between profiles were analysed by MANOVA and ANOVAs as a follow-up., Results: The LPA results showed that the three-profile model was the most suitable and supported the existence of three distinct QOL profiles: low and very low (28.3%), moderate (63.3%) and high (8.4%). The relative entropy value was high (0.86), results pointed to a good profile solution and the three profiles differed significantly from one another., Conclusion: Our results reveal heterogeneity within the older adult sample and provide meaningful information to better tailor QOL improvement programs to the needs of older patient groups, especially those designed for patients of profiles related to poorer QOL in different domains., (© 2022. The Author(s).)

Purpose: To present an insight of the situation of geriatric medicine in Balkan countries, as it was presented in the context of the 2nd pre-congress seminar of the 16th European Geriatric Medicine Society (EuGMS) Congress Athens 2021., Methods: Representatives from 8 Balkan countries (Albania, Croatia, Greece, Republic of North Macedonia, Romania, Serbia, Slovenia, Turkey) answered 3 questions to reflect the state of geriatric medicine in their country: education on geriatrics; systems/methods for assessment of functional status and frailty; pre-operative risk assessment. An open discussion followed., Results: Undergraduate education in geriatric medicine seems underestimated in medical faculties of Balkan countries, whereas a high heterogeneity is observed at a post-graduate level. Only a few Balkan countries have geriatric medicine as a recognized medical specialty or subspecialty. Functional status and frailty are only sporadically assessed, and pre-operative risk assessment is very rarely performed with a geriatric focus. Scarcity of expertise and structures relevant to geriatric medicine seems to be common. Developing a training curriculum and geriatrics-related structures are two interconnected aspects. Cooperation among physicians and multidisciplinary teams are essential for the practice of geriatric medicine. A functional geriatric network is eventually necessary and ambulatory geriatric expertise is probably a feasible and clinically relevant starting point. Providing pragmatic solutions to the pressing challenges in variable clinical settings, supplementing and working in harmony with existing components of each health system, is probably the most convincing strategy to gain political support in developing geriatric medicine., Conclusion: Balkan countries share common experiences and challenges in developing geriatrics. Whilst the principles of geriatric medicine are perhaps universal, proposed solutions should be adapted to each country's specific circumstances. Cooperation of the Balkan countries could promote in each the development of geriatric medicine. EuGMS is willing to foster relevant actions.

Objectives: Interventions to increase fruit and vegetable intake among community-dwelling older people have shown mixed effects. We investigated whether an intervention based on an initial multidimensional health risk assessment and subsequent physician-lead nutrition counselling has favourable effects on dietary intake among community-dwelling older people., Design: Randomised controlled trial comparing the intervention versus usual care., Setting and Participants: Non-disabled persons aged 65 years or older at an ambulatory geriatric clinic in Bucharest, Romania, allocated to intervention (n=100) and control (n=100) groups., Intervention: Participants received a computer-generated health profile report based on answers to a health risk assessment questionnaire, followed by monthly individual counselling sessions with a geriatrician on topics related to health promotion and disease prevention, with a special focus on adequate fruit and vegetable consumption., Measurements: Fruit and vegetable intake at baseline and at 6-month follow-up., Results: At baseline, fruit and vegetable intake was below the recommended five portions per day in most study participants (85% in the intervention group, and 86% among controls, respectively). At six months, intake increased in the intervention group from a median of 3.8 to 4.6 portions per day, and decreased in the control group due to a seasonal effect from a median of 3.8 to 3.1 portions per day. At six months, fruit and vegetable consumption was significantly higher among persons in the intervention group as compared to controls (median difference 1.4 portions per day, 95% confidence interval 1.1-1.7, p<0.001)., Conclusion: Personalised food-based dietary guidance, delivered as part of multidimensional preventive health counselling during geriatric clinic visits, results in relevant improvement of fruit and vegetable intake in community-dwelling older adults., Competing Interests: The authors have no financial or personal conflicts to disclose.

Background: the European Union of Medical Specialists (UEMS-GMS) recommendations for training in Geriatric Medicine were published in 1993. The practice of Geriatric Medicine has developed considerably since then and it has therefore become necessary to update these recommendations., Methods: under the auspices of the UEMS-GMS, the European Geriatric Medicine Society (EuGMS) and the European Academy of Medicine of Ageing (EAMA), a group of experts, representing all member states of the respective bodies developed a new framework for education and training of specialists in Geriatric Medicine using a modified Delphi technique. Thirty-two expert panel members from 30 different countries participated in the process comprising three Delphi rounds for consensus. The process was led by five facilitators., Results: the final recommendations include four different domains: 'General Considerations' on the structure and aim of the syllabus as well as quality indicators for training (6 sub-items), 'Knowledge in patient care' (36 sub-items), 'Additional Skills and Attitude required for a Geriatrician' (9 sub-items) and a domain on 'Assessment of postgraduate education: which items are important for the transnational comparison process' (1 item)., Conclusion: the current publication describes the development of the new recommendations endorsed by UEMS-GMS, EuGMS and EAMA as minimum training requirements to become a geriatrician at specialist level in EU member states., (© The Author(s) (2019). Published by Oxford University Press on behalf of the British Geriatrics Society.)

Insulin and leptin have an overlapping anorexigenic action as well as opposite effects on glucose and lipid metabolism. The study focuses on the biochemical and clinical relevance of new indices of insulin-leptin axis utilized in the study of the relationships between leptinemia, insulin sensitivity and oxidative stress, in elderly subjects with metabolic syndrome. We conducted clinical studies on elderly people with metabolic syndrome versus control subjects by creating new insulin-adipogenic indices, namely Insulin-to-Leptin Ratio (ILR) and Insulin-Adipogenic Resistance index (IAR-index). Inflammation and oxidative stress biomarkers evaluated were the high-sensitivity C-reactive protein (hsCRP), the advanced oxidation protein products (AOPP), and the serum antioxidant capacity measured as ferric reducing antioxidant potential (FRAP). The metabolic syndrome group showed significantly (p<0.01) lower levels of ILR and not significant (p=0.09) higher values of IAR-index, as compared to the control group. In metabolic syndrome subjects, the IAR-index was significantly positively correlated with uric acid (r=0.313, p<0.05), FRAP (r=0.347, p<0.05) and AOPP (r=0.677, p<0.01), and negatively correlated with HDL-cholesterol (r=- 0.340, p<0.05) as well as with the ratio FRAP/uric acid (r=- 0.315, p<0.05). ILR and IAR-index reflected the biological state of adipose and pancreatic β-cells and seem to depict the adipo-insular axis status related to metabolic and oxidative stress better than individual markers. Therefore, ILR and IAR-index could represent integrated high-potential biomarkers for disease and patient stratification., Competing Interests: The authors declare that they have no conflict of interest., (© Georg Thieme Verlag KG Stuttgart · New York.)

Objective: The aim of this study was to evaluate the relationships between the serum levels of adiponectin and systemic oxidative stress exerted on lipids, proteins, as well as endothelial function and cardiovascular diseases (CVD) risk markers, in elderly subjects with metabolic syndrome (MS)., Methods: The serum advanced glycation and oxidation protein products, low-density lipoprotein susceptibility to oxidation (oxLDL), nitric oxide metabolic pathway products (NOx), serum lipid peroxidation, as well as total antioxidant/oxidative capacity (TAC/TOC), were analyzed in elderly subjects with MS (n = 44), compared to aged-matched control (n = 39)., Results: We pointed out significantly lower levels of adiponectin in elderly MS subjects concomitantly with significantly higher levels of oxidative stress and CVD risk markers. Significant positive correlations were found between serum adiponectin levels and HDL-cholesterol (p < 0.05) and the total cholesterol/LDL-cholesterol ratio (p < 0.01). Additionally, adiponectin levels were significantly inversely associated with insulin resistance index (HOMA-IR, r = -0.348; p < 0.05) and serum lipid peroxidation (r = -0.337; p < 0.05), and significantly positively with the antioxidant capacity (TAC, r = 0.339; p < 0.05). Conversely, adiponectin levels were significantly negatively (r = -0.310; p < 0.05) associated with serum uric acid concentration., Conclusions: The major protective role of adiponectin versus stress related to an impaired glucose and lipid metabolism suggests that adiponectin plays a critical role in adiposity-related metabolic stress and redox homeostasis.

Background: Interventions to increase physical activity (PA) among older community-dwelling adults may be enhanced by using multidimensional health risk assessment (HRA) as a basis for PA counselling., Methods: The study was conducted among nondisabled but mostly frail persons 65 years of age and older at an ambulatory geriatric clinic in Bucharest, Romania. From May to July 2014, 200 participants were randomly allocated to intervention and control groups. Intervention group participants completed an initial HRA questionnaire and then had monthly counselling sessions with a geriatrician over a period of six months that were aimed at increasing low or maintaining higher PA. Counselling also addressed the older persons' concomitant health risks and problems. The primary outcome was PA at six months (November 2014 to February 2015) evaluated with the International Physical Activity Questionnaire., Results: At baseline, PA levels were similar in intervention and control groups (median 1089.0, and 1053.0 MET [metabolic equivalent of task] minutes per week, interquartile ranges 606.0-1401.7, and 544.5-1512.7 MET minutes per week, respectively). Persons in the intervention group had an average of 11.2 concomitant health problems and risks (e.g., pain, depressive mood, hypertension). At six months, PA increased in the intervention group by a median of 180.0 MET minutes per week (95% confidence interval (CI) 43.4-316.6, p = 0.01) to 1248.8 MET minutes per week. In the control group, PA decreased by a median of 346.5 MET minutes per week (95% CI 178.4-514.6, p<0.001) to 693.0 MET minutes per week due to a seasonal effect, resulting in a difference of 420.0 MET minutes per week (95% CI 212.7-627.3, p< 0.001) between groups., Conclusion: The use of HRA to inform individualized PA counselling is a promising method for achieving improvements in PA, and ultimately health and longevity among large groups of community-dwelling older persons., Trial Registration: International Standard Randomized Controlled Trial Number: ISRCTN11166046.

Background: Dementia is one of the most disabling conditions associated with old age. With increasing life expectancy, prevalence of both dementia and diabetes is rising. The complex pathological relationship between diabetes mellitus (DM) and dementia has been studied, but is not yet fully understood., Aims: The main objective of this study was to investigate the relationship between metabolic parameters and the cognitive function in older diabetics., Methods: A total number of 360 diabetic subjects, age 65 years and over, and 300 older people controls were included. Clinical and biological parameters, together with the cognitive function, were assessed every 6 months over a 18-month period, for each study participant., Results: By employing a multivariate linear regression analysis, several significant relationships have been identified: between Clock Drawing Test (CDT) scores and HbA1c (R 2  = 0.68); between CDT scores (R 2  = 0.51) and overall MMSE scores (R 2  = 0.43) on one hand, and DM duration in years, on the other hand; also between CDT scores and BMI (R 2  = 0.59). There was no significant association between fasting serum glucose (FSG), total serum cholesterol, LDL cholesterol or triglycerides levels and cognitive function scores (p > 0.05)., Conclusions: The close detailed monitoring of the cognitive function and a rigorous metabolic control are important, especially in the very early stages of DM. Addressing factors such as weight control in older diabetic patients could contribute to better cognitive outcomes.

Oxidized LDL (oxLDL) and nitric oxide (NO) exert contradictory actions within the vascular endothelium microenvironment influencing key events in atherogenesis. OxLDL and NO are so far regarded as representative parameters of oxidative stress and endothelial dysfunction, new targets in prevention, diagnosis and therapy of cardiovascular diseases, and also as candidate biomarkers in evaluating the human biological age. The aim of this review is to explore recent literature on molecular mechanisms and pathophysiological relationships between LDL oxidation, NO synthesis and vascular endothelium function/dysfunction in ageing, focusing on the following aspects: (1) the impact of metabolic status on both LDL oxidation and NO synthesis in relation with oxidative stress, (2) the use of oxidized LDL and NO activity as biomarkers in human studies reporting on cardiovascular outcomes, and (3) evidences supporting the importance of oxidized LDL and NO activity as relevant biomarkers in vascular ageing and age-related diseases., (Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.)

Background and Aims: Vitamin D deficiency has been identified in the elderly as a potential risk factor for cardiovascular disease development, possibly through its association with other risk factors, such as type 2 diabetes mellitus (T2DM), hypercholesterolemia and hypertension. The aim of this cross-sectional study was to evaluate the vitamin D status in elderly subjects with impaired fasting glucose (IFG) or T2DM, and to examine its relationships to systemic oxidative stress and biochemical markers of endothelial dysfunction., Methods: Serum 25-hydroxyvitamin D [25(OH)D], fasting glucose, insulin, lipid profile, advanced glycation end products (AGEs), advanced oxidation protein products (AOPPs), low-density lipoprotein susceptibility to oxidation (oxLDL) and nitric oxide metabolic pathway products (NOx) were analyzed in elderly subjects with IFG (n=30) and T2DM (n=35) compared with aged-matched controls (n=25)., Results: 25(OH)D levels in the IFG and T2DM groups were significantly lower than in controls (31.9±1.9 and 28.5±1.9 vs 39.4±2.4 ng/mL, p<0.001), and associated with significantly (p<0.001) higher levels of the oxidative stress parameters AGEs, AOPPs, oxLDL and NOx. Hypovitaminosis D [25(OH)D)<30 ng/ml] markedly enhanced the oxidative stress and cardiovascular risk in hyperglycemic subjects compared with sufficient vitamin D [25(OH)D)≥30 ng/mL] status subjects. In subjects with IFG and T2DM (n=65), the vitamin D status was significantly inversely correlated both with oxLDL (r=-0.413, p=0.001) and AOPPs (r=-0.475, p<0.001), and strongly positively associated with highdensity lipoprotein cholesterol (r=0.609, p<0.001)., Conclusions: In the elderly with impaired glucose metabolism the vitamin D status is inversely associated with levels of circulating markers of oxidative stress and endothelial dysfunction, especially in subjects with hypovitaminosis D.

Background: There has been concern about under-representation of older people in clinical trials. The PREDICT study reported that older people and those with co-morbidity continue to be excluded unjustifiably from clinical trials. However, there is no information about differences of opinion on these issues between EU countries. The results of a survey of health-related professionals from nine EU countries that participated in the PREDICT study are presented in this study., Objective: The aim of the study was to identify and examine any differences of opinion between EU countries on the inclusion of older patients in clinical trials., Methods: A questionnaire using a Likert scale and free text was completed by 521 general practitioners, geriatricians, clinical researchers, ethicists, nurses and industry pharmacologists/pharmacists. The questions explored the impact of the present situation, possible reasons for under-representation and potential methods of improving participation. Countries participating were the Czech Republic, Israel, Italy, Lithuania, the Netherlands, Poland, Romania, Spain and the UK., Results: There was agreement that exclusion from clinical trials on age grounds alone was unjustified (87%) and that under-representation of older people in trials caused difficulties for prescribers (79%) and patients (73%). There were national differences between professionals. All but the Lithuanians believed that older people were disadvantaged because of under-representation. The Czech, Lithuanian and Romanian professionals felt that it was justified to have age limits based on co-morbidity (61-83%) and polypharmacy (63-85%). Romanians also thought that having age limits on trial participation was justified because of reduced life expectancy (62%) and physical disability (58%) in older people. All but the Romanian professionals felt that the present arrangements for clinical trials were satisfactory (62%). All but the Israelis (56%) and Lithuanians (70%) agreed that regulation of clinical trials needed alteration., Conclusions: Although respondent selection bias cannot be excluded, the differences that emerged between countries may be the result of the political and healthcare-system differences between older and newer members of the EU. These differences may influence decision making about clinical trial regulations and practice in older people.

Background: Much clinical research of relevance to elderly patients examines individuals who are younger than those who have the disease in question. A good example is heart failure. Therefore, we investigated the extent of exclusion of older individuals in ongoing clinical trials regarding heart failure., Methods: In the context of the Increasing the PaRticipation of the ElDerly in Clinical Trials (PREDICT) study, data from ongoing clinical trials regarding heart failure were extracted from the World Health Organization Clinical Trials Registry Platform on December 1, 2008. Main outcome measures were the proportion of trials excluding patients by an arbitrary upper age limit or by other exclusion criteria that might indirectly cause limited recruitment of older individuals. We classified exclusion criteria into 2 categories: justified or poorly justified., Results: Among 251 trials investigating treatments for heart failure, 64 (25.5%) excluded patients by an arbitrary upper age limit. Such exclusion was significantly more common in trials conducted in the European Union than in the United States (31/96 [32.3%] vs 17/105 [16.2%]; P = .007) and in drug trials sponsored by public institutions vs those by private entities (21/59 [35.6%] vs 5/36 [13.9%]; P = .02). Overall, 109 trials (43.4%) on heart failure had 1 or more poorly justified exclusion criteria that could limit the inclusion of older individuals. A similar proportion of clinical trials with poorly justified exclusion criteria was found in pharmacologic and nonpharmacologic trials., Conclusion: Despite the recommendations of national and international regulatory agencies, exclusion of older individuals from ongoing trials regarding heart failure continues to be widespread.

The present paper makes a contribution to the study of the multidimensional variational network of the human gerontogenesis (G. Acălugăritei, 1993-1995). In this respect was rendered evident the variation of the multiple regression coefficient (R) in relation to four sets of variables, as follows: a set of fundamental variables, a set of variational variables (variation ranks of the R), a set of reference variables (R, aging, blood pressure, sex and ABO genetic system) and a set of relational variables (relations).

Researches concerning the variation of correlation coefficient (r) in man in relation to four sets of variables were carried out, namely: a set of ten fundamental variables (in which the dependent variable is represented by aging), a set of variational variables (variation ranks of the r), a set of reference variables (r, age, blood pressure, sex and ABO genetic system) and a set of relational variables (relations). This research contributes to the study of multidimensional variational network of the human gerontogenesis (G. Acĭlugăritei, 1993-1995).