The Epidemiology of Cognitive Impairment in the Aging Population: Implications for Hearing Loss.

Cognitive impairment and dementia are characterized by a progressive and devastating reduction in most cognitive abilities, functional independence, and social relationships. Dementia represents a substantial financial burden on society, one that is comparable to the financial burden of heart disease and cancer. Due to its insidious onset, cognitive impairment can be clinically silent for several years; therefore, diagnosis occurs late in the disease process, and treatment becomes almost useless. The identification of predictors of dementia may help identify the pathophysiological mechanisms underlying the disease and lead to the development of a more effective medical diagnosis and therapy, and thus an early treatment. Review of the literature suggests that in those individuals with less cognitive impairment (normal/predementia group), hearing loss has an association with language comprehension, and when cognitive impairment increases (moderate or severe dementia group), the contributing effect of hearing loss as a cognitive ability-impairing factor also increases. Greater understanding of the links between hearing impairment and cognition may have important implications for the screening and diagnosis of cognitive decline in older people with hearing impairment.

Copeptin (CTproAVP), a new tool for understanding the role of vasopressin in pathophysiology.

Arginine vasopressin (AVP) plays a key role in many physiologic and pathologic processes. The most important stimulus for AVP release is a change in plasma osmolality. AVP is also involved in the response and adaptation to stress. Reliable measurement of AVP is hindered by several factors. Over 90% of AVP is tightly bound to platelets, and its estimation is influenced by the number of platelets, incomplete removal of platelets or pre-analytical processing steps. Copeptin (CTproAVP), a 39-aminoacid glycopeptide, is a C-terminal part of the precursor pre-provasopressin (pre-proAVP). Activation of the AVP system stimulates CTproAVP secretion into the circulation from the posterior pituitary gland in equimolar amounts with AVP. Therefore CTproAVP directly reflects AVP concentration and can be used as a surrogate biomarker of AVP secretion. In many studies CTproAVP represents AVP levels and its behavior represents changes in plasma osmolality, stress and various disease states, and shows some of the various physiologic and pathophysiologic conditions associated with increased or decreased AVP. Increased CTproAVP concentration is described in several studies as a strong predictor of mortality in patients with chronic heart failure and acute heart failure. Autosomal polycystic kidney disease (ADPKD) patients have both central and nephrogenic defects in osmoregulation and CTproAVP balance. A possibility raised by these clinical observations is that CTproAVP may serve to identify patients who could benefit from an intervention aimed at countering AVP.

Hearing loss and dementia in the aging population.

For some years, policy makers and medical scientists have both begun to focus more on chronic noncommunicable diseases. It is well known that cardio-cerebrovascular disease, tumors, diabetes, and chronic obstructive pulmonary disease (COPD), are considered areas of major interest in many scientific projects and health programs. The economic impact of cardio-cerebrovascular disease in EU alone is more than EUR 200 billion, while tumors have an impact of EUR 150 billion. The direct and indirect cost of brain disorders exceeds EUR 700 billion a year. Among the brain disorders, the devastating impact of dementia on affected individuals and the burden imposed on their families and society has made prevention and treatment of dementia a public health priority. Interventions that could merely delay the onset of dementia by 1 year would result in a more than 10% decrease in the global prevalence of dementia in 2050. Unfortunately, there are no known interventions that currently have such effectiveness. The manifestations of age-related hearing loss in many older adults are subtle and, thus, hearing loss is often perceived as an unfortunate but inconsequential part of aging. Researchers report that hearing loss seems to speed up age-related cognitive decline. Researchers suggest that treating hearing loss more aggressively could help delay cognitive decline and dementia. Furthermore, there is an increasing interest in better understanding the pathophysiologic correlations between hearing loss and dementia. Hearing loss in older adults, in fact, is associated independently with poorer cognitive functioning, incident dementia, and falls. Further research investigating the basis of this connection as well as the pathomechanism of the two diseases will further our ability to treat dementia.

Hearing loss and cognitive decline in older adults: questions and answers.

The association between hearing impairment, the diagnosis of dementia, and the role of sensory therapy has been proposed for some time, but further research is needed. Current understanding of this association requires the commitment of those experts who can integrate experience and research from several fields to be able to understand the link from hearing to dementia. A workshop whose panelists included experts from many areas, ranging from ear, nose and throat (ENT) to dementia's specialists, was promoted and organized by the Giovanni Lorenzini Medical Science Foundation (Milan, Italy; Houston, TX, USA) to increase the awareness of the relationship between hearing loss and dementia, and included questions and comments following a presentation from the clinical researcher, Frank Lin, who has been evaluating the relationship between hearing loss and cognitive decline since 2009.

Towards the eradication of HPV infection through universal specific vaccination.

BACKGROUND: The Human Papillomavirus (HPV) is generally recognized to be the direct cause of cervical cancer. The development of effective anti-HPV vaccines, included in the portfolio of recommended vaccinations for any given community, led to the consolidation in many countries of immunization programs to prevent HPV-related cervical cancers. In recent years, increasing evidence in epidemiology and molecular biology have supported the oncogenic role of HPV in the development of other neoplasm including condylomas and penile, anal, vulvar, vaginal, and oro-pharyngeal cancers. Men play a key role in the paradigm of HPV infection: both as patients and as part of the mechanisms of transmission. Data show they are affected almost as often as women. Moreover, no screening procedures for HPV-related disease prevention are applied in men, who fail to undergo routine medical testing by any medical specialist at all. They also do not benefit from government prevention strategies. DISCUSSION: A panel of experts convened to focus on scientific, medical, and economic studies, and on the achievements from health organizations' intervention programs on the matter. One of the goals was to discuss on the critical issues emerging from the ongoing global implementation of HPV vaccination. A second goal was to identify contributions which could overcome the barriers that impede or delay effective vaccination programs whose purpose is to eradicate the HPV infection both in women and men. SUMMARY: The reviewed studies on the natural history of HPV infection and related diseases in women and men, the increasing experience of HPV vaccination in women, the analysis of clinical effectiveness vs economic efficacy of HPV vaccination, are even more supportive of the economic sustainability of vaccination programs both in women and men. Those achievements address increasing and needed attention to the issue of social equity in healthcare for both genders.

Considerations for early acute myocardial infarction rule-out for emergency department chest pain patients: the case of copeptin.

The evaluation of patients admitted at the emergency department (ED) for chest pain is challenging and involves many different clinical specialists including emergency physicians, laboratory professionals and cardiologists. The preferable approach to deal with this issue is to develop joint protocols that will assist the clinical decision-making to quickly and accurately rule-out patients with non life-threatening conditions that can be considered for early and safe discharge or further outpatient follow-up, rule-in patients with acute coronary syndrome and raise the degree of alert of the emergency physicians on non-cardiac life-threatening emergencies. The introduction of novel biomarkers alongside the well-established troponins might support this process and also provide prognostic information about acute short-term or chronic long-term risk and severity. Among the various biomarkers, copeptin measurement holds appealing perspectives. The utility of combining troponin with copeptin might be cost-effective due to the high negative predictive value of the latter biomarker in the rule-out of an acute coronary syndrome. Moreover, in the presence of a remarkably increased concentration (e.g., more than 10 times the upper limit of the reference range), to reveal the presence of acute life-threatening conditions that may not necessarily be identified with the use of troponin alone. The aim of this article is to review current evidence about the clinical significance of copeptin testing in the ED as well as its appropriate placing within diagnostic protocols.

2017 Position Paper of the Italian Society for Cardiovascular Prevention (SIPREC) for an Updated Clinical Management of Hypercholesterolemia and Cardiovascular Risk: Executive Document.

The benefits achieved by implementing cardiovascular prevention strategies in terms of reduced incidence of atherosclerotic diseases and mortality are accepted, worldwide. In particular, the clinical management of hypercholesterolemia has a fundamental role for all preventive strategies, both in primary and secondary prevention, at each stage of cardiovascular risk. Since the net clinical benefit of lipid-lowering therapy largely depends on baseline individual cardiovascular risk profile, the assessment of individual risk is essential to establish type and intensity of both preventive and therapeutic strategies. Thus, the real challenge in a setting of clinical practice is not only to identify whom to treat among individuals at low-to-moderate risk, but mostly how much and how long to treat high or very-high risk patients. This manuscript, which reflects concepts and positions that have been published in a more extensive document of the Italian Society for Cardiovascular Prevention (SIPREC), deals with the diagnostic and therapeutic management of patients with dyslipidaemia, with an evidence-based approach adapted and updated from recent guidelines of the European Society of Cardiology and very recent results of randomized clinical trials. The purpose is to suggest a multidimensional and integrated actions aimed at eliminating or minimizing the impact of cardiovascular diseases and their related disabilities and mortality in patients with hypercholesterolemia.

Perspective: Improving Nutritional Guidelines for Sustainable Health Policies: Current Status and Perspectives.

A large body of evidence supports the notion that incorrect or insufficient nutrition contributes to disease development. A pivotal goal is thus to understand what exactly is appropriate and what is inappropriate in food ingestion and the consequent nutritional status and health. The effective application of these concepts requires the translation of scientific information into practical approaches that have a tangible and measurable impact at both individual and population levels. The agenda for the future is expected to support available methodology in nutrition research to personalize guideline recommendations, properly grading the quality of the available evidence, promoting adherence to the well-established evidence hierarchy in nutrition, and enhancing strategies for appropriate vetting and transparent reporting that will solidify the recommendations for health promotion. The final goal is to build a constructive coalition among scientists, policy makers, and communication professionals for sustainable health and nutritional policies. Currently, a strong rationale and available data support a personalized dietary approach according to personal variables, including sex and age, circulating metabolic biomarkers, food quality and intake frequency, lifestyle variables such as physical activity, and environmental variables including one's microbiome profile. There is a strong and urgent need to develop a successful commitment among all the stakeholders to define novel and sustainable approaches toward the management of the health value of nutrition at individual and population levels. Moving forward requires adherence to well-established principles of evidence evaluation as well as identification of effective tools to obtain better quality evidence. Much remains to be done in the near future.

Public health value of universal HPV vaccination.

BACKGROUND: The story of Human Papillomavirus vaccination demands reflection not only for its public health impact on the prophylactic management of HPV disease, but also for its relevant economic and social outcomes. Greater than ever data confirm the efficacy and support the urge for effective vaccination plans for both genders before sexual debut. METHODS: A review of previous experience in gender-restricted vaccination programs has demonstrated a lower effectiveness. Limiting vaccination to women might increase the psychological burden on women by confirming a perceived inequality between genders; and even if all women were immunized, the HPV chain of transmission would still be maintained through men. RESULTS: The cost-effectiveness of including boys into HPV vaccination programs should be re-assessed in view of the progressive drop of the economic burden of HPV-related diseases in men and women due to universal vaccination. The cost of the remarkable increase in anal and oropharyngeal HPV driven cancers in both sexes has been grossly underestimated or ignored. CONCLUSIONS: Steps must be taken by relevant bodies to achieve the target of universal vaccination. The analysis of HPV vaccination's clinical effectiveness vs. economic efficacy are supportive of the economic sustainability of vaccination programs both in women and men. In Europe, these achievements demand urgent attention to the social equity for both genders in healthcare. There is sufficient ethical, scientific, strategic and economic evidence to urge the European Community to develop and implement a coordinated and comprehensive strategy aimed at both genders and geographically balanced, to eradicate cervical cancer and other diseases caused by HPV in Europe. Policymakers must take into consideration effective vaccination programs in the prevention of cancers.

Steps forward in regulatory pathways for acute and chronic heart failure.

A workshop was organized by the Agenzia Italiana del Farmaco (AIFA) to discuss unmet needs and ways forward in the development of medicines in heart failure, their rationale, and cost-effective use. An integrated, multidisciplinary approach, including patients' needs and perspectives, was advocated by all the participants as the way to the most effective treatment regimens. More work is needed for reaching consensus on clinical and functional endpoints, for validating patient reported outcomes and measurements of well-being. Similarly, the integration into the clinical programmes of the health technology assessment/payers perspective, in particular, the evaluation of 'real-life' treatment effectiveness and of health as a value, would help in shifting the development and authorization of medicines from the molecule paradigm to their evaluation in the context of the whole health care regimen. Through this kind of workshop, AIFA is trying to build a template for meetings devoted to debate unmet needs with all stakeholders towards tentative road maps for the future.

Steps forward in regulatory pathways for acute and chronic heart failure.

A workshop was organized by the Agenzia Italiana del Farmaco (AIFA) to discuss unmet needs and ways forward in the development of medicines in heart failure, their rationale, and cost-effective use. An integrated, multidisciplinary approach, including patients' needs and perspectives, was advocated by all the participants as the way to the most effective treatment regimens. More work is needed for reaching consensus on clinical and functional endpoints, for validating patient reported outcomes and measurements of well-being. Similarly, the integration into the clinical programmes of the health technology assessment/payers perspective, in particular, the evaluation of 'real-life' treatment effectiveness and of health as a value, would help in shifting the development and authorization of medicines from the molecule paradigm to their evaluation in the context of the whole health care regimen. Through this kind of workshop, AIFA is trying to build a template for meetings devoted to debate unmet needs with all stakeholders towards tentative road maps for the future.

Translating the basic knowledge of mitochondrial functions to metabolic therapy: role of L-carnitine.

Mitochondria play important roles in human physiological processes, and therefore, their dysfunction can lead to a constellation of metabolic and nonmetabolic abnormalities such as a defect in mitochondrial gene expression, imbalance in fuel and energy homeostasis, impairment in oxidative phosphorylation, enhancement of insulin resistance, and abnormalities in fatty acid metabolism. As a consequence, mitochondrial dysfunction contributes to the pathophysiology of insulin resistance, obesity, diabetes, vascular disease, and chronic heart failure. The increased knowledge on mitochondria and their role in cellular metabolism is providing new evidence that these disorders may benefit from mitochondrial-targeted therapies. We review the current knowledge of the contribution of mitochondrial dysfunction to chronic diseases, the outcomes of experimental studies on mitochondrial-targeted therapies, and explore the potential of metabolic modulators in the treatment of selected chronic conditions. As an example of such modulators, we evaluate the efficacy of the administration of L-carnitine and its analogues acetyl and propionyl L-carnitine in several chronic diseases. L-carnitine is intrinsically involved in mitochondrial metabolism and function as it plays a key role in fatty acid oxidation and energy metabolism. In addition to the transportation of free fatty acids across the inner mitochondrial membrane, L-carnitine modulates their oxidation rate and is involved in the regulation of vital cellular functions such as apoptosis. Thus, L-carnitine and its derivatives show promise in the treatment of chronic conditions and diseases associated with mitochondrial dysfunction but further translational studies are needed to fully explore their potential.

Assessment of nutritional profiles: a novel system based on a comprehensive approach.

The prevalence of non-communicable diseases (for example, cardiovascular disorders, type 2 diabetes and cancer) is rampant in Western societies, accounting for approximately 60 % of all causes of death. A large proportion of non-communicable diseases can be prevented through appropriate diets and lifestyles. Accordingly, several health authorities and regulatory bodies are assessing the nutritional profiles of food items and whole diets, to implement guidelines aimed at improving the diet of the general population. While a global approach is desirable, the need of individuals to maintain their distinct dietary habits must also be taken into account. The portion sizes of food as well as pattern of food consumption, for example during or between the main meals, are very important in determining the nutritional profile of a diet. A novel method to assess the nutritional profile of foods is being proposed and made available on-line. Its main innovative aspects are (1) the comprehensive manner with which the system analyses and computes a great range of features of individual food items and (2) the distinction among eating occasions, namely during or in-between the main meals. Moreover, this approach allows for rapid modification and great flexibility to suit individual needs and gastronomic habits.