“The clinical approach characterizing gender medicine is not only interdisciplinary and transversal, covering every branch and specialty, but above all multidimensional. According to a global vision of the concept of health, the provision of appropriate care implies taking charge of the sick ‘person’, evaluated not only with regard to the biological and clinical characteristics of the disease, but also based on all the personal, cultural and social factors that characterize their past experiences, exploring which it is possible to grasp the aspects that distinguish and define the gender, from the management of everyday life, in relation to therapeutic treatments, to the impact of the disease on the relationship between the individual person and their social context”.1 The Plan for the application and dissemination of gender medicine drawn up by the Ministry of Health, envisaged by Law 3/2018 and signed on June 13, 2019, clearly states that the new legislation aims to guarantee the quality and appropriateness of the services to be uniformly provided by the Italian National Health Service (NHS) throughout the national territory. Quality and appropriateness are also the keywords that guide the daily activities of the National Agency for Regional Health Services (Agenas, Agenzia nazionale per i servizi sanitari regionali), which was established in 1993 as a technical-scientific body of the NHS and that, over time, has consolidated in Italy its mission as a point of connection between the central and the regional levels, carrying out research and support activities for the Minister of Health, the Regions and the Autonomous Provinces of Trento and Bolzano in areas concerning the effectiveness of health interventions, as well as the quality, safety and humanization of healthcare. The work of the Agency deals both with the governance of what already exists and with the research activity. The latter cannot focus only on the development of innovative therapies, but must also take into the utmost account the development of more efficient and equitable organizational models; an activity that, on the one hand, should involve all the regional situations of our Country and, on the other, cannot avoid being compared and related with the healthcare systems of other nations, since in most cases the issues and uncertainties affecting the development and implementation of the healthcare programs of comparable Countries are similar. From these interactions, different solutions often arise, in line with the peculiarities of cultures and organizational structures. One of the main missions of Agenas is to be able to interpret, measure and define the best organizational models and, if possible, anticipate problems. Looking at a more sensitive, precise and relevant healthcare research, there is a growing focus on genderoriented medicine. In recent years, extraordinary advances have been made in gender-specific clinical research, and the design and subsequent analyses of the data aimed at investigating gender peculiarities are now part of the cultural background of both methodologists and researchers. Although much has been done, however, there are still many obstacles to overcome, such as, for example, a still perfectible attention to gender in the training of healthcare professionals: the key to highlighting the values expressed by a gender-specific approach in health policies implies the acceleration of a process which, as previously mentioned, can no longer be stopped. As we know – and as also underlined at the opening of the Plan for the application and dissemination of gender medicine – some areas of clinical medicine have developed a greater knowledge and familiarity with this approach than others. In fact, we cannot forget that – while gender has been a leading dimension in the social sciences for many years and has long influenced research – only relatively recently it has begun to enter the lexicon of biomedical and public health researchers. In the latter context, the prospects offered by greater attention to gender are extremely promising. Gender-related experiences are firmly linked to social, political and economic contexts: gender is part of all human interactions, and can also prove to be a determining and “stable” form of inequality.2 Gender-related experiences – and the cultural values connected to them – often translate into socially pre-established gender roles that determine different behaviors, interests, expectations and professional consequences for women and men, with a direct impact on health. Health policies attentive to gender-specific effects can be an instrument to reduce – if not to eliminate – inequalities, to promote equity and to truly restore centrality to the citizen, to the patient and their families. Gender-specific medicine, healthcare system and citizens’ rights
SummaryData from adult studies how that COVID-19 is more severe in men than women. However, no data are available for the pediatric population. For this reason, we performed this study aiming to understand if sex influenced disease severity and outcomes in a large cohort of latin-american children with COVID-19 and Multisystem Inflammatory Syndrome (MIS-C). We found that a higher percentage of male children developed MIS-C (8.9% vs 5% in females) and died (1.2% and 0.4% in females), although on multivariate adjusted analyses the only statistically significant difference was found in need of hospitalization, with females less frequently admitted compared with boys (25.6% vs 35.4%). This data are preliminary and need further independent studies to better assess the role of sex.
In the last and in the current year health research and health research policy had to address the challenges of the COVID-19 pandemic. Given the role of sex and gender in viral infection and disease development, consideration of these variables in COVID-19 research appears imperative. Biological sex can modulate immunological and pharmacological responses;gender-related aspects can impact access to testing and care as well as long-term socioeconomic consequences of the pandemic. In light of these considerations, both European and national research effects have come to address the topic. In the following manuscript we draw on years of study of the incorporation of sex and gender into EU research and innovation. We highlight the supranational approach and its national trickle-down effect using the example of the Netherlands. We provide an overview of implementation steps needed to achieve a thorough incorporation of sex and gender in the research process in an intersectional manner. The illustrated process could be adapted to local European contexts in consideration of their national priorities, political situation and available resources supporting the EU-wide institutionalization of the topic. © 2021, Il Pensiero Scientifico Editore s.r.l.. All rights reserved.
The literature states that a gender-oriented approach ensures better performance and equity in medical care and treatment in several areas, such as prevention, diagnosis, therapy and rehabilitation, thus becoming an instrument of clinical governance. Despite this, the dissemination of gender-related medical culture and practices remains severely inadequate. The lack of knowledge of gender medicine principles is particularly evident in all fields of care. This paper reports the results of a descriptive-phenomenological qualitative study aimed at understanding the healthcare professionals’ level of confidence with gender medicine. The knowledge, opinions, experiences gained, as well as the projects revolving around gender medicine, were investigated through semi-structured interviews involving 16 healthcare professionals with different profiles who work within the Ausl of Bologna.
Background and aim. The BRASS index is a tool used to identify patients at risk of difficult or prolonged hospitalization. The purpose of the study is to analyze whether there are differences in the evaluation of the BRASS index upon admission and upon discharge with regard to sex and to the length of hospital stay (in days). Methods. The BRASS assessment was performed upon admission (T0) and upon discharge (T1) for each participant, according to their sex and age. Statistical differences were evaluated on the basis of sex and the risk associated with the BRASS score. Spearman’s correlations were assessed among all the variables considered. Results. Ninety-five patients (43 males and 52 females) participated in this study. The average age was 80 ± 9 years. The BRASS index at T0 was 12.51 ± 7.66 and at T1 13.91 ± 8.61. The average length of hospitalization was 13 ± 7 days. There were statistically significant differences between the sex and the BRASS index risk assessment at T0 (p <0.001) and also at T1 (p <0.001) according to the sex variable, respectively. Correlations were also statistically significant between: sex and age (p = 0.016), sex and risk assessment both at T0 (p <0.001) and T1 (p <0.001), age and risk assessment both at T0 (p <0.001) and T1 (p <0.001) and age and days of hospitalization (p = 0.005). Conclusions. Data showed a significant increase in the BRASS index for female patients, both at T0 and T1. However, the BRASS assessment did not correlate with the length of hospital stay (in days). Nursing could play an important role in the BRASS assessment, both at T0 and T1, in order to better refer the patient to the most appropriate nursing setting after hospitalization.
The awareness of the need of studying the influence of sex and gender on diseases started to spread in the ’90s but, almost 30 years later, progress in this area is not sufficient to rule out concerns about a possible inequality in medicine. In order to understand the difficulties behind the persisting gap in knowledge, it is important to be aware of the reasons that led to the regular exclusion of women from clinical research. This paper presents a historical reconstruction of the ethical debate about the involvement of women in research: from the protectionist approach of the ’70s to the demands for inclusion of the ’80s and the ’90s. Such reconstruction shows that the main ethical arguments in favour of inclusion, i.e. the principles of beneficence and justice, also justify the need for a gender-specific medicine. The paper discusses some elements that could have hampered the efforts to reduce the male bias, such as the emphasis on the issue of women inclusion in research, instead of the focus on women’s health needs. Moreover, it is argued that a participatory approach to research – i.e. an approach that considers women as partners who can offer a contribution at all levels of biomedical research – is the most effective in order to achieve the goal of including attention to women’s health into the research agenda.
Italy was the first European country hit by the COVID-19 pandemic. As of March 3, 2021, the Italian national surveillance system had registered 2,953,120 cases and 96,977 deaths, with gender differences both in terms of cases and deaths. Therefore, the aim of this observational ecological study is to analyze gender differences during the first year of COVID-19 pandemic in Italy in terms of crude mortality rate (CMR) and case fatality rate (CFR). We collected data from the official database of the Italian National Institute of Health (Istituto Superiore di Sanità – ISS). We considered the two waves of the pandemic, using the date between the two peaks that had the trough (lowest number of deaths) for a 7-day average to separate the two periods). Then, we calculated the CMR and CFR by age group for males and females, considering three periods: overall, first wave and second wave. Our study shows that male gender reported both higher CMR and CFR than female, and this data is confirmed for all the age group. Although many demographic, socioeconom-ic, hormonal, genetic, and epigenetic factors may explain these differences, further studies are required in order to understand the pathophysiological mechanisms underlying gender differences in CMR and CFR due to COVID-19. © 2021, Il Pensiero Scientifico Editore s.r.l.. All rights reserved.
The coronavirus disease 2019 (COVID-19) has rapidly spread all over the world, causing a great number of casualties. From the very beginning of the pandemic, it has become apparent that there are multiple risk factors associated with an increased risk of disease severity and death. These include older age, smoking and several underlying comorbidities, as well as gender.1 Susceptibility for SARS-CoV-2 infection appears to be similar in men and women, and yet most of the clinical and epidemiological data has shown that almost twice as many men with COVID-19 suffer severe symptoms or death as women.2 Despite a similar incidence between the two genders, men consistently show a more severe phenotype and an increased mortality rate (62.4%) across age groups at global level.3 A large population-based study performed in England, which included over 17 million adults and 10,926 COVID-19-related deaths, found that males had a significantly higher risk of death (HR 1.59; 95% CI, 1.53-1.65) than females.4 A recently published review reported that, overall, males account for 59-75% of all COVID-19 deaths.5 Sexual dimorphism in COVID-19 should not come as a surprise, because it is well known that men and women respond to viral infections differently, as already reported during other flu outbreaks.6 Many of the genes playing a key role in the immune response are located on the X chromosome, including those involved in determining the innate and adaptive immune responses to viral infections.7 Interestingly, gene encoding for the ACE2 receptor – through which SARS-CoV-2 binds to the cell membrane and enters the host cell – is also located on the X chromosome, so that a higher degree of protein expression could be expected in the female gender, which may increase the risk of viral infection.8 However, a higher ACE2 activity – particularly in the lungs and in the cardiovascular system – has been claimed to confer some protection, which may account for the less severe form of COVID-19 in women.9 Consistent with this hypothesis is the finding that the male heart has less ACE2-expressing cells than the female one,10 which provides support to a sex-specific regulation of ACE2. Nevertheless, such sex-dependent ACE2 expression has not yet been validated in humans, and no relevant influence of medications such as ACE-inhibitors has been documented. Sex differences in the manifestation of infectious diseases have long been attributed also to the influence of sex hormones. Experimental work performed in a murine model of SARS-CoV-2 infection has shown that male animals were more susceptible to infection and had higher mortality than females. Interestingly, the estrogen deprivation obtained by ovariectomy nullified this protection, causing an increase in mortality.11 These results indicate how the balance between androgens and estrogens is likely to play an important role in modulating immune responses in coronavirus infections. Conversely, men receiving androgen deprivation therapy seem to be protected from SARS-CoV-2 infection, which further supports the concept of sexual dimorphism in response to the SARS-CoV-2 infection.12 A gene expression study on the immune system of mice indicated that this sexual dimorphism is mainly limited to macrophages, with an up-regulation of macrophages-specific genes (eg., complement-related and IFN-stimulated genes) found in female cells.13 Thus, females could show a more activated innate response pathway prior to an infection with a pathogen. Furthermore, TLR7 signaling and IFN production seem to be more expressed in females, while estrogen also increases TLR7 expression. Finally, the immune system has been implicated in driving a detrimental and dysregulated inflammation in COVID-19,14 therefore it may seem counterintuitive that males are at greater risk of COVID-19 hyperinflammation, considering that females have been described to mount stronger immune responses to viral infections. This highlights once again the complexity of the differences between the male and female immune systems, and their responses to infection. In summary, infection rates appear to be similar between men and women, although the response to infection differs between the sexes. It has been suggested that anti-viral responses and viral clearance, mediated by IFN and TLR7, are increased in females, contributing to the reduced COVID-19 mortality observed in women compared with men. In men, dysregulated inflammation and an increased cytokine release are likely to be responsible for the increase in ARDS, respiratory failure Metabolic issues during the COVID-19 pandemic: gender difference
Psoriasis is a chronic multifactorial skin disease, characterized by inflammation and a strong genetic predisposition. The prevalence of psoriasis ranges between 0.4 and 5% worldwide. Psoriasis is often associated with a poor quality of life and high physical and psychosocial burden. Several therapies are now available for the treatment of psoriasis. Patients are treated with different drugs, depending on the severity of disease, as indicated by the PASI (Psoriasis Area Severity Index) score. Mild-to-moderate subjects are usually treated with topical treatments, while moderate-tosevere psoriatic patients often require systemic treatments. Among the systemic drugs, biological therapies have been revolutionizing the treatment of psoriatic patients. These are target-specific drugs, mainly monoclonal antibodies and receptor fusion proteins. Biologics are able to improve therapeutic outcomes, and have a favorable tolerability. Biological therapies used in psoriasis include antagonists of cytokines or their receptors, such as anti-TNF agents, anti-IL12/23, anti-IL17, anti-IL17-receptor, and anti-IL23 antibodies. Biologic agents lead to a significant improvement in symptoms; however, psoriasis remains a condition with no permanent resolution. Thus, innovative mechanisms of action are currently being investigated, in order to identify new possible therapeutic targets. The prevalence of psoriasis among men and women is known to be balanced. However, the severity of the disease can vary between genders: several studies show that, in fact, female patients are less severely affected by psoriasis than males. The median PASI score is often lower in women, regardless of age, thus female patients receive systemic treatments less frequently. However, in many cases women suffer from a greater psychological distress. For all these reasons, physicians should consider gender perspective in the management of psoriatic patients and their comorbidities. No clear differences have been observed in the response to treatment of psoriatic patients, regardless of their lifestyle, race/ethnicity, geographic location or gender. In spite of their higher cost, biologics are currently the treatment of choice of moderate-to-severe psoriatic patients, due to their favorable safety and efficacy profiles.
Hypertension is an important cardiovascular risk factor, and its treatment is undoubtedly effective in reducing the incidence of cardiovascular and renal events in both sexes, as also reaffirmed by the most recent ESC-ESH guidelines. Our knowledge of the hypertension therapy derives from the evidence generated by a large number of controlled clinical studies carried out over the last decades; however, the authors of these studies did not always evaluate the results obtained separately for males and females. After examining the major controlled clinical studies in the field of hypertension therapy, mentioned in the guidelines, our study found that the analysis of the results had taken account of sex in 21 out of 33 cases only. The most recent meta-analyses – which in some cases concern hundreds of thousands of subjects – were then evaluated, noticing that only in a small minority of cases did the analysis of the results take sex into consideration as a variable; significant problems, such as the treatment of hypertension in the elderly or the pressure levels to be reached with treatment, have never been evaluated from a gender perspective. The study does not demonstrate the existence of gender differences, because this was not its objective, but from an extensive analysis of the literature it concludes that the existence of possible gender differences in the context of high blood pressure therapy is not being sufficiently investigated yet.
Dietary supplements are needed when nutritional requirements cannot be met through diet alone. The consumption of supplements is generally recommended in the more vulnerable population groups, such as children, the elderly, and pregnant or lactating women. In the general population, by following a diet as close as possible to that recommended by the guidelines it is possible to easily cover the nutritional needs of the body. Therefore, rather than thinking about gender-specific food supplements, we should promote more the adoption of a balanced diet for both sexes. Data on the use of supplements based on gender differences are not very consistent yet.
