Emanuela Zagni

Sex and Gender Differences in Central Nervous System-Related Disorders

There are important sex differences in the brain that seem to arise from biology as well as psychosocial influences. Sex differences in several aspects of human behavior and cognition have been reported. Gonadal sex steroids or genes found on sex chromosomes influence sex differences in neuroanatomy, neurochemistry and neuronal structure, and connectivity. There has been some resistance to accept that sex differences in the human brain exist and have biological relevance; however, a few years ago, it has been recommended by the USA National Institute of Mental Health to incorporate sex as a variable in experimental and clinical neurological and psychiatric studies. We here review the clinical literature on sex differences in pain and neurological and psychiatric diseases, with the aim to further stimulate interest in sexual dimorphisms in the brain and brain diseases, possibly encouraging more research in the field of the implications of sex differences for treating these conditions.

Clinical experience with daptomycin in Italy: results from a registry study of the treatment of Gram-positive infections between 2006 and 2009

Abstract The purpose of this study was to evaluate post-marketing efficacy and safety data for therapy with daptomycin (DAP) in Italy. Data from patients treated with DAP at 30 centres between January 2006 and July 2009 were analysed according to the protocol of the EU-CORESM. In 359 patients, DAP was most commonly prescribed for skin and skin-structure infections (55%), infective endocarditis (13%), and bacteraemia (12·5%). DAP was associated with rapid improvement, and clinical success rates ranging from 77 to 91%, despite almost half of the patient population being ⩾65 years of age, 86% having significant underlying disease, and many being affected by drug-resistant pathogens. Staphylococcus aureus represented 35% of all pathogens isolated. Success rates for all staphylococcal and enterococcal infections were >80%, including methicillin-resistant S. aureus (MRSA) and methicillin-susceptible S. aureus (MSSA). Clinical outcomes were similar for DAP whether used as first- or second-line therapy. DAP was well tolerated even with prolonged treatment.

Gender differences in the adverse events’ profile registered in seven observational studies of a wide gender-medicine (MetaGeM) project: the MetaGeM safety analysis

Background MetaGeM is a wide gender-medicine project comprising post hoc and meta-analyses by gender of clinical outcomes, therapeutic approaches, and safety data from previously conducted observational studies to explore possible gender differences in real-life clinical settings. We report the results of the safety meta-analysis of seven MetaGeM studies, evaluating gender differences in adverse event (AE) incidence and severity. Methods Data were collected between February 2002 and July 2013. Male and female patients were compared for the main safety variables, using Student’s t-test, χ2 test, or Fisher’s exact test as appropriate. As supportive analysis, a logistic regression model was estimated to evaluate associations between gender and outcome. Results In total, 4,870 patients (46% females, 54% males) were included in the analysis; age was higher for females (mean ± standard deviation 61.2±18.3 years) than males (56.3±16.6 years). Overall, 264 AEs were reported (59.1% in males). There were no significant gender differences in the percentage of patients with at least one AE: 3.0% for females versus 3.9% for males, χ2 test P>0.05. According to the logistic regression model results, no association between gender and AEs occurrence seems to exist. A statistically significant gender difference in the percentage of drug-related AEs emerged (37.6% in females vs 20.8% in males, χ2 P=0.0039). Slightly significantly more AEs in females were addressed with treatment compared with males (78.1% vs 66.7%, χ2 P=0.0485). Total serious AEs (SAEs) were 47 (72% in males). The frequency of patients with ≥1 SAE was 0.6% in females versus 1.2% in males (χ2 test P=0.0246). Conclusion This safety analysis on a large sample of almost 5,000 patients with different diseases and treated with a wide range of different drugs provides a useful overview on possible gender differences in drug tolerability, which may be helpful in more accurately designing future clinical trials from a gender-specific perspective.

A gender-medicine post hoc analysis (MetaGeM) project to test sex differences in previous observational studies in different diseases: methodology

Only recently has medical research begun to understand the importance of taking sex into account, recognizing that symptoms and responses to medical treatment may be very different between males and females. However, the analyses provided by the pharmaceutical industry to regulatory authorities often do not present safety and efficacy data by sex. Novartis has started a gender-medicine project called MetaGeM, which includes nine observational studies sponsored by Novartis Farma, Italy; conducted in Italy between 2002 and 2013 in a range of different clinical areas. The MetaGeM project aims to analyze and describe by means of post hoc analyses and meta-analyses, clinical outcomes, therapeutic approaches, and safety data of these studies, by sex: PSYCHAE; GENDER ATTENTION in psoriasis; Synergy in psoriatic arthritis; ICEBERG in HBsAg carriers; SURF and CETRA in liverand renal transplanted patients, respectively; DEEP in Parkinson’s disease; and EVOLUTION and AXEPT in Alzheimer’s disease. The present paper describes the methodology of the MetaGeM project.

The Cost of Psoriasis in Patients under Conventional Systemic Therapy or Biologic: The Results of a Retrospective Analysis Carried out in an Italian Center

Objective: To present an update of the cost profile of psoriasis in patients with conventional systemic therapy or biologic referring to a Center of the Piedmont Region. Methods: A retrospective, observational cohort study was conducted to estimate the cost of the treatment with conventional systemic therapy or biologic of adult patients with psoriasis referring to an Italian Center. The enrollment window started on July 1, 2017 and ended on January 31, 2018. Each patient identified was followed-up retrospectively for six months. The database collected the main details on demographics, clinical data and resource consumption (treatments administered, visits, blood tests and instrumental examinations, etc.) for each patient enrolled. The PASI index was evaluated to reconstruct the evolution over time of the seriousness of psoriasis for each patient enrolled. Results: 181 patients were considered, 45.9% treated with a biologic and 54.1% with a conventional systemic therapy. During the 6 months follow-up, 2.4% patients with biologic and 11.2% with conventional systemic therapy discontinued the treatment (p=0.0233). At the beginning (baseline) a more compromised disease activity (PASI score) in patients with the biologic emerged (19.8 vs. 13.9; p=0.0005). Twelve months before enrolment the average PASI score showed a substantial overlap (5.9 vs. 5.8; p=0.9375). Upon enrollment patients treated with the biologic reported the lowest mean PASI score (2.7 vs. 3.8; p=0.1127). The 6 months cost of treatment was € 5,675 for biologic and € 321 for conventional systemic therapy (p<0.0001). The cost for the management of psoriasis was significantly higher in patients with moderate-to-severe PASI. Conclusions: The data collected seem to be sufficient to state that psoriasis is a disease with a quite high overall cost for the NHS and/or society, and that, due to its chronicity, such cost is likely to increase with the progression of severity.

Gender Medicine and Pharmacoeconomics: A Narrative Review of the International Literature of the Last 5 Years. A Revision of Evidences about the Relationship Between Gender and Economic Consumption in Health

INTRODUCTION The influence of patient gender on the economic impact of health care has increasingly been examined in the recent literature. Gender appears to have an impact on healthcare resource consumption, due to possible differences in the patients response to a chosen therapeutic management strategy or to a healthcare intervention. OBJECTIVE The present work is aimed at collecting and reviewing evidences about the relationship between gender and economic consumption in health based on worldwide scientific literature published in the last 5 years. METHOD We conducted a narrative review of evidence from an initial pool of 904 articles, selecting information about gender-specific economic impact in any therapeutic area. RESULTS After title, abstract and full text review, 111 articles were relevant to the paper scope. The reviewed studies seem to be confirming that a difference exists between males and females in the economic implications of healthcare management and that those differences are particularly relevant for cardiovascular and metabolic pathologies. Preliminary evidence suggests overall healthcare costs are slightly higher in females than males, while some specific and non-quantitative items of resource consumption, such as quality of prescriptions, might favour male patients. Results do not allow to clearly claiming an overall cost shift towards males or females, since their polarization varies depending on the considered cost item or event category. CONCLUSION Studies suggested the presence of a gender difference in overall healthcare resource consumption and costs. Nevertheless, these aspects still lack thorough examination in literature and further analyses would be required on longer time periods.

Observational analysis of antineoplastic and immunomodulating drug expenditure in two Local Health Units in Northern Italy during the period 2009-2011

Background The past few years, the Italian National Health Service (INHS) has faced the challenge of ensuring sustainable costs for antineoplastic and immunomodulating drugs. The aim of this study was to analyse expenditure trends for these drugs in two Local Health Units during the period 2009-2011. Methods Data for this retrospective study were derived from the administrative databases of two Local Health Units in Northern Italy. A sample was built up by selecting all patients with at least one antineoplastic and immunomodulating drug prescription between 2009 and 2011. The study evaluated the annual, per capita and per user drug expenditure. The antineoplastic and immunomodulating drug expenditure was also analysed by therapeutic indication. Results The number of users (annual mean rate: 12.1%) and the antineoplastic and immunomodulating drug expenditure (annual mean rate: 15.7%) were increased in the three-year period. The mean annual per capita cost was €18.40 in the first year (2009), €22.18 in the second year (2010) and €24.23 in the last year (2011). Taking into account the last year of the analysis (2011), monoclonal antibody drugs showed the highest per capita drug spending (€9.36), followed by TNF-alpha inhibitors (€6.61) and tyrosine kinase inhibitors (€5.75). The highest mean annual expenditure was on cancer drugs (€15,046,773), followed by rheumatoid arthritis (€3,596,925), psoriatic arthritis (€925,510), ankylosing spondylitis (€626,050) and psoriasis (€622,332). Conclusions Spending on antineoplastic and immunomodulating drugs increased over the three-year period of the analysis and the oncological disease was the main therapeutic indication.