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Background and Rationale: Treatment persistence combines clinician and patient judgment of efficacy, tolerability and safety into a comprehensive measure of effectiveness and is defined as the act of continuing a treatment over time. Studies have reported poor treatment persistence to antipsychotic medications in patients with schizophrenia. This study evaluated treatment persistence to lurasidone (LUR) in patients with schizophrenia in a real-world Italian setting., Methods: This was a retrospective observational study of patients with schizophrenia who started treatment with LUR ≥ 6 months before inclusion. Following informed consent, data were collected starting from the index date (start of LUR treatment) at all visits occurring as per clinical practice. The primary endpoint was treatment persistence during the first 6 months, defined as the time between index date and all-cause discontinuation. Patients treated with LUR > 180 days were considered persistent. As secondary endpoint, treatment persistence was evaluated for a period of  ≥ 18 months., Results: Forty-five patients were enrolled and 41 (91.11%) completed the study. Forty-one patients (91.11%) were included in the eligible population as they initiated LUR treatment  ≥ 6 months before data collection. Patients were 43.0 ± 15.89 years old and 61% were female. Twenty-two patients (53.66%) started LUR treatment in a hospital setting and 19 (46.34%) in an outpatient setting. Based on Clinical Global Impression-Severity scale (CGI-S) at LUR initiation, 12 patients (29.27%) were severely ill, 17.07% markedly ill, 19.51% moderately ill, 2.44% mildly ill and 4.88% borderline mentally ill. Thirty-two patients (78.05%) were treatment persistent for  ≥ 180 days. Among the 19 patients observed for  ≥ 18 months, 11 (57.89%) were persistent for  ≥ 18 months. Among the 22 study patients observed for  < 18 months, 12 (54.54%) were persistent. An improvement in schizophrenia severity according to CGI-S was observed at inclusion (following LUR therapy) compared to the index date. Six patients (14.63%) experienced at least one adverse drug reaction: akathisia (7.32%), extrapyramidal disorder (4.88%), hyperprolactinemia (2.44%), restlessness (2.44%), and galactorrhea (2.44%). None were serious., Conclusions: Persistence to LUR in patients with schizophrenia was relatively high: 78% and 58% of patients were still on LUR after 6 and 18 months of treatment, respectively. This may reflect LUR's relatively favorable balance between efficacy and tolerability, as well as favorable patient satisfaction and acceptance., (© 2022. The Author(s).)

This study presents the final report of a long-term psychological assessment of men with haemophilia and HIV infection. The knowledge, emotional impact regarding HIV infection and prospective changes over time and the need for psychological support were evaluated. The study group comprised 118 men with haemophilia, 66 HIV seropositive and 52 seronegative, from the Haemophilia Centres in Bari, Florence, Milan and Naples. All subjects performed psychological tests (STAI: state and trait anxiety inventory; SDS: self-rating depression scale) and completed questionnaires to ascertain their knowledge and the emotional impact of AIDS. After enrollment (1992-93) the assessment was repeated twice over a 2-year period. A high percentage of subjects in both groups answered the questionnaire on knowledge correctly and, more specifically, all (100%) admitted knowing that sexual intercourse was a risk factor for HIV infection, adding that sexual partners of haemophiliacs with HIV should be regularly tested. The percentage, however, decreased for seropositives who admitted to always using a condom during sexual intercourse (86%) and for those who declared that partners were periodically tested for HIV (60%). The most important feature of the study is that, contrary to predicted expectations, seropositive and seronegative subjects presented the same degree of emotional involvement: there are no statistically significant differences in average scores between groups either on the anxiety or depression scales. Moreover, for certain aspects, seronegatives revealed greater emotional involvement: at baseline evaluation, they felt more fear and unhappiness with statistically significant differences compared to asymptomatics. Furthermore, seronegatives more than seropositives continue to feel reluctance towards infusion and avoid blood products after learning of AIDS. These results emphasize the importance of paying due attention to the emotional status of seronegatives. Their reluctance towards the use of blood products (despite present safety) is a very important issue for the possible consequences of treatment with the risk of worsening the clinical condition. In conclusion, we believe that counselling on HIV infection/AIDS needs to address every person with haemophilia regardless of HIV status.

With the aim of developing a new series of steroidal affinity labels of the estrogen receptor, six electrophilic 11 beta-ethyl (C2), 11 beta-butyl (C4), or 11 beta-decyl (C10) derivatives of estradiol bearing an 11 beta-terminal electrophilic functionality, i.e. bromine (C4), (methylsulfonyl)oxy (C2 and C4), bromoacetamido (C2 and C4), and (p-tolylsulfonyl)oxy (C10), were synthesized. The range of their affinity constants for binding the estrogen receptor was 0.4-37% that of estradiol; the order of increasing affinity (i) relative to the 11 beta-alkyl arm was ethyl < butyl and (ii) relative to the electrophilic functionality was bromoacetamido < bromine < (methylsulfonyl)oxy. Regardless of the conditions used, including prolonged exposure of the receptor to various pH levels (7-9) and temperatures (0-25 degrees C), the extent of receptor affinity labeling by the 11 beta-ethyl and 11 beta-butyl compounds, if any, was under 10%. This was in sharp contrast to results obtained using 11 beta-((tosyloxy)decyl)estradiol which labeled from 60% to 90% of the receptor hormone-binding sites with an EC50 of approximately 10 nM. Estrogenic and antiestrogenic activities of the compounds were determined using the MVLN cell line, which was established from the estrogen-responsive mammary tumor MCF-7 cells by stable transfection of a recombinant estrogen-responsive luciferase gene. The two 11 beta-ethyl compounds were mainly estrogenic, whereas the three 11 beta-butyl and the 11 beta-decyl compounds essentially showed antiestrogenic activity. The fact that the chemical reactivities of 11 beta-ethyl and 11 beta-butyl compounds were not compromised by interaction with the estrogen receptor made the synthesized high-affinity compounds potential cytotoxic agents which might be able to exert either (i) a specific action on estrogen-regulated genes or (ii) a more general action in estrogen-target cells. Therefore the ability of the compounds (1) to irreversibly abolish estrogen-dependent expression of the luciferase gene and (2) to affect the proliferation of MVLN cells were determined. All electrophiles were able to irreversibly suppress expression of the luciferase gene; the antiestrogenic electrophiles were more potent than the estrogenic ones but less efficient than 4-hydroxytamoxifen, a classical and chemically inert triphenylethylene antiestrogen. Only the antiestrogenic electrophiles decreased cell proliferation; however, they were less potent than 4-hydroxytamoxifen. In conclusion, the synthesized electrophilic estradiol 11 beta-ethyl and 11 beta-butyl derivatives (i) were not efficient affinity labels of the estrogen receptor and (ii) did not display significant cytotoxicity in estrogen-sensitive mammary tumor cells. However, since these derivatives displayed high affinity for the estrogen receptor, they could be used to prepare potential cytotoxic agents which might be selective for tumors affecting estrogen-target tissues, by coupling them with a toxic moiety.

This study aimed to assess the psychological status of men with haemophilia and HIV infection and to monitor changes in psychlogical status over time, in order to evaluate the need for psychological support. The study included 24 HIV seropositive men and a control group of 21 HIV seronegative men who attended the Haemophilia Centre in Bari (Italy). Subjects underwent psychological tests (STAl-Y: State and Trait Anxiety Inventory; SDS: Self-Rating Depression Scale) and completed a questionnaire on the emotional impact of AIDS. Assessment was repeated at 6-monthly intervals over a 2-year period. Contrary to expectation, HIV seronegative men with haemophilia had worse anxiety and depression scores, reported more confusion and fear, and had more reluctance towards the use of blood products (despite their present safety) than HIV seropositives. Possible reasons for these findings are considered, and their implications for clinical practice discussed.