Rationale and design of an independent randomised controlled trial evaluating the effectiveness of aripiprazole or haloperidol in combination with clozapine for treatment-resistant schizophrenia

<p>Abstract</p> <p>Background</p> <p>One third to two thirds of people with schizophrenia have persistent psychotic symptoms despite clozapine treatment. Under real-world circumstances, the need to provide effective therapeutic interventions to patients who do not have an optimal response to clozapine has been cited as the most common reason for simultaneously prescribing a second antipsychotic drug in combination treatment strategies. In a clinical area where the pressing need of providing therapeutic answers has progressively increased the occurrence of antipsychotic polypharmacy, despite the lack of robust evidence of its efficacy, we sought to implement a pre-planned protocol where two alternative therapeutic answers are systematically provided and evaluated within the context of a pragmatic, multicentre, independent randomised study.</p> <p>Methods/Design</p> <p>The principal clinical question to be answered by the present project is the relative efficacy and tolerability of combination treatment with clozapine plus aripiprazole compared with combination treatment with clozapine plus haloperidol in patients with an incomplete response to treatment with clozapine over an appropriate period of time. This project is a prospective, multicentre, randomized, parallel-group, superiority trial that follow patients over a period of 12 months. Withdrawal from allocated treatment within 3 months is the primary outcome.</p> <p>Discussion</p> <p>The implementation of the protocol presented here shows that it is possible to create a network of community psychiatric services that accept the idea of using their everyday clinical practice to produce randomised knowledge. The employed pragmatic attitude allowed to randomly allocate more than 100 individuals, which means that this study is the largest antipsychotic combination trial conducted so far in Western countries. We expect that the current project, by generating evidence on whether it is clinically useful to combine clozapine with aripiprazole rather than with haloperidol, provides physicians with a solid evidence base to be directly applied in the routine care of patients with schizophrenia.</p> <p>Trial Registration</p> <p><b>Clincaltrials.gov Identifier</b>: NCT00395915</p

Disparities in access to COVID-19 vaccine in Verona, Italy: a cohort study using local health immunization data

Introduction: Migrant populations worldwide were disproportionately impacted by the COVID-19 pandemic. Although substantial resources have been invested in scaling COVID-19 vaccination campaigns, globally vaccine rate and uptake remained low among migrants from across many countries. This study aimed to explore the country of birth as a factor influencing access to the COVID-19 vaccine. Methods: This retrospective cohort study included adults vaccinated against SARS-CoV-2 receiving at least one dose in the Verona province between 27 December 2020 and 31 December 2021. Time-to-vaccination was estimated as the difference between the actual date of each person's first dose of COVID-19 vaccination and the date in which the local health authorities opened vaccination reservations for the corresponding age group. The birth country was classified based on both the World Health Organization regions and the World Bank country-level economic classification. Results were reported as the average marginal effect (AME) with corresponding 0.95 confidence intervals (CI). Results: During the study period, 7,54,004 first doses were administered and 5,06,734 (F = 2,46,399, 48.6%) were included after applying the exclusion criteria, with a mean age of 51.2 years (SD 19.4). Migrants were 85,989 (17.0%, F = 40,277, 46.8%), with a mean age of 42.4 years (SD 13.3). The mean time-to-vaccination for the whole sample was 46.9 days (SD 45.9), 41.8 days (SD 43.5) in the Italian population, and 71.6 days (SD 49.1) in the migrant one (p &lt; 0.001). The AME of the time-to-vaccination compared to the Italian population was higher by 27.6 [0.95 CI 25.4-29.8], 24.5 [0.95 CI 24.0-24.9], 30.5 [0.95 CI 30.1-31.0] and 7.3 [0.95 CI 6.2-8.3] days for migrants from low-, low-middle-, upper-middle- and high-income countries, respectively. Considering the WHO region, the AME of the time-to-vaccination compared to the Italian group was higher by 31.5 [0.95 CI 30.6-32.5], 31.1 [0.95 CI 30.6-31.5], and 29.2 [0.95 CI 28.5-29.9] days for migrants from African, European, and East-Mediterranean regions, respectively. Overall, time-to-vaccination decreased with increasing age (p &lt; 0.001). Although both migrants and Italians mainly used hub centers (&gt;90%), migrants also used pharmacies and local health units as alternative sites (2.9% and 1.5%, respectively), while Italians (3.3%) and migrants from the European region (4.2%) relied more on family doctors. Conclusion: The birth country of migrants influenced access to COVID-19 vaccine both in terms of time-to-vaccination and vaccination points used, especially for the LIC migrant group. Public health authorities should take socio-cultural and economic factors into consideration for tailored communication to people from migrant communities and for planning a mass vaccination campaign