Determinants of immunosuppressive therapy in renal transplant recipients: an Italian observational study (the CESIT project).

BACKGROUND: Very scanty evidence is available on factors influencing the choice of immunosuppressive drug therapy after kidney transplantation. METHODS: An Italian multiregional real-world study was conducted integrating national transplant information system and claims data. All patients undergoing kidney transplantation for the first time during 2009-2019 (incident patients) were considered. Multilevel logistic models were used to estimate Odds Ratio (OR) and corresponding 95% Confidence intervals. Factors with statistically significance were identified as characteristics associated with treatment regimens: cyclosporin-CsA vs tacrolimus-Tac and, within the latter group, mTOR inhibitors vs mycophenolate-MMF. RESULTS: We identified 3,622 kidney patients undergoing transplantation in 17 hospitals located in 4 Italian regions, 78.3% was treated with TAC-based therapy, of which 78% and 22% in combination with MMF and mTOR, respectively. For both comparison groups, the choice of immunosuppressive regimens was mostly guided by standard hospital practices. Only few recipient and donor characteristics were found associated with specific regimen (donor/receipt age, immunological risk and diabetes). CONCLUSIONS: The choice of post-renal transplant immunosuppressive therapy seems to be mostly driven by standard Centre practices, while only partially based on patient's characteristics and recognized international guidelines.

The Opportunity Provided by Vaccination Offer to Refugees from Ukraine in European Countries.

(1) The Russian invasion of Ukraine forced many people to leave their country and seek asylum in various European countries, with serious consequences from a health perspective. In this context, we describe the health measures undertaken by AcToVax4NAM Consortium Countries (Cyprus-Germany-Greece-Italy-Malta-Poland-Romania-Spain) to prevent Vaccine-Preventable Disease (VPD) outbreaks in the context of mass movements of populations that resulted from the crisis in Ukraine. (2) We collected information on the vaccinations offered to Ukrainians in the Consortium Countries. (3) All these countries have provided Temporary Protection (TP) status to refugees from Ukraine and have followed the recommendations of European and International Agencies to offer them vaccinations according to the National Immunisation Programmes. The COVID-19 vaccination is offered in all countries with regard to the general population. Most countries provide information on TP and access to health/vaccination services in the Ukrainian language. (4) The information collected shows a common effort to ensure the adequate planning of health and vaccination services for refugees from Ukraine and, very often, to include them in the national vaccination offer. It is important that this initial response towards people who have fled Ukraine will be continued following the emergency but, more importantly, that it serves as a best practice towards all migrants and refugees entering the EU.

Immunosuppression with Generics in Liver and Kidney Transplantation: A Real-World Evidence Study.

Purpose: This study evaluates the use, benefit-risk profile, and economic impact of generic immunosuppressants (tacrolimus-TAC, cyclosporine-CsA, and mycophenolate-MYC) in kidney and liver transplant recipients compared to brand-name drugs. Patients and Methods: A retrospective multicentre observational study, involving four Italian regions, was conducted based on the national transplant Information system and regional healthcare claims data. The analysis focused on incident patients who received kidney and liver transplants between 2013 and 2019 and evaluated the use of generic of CsA, TAC, and MYC during the 30-day period following discharge. For each type of transplant and immunosuppressive agent, the benefit-risk profile of generic vs branded drugs in a two-year window was estimated by multivariate Cox models (HR; 95% CI). Furthermore, the potential cost savings per person associated with one year of treatment using generics were calculated. Results: The utilization of generic drugs showed a significant increase; over the study years, the proportion of users among kidney recipients ranged from 14.2% to 40.5% for TAC, from 36.9% to 56.7% for MYC, and from 18.2% to 94.7% for CsA. A great variability in generic uptake for region was found. A comparable risk-benefit profile between generic and branded formulations was shown for all immunosuppressors considered. Choosing generic immunosuppressants during maintenance could result in yearly savings of around 2000 euros per person for each therapy ingredient. Conclusion: The study shows an increasing proportion of patients using generic immunosuppressive drugs over time suggesting a growing acceptance of generics within the transplant community and reveals comparable risk-benefit profiles between the generic and branded formulations of TAC, CsA, and MYC. A significant variability in the use of generics immunosuppressive agents was found both at the regional level and among transplant centers and future research should delve into regional prescribing variations.

Effectiveness and safety of immunosuppressive regimens used as maintenance therapy in kidney transplantation: The CESIT study.

Maintenance immunosuppressive therapy used in kidney transplantation typically involves calcineurin inhibitors, such as tacrolimus or cyclosporine, in combination with mycophenolate or mechanistic target of rapamycin (mTORi) with or without corticosteroids. An Italian retrospective multicentre observational study was conducted to investigate the risk-benefit profile of different immunosuppressive regimens. We identified all subjects who underwent kidney transplant between 2009 and 2019, using healthcare claims data. Patients on cyclosporine and tacrolimus-based therapies were matched 1:1 based on propensity score, and effectiveness and safety outcomes were compared using Cox models (HR; 95%CI). Analyses were also conducted comparing mTORi versus mycophenolate among tacrolimus-treated patients. Patients treated with cyclosporine had a higher risk of rejection or graft loss (HR:1.69; 95%CI:1.16-2.46) and a higher incidence of severe infections (1.25;1.00-1.55), but a lower risk of diabetes (0.66;0.47-0.91) compared to those treated with tacrolimus. Among tacrolimus users, mTORi showed non-inferiority to MMF in terms of mortality (1.01;0.68-1.62), reject/graft loss (0.61;0.36-1.04) and severe infections (0.76;0.56-1.03). In a real-life setting, tacrolimus-based immunosuppressive therapy appeared to be superior to cyclosporine in reducing rejection and severe infections, albeit with an associated increased risk of diabetes. The combination of tacrolimus and mTORi may represent a valid alternative to the combination with mycophenolate, although further studies are needed to confirm this finding.

Access to Vaccination for Newly Arrived Migrants: Developing a General Conceptual Framework for Understanding How to Improve Vaccination Coverage in European Countries.

Objectives: Access to vaccination for newly arrived migrants (NAMs) is a relevant concern that requires urgent attention in EU/EEA countries. This study aimed to develop a General Conceptual Framework (GCF) for understanding how to improve vaccination coverage for NAMs, by characterizing and critically analyzing system barriers and possible strategies to increase vaccination. Methods: A theoretical conceptualization of the GCF was hypothesized based on conceptual hubs in the immunization process. Barriers and solutions were identified through a non-systematic desktop literature review and qualitative research. The GCF guided the activities and facilitated the integration of results, thereby enriching the GCF with content. Results: The study explores the vaccination of NAMs and proposes strategies to overcome barriers in their vaccination process. It introduces a framework called GCF, which consists of five interconnected steps: entitlement, reachability, adherence, achievement, and evaluation of vaccination. The study also presents barriers and solutions identified through literature review and qualitative research, along with strategies to enhance professionals' knowledge, improve reachability, promote adherence, achieve vaccination coverage, and evaluate interventions. The study concludes by recommending strategies such as proximity, provider training, a migrant-sensitive approach, and data collection to improve vaccination outcomes for NAMs. Conclusion: Ensuring equitable access to healthcare services, including vaccination, is crucial not only from a humanitarian perspective but also for the overall public health of these countries.

Acinetobacter baumannii Isolates from COVID-19 Patients in a Hospital Intensive Care Unit: Molecular Typing and Risk Factors.

Infections caused by Acinetobacter baumannii represent a major concern for intensive care unit (ICU) patients. However, the epidemiology of these infections among COVID-19 patients has not been fully explored. The aims of this study were (i) to characterize the clonal spread of A. baumannii among COVID-19 patients admitted to the ICU of the Umberto I hospital of Rome during the first year of the pandemic and (ii) to identify risk factors for its acquisition. Isolates were analysed by pulsed-field gel electrophoresis, and a multivariable regression model was constructed. Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were calculated. Overall, 193 patients were included, and 102 strains were analysed. All isolates had highly antibiotic-resistant profiles and derived from two genotypes. The cumulative incidence of A. baumannii acquisition (colonization or infection) was 36.8%. Patients with A. baumannii had higher mortality and length of stay. Multivariable analysis showed that previous carbapenem use was the only risk factor associated with A. baumannii acquisition (aOR: 4.15, 95% CI: 1.78-9.64). We documented substantial A. baumannii infections and colonization and high levels of clonal transmission. Given the limited treatment options, effective prevention and containment strategies to limit the spread of A. baumannii should be implemented.

Comparing the Occurrence of Healthcare-Associated Infections in Patients with and without COVID-19 Hospitalized during the Pandemic: A 16-Month Retrospective Cohort Study in a Hospital Intensive Care Unit.

The COVID-19 pandemic has increased the healthcare-associated infection (HAI) risk in intensive care unit (ICU) patients. However, a comparison between patients with and without COVID-19 in terms of HAI incidence has been rarely explored. In this study, we characterized the occurrence of HAI among patients with and without COVID-19 admitted to the ICU of the Umberto I hospital of Rome during the first 16 months of the pandemic and also identified risk factors for HAI acquisition. Patients were divided into four groups according to their ICU admission date. A multivariable conditional risk set regression model for multiple events was constructed for each admission period. Adjusted hazard ratios and 95% confidence intervals were calculated. Overall, 352 COVID-19 and 130 non-COVID-19 patients were included, and a total of 361 HAIs were recorded. We found small differences between patients with and without COVID-19 in the occurrence and type of HAI, but the infections in the two cohorts mostly involved different microorganisms. The results indicate that patient management was likely an important factor influencing the HAI occurrence during the pandemic. Effective prevention and control strategies to reduce HAI rates should be implemented.