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Background The aims of this study were: to investigate the capacity of the rare disease healthcare network in Campania to diagnose patients with rare diseases during the outbreak of Covid-19; and to shed light on problematic diagnoses during this period. Methods To describe the impact of the Covid-19 pandemic on the diagnosis of patients with rare diseases, a retrospective analysis of the Campania Region Rare Disease Registry was performed. A tailored questionnaire was sent to rare disease experts to investigate major issues during the emergency period. Results Prevalence of new diagnoses of rare disease in March and April 2020 was significantly lower than in 2019 (117 versus 317, P Conclusions This study describes the effects of the Covid-19 outbreak on the diagnosis of rare disease in a single Italian region and investigates potential issues of diagnosis and management during this period.

In this paper, we study collective interaction dynamics emerging in the game of football (soccer). To do so, we surveyed a database containing body-sensor traces measured during three professional football matches, where we observed statistical patterns that we used to propose a stochastic model for the players' motion in the field. The model, which is based on linear interactions, captures to a good approximation the spatiotemporal dynamics of a football team. Our theoretical framework, therefore, can be an effective analytical tool to uncover the underlying cooperative mechanisms behind the complexity of football plays. Moreover, we showed that it can provide handy theoretical support for coaches to evaluate teams' and players' performances in both training sessions and competitive scenarios.

Pereira, Ana Margarida/0000-0002-5468-0932; Briedis, Vitalis/0000-0002-5106-6638; Johnston, Sebastian Lennox/0000-0003-3009-9200; Orlando, Valentina/0000-0002-8209-8878; Sova, Milan/0000-0002-8542-7841; Chung, Kian Fan/0000-0001-7101-1426; Ciprandi, Giorgio/0000-0001-7016-8421; Yusuf, M Osman/0000-0002-8067-1204; stelmach, rafael/0000-0002-5132-1934; Sunyer, Jordi/0000-0002-2602-4110; Martins, Pedro/0000-0002-4129-133X; Demoly, Pascal/0000-0001-7827-7964; Fonseca, Joao Almeida/0000-0002-0887-8796; Anto, J M/0000-0002-4736-8529; IACCARINO, Guido/0000-0002-8997-835X; Custovic, Adnan/0000-0001-5218-7071; Lourenco, Olga/0000-0002-8401-5976; Pugin, Benoit/0000-0001-7132-9477; Chavannes, Niels/0000-0002-8607-9199; Rodo, Xavier/0000-0003-4843-6180; Nadif, Rachel/0000-0003-4938-9339; Plavec, Davor/0000-0003-2020-8119; Vicheva, Dilyana/0000-0002-6805-3825; Iaccarino, Guido/0000-0002-8997-835X; Annesi-Maesano, Isabella/0000-0002-6340-9300; N.G., Papadopoulos/0000-0002-4448-3468; J, Garcia-Aymerich/0000-0002-7097-4586; Humbert, Marc/0000-0003-0703-2892; Barbara, C./0000-0003-0915-4105; Gemicioglu, Bilun/0000-0001-5953-4881; Caimmi, Davide/0000-0003-4481-6194; Namazova-Baranova, Leyla/0000-0002-2209-7531; Basagana, Xavier/0000-0002-8457-1489; Midao, Luis/0000-0003-1981-2554; Sheikh, Aziz/0000-0001-7022-3056; O'Hehir, Robyn/0000-0002-3489-7595; Cardona, Victoria/0000-0003-2197-9767; Mota-Pinto, Anabela/0000-0002-0820-9568; Cecchi, Lorenzo/0000-0002-0658-2449; Bindslev-Jensen, Carsten/0000-0002-8940-038X; Costa, Elisio/0000-0003-1158-1480; Kuna, Piotr/0000-0003-2401-0070; Malva, Joao/0000-0002-5438-4447; Zuberbier, Torsten/0000-0002-1466-8875; Toppila-Salmi, Sanna/0000-0003-0890-6686; Nogueira-Silva, Luis/0000-0002-5519-707X; Ivancevich, Juan Carlos/0000-0001-8713-6258 WOS:000463761700007 PubMed ID: 30597673 Background: Mobile technology may help to better understand the adherence to treatment. MASK-rhinitis (Mobile Airways Sentinel NetworK for allergic rhinitis) is a patient-centred ICT system. A mobile phone app (the Allergy Diary) central to MASK is available in 22 countries. Objectives: To assess the adherence to treatment in allergic rhinitis patients using the Allergy Diary App. Methods: An observational cross-sectional study was carried out on all users who filled in the Allergy Diary from 1 January 2016 to 1 August 2017. Secondary adherence was assessed by using the modified Medication Possession Ratio (MPR) and the Proportion of days covered (PDC) approach. Results: A total of 12143 users were registered. A total of 6949 users reported at least one VAS data recording. Among them, 1887 users reported >= 7 VAS data. About 1195 subjects were included in the analysis of adherence. One hundred and thirty-six (11.28%) users were adherent (MPR >= 70% and PDC = 70% and PDC = 1.50) and 176 (14.60%) were switchers. On the other hand, 832 (69.05%) users were non-adherent to medications (MPR

The aim of this study was to compare survival of resected and unresected patients in a large cohort of patients with metastases to the pancreas from renal cell carcinoma (PM-RCC). Data from 16 Italian centers involved in the treatment of metastatic RCC were retrospectively collected. The Kaplan–Meier and log-rank test methods were used to evaluate overall survival (OS). Clinical variables considered were sex, age, concomitant metastasis to other sites, surgical resection of PM-RCC, and time to PM-RCC occurrence. Overall, 103 consecutive patients with radically resected primary tumors were enrolled in the analysis. PM-RCCs were synchronous in only three patients (3 %). In 56 patients (54 %), the pancreas was the only metastatic site, whereas in the other 47 patients, lung (57 %), lymph nodes (28 %), and liver (21 %) were the most common concomitant metastatic sites. Median time for PM-RCC occurrence was 9.6 years (range 0–24 years) after nephrectomy. Surgical resection of PM-RCC was performed in 44 patients (median OS 103 months), while 59 patients were treated with tyrosine kinase inhibitors (TKIs; median OS 86 months) (p = 0.201). At multivariate analysis, Memorial Sloan Kettering Cancer Center risk group was the only independent prognostic factor. None of the other clinical variables, such as age, sex, pancreatic surgery, or the presence of concomitant metastases, were significantly associated with outcome in PM-RCC patients. The presence of PM-RCC is associated with a long survival, and surgical resection does not improve survival in comparison with TKI therapy. However, surgical resection leads to a percentage of disease-free PM-RCC patients.

Seeks to find predictors of learning organizations as determined by Marquardt’s Learning Organization Profile (1996). For this study, male and female professionals were asked to rate their perceptions about their organizations. They were asked to rate their organizational perceptions on rewards and recognition, training and education, information flow, vision and strategy, and individual team development. Finds that appropriate rewards and recognition are an undergirding structure to the learning organization and that an environment of knowledge sharing and learning systems is an indication of a learning organization. Results support the notion that interventions intended to aid in the metamorphose from a current organization state to that of a learning organization may wish to focus initially on these aspects.

Problem statement: The purpose of this study was to determine undergra duate student perceptions in the areas of group experience within the context of an undergraduate organizational behavior business class community service assignment. College students, as part of an in-class service - learning project, were assigned to teach business r elated curriculum to at-risk high school students. Approach: Students, enrolled in the required senior level bu siness course, were then assessed in the following areas: service learning experience and gr oup experience. A multiple-choice questionnaire was administered to undergraduate students in an or ganizational and administrative behavior class and analyzed for correlations and relationships. The su rvey was administered in week eleven of a traditional semester and in the last week of the co mmunity service project. The survey was comprised of seven questions relating to group experience and one based on the impact of the community service project itself. Results: Significant findings revealed a positive correlati on between the group experience and the feelings toward the project. In addition, multiple linear regressions suggested a positive an d significant prediction. Conclusion: From the findings, implications for the developmen t of experiential learning projects for use in the college classroom will be discussed. When paired with the results of previous research, the findings of this research ca n be very useful in developing group based service learning projects at the undergraduate level. Based upon the importance of service learning as an experiential teaching style, it is critical to unde rstand how to better use this vehicle for discovery .

A mentoring relationship has the potential to be widely used throughout an individual’s lifespan. Including mentoring relationships into one’s life can assist with transition management in and out of various life scenarios. A mentoring model has been proposed that blends human development with the dimensions of mentoring. It is assumed that the dimensions of the model are continuous and multidimensional. We recognize three interactive dimensions that surround the mentoring interaction which shape the mentor and protégé relationship. These dimensions are defined as: socialization; task development; and lifespan development. The model can be utilized as a diagnostic tool or as a training model to promote mentoring relationships.

The study investigated the relationships of margin in life (MIL) and demographic variables to readiness for change. Results, based on 131 employees of a manufacturing company, showed that overall MIL and five work subscales had significant positive relationships with readiness for change. The demographic variables of department, position, and length of employment were also related to readiness for change but not to MIL. Three variables combined to predict readiness: employees who get more personal power than burden from their relations with managers, employees who themselves are in managerial positions, and employees who are relatively new to the company. Among the MIL subscales, all of the work aspects, except social relations in the workplace, had higher ratings on load than on power, whereas the reverse was true for the nonwork aspects of family, self, and health. The results suggest strategies to facilitate effective change interventions.

The incidence of HIV is nowadays the most valuable indicator of epidemiologic surveillance, both to guide prevention activities and to monitor ongoing interventions. This paper addresses a method to estimate the HIV incidence in Brazil in recent years.

Background The novel coronavirus (SARS-CoV-2) pandemic spread rapidly worldwide increasing exponentially in Italy. To date, there is lack of studies describing clinical characteristics of the people at high risk of infection. Hence, we aimed (i) to identify clinical predictors of SARS-CoV-2 infection risk, (ii) to develop and validate a score predicting SARS-CoV-2 infection risk, and (iii) to compare it with unspecific scores. Methods Retrospective case-control study using administrative health-related database was carried out in Southern Italy (Campania region) among beneficiaries of Regional Health Service aged over than 30 years. For each person with SARS-CoV-2 confirmed infection (case), up to five controls were randomly matched for gender, age and municipality of residence. Odds ratios and 90% confidence intervals for associations between candidate predictors and risk of infection were estimated by means of conditional logistic regression. SARS-CoV-2 Infection Score (SIS) was developed by generating a total aggregate score obtained from assignment of a weight at each selected covariate using coefficients estimated from the model. Finally, the score was categorized by assigning increasing values from 1 to 4. Discriminant power was used to compare SIS performance with that of other comorbidity scores. Results Subjects suffering from diabetes, anaemias, Parkinson’s disease, mental disorders, cardiovascular and inflammatory bowel and kidney diseases showed increased risk of SARS-CoV-2 infection. Similar estimates were recorded for men and women and younger and older than 65 years. Fifteen conditions significantly contributed to the SIS. As SIS value increases, risk progressively increases, being odds of SARS-CoV-2 infection among people with the highest SIS value (SIS = 4) 1.74 times higher than those unaffected by any SIS contributing conditions (SIS = 1). Conclusion Conditions and diseases making people more vulnerable to SARS-CoV-2 infection were identified by the current study. Our results support decision-makers in identifying high-risk people and adopting of preventive measures to minimize the spread of further epidemic waves.

Background: Dimethyl-fumarate (DMF) was effective and safe in relapsing–remitting multiple sclerosis (MS) in randomized clinical trials. We aimed to evaluate the efficacy and safety of DMF and factors related to drug response in real-life setting. Methods: We analysed prospectively collected demographic and clinical data for patients treated with DMF in six multiple sclerosis (MS) centers from 2015 to 2017 in Campania region, Italy. We performed univariate and multivariate analyses to assess relationships between baseline parameters and DMF efficacy outcomes, Annualized Relapse Rate (ARR), Expanded Disability Status Scale (EDSS) progression and No Evidence of Disease Activity (NEDA-3) status. Results: we analyzed data of 456 patients (67% female subjects, mean age 40 ± 12 years, mean disease duration 9 ± 9 years, mean treatment duration 18 ± 11 months, median EDSS 2.5, 0–8). Proportion of Naïve versus pretreated with other DMTs patients was 149/307 (32.7%), with 122 patients switching to DMF for disease activity (26.7%) and 185 for safety and tolerability issues (40.6%). During treatment with DMF, the annualized relapse rate was reduced by 75% respect to the pre-treatment ARR [incidence-rate-ratio (IRR) = 0.25, p < 0.001, CI 0.18–0.33]. Factors influencing ARR rate while on DMF were relapsing remitting (RR) MS course (IRR = 2.0, p =

This study aims to identify baseline medications that, as a proxy for the diseases they are dispensed for, are associated with increased risk of mortality in COVID-19 patients from two regions in Spain and Italy using real-world data. We conducted a cross-country, retrospective, observational study including 8570 individuals from both regions with confirmed SARS-CoV-2 infection between 4 March and 17 April 2020, and followed them for a minimum of 30 days to allow sufficient time for the studied event, in this case death, to occur. Baseline demographic variables and all drugs dispensed in community pharmacies three months prior to infection were extracted from the PRECOVID Study cohort (Aragon, Spain) and the Campania Region Database (Campania, Italy) and analyzed using logistic regression models. Results show that the presence at baseline of potassium-sparing agents, antipsychotics, vasodilators, high-ceiling diuretics, antithrombotic agents, vitamin B12, folic acid, and antiepileptics were systematically associated with mortality in COVID-19 patients from both countries. Treatments for chronic cardiovascular and metabolic diseases, systemic inflammation, and processes with increased risk of thrombosis as proxies for the conditions they are intended for can serve as timely indicators of an increased likelihood of mortality after the infection, and the assessment of pharmacological profiles can be an additional approach to the identification of at-risk individuals in clinical practice.

Because of the current limits of immunological tests in the diagnosis of tuberculosis there is a need to identify new and rapid tests that can be carried out on a large scale in endemic countries and useful in the identification of infected subjects, but also able to discriminate those with latent infection from subjects with active. We have taken into consideration and analysed the LIODetect®TB-ST Tuberculosis Rapid Test, a membrane test for the qualitative detection of specific IgG, IgA, and IgM antibodies against Mycobacterium tuberculosis, performed on serum, plasma, or whole blood.85 samples positive to QuantiFERON TB-GOLD PLUS test were processed using this test and the results obtained were concordant with clinical diagnosis.To our knowledge, the LIODetect®TB-ST Tuberculosis Rapid Test is the only test; that identifies active tuberculosis disease with high sensitivity and specificity and its use might be of help in the diagnosis of tuberculosis, especially in endemic countries.

The pressing problem of multimorbidity and polypharmacy is aggravated by the lack of specific care models for this population. We aimed to investigate the evolution of multimorbidity and polypharmacy patterns in a given population over a 4-year period (2011–2015). A cross-sectional, observational study among the EpiChron Cohort, including anonymized demographic, clinical and drug dispensation information of all users of the public health system ≥65 years in Aragon (Spain), was performed. An exploratory factor analysis, stratified by age and sex, using an open cohort was carried out based on the tetra-choric correlations among chronic diseases and dispensed drugs during 2011 and compared with 2015. Seven baseline patterns were identified during 2011 named as: mental health, respiratory, allergic, mechanical pain, cardiometabolic, osteometabolic, and allergic/derma. Of the epidemiological patterns identified in 2015, six were already present in 2011 but a new allergic/derma one appeared. Patterns identified in 2011 were more complex in terms of both disease and drugs. Results confirmed the existing association between age and clinical complexity. The systematic associations between diseases and drugs remain similar regarding their clinical nature over time, helping in early identification of potential interactions in multimorbid patients with a high risk of negative health outcomes due to polypharmacy.

Coronavirus disease 2019 (COVID-19) has substantially challenged healthcare systems worldwide. By investigating population characteristics and prescribing profiles, it is possible to generate hypotheses about the associations between specific drug-utilisation profiles and susceptibility to COVID-19 infection. A retrospective drug-utilisation study was carried out using routinely collected information from a healthcare database in Campania (Southern Italy). We aimed to discover the prevalence of drug utilisation (monotherapy and polytherapy) in COVID-19 versus non-COVID-19 patients in Campania (~ 6 million inhabitants). The study cohort comprised 1532 individuals who tested positive for COVID-19. Drugs were grouped according to the Anatomical Therapeutic Chemical (ATC) classification system. We noted higher prevalence rates of the use of drugs in the ATC categories C01, B01 and M04, which was probably linked to related comorbidities (i.e., cardiovascular and metabolic). Nevertheless, the prevalence of the use of drugs acting on the renin-angiotensin system, such as antihypertensive drugs, was not higher in COVID-19 patients than in non-COVID-19 patients after adjustments for age and sex. These results highlight the need for further case–control studies to define the effects of medications and comorbidities on susceptibility to and associated mortality from COVID-19.

Background: Antihypertensive drugs play a crucial role in reducing cardiovascular morbidity and mortality. Variability in prescribing patterns constitutes a major challenge for current healthcare systems. This study aimed to compare patterns of use of antihypertensives in general practice in two southern European populations. Methods: Observational study. Data on antihypertensive drugs consumption in primary care setting (2016) were obtained from pharmacy refill records in Campania (Italy) and Aragon (Spain). Prescribing rates and the number of defined daily doses [DDD/1, 000 inhabitants/day (DID)] were calculated, and the Drug Utilization 90% (DU90%) approach used to reveal differences in prescribing patterns in both regions. Results: Antihypertensive prescribing rates in Campania and Aragon were 250.8 (95%CI: 250.2–251.3) and 201.7 (95%CI: 200.9–202.5) users/1, 000 inhabitants/year. Overall consumption was of 310.1 and 256.8 DID, respectively. Spanish users, especially women and the elderly, consumed a greater volume of diuretics. Conversely, other therapeutic subgroups were more consumed in Campania. However, the most prescribed subgroups accounted for comparable proportions of the total consumption in each region. Conclusions: Both prescribing rates and intensity of antihypertensive use were higher in Campania. Pharmacy refill records in cross-country comparisons allow to know the factors influencing variability in prescribing habits with a view to improving prescribing quality.

Enrica Menditto,1,* Caitriona Cahir,2,* Mercedes Aza-Pascual-Salcedo,3,4 Dario Bruzzese,5 Beatriz Poblador-Plou,3 Sara Malo,6 Elisio Costa,7 Francisca González-Rubio,3,4,6 Antonio Gimeno-Miguel,3 Valentina Orlando,1 Przemyslaw Kardas,8 Alexandra Prados-Torres3 1CIRFF, Center of Pharmacoeconomics, University of Naples Federico II, Naples, Italy; 2Division of Population Health Sciences, Royal College of Surgeons in Ireland, Dublin, Ireland; 3Aragon Health Sciences Institute (IACS), IIS Aragón, REDISSEC ISCIII, Madrid, Spain; 4Aragon Health Service (SALUD), Aragon, Spain; 5Department of Public Health, Federico II University, Naples, Italy; 6University of Zaragoza, Zaragoza, Spain; 7UCIBIO, REQUINTE, Faculty of Pharmacy, Porto4ageing Reference Site, University of Porto, Porto, Portugal; 8Department of Family Medicine, Medical University of Lodz, Lodz, Poland*These authors contributed equally to this workPurpose: The purpose of this study was to evaluate and compare medication adherence to chronic therapies in older populations across different regions in Europe.Methods: This explorative study applied a harmonized method of data extraction and analysis from pharmacy claims databases of three European countries to compare medication adherence at a cross-country level. Data were obtained for the period between January 1, 2010, and December 31, 2011. Patients (aged ≥65 years) who newly initiated to oral antidiabetics, antihyperlipidemics, or antiosteoporotics were identified and followed for over a 12-month period. Main outcome measures were medication adherence (medication possession ratio, [MPR]; implementation) and persistence on index treatment. All country-specific data sets were prepared by employing a common data input model. Outcome measures were calculated for each country and pooled using random effect models.Results: In total, 39,186 new users were analyzed. In pooled data from the three countries, suboptimal implementation (MPR 50% of older people non-adherent to antihyperlipidemics and antiosteoporotics in the three European cohorts. However, the degree of variability in adherence rates among the three countries was high. A harmonized method of data extraction and analysis across health-related database in Europe is useful to compare medication-taking behavior at a cross-country level. Keywords: drug utilization, medication adherence, medication persistence, prescribing

IntroductionThe combination of biomarkers and drugs is the subject of growing interest both from regulators, physicians and companies. This study protocol of a systematic review is aimed to describe available literature evidences about the cost-effectiveness, cost-utility or net-monetary benefit of the use of biomarkers in solid tumour as tools for customising immunotherapy to identify what further research needs.Methods and analysisA systematic review of the literature will be carried out according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement guidelines. PubMed and Embase will be queried from June 2010 to June 2021. The PICOS model will be applied: target population (P) will be patients with solid tumours treated with immune checkpoint inhibitors (ICIs); the interventions (I) will be test of the immune checkpoint predictive biomarkers; the comparator (C) will be any other targeted or non-targeted therapy; outcomes (O) evaluated will be health economic and clinical implications assessed in terms of incremental cost-effectiveness ratio, net health benefit, net monetary benefit, life years gained, quality of life, etc; study (S) considered will be economic evaluations reporting cost-effectiveness analysis, cost-utility analysis, net-monetary benefit. The quality of the evidence will be graded according to Grading of Recommendations Assessment, Development and Evaluation.Ethics and disseminationThis systematic review will assess the cost-effectiveness implications of using biomarkers in the immunotherapy with ICIs, which may help to understand whether this approach is widespread in real clinical practice. This research is exempt from ethics approval because the work is carried out on published documents. We will disseminate this protocol in a related peer-reviewed journal.PROSPERO registration numberCRD42020201549.

BackgroundSeveral epidemiological and pathological findings suggest that the female sex hormones may influence the development of meningiomas. However, the role of pregnancy, oral contraceptives, and fertilization therapies is still controversial.MethodsFrom the surgical series of 354 patients with meningiomas operated between 2006 and 2019, the group of 72 premenopausal women was separately considered. The tumor location, WHO grade, Ki67-labeling index (LI), progesterone receptor (PR) expression, and histological types were studied in premenopausal women with and without hormone-related conditions were compared.ResultsIn this premenopausal group, 24 patients had hormone-related conditions, including use of oral contraceptives in 16, intrauterine fertilization in one, pregnancy in three, and tumors of the female reproductive system in four. The group of patients with hormone-related conditions, as compared to that with no hormone related conditions, showed slightly lower median age (38 versus 43 years) and no significant difference of meningioma location WHO grade, Ki 67-Li, PR expression and histological type. The clinical onset during pregnancy in three patients and tumor growth during contraceptive progesterone therapy in two others were evidenced.ConclusionThe biological behavior of meningiomas and their pathological findings, including PR expression, are not correlated with the different hormone related conditions in premenopausal female patients. Contraceptives and fertilization therapies, mainly with progesterone, should be avoided in patients with meningiomas.

Even if the incidence of tuberculosis (TB) has been decreasing over the last years, the number of patients with TB is increasing worldwide. The emergence of multidrug-resistant and extensively drug-resistant TB is making control of TB more difficult. Mycobacterium bovis bacillus Calmette–Guérin vaccine fails to prevent pulmonary TB in adults, and there is an urgent need for a vaccine that is also effective in patients with human immunodeficiency virus (HIV) coinfection. Therefore, TB control may benefit on novel therapeutic options beyond antimicrobial treatment. Host-directed immunotherapies could offer therapeutic strategies for patients with drug-resistant TB or with HIV and TB coinfection. In the last years, the use of donor lymphocytes after hematopoietic stem cell transplantation has emerged as a new strategy in the cure of hematologic malignancies in order to induce graft-versus leukemia and graft-versus-infection effects. Moreover, adoptive therapy has proven to be effective in controlling cytomegalovirus and Epstein-Barr virus reactivation in immunocompromised patients with ex vivo expanded viral antigen-specific T cells. Unconventional T cells are a heterogeneous group of T lymphocytes with limited diversity. One of their characteristics is that antigen recognition is not restricted by the classical major histocompatibility complex (MHC). They include CD1 (cluster of differentiation 1)–restricted T cells, MHC-related protein-1–restricted mucosal-associated invariant T (MAIT) cells, MHC class Ib–reactive T cells, and γδ T cells. Because these T cells are genotype-independent, they are also termed “donor unrestricted” T cells. The combined features of low donor diversity and the lack of genetic restriction make these cells suitable candidates for T cell–based immunotherapy of TB.

Introduction: Pharmacological intervention is an important component of patient care. However, drugs are often inappropriately used. It is necessary for countries to implement strategies to improve the rational use of drugs, including independent information for healthcare professionals and the public, which must be supported by well-trained staff. The primary objectives of the EDU.RE.DRUG (Effectiveness of informative and/or educational interventions aimed at improving the appropriate use of drugs designed for general practitioners and their patients) study are the retrospective evaluation of rates of appropriate prescribing indicators (APIs) and the assessment of the effectiveness of informative and/or educational interventions addressed to general practitioners (GPs) and their patients, aimed at improving prescribing quality and promoting proper drug use. Methods and analysis: This is a prospective, multicentre, open-label, parallel-arm, controlled, pragmatic trial directed to GPs and their patients in two Italian regions (Campania and Lombardy). The study data are retrieved from administrative databases (Demographic, Pharmacy-refill, and Hospitalization databases) containing healthcare information of all beneficiaries of the National Health Service in the Local Health Units (LHUs) involved. According to LHU, the GPs/patients will be assigned to one of the following four intervention arms: (1) intervention on GPs and patients; (2) intervention on GPs; (3) intervention on patients; and (4) no intervention (control). The intervention designed for GPs consists of reports regarding the status of their patients according to the APIs determined at baseline and in two on-line Continuous Medical Education (CME) courses. The intervention designed for patients consists in flyers and posters distributed in GPs ambulatories and community pharmacies, focusing on correct drug use. A set of indicators (such as potential drug–drug interactions, unnecessary duplicate prescriptions, and inappropriate prescriptions in the elderly), adapted to the Italian setting, has been defined to determine inappropriate prescription at baseline and after the intervention phase. The primary outcome was a composite API. Ethics and dissemination: The study was approved by the Ethics Committee of the University of Milan on 7th June 2017 (code 15/17). The investigators will communicate trial results to stakeholders, collaborators, and participants via appropriate presentations and publications. Registration details: NCT04030468. EudraCT number 2017-002622-21

Different and several public health strategies have been planned to reduce transmission of pandemic due to SARS-CoV-2 since it started. None drugs have been confirmed as able to prevent viral transmission. Hydroxychloroquine with its immunomodulatory properties has been proposed as potential anti-viral drug in particular for prevention once viral exposure has been happen or in first phases of infection. Furthermore, in several immunological systemic disease hydroxychloroquine was able to reduce the number of thrombotic complications. So, because COVID-19 was associated to immunological imbalance and to thrombotic complications, we retrospectively analyzed the rate of infection in those patients being under treatment with this drug during COVID-19 epidemic outbreak from 8 March until 28 April in particular comparing those with pre-exposure to this treatment and those that were not taking this medication before SARS-CoV-2 viral infections.

Objective: To assess whether the introduction of the new diagnostic criteria and disease modifying therapies (DMTs) is associated with higher cost for treating multiple sclerosis (MS). Methods: This is a regression-based quasi-experimental study employing interrupted time series analysis, including data from 2229 patients (age 42.1 ± 11.2 years; female 63.34%), with incident diagnosis of relapsing remitting MS (RRMS) and followed up from 1997 to 2017, extracted from the database of the MS Clinical Care and Research Centre of the Federico II University Hospital of Naples (Italy). Annual healthcare costs for DMT (e.g., prescription, staff involved in DMT administration) and management (e.g., neurological consultations, other consultations related to DMT safety, MRI, laboratory exams), were calculated and inflated to the most recent value. Results: Annual costs per patient for DMT prescription and management were not affected by the introduction of 2001 and 2005 criteria, but decreased by 0.4% after the introduction of 2011 criteria (PD= -0.4%; 95% C.I. -0.7%/-0.0%; p=0.023). Annual costs per patient increased by 11.2% after the introduction of Natalizumab in 2007 (PD= 11.2%; 95% C.I.= 9.4%/13.0%; p

Background: The steady increase in type 2 diabetes prevalence and the availability of new antidiabetic drugs (AD) have risen the use of these drugs with a change in the patterns of specific drug utilization. The complexity of this treatment is due to successive treatment initiation, switching and addition in order to maintain glycaemic control. The purpose of this study was to describe the utilization patterns of ADs at initiation, treatment addition and switching profiles and to measure factors influencing persistence to therapy. Methods: Retrospective observational study. Data were retrieved from the Campania Regional Database for Medication Consumption. Population was composed by patients receiving at least one prescription of ADs between January 1 and December 31, 2016. We calculated time to treatment switching or add-on as median number of days and interquartile range (IQR). Persistence rates were estimated using the Kaplan-Meier method. We used Cox regression models to estimate the likelihood of non-persistence over one year of follow-up. Hazard ratios and 95% confidence intervals were calculated. Results: Of 14,679 subjects, 86.9% started with monotherapy and 13.1% with combination therapy. Most common initial treatment was metformin, both in monotherapy and combination therapy. First-line prescription of sulfonylurea was observed in 6.9% of patients aged 60-79 years and in 10.8% of patients aged ≥80 years. Patients starting with metformin showed fewer treatment modifications (10.4%) compared to patients initiating with sulfonylureas (35.2%). Newer ADs were utilized during treatment progression. Subjects initiated with sulfonylurea were approximately 70% more likely to discontinue treatment compared to those initiated on metformin. Oldest age group (≥80years) was more likely to be non-persistent and likelihood of non-persistence was highest in polymedicated patients. Patients changing therapy were more likely to be persistent. Conclusions: Our results show that treatment of T2D in Italy is consistent with clinical guidelines. Even if newer ADs were utilized during disease progression, they seem not to be preferred in patients with a higher comorbidity score although these patients could benefit from this kind of treatment. Our study highlights patients’ characteristics that may help identify those who would benefit from counselling from their health-care practitioner on better ADs usage.

Objectives: The objective was to identify the systematic associations among chronic diseases and drugs in the form of patterns and to describe and clinically interpret the constituted patterns with a focus on exploring the existence of potential drug-drug and drug-disease interactions and prescribing cascades. Methods: This observational, cross-sectional study used the demographic and clinical information from electronic medical databases and the pharmacy billing records of all users of the public health system of the Spanish region of Aragon in 2015. An exploratory factor analysis was conducted based on the tetra-choric correlations among the diagnoses of chronic diseases and the dispensed drugs in 887, 572 patients aged 65 years. The analysis was stratified by age and sex. To name the constituted patterns, assess their clinical nature, and identify potential interactions among diseases and drugs, the associations found in each pattern were independently reviewed by two pharmacists and two doctors and tested against the literature and the information reported in the technical medicinal forms. Results: Six multimorbidity-polypharmacy patterns were found in this large-scale population study, named as respiratory, mental health, cardiometabolic, endocrinological, osteometabolic, and mechanical-pain. The nature of the patterns in terms of diseases and drugs differed by sex and age and became more complex as age advanced. Conclusions: The six clinically sound multimorbidity-polypharmacy patterns described in this non-elderly population confirmed the existence of systematic associations among chronic diseases and medications, and revealed some unexpected associations suggesting the prescribing cascade phenomenon as a potential underlying factor. These findings may help to broaden the focus and orient the early identification of potential interactions when caring for multimorbid patients at high risk of adverse health outcomes due to polypharmacy.

Background Nonadherence can reduce treatment effectiveness and can negatively affect healthcare costs and thus the treatments’ cost-effectiveness. Adherence in the setting of osteoporosis has been shown to be just as problematic, if not worse, than that in other chronic diseases. Economic evaluations based on modelling are commonly used to compare alternative treatment strategies in osteoporosis, to support decision-makers and to inform treatment guidelines. Objectives The aim of this study is to analyse healthcare costs of osteoporosis and to build a economic model cost-effectiveness of pharmacological intervents based on real world data. Methods The data of the analysed subjects were drawn from the administrative databases of four Local Health Authorities in the Abruzzo Region. Patients 60 years of age or older were included if at least one prescription for any antiosteoporosis drugs had been filled in between January 1, 2006 and December 31, 2006. The patients were classified as exposed or not exposed to osteoporotic fracture. For each group, compliance with antiosteoporosis drugs was calculated. Patients were considered compliant if their Medication Possession Ratio (MPR) was ≥80%. The cost analysis was conducted taking each healthcare service into account, i.e. drug therapy, diagnostic tests and hospitalisation admissions, during the study period. A hypothetical scenario based on the real-life available evidence was constructed. The mean level of adherence to populate the hypothetical scenario of “full adherence” was set at MPR>80%. The model built by adding a step value, constrained by a normal random variable, to the real-word adherence of each subject so that the subject shifted to the hypotetical scenario of full adherence, in order to quantify the clinical outcome (number of fractures) achievable in the hypotetical scenario. Cost-effectiveness of full adherence compared to real world adherence was expressed in terms of Incremental Cost Effectiveness Ratio (ICER) and the number of fractures avoided was set as an effectiveness unit of measure. Results The mean annual healthcare cost per fracture avoided was € 247.44, of which medical treatments and diagnostic tests accounted for € 103.60 (41.9%) and € 143.84 (58.1%), respectively. The mean annual helathcare cost per fractured patient was € 1,044.85, of which medical treatments, diagnostic tests and hospitalizations for osteoporotic fracture accounted for € 88.73 (8.5%), € 169.48 (16.2%) and € 786.65 (75.3%), respectively. Conclusions Costs per fractured patients resulted to be about four times greater than those of not fractured patients. Therefore, only enhancing adherence to medication may lead to reductions in the number of patients requiring hospitalisation. References [1] Hiligsmann M, Boonen A, Rabenda V, Reginster JY. The importance of integrating medication adherence into pharmacoeconomic analyses: the example of osteoporosis2012;159–166. [2] Scotti L, Arfe A, Zambon A, Merlino L, Corrao G. Cost-effectiveness of enhancing adherence with oral bisphosphonates treatment in osteoporotic women: an empirical approach based on healthcare utilisation databases. BMJ open2014;4(3),e003758. Disclosure of Interest None declared

Background Osteoporosis is mostly defined as the disease of women, because the prevalence and fracture rates are much higher in postmenopausal women than in older men. However, there has been increasing recognition that male osteoporosis also represents an important burden as a common cause of morbidity, mortality and health care expenditure. Also, men are more likely than women to have osteoporosis that is undiagnosed and undertreated. Moreover, bone fracture are important factors of high mortality and morbidity rates in osteoporotic patients. Lack of persistence is common among subjects using oral anti-osteoporotic drugs, and leads to increased risk of fragility fracture. Objectives The aim of this study is to perform gender specific analysis regarding the persistence to antiosteoporosis drugs. Methods We conducted a retrospective cohort study using administrative data from four local health authorities in the Abruzzo Region (Central Italy), which comprise about 9 00 000 inhabitants (68% of the overall regional population). Patients 60 years of age or older were included if at least one prescription for any antiosteoporosis drugs had been filled in between January 1, 2006 and December 31, 2006. Persistence estimates over time (discontinuation rates were assessed at 365 days) were derived using Kaplan–Meier survival analysis, stratifying for gender, considering treatment discontinuation as failure event and comparing differences using Log-rank test (1 degree of freedom). Results The final cohort consisted of a total of 7867 patients (87.2% women). The mean patient age for both genders at the index date was 74.5 years. The crude analysis of long-term gender persistence showed a significant difference between women and men: the relative number of persistence patients after 1 year was 66.4% in men and 44.7% in women. The Kaplan Meier plots of time to persistence start to differ for men vs women approximately 60 days after treatment start (figure 1). Conclusions The results showed that gender influences adherence to therapy and this is an issue that could be taken in strong consideration in tailor intervention to improve adherence. References [1] Cawthon PM. Gender differences in osteoporosis and fractures. Clinical Orthopaedics and Related Research2011;469(7):1900–1905. [2] Bor A, Matuz M, Gyimesi N, et al. Gender inequalities in the treatment of osteoporosis. Maturitas2015;80:162–169. [3] Christopher J, et al. Sex and gender considerations in male patients with osteoporosis. Clinical Orthopaedics and Related Research2011;469(7):1906–1912. Disclosure of Interest None declared

Background Osteoporosis is a chronic progressive disease characterised by low bone mass and deterioration of bone structure, leading to an increate risk of fractures. It is a major public health problem, affecting hundreds of millions of people worldwide. The primary aim of pharmaceutical therapy is to reduce the risk of osteoporotic fractures. However, long-term adherence to therapy is requie for optimal therapeutic benefit for patients with osteoporosis. Poor adherence is considered to be one primary reason for suboptimal clinical benefit. Objectives The aim of this study was to investigate the determinants of non-persistence and impact of persistence on the risk of fractures by using administrative databases. Methods We conducted a retrospective cohort study using administrative data from four local health authorities in the Abruzzo Region (Central Italy), which comprise about 9 00 000 inhabitants (68% of the overall regional population). The final cohort consisted of a total of 7862 patients, aged ≥60 years, identified through records of filled prescriptions for an antiosteoporotic drug between January 1, 2006 to December 31, 2006. The primary outcome of this study was persistence at one year. Persistence was defined as the length of time (in days) from the date of the index prescription to the date of discontinuation therapy. Results Kaplan – Meier analysis showed that 3733 patients (47.5%) were persistent with antiosteoporotic drugs after 1 year. An adjusted analysis showed that there is a big difference in persistence between women and men: women are more likely to be non-persistent than men (HR:1.94). Switcher patients were more likely to be non-persistent (HR:1.22). The odds of fracture were significantly higher for patients with previous fractures in comparison with those without previous fractures [OR, 1.70, (95% CI, 1.12–2.59)] (table 1) Table 1 Logistic regression model: impact of persistence and other factors on the risk fracture Conclusions Persistence with antiosteoporotic drugs is a significant predictor of incurring a fracture. For these reason, improving osteoporosis treatment compliance and persistence represents one of a major challenge for the future. References [1] Casula M, Filippi A, Flacco E, Gambera M, Manzoli L, Menditto E, Orlando V, Piccinelli R, Tragni E, Catapano A. Assessment and potential determinats of compliance and persistence to anti-osteoporosis therapy in Italy. Am J Manag Care2014;20(5):e138-e145. [2] Iolascon G, Gimigliano F, Orlando V, Capaldo A, Di Somma C, Menditto E. Osteoporosis drugs in real-world clinical practice: an analysis of persistence. Aging Clin Exp Res2013Oct;25 Suppl 1:S137–41. Disclosure of Interest None declared

Infections by multidrug-resistant (MDR) bacteria are a worrisome phenomenon in hematological patients. Data on the incidence of MDR colonization and related bloodstream infections (BSIs) in haematological patients are scarce. A multicentric prospective observational study was planned in 18 haematological institutions during a 6-month period. All patients showing MDR rectal colonization as well as occurrence of BSI at admission were recorded. One-hundred forty-four patients with MDR colonization were observed (6.5% of 2226 admissions). Extended spectrum beta-lactamase (ESBL)-producing (ESBL-P) enterobacteria were observed in 64/144 patients, carbapenem-resistant (CR) Gram-negative bacteria in 85/144 and vancomycin-resistant enterococci (VREs) in 9/144. Overall, 37 MDR-colonized patients (25.7%) developed at least one BSI; 23 of them (62.2%, 16% of the whole series) developed BSI by the same pathogen (MDRrel BSI), with a rate of 15.6% (10/64) for ESBL-P enterobacteria, 14.1% (12/85) for CR Gram-negative bacteria and 11.1% (1/9) for VRE. In 20/23 cases, MDRrel BSI occurred during neutropenia. After a median follow-up of 80 days, 18 patients died (12.5%). The 3-month overall survival was significantly lower for patients colonized with CR Gram-negative bacteria (83.6%) and VRE (77.8%) in comparison with those colonized with ESBL-P enterobacteria (96.8%). CR-rel BSI and the presence of a urinary catheter were independent predictors of mortality. MDR rectal colonization occurs in 6.5% of haematological inpatients and predicts a 16% probability of MDRrel BSI, particularly during neutropenia, as well as a higher probability of unfavourable outcomes in CR-rel BSIs. Tailored empiric antibiotic treatment should be decided on the basis of colonization.

Causality assessment is a fundamental biomedical technique for the signal detection performed by Pharmacovigilance centers in a Spontaneous reporting system. Moreover, it is a crucial and important practice for detecting preventable adverse drug reactions. Among different methods for causality assessment, algorithms (such as the Naranjo, or Begaud Methods) seem for their operational procedure and easier applicability one of the most commonly used methods. With the upcoming of the new European Pharmacovigilance legislation including in the definition of the adverse event also effects resulting from abuse, misuse and medication error, all well-known preventable causes of ADRs, there was an emerging need to evaluate whether algorithms could fulfill this new definition. In this review, twenty-two algorithmic methods were identified and none of them seemed to fulfill perfectly the new criteria of adverse event although some of them come close. In fact, several issues were arisen in applying causality assessment algorithms to these new definitions as for example the impossibility to answer the rechallenge question in case of medication error or AEFI (Adverse Event Following Immunization). Moreover, the exact conditions at which events occurred, as for example dosage or mode of administration should be considered to better assess causality in conditions of abuse/overdose, or misuse as well as in conditions of lack of expected efficacy reports for biotechnological drugs and adverse event occurring after mixing of vaccines. Therefore, this review highlights the need of updating algorithmic methods to allow a perfect applicability in all possible clinical scenarios accordingly or not with the terms of marketing authorization.

Tuberculosis (TB) is one of the most important cause of morbidity and death among infectious diseases, and continuous efforts are needed to improve diagnostic tools and therapy. Previous published studies showed that the absolute cells number of monocytes or lymphocytes in peripheral blood or yet the ratio of monocytes to lymphocytes displayed the ability to predict the risk of active TB. In the present study we evaluated the ratio of monocytes to lymphocytes variation and we also analyzed the ex-vivo expression of CD64 on monocytes as tools to identify biomarkers for discriminating TB stages. Significant differences were found when the average ratio of monocytes to lymphocytes of active TB patients was compared with latent TB infection (LTBI) subjects, cured TB and healthy donors (HD). By the receiver operator characteristics (ROC) curve analysis the cut-off value of 0.285, allowed the discrimination of active TB from HD, with a sensitivity of 91.04% and a specificity of 93.55% (95% of confidence interval: 0.92–0.99). The ROC curve analysis comparing TB patients and LTBI groups, led to a sensitivity and the specificity of the assay of 85.07% and 85.71%, respectively (95% of confidence interval: 0.85 to 0.96). The upregulation of CD64 expression on circulating monocytes in active TB patients could represent an additional biomarker for diagnosis of active TB. In conclusion, we found that the ML ratio or monocyte absolute count or phenotypic measures show predictive value for active TB.

Subjects with chronic diseases are more likely to be nonpersistent to pharmacological treatment. Lack of persistence is common among subjects using oral anti-osteoporotic drugs, and leads to increased risk of fragility fracture. The aim of our retrospective study is to analyze the rates and reasons for discontinuation of anti-osteoporotic drugs in the Campania Region. Subjects aged over 40 years were included if they had received at least one prescription for any anti-osteoporotic drugs. Data were obtained from an administrative database of regional data on outpatient drug prescriptions reimbursed by the National Health Service. Patients were followed until the discontinuation of anti-osteoporotic therapy or until the end of the observation period. A total of 30,048 were incident users of anti-osteoporotic drugs: 28,317 (94.2%) females. The mean age of the cohort was 69.0±10.0 years. Weekly bis-phosphonates (51.1%) were the most commonly prescribed drugs. In the overall population, persistence rates were 34.8% after 6 months and 13.4% at one year. A multivariate Cox proportional hazard analysis showed that daily regimen (HR 1.9) treatments remained at higher risk of early discontinuation compared to weekly regimen therapies. Our data showed that the persistence to osteoporosis therapy is significantly worse than reported in literature.

Objectives Biological drugs have improved the management of moderate to severe psoriasis. Little is known about their drug utilization pattern in daily clinical practice. The aim of this study was to estimate the treatment patterns and drug-related cost among patients with psoriasis who initiated biologic therapy. Methods The data used for this retrospective study was obtained from the health administrative database of Caserta Local Health Authority (1 million inhabitants, South of Italy). The health administrative database of Caserta is a data warehouse integrating information from hospital discharge records, pharmacy records, and ambulatory records. We included in the study all subjects that received at least one dispensing of biological drugs (adalimumab, etanercept, infliximab or ustekinumab) from January 2010 to December 2014. Indication for biological drug treatment was retrieved from therapeutically plan. An incident user was defined as a subject who filled his first prescription (index-date) after 2 years biological drugs-free run-in period. Incident biologic users were categorized according to type of biologic prescribed. Medication use patterns, including switching, were identified during a 1-year follow-up period. Results 387 subjects treated with biological drugs for psoriasis were identified in the study period. 125 incident users were analyzed. Among these, 56.8% received etanercept as first therapy, 26.4% adalimumab, 9.6% ustekinumab, 7.2% infliximab. In 1-year follow-up period, incident users continued their index biologic with an average time to switch of 138.8 days. Rates of switching, was 8.0%, for all patients. Pharmacy expenditure, calculated as annual average cost/per patient, was higher for the switching cohort than the non-switching cohort (14,210 Euro vs 10, 942 Euro). Conclusions The pharmacy expenditure is highly influenced by switch. Our findings may have implications for real-world practice studies.

The aim of our retrospective cohort study is to analyze the persistence rates in relation to antiosteoporotic drugs using administrative databases in the Campania Region. Patients, aged ≥40 years, were included if at least one prescription for any antiosteoporotic drugs had been filled in between January 1, 2009 and December 31, 2009. Overall, 37,594 patients were incident users of antiosteoporotic drugs. Among them, 15,978 patients had undergone spot-therapies. A total of 2,618 (14.1 %) were classified as switchers. Switching rates were highest for patients taking Alendronate 18.9 or Strontium Ranelate 15.0 and lower for patients taking Ibandronate 12.8 or Risedronate 10.8. In the overall population, 33.5 % of subjects were still on therapy after 6 months. At 1 year, persistence rates were: Ibandronate 21.6 %, Risedronate 15.8 %, Alendronate + Vitamin D 15.7 %, Raloxifene 14.3 %, Alendronate 12.6 % and Strontium Ranelate 5.0 %.

Although the micronutrient deficiencies and the related neurological manifestations are widely reported after malabsorbitive weight loss surgery, little is known about cerebral dysfunction secondary to micronutrient impairment in subjects undergoing restrictive interventions (that is, sleeve gastrectomy). We describe a case of a 27-year-old woman with a late development of a Wernicke's encephalopathy (WE) and of severe polyneuropathy following a sleeve gastrectomy without any sleeve stenosis. The impact of WE after bariatric surgery is significantly underestimated. Such a risk should be taken into consideration also after restrictive weight loss surgery. Thus, surgeoun/clinicians involved in bariatric patients management must be aware of neurological sequelae related to this intervention.European Journal of Clinical Nutrition advance online publication, 8 February 2012; doi:10.1038/ejcn.2012.10.

The potent anti-tumor activities of γδ T cells, their ability to produce pro-inflammatory cytokines, and their strong cytolytic activity have prompted the development of protocols in which γδ agonists or ex vivo-expanded γδ cells are administered to tumor patients. γδ T cells can be selectively activated by either synthetic phosphoantigens or by drugs that enhance their accumulation into stressed cells as aminobisphosphonates, thus offering new avenues for the development of γδ T cell-based immunotherapies. The recent development of small drugs selectively activating Vγ9Vδ2 T lymphocytes, which upregulate the endogenous phosphoantigens, has enabled the investigators to design the experimental approaches of cancer immunotherapies; several ongoing phase I and II clinical trials are focused on the role of the direct bioactivity of drugs and of adoptive cell therapies involving phosphoantigen- or aminobisphosphonate-activated Vγ9Vδ2 T lymphocytes in humans. In this review, we focus on the recent advances in the activation/expansion of γδ T cells in vitro and in vivo that may represent a promising target for the design of novel and highly innovative immunotherapy in patients with hematologic malignancies.

The potent anti-tumour activities of gamma delta T cells have prompted the development of protocols in which gamma delta-agonists are administered to cancer patients. Encouraging results from small Phase I trials have fuelled efforts to characterize more clearly the application of this approach to unmet clinical needs such as metastatic carcinoma. To examine this approach in breast cancer, a Phase I trial was conducted in which zoledronate, a V gamma 9V delta 2 T cell agonist, plus low-dose interleukin (IL)-2 were administered to 10 therapeutically terminal, advanced metastatic breast cancer patients. Treatment was well tolerated and promoted the effector maturation of V gamma 9V delta 2 T cells in all patients. However, a statistically significant correlation of clinical outcome with peripheral V gamma 9V delta 2 T cell numbers emerged, as seven patients who failed to sustain V gamma 9V delta 2 T cells showed progressive clinical deterioration, while three patients who sustained robust peripheral V gamma 9V delta 2 cell populations showed declining CA15-3 levels and displayed one instance of partial remission and two of stable disease, respectively. In the context of an earlier trial in prostate cancer, these data emphasize the strong linkage of V gamma 9V delta 2 T cell status to reduced carcinoma progression, and suggest that zoledronate plus low-dose IL-2 offers a novel, safe and feasible approach to enhance this in a subset of treatment-refractory patients with advanced breast cancer.

Imatinib mesylate (imatinib), a competitive inhibitor of the BCR-ABL tyrosine kinase, is highly effective against chronic myelogenous leukemia (CML) cells. However, because 20–30% of patients affected by CML display either primary or secondary resistance to imatinib, intentional activation of Vγ9Vδ2 T cells by phosphoantigens or by agents that cause their accumulation within cells, such as zoledronate, may represent a promising strategy for the design of a novel and highly innovative immunotherapy capable to overcome imatinib resistance. In this study, we show that Vγ9Vδ2 T lymphocytes recognize, trogocytose, and efficiently kill imatinib-sensitive and -resistant CML cell lines pretreated with zoledronate. Vγ9Vδ2 T cell cytotoxicity was largely dependent on the granule exocytosis- and partly on TRAIL-mediated pathways, was TCR-mediated, and required isoprenoid biosynthesis by zoledronate-treated CML cells. Importantly, Vγ9Vδ2 T cells from patients with CML can be induced by zoledronate to develop antitumor activity against autologous and allogeneic zoledronate-treated leukemia cells, both in vitro and when transferred into immunodeficient mice in vivo. We conclude that intentional activation of Vγ9Vδ2 T cells by zoledronate may substantially increase their antileukemia activities and represent a novel strategy for CML immunotherapy.