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Simple Summary: This study analyzes the use of rituximab (RTX) in the daily clinical practice of several Italian oncohematology centers, with a particular focus on the adoption of biosimilars. The results show that only a minority of patients (22%) switched between different biosimilars, while the majority continued treatment with the biosimilars Rixathon and Truxima. This finding suggests that the proactive sharing of guidelines between regulators and prescribers, from the outset, may be an effective strategy to further promote the adoption of biosimilars. This approach could be particularly useful in those areas where the use of biosimilars is still lower than the national average, helping to free up economic resources that could be redirected towards other healthcare opportunities. The clinical safety and efficacy of rituximab biosimilars compared to the reference rituximab (Mabthera) have been well established in randomized trials. However, concerns persist regarding the safety of changing from the reference product to biosimilars, and particularly between different biosimilars. This prospective multicenter observational study was conducted in 13 oncohematology units of eight Italian regions. The study included 800 patients with non-Hodgkin lymphoma (NHL) or chronic lymphocytic leukemia (CLL) who received rituximab between March 2018 and June 2022. To minimize survivorship bias, only newly diagnosed patients (i.e., those without prior rituximab treatment) were included in the analysis of adverse drug reactions (ADRs). Thus, this study focused on 505 incident cases (79.8% of the initial cohort) from 13 centers. A total of 3681 rituximab infusions were administered, and 16.8% of the patients experienced at least one ADR. These were observed most frequently during the first infusion (44 patients, 52%) and the second infusion (17 patients, 20%). The most frequent reactions were general disorders and administration site conditions (n. 50, 8% serious). These findings support the clinical safety of rituximab biosimilars and suggest that switching between biosimilars does not increase the risk of adverse events. This evidence may alleviate concerns about biosimilar use, potentially leading to broader acceptance and reduced healthcare costs. [ABSTRACT FROM AUTHOR]

The implementation of public health knowledge is a complex process; researchers focus on organizational barriers but generally give little attention to the format and validity of relevant information. Primary and secondary papers and practice guidelines should represent valid and relevant sources of knowledge for clinicians and others involved in public health. However, this information is usually targeted at researchers rather than practitioners; it is often not completely intelligible, does not explain what it really adds to existing knowledge or which clinical/organizational context to place it in, and often lacks 'appeal' for those who are less informed. Moreover, this information is sometimes founded on biased research, shaped by sponsors to give scientific plausibility to market-driven messages. A 'social marketing' approach can help public health researchers make evidence-based information clear and appealing. The validity and relevance of this information can be explained to target readers in light of their own knowledge levels and in terms of how this information could help their practice. In this paper we analyse the barriers to knowledge transfer that are often inherent in the format of the information, and propose a more user-friendly, enriched and non-research-article format. Keywords: Independent drug information; Knowledge translation; Evidence-based medicine; Social marketing; Critical appraisal

Objective: Presenting an approach to synthesize quantitative and qualitative information from systematic reviews of multiple health interventions. Methods: Within the context of an EUnetHTA multi-health technology assessment of twenty-three surgical techniques, we developed synthetic single tables, using color gradients and abbreviations, with information on which technologies had been compared, estimates of the size of differences for available comparisons, their clinical relevance, and certainty of the related evidence. Results: The proposed methodology provided, through a single depiction, information normally included in multiple figures/tables such as network plots, league tables, and summary of findings tables. Conclusion: Transferring information on benefits, risks, and certainty of the available evidence on health interventions may be challenging, especially when assessing multiple treatments: more pieces of information need to be integrated in order to show an overall picture for each of the chosen outcomes, and usual reporting tools may be targeted to researchers more than to different kinds of decision makers. While more in-depth layers of information can always be added to satisfy needs of different audiences, the proposed tools could favor a quick interpretation of articulated scientific data by both decision makers and researchers. [ABSTRACT FROM AUTHOR]

Abstract Background Coxibs are claimed to be cost-effective drugs and reduced prescription of gastroprotective agents is assumed to be one of their major benefits. Real life prescription of these drugs may be substantially different than that considered in pharmacoeconomic analyses or claimed by drug companies, yet. Our objective was to evaluate whether coxibs were associated with reduced prescription of gastro-protective agents (GPAs, specifically proton pump inhibitors, H2 blockers and misoprostol) compared to non selective NSAIDs. Methods A record-linkage study was performed using 2001 outpatient prescription data from the province of Modena (about 632,000 inhabitants, in Northern Italy). Logistic regression was used to calculate the odds ratio of GPA prescription for coxib and non-selective NSAID adult users (> 14 years). Three categories of users were further investigated: "acute", "chronic and "incident or new". Main outcome measures were same-day co-prescription and 30 days prescription of GPAs in coxibs and non selective NSAIDs users. To limit selection bias, data were adjusted for age, sex, DDD of coxibs and non selective NSAIDs received during 2001, DDD of GPAs and (for non-incident users) DDD of NSAIDs received during the previous 4 years Results Same day co-prescription rates were similar considering the overall population and "acute" users. Chronic coxibs users instead showed higher co-prescription rates than chronic NSAIDs users (OR = 1.2, p < 0.05). GPA prescription within thirty days was also higher among all subgroups of coxibs users (OR ranging from 1.6 to 2.0, p < 0.001). Conclusion Assumptions made in pharmacoeconomic analyses on coxibs (lower GPA prescription associated with coxibs use) may be overly optimistic. Claims made through cost-effectiveness data should be carefully interpreted, and mechanisms for attributing drug prices revised accordingly.

Abstract Background Research has shown that many healthcare professionals have problems with guidelines as they would prefer to be given all relevent information relevent to decision-making rather than being told what they should do. This study assesses doctors' judgement of the validity, relevance, clarity and usability of the Italian translation of Clinical Evidence (CE) after its free distribution launched by the Italian Ministry of Health Methods Opinions elicited using a standardised questionnaire delivered either by mail or during educational or professional meetings Results Twenty percent (n = 1350) doctors participated the study. Most of them found CE's content valid, useful and relevant for their clinical practice, and said CE can foster communications among clinicians, particularly among GPs and specialists. Hospital doctors (63%) more often than GPs (48%) read the detailed presentation of individual chapters. Twenty-nine percent said CE brought changes in their clinical practice. Doctors appreciated CE's nature of an evidence-based information compendium and would have not preferred a collection of practice guidelines. Conclusions Overall, the pilot initiative launched by the Italian Ministry of Health seems to have been well received and to support the subsequent decision to make the Italian edition of Clinical Evidence concise available to all doctors practising in the country. Local implementation initiatives should be warranted to favour doctor's use of CE.

Background: Laboratory data and computed tomography (CT) have been used during the COVID-19 pandemic, mainly to determine patient prognosis and guide clinical management. The aim of this study was to evaluate the association between CT findings and laboratory data in a cohort of COVID-19 patients.Methods: This was an observational cross-sectional study including consecutive patients presenting to the Reggio Emilia (Italy) province emergency rooms for suspected COVID-19 for one month during the outbreak peak, who underwent chest CT scan and laboratory testing at presentation and resulted positive for SARS-CoV-2.Results: Included were 866 patients. Total leukocytes, neutrophils, C-reactive protein (CRP), creatinine, AST, ALT and LDH increase with worsening parenchymal involvement; an increase in platelets was appreciable with the highest burden of lung involvement. A decrease in lymphocyte counts paralleled worsening parenchymal extension, along with reduced arterial oxygen partial pressure and saturation. After correcting for parenchymal extension, ground-glass opacities were associated with reduced platelets and increased procalcitonin, consolidation with increased CRP and reduced oxygen saturation.Conclusions: Pulmonary lesions induced by SARS-CoV-2 infection were associated with raised inflammatory response, impaired gas exchange and end-organ damage. These data suggest that lung lesions probably exert a central role in COVID-19 pathogenesis and clinical presentation. [ABSTRACT FROM AUTHOR]

Purpose Whether inhaled medications improve long-term survival in Chronic Obstructive Pulmonary Disease (COPD) is an open question. The purpose of this study is to assess the impact of adherence to inhaled drug use on 5-year survival in COPD. Methods A population-based cohort study in three Italian regions was conducted using healthcare linked datasets (hospitalization, mortality, drugs). Individuals (45+ years) discharged after COPD exacerbation in 2006-2009 were enrolled. Inhaled drug daily use during 5-year follow-up was determined through Proportion of Days Covered on the basis of Defined Daily Doses. Five levels of time-dependent exposure were identified: (i) long-acting β2 agonists and inhaled corticosteroids (LB/ICS) regular use; (ii) LB/ICS occasional use; (iii) LB regular use; (iv) LB occasional use; and (v) respiratory drugs other than LB. Cox regression models adjusted for baseline (socio-demographic, comorbidities, drug use) and time-dependent characteristics (COPD exacerbations, cardiovascular hospitalizations, cardiovascular therapy) were performed. Results A total of 12 124 individuals were studied, 46% women, mean age 73,8 years. Average follow-up time 2,4 year. A total of 3415 subjects died (mortality rate = 11.9 per 100 person years). In comparison to LB/ICS regular use, higher risks of death for all remaining treatments were found, the highest risk for respiratory drugs other than LB category (HR = 1.63, 95%CI 1.43-1.87). Patients with regular LB use had higher survival than those with LB/ICS occasional use (HR = 0.89, 95%CI 0.79-0.99). Conclusions These findings support clinical guidelines and recommendations for the regular use of inhaled drugs to improve health status and prognosis among moderate-severe COPD patients. © 2016 The Authors. Pharmacoepidemiology and Drug Safety Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Combined inhaled therapy in chronic obstructive pulmonary disease (COPD) is commonly used, but its benefits remain controversial. We assessed the effect of tiotropium in reducing COPD exacerbations when combined with long-acting β2 agonists (LABA) and/or inhaled corticosteroids (ICS). This new-user cohort study is based on administrative data from 3 Italian regions. We identified adults hospitalized for COPD from 2006 to 2009 who were newly prescribed a fixed LABA/ICS combination (double therapy). We classified patients according to whether tiotropium was also prescribed (triple therapy), using both intention-to-treat and as-treated approaches, and followed them for 1 year. COPD exacerbations were measured as outcomes. Multivariate and propensity score-adjusted hazard ratios (HRs, 95%CI) were calculated with Cox regression models. We identified 5717 new users of LABA/ICS of which 31.9% initiated triple therapy. In the intention-to-treat analysis, the multivariate adjusted HR for moderate, severe, and any exacerbations were 1.02 (95%CI 0.89-1.16), 0.92 (95%CI 0.76-1.12), and 1.08 (95%CI 0.91-1.28), respectively. The propensity score adjustment produced similar results. In the subcohort of patients with previous exacerbations, triple therapy was significantly associated with reduced risk of moderate exacerbations, compared to double therapy (HR 0.68, 95%CI 0.48-0.98 in intention-to-treat approach). In conclusion, the addition of tiotropium to LABA/ICS did not reduce COPD exacerbations compared to LABA/ICS alone. A protective role for moderate exacerbations was found in patients at risk of frequent exacerbations. Given the impact of exacerbations on health status and prognosis, it is crucial to target COPD patients for optimal treatment. [ABSTRACT FROM AUTHOR]

Introduction: Information on benefits and risks of drugs is a key element affecting doctors’ prescribing decisions. Outreach visits promoting independent information have proved moderately effective in changing prescribing behaviours. Objectives: Testing the short and long-term effectiveness on general practitioners’ prescribing of small groups meetings led by pharmacists. Methods: Two cluster open randomised controlled trials (RCTs) were carried out in a large scale NHS setting. Ad hoc prepared evidence based material were used considering a therapeutic area approach - TEA, with information materials on osteoporosis or prostatic hyperplasia - and a single drug oriented approach - SIDRO, with information materials on me-too drugs of 2 different classes: barnidipine or prulifloxacin. In each study, all 115 Primary Care Groups in a Northern Italy area (2.2 million inhabitants, 1737 general practitioners) were randomised to educational small groups meetings, in which available evidence was provided together with drug utilization data and clinical scenarios. Main outcomes were changes in the six-months prescription of targeted drugs. Longer term results (24 and 48 months) were also evaluated. Results: In the TEA trial, one of the four primary outcomes showed a reduction (prescription of alfuzosin compared to tamsulosin and terazosin in benign prostatic hyperplasia: prescribing ratio −8.5%, p = 0.03). Another primary outcome (prescription of risedronate) showed a reduction at 24 and 48 months (−7.6%, p = 0.02; and −9,8%, p = 0.03), but not at six months (−5.1%, p = 0.36). In the SIDRO trial both primary outcomes showed a statistically significant reduction (prescription of barnidipine −9.8%, p = 0.02; prescription of prulifloxacin −11.1%, p = 0.04), which persisted or increased over time. Interpretation: These two cluster RCTs showed the large scale feasibility of a complex educational program in a NHS setting, and its potentially relevant long-term impact on prescribing habits, in particular when focusing on a single drug. National Health systems should invest in independent drug information programs. Trial Registration: Controlled-Trials.com [ABSTRACT FROM AUTHOR]

Background: Suboptimal translation of valid and relevant information in clinical practice is a problem for all health systems. Lack of information independent from commercial influences, limited efforts to actively implement evidence-based information and its limited comprehensibility are important determinants of this gap and may influence an excessive variability in physicians' prescriptions. This is quite noticeable in Italy, where the philosophy and methods of Evidence-Based Medicine still enjoy limited diffusion among practitioners. Academic detailing and pharmacist outreach visits are interventions of proven efficacy to make independent and evidence-based information available to physicians; this approach and its feasibility have not yet been tested on a large scale and, moreover, they have never been formally tested in Italy. Methods/Design: Two RCTs are planned: 1) a two-arm cluster RCT, carried out in Emilia-Romagna and Friuli Venezia Giulia, will evaluate the effectiveness of small group meetings, randomising about 150 Primary Care Groups (corresponding to about 2000 GPs) to pharmacist outreach visits on two different topics. Physicians' prescriptions (expressed as DDD per 1000 inhabitants/day), knowledge and attitudes (evaluated through the answers to a specific questionnaire) will be compared for target drugs in the two groups (receiving/not receiving each topic). 2) A three-arm RCT, carried out in Sardinia, will evaluate both the effectiveness of one-to-one meetings (one pharmacist visiting one physician per time) and of a 'new' information format (compared to information already available) on changing physicians' prescription of specific drugs. About 900 single GPs will be randomised into three groups: physicians receiving a visit supported by "traditional" information material, those receiving a visit with "new" information material on the same topic and those not receiving any visit/material. Discussion: The two proposed RCTs aim to evaluate the organisational feasibility and barriers to the implementation of independent information programs led by NHS pharmacists. The objective to assess a 10 or 15% decreases in the prescription of the targeted drugs is quite ambitious in such 'natural' settings, which will be minimally altered by the interventions themselves; this in spite of the quite large sample sizes used comparing to other studies of these kind. Complex interventions like these are not easy to evaluate, given the many different variables into play. Anyway, the pragmatic nature of the two RCTs appears to be also one of their major strengths, helping to provide a deeper insight on what is possible to achieve -- in terms of independent information -- in a National Health System, with special reference to Italy. Trial registration: ISRCTN05866587 (cluster RCT) and ISRCTN28525676 (single GPs RCT) [ABSTRACT FROM AUTHOR]