Drug utilization in patients starting haemodialysis with a focus on cardiovascular and antidiabetic medications: an epidemiological study in the Lazio region (Italy), 2016-2020.

BACKGROUND: Entering dialysis is a critical moment in patients' healthcare journey, and little is known about drug therapy around it. A study funded by the Italian Medicines Agency offered the opportunity to leverage data from the Lazio Regional Dialysis and Transplant Registry (RRDTL) and perform an observational study on drug use patterns before and after initiating chronic dialysis. METHODS: Individuals initiating dialysis in 2016-2020 were identified from RRDTL, excluding patients with prior renal transplantation, stopping dialysis early, or dying within 12 months. Use of study drugs, predefined by clinicians, in the two years around the index date was retrieved from the drug claims register and described by semester. For each drug group, proportions of users (min 2 claims in 6 months) by semester, and intensity of treatment in terms of Defined Daily Doses (DDDs) for cardiovascular and antidiabetic agents were compared across semesters, stratifying by sex and age. RESULTS: In our cohort of 3,882 patients we observed a general increase in drug use after initiating dialysis, with the mean number rising from 5.5 to 6.2. Cardiovascular agents accounted for the highest proportions, along with proton pump inhibitors and antithrombotics over all semesters. Dialysis-specific therapies showed the most evident increase, in particular anti-anaemics (iron 4-fold, erythropoietins almost 2-fold), anti-parathyroids (6-fold), and chelating agents (4-fold). Use of cardiovascular and antidiabetic drugs was characterised by significant variations in terms of patterns and intensity, with some differences between sexes and age groups. CONCLUSIONS: Entering dialysis is associated with increased use of specific drugs and goes along with adaptations of chronic therapies.

Investigating socioeconomic disparities in lung cancer diagnosis, treatment and mortality: an Italian cohort study.

BACKGROUND: Lung cancer is one of the most lethal cancers worldwide and patient clinical outcomes seem influenced by their socioeconomic position (SEP). Since little has been investigated on this topic in the Italian context, our aim was to investigate the role of SEP in the care pathway of lung cancer patients in terms of diagnosis, treatment and mortality. METHODS: This observational retrospective cohort study included patients discharged in the Lazio Region with a lung cancer diagnosis between 2014 and 2017. In the main analysis, educational level was used as SEP measure. Multivariate models, adjusted for demographic and clinical variables, were applied to evaluate the association between SEP and study outcomes, stratified for metastatic (M) and non-metastatic (NM) cancer. We defined a diagnosis as 'delayed' when patients received their initial cancer diagnosis after an emergency department admission. Access to advanced lung cancer treatments (high-cost, novel and innovative treatments) and mortality were investigated within the 24-month period post-diagnosis. Moreover, two additional indicators of SEP were examined in the sensitivity analysis: one focusing on area deprivation and the other on income-based exemption. RESULTS: A total of 13,251 patients were identified (37.3% with metastasis). The majority were males (> 60%) and over half were older than 70 years. The distribution of SEP levels among patients was as follow: 31% low, 29% medium-low, 32% medium-high and 7% high. As SEP increased, the risks of receiving a delayed diagnosis ((high vs low: M: OR = 0.29 (0.23-0.38), NM: OR = 0.20 (0.16-0.25)) and of mortality ((high vs low M: OR = 0.77 (0.68-0.88) and NM: 0.61 (0.54-0.69)) decreased. Access to advanced lung cancer treatments increased in accordance with SEP only in the M cohort (high vs low: M: OR = 1.57 (1.18-2.09)). The primary findings were corroborated by sensitivity analysis. CONCLUSIONS: Our study highlighted the need of public health preventive and educational programs in Italy, a country where the care pathway of lung cancer patients, especially in terms of diagnosis and mortality, appears to be negatively affected by SEP level.

[How to optimize Audit&Feedback: experience from the EASY-NET programme]. / Come rendere più efficace l'Audit&Feedback: riflessioni dal programma di rete EASY-NET.

This is the second of a series of papers dedicated to the EASY-NET research programme (NET-2016-02364191). The rationale, structure and methodologies are described in the previous contribution. Scientific literature demonstrated that Audit & Feedback (A&F) is an effective strategy for continuous quality improvement and its effectiveness varies considerably according to factors that are currently little known. Some recent publication pointed out, with the contribution of an international group of experts, 15 suggestions to optimize A&F and developed a tool to evaluate their application. This tool, called REFLECT-52, includes 52 items related to the 15 suggestions and organized into four categories relating to the "Nature of the desired action", to the "Nature of the data available for feedback", to the "Feedback Display" and to the "Intervention delivery". Then, the aim of this work was to evaluate the level of adherence of A&F interventions tested in EASY-NET to suggestions from the literature by using a slightly adapted version of the REFLECT-52 tool, in its original language. In EASY-NET, 14 A&F interventions with different characteristics and in different clinical and organizational contexts were tested in seven Italian regions, each of these was evaluated by the respective research groups. Overall, the level of adherence was high in three of the four categories analysed, with some difficulties reported regarding the nature of the data available for feedback. In fact, contrary to what the literature suggests, it was not possible to send repeated feedback for some interventions and, in some cases, the data available for feedback presented a delay longer than one year. In summary, this analysis has confirmed a high level of compliance of the interventions tested with the suggestions from the literature, but it has also allowed researchers to identify critical aspects that need to be addressed for the future development of these strategies.

Long-term mitral valve repair outcomes and hospital volume: 15 years' analysis of an administrative dataset.

BACKGROUND: Procedural volume has been documented as an important contributor to operative outcomes for most complex surgical procedures. Mitral valve repair (MVRep) has been associated with excellent results, and it is increasingly adopted in many cardiac surgical centers. We sought to investigate if procedural volume is associated with better clinical long-term outcomes after MVRep. METHODS: We analyzed the 10-year outcomes after MVRep by procedural volume for each cardiac surgery center in an Italian Region, Lazio, during the last 15 years, using a regional administrative dataset. RESULTS: Between 2006 and 2020, 4961 patients were treated in seven cardiac surgery centers for an isolated mitral valve surgery (2677 underwent MVRep). At multivariate analysis, mitral valve replacement (MVR) (vs. MVRep) resulted one of the independent predictors of 30-day mortality [adjusted odds ratio (OR) 3.40; 95% confidence interval (CI) 1.96-5.90; P  < 0.0001]. Notably, a clear association between hospital volume of mitral valve surgery (>40 per year) and high rate of MVRep (>50%) was found. At 10 years, the incidence of mortality and the rate of death and rehospitalization for heart failure after MVRep were significantly lower in high-volume vs. low-volume hospitals. CONCLUSION: Our data suggest that hospital volume is associated with a high rate of MVRep and long-term benefits in terms of mortality and recurrence of heart failure.

EASY-NET Program: Effectiveness of an Audit and Feedback Intervention in the Emergency Care for Acute Conditions in the Lazio Region.

The EASY-NET network program (NET-2016-02364191)-effectiveness of audit and feedback (A&F) strategies to improve health practice and equity in various clinical and organizational settings), piloted a novel and more structured A&F strategy. This study compared the effectiveness of the novel strategy against the sole periodic dissemination of indicators in enhancing the appropriateness and timeliness of emergency health interventions for patients diagnosed with acute myocardial infarction (AMI) and ischemic stroke in the Lazio Region. The efficacy of the intervention was assessed through a prospective quasi-experimental design employing a pre- and post-intervention (2021-2022) comparison with a control group. Participating hospitals in the Lazio Region, where professional teams voluntarily engaged in the intervention, constituted the exposed group, while the control group exclusively engaged in routine reporting activities. Effectiveness analysis was conducted at the patient level, utilizing regional health information systems to compute process and outcome indicators. The effectiveness of the intervention was evaluated using difference-in-difference models, comparing pre- and post-intervention periods between exposed and control groups. Estimates were calculated in terms of the difference in percentage points (PP) between absolute risks. Sixteen facilities for the AMI pathway and thirteen for the stroke pathway participated in the intervention. The intervention yielded a reduction in the proportion of 30-day readmissions following hospitalization for ischemic stroke by 0.54 pp in the exposed patients demonstrating a significant difference of -3.80 pp (95% CI: -6.57; -1.03; 5453 patients, 63.7% cases) in the exposed group compared to controls. However, no statistically significant differences attributable to the implemented A&F intervention were observed in other indicators considered. These results represent the first evidence in Italy of the impact of A&F interventions in an emergency setting, utilizing aggregated data from hospitals involved in the Lazio Region's emergency network.

Extended septal myectomy for obstructive hypertrophic cardiomyopathy and its impact on mitral valve function.

AIMS: Septal myectomy is the treatment of choice for hypertrophic obstructive cardiomyopathy (HOCM). Around 30-60% of patients with HOCM have a secondary mitral valve regurgitation due to systolic anterior motion (SAM). We report our experience with extended septal myectomy and its impact on the incidence of concomitant mitral valve procedures. METHODS: This is a retrospective study on 84 patients who underwent SM from January 2008 to February 2022. Surgical procedure was performed according to the concept of 'extended myectomy' described by Messmer in 1994. Follow-up outcomes in terms of survival, hospital admissions for heart failure or MV disease, cardiac reoperations, and pacemaker (PMK) implantation were recorded. RESULTS: Mean age was 61 ±â€Š15 years. Mitral valve surgery was performed in seven cases (8%); particularly only one patient without degenerative mitral valve disease underwent mitral valve surgery, with a plicature of the posterior leaflet. In-hospital mortality was 5%. Mitral valve regurgitation greater than mild was present in four patients (5%) at discharge. Twelve-year survival was 78 ±â€Š22%. Cumulative incidence of rehospitalization for heart failure and rehospitalization for mitral valve disease was 10 ±â€Š4 and 2.5 ±â€Š2.5%, respectively. PMK implantation was 5% at discharge, with a cumulative incidence of 15 ±â€Š7%. Freedom from cardiac reoperations was 100%. CONCLUSION: Septal myectomy for HOCM is associated with good outcomes. Although concomitant surgery on the mitral valve to address SAM and associated regurgitation has been advocated, these procedures were needed in our practice only in patients with intrinsic mitral valve disease. Adequate myectomy addresses the underlying pathophysiology in most patients.

Cost-effectiveness of outpatient adherence to recommendations for monitoring of patients hospitalized for heart failure.

AIMS: A set of indicators to assess the quality of care for patients hospitalized for heart failure was developed by an expert working group of the Italian Health Ministry. Because a better performance profile measured using these indicators does not necessarily translate to better outcomes, a study to validate these indicators through their relationship with measurable clinical outcomes and healthcare costs supported by the Italian National Health System was carried out. METHODS AND RESULTS: Residents of four Italian regions (Lombardy, Marche, Lazio, and Sicily) who were newly hospitalized for heart failure (irrespective of stage and New York Heart Association class) during 2014-2015 entered in the cohort and followed up until 2019. Adherence to evidence-based recommendations [i.e. renin-angiotensin-aldosterone system (RAS) inhibitors, beta-blockers, mineralocorticoid receptor antagonists (MRAs), and echocardiograms (ECCs)] experienced during the first year after index discharge was assessed. Composite clinical outcomes (cardiovascular hospital admissions and all-cause mortality) and healthcare costs (hospitalizations, drugs, and outpatient services) were assessed during the follow-up. The restricted mean survival time at 5 years (denoted as the number of months free from clinical outcomes), the hazard of clinical outcomes (according to the Cox model), and average annual healthcare cost (expressed in euros per person-year) were compared between adherent and non-adherent patients. A non-parametric bootstrap method based on 1000 resamples was used to account for uncertainty in cost-effectiveness estimates. A total of 41 406 patients were included in this study (46.3% males, mean age 76.9 ± 9.4 years). Adherence to RAS inhibitors, beta-blockers, MRAs, and ECCs were 64%, 57%, 62%, and 20% among the cohort members, respectively. Compared with non-adherent patients, those who adhered to ECCs, RAS inhibitors, beta-blockers, and MRAs experienced (i) a delay in the composite outcome of 1.6, 1.9, 1.6, and 0.6 months and reduced risks of 9% (95% confidence interval, 2-14%), 11% (7-14%), 8% (5-11%), and 4% (-1-8%), respectively; and (ii) lower (€262, €92, and €571 per year for RAS inhibitors, beta-blockers, and MRAs, respectively) and higher costs (€511 per year for ECC). Adherence to RAS inhibitors, beta-blockers, and MRAs showed a delay in the composite outcome and a saving of costs in 98%, 84%, and 93% of the 1000 bootstrap replications, respectively. CONCLUSIONS: Strict monitoring of patients with heart failure through regular clinical examinations and drug therapies should be considered the cornerstone of national guidelines and audits.

[Survey on maintenance immunosuppressive therapy in patients undergoing solid organ transplantation: experiences from Italian transplant centers.] / Terapia immunosoppressiva di mantenimento nei pazienti sottoposti a trapianto di organo solido: survey delle esperienze dai centri-trapianto italiani.

The post-organ transplant immunosuppressive therapy includes the administration of tacrolimus (Tac) or cyclosporine (CsA), along with antimetabolites (Antim) or mTOR inhibitors, with or without prednisone. A survey was conducted to investigate clinical experience regarding the use, efficacy, safety profile, and determinants of choice of maintenance immunosuppressive therapies. The questionnaire was sent to healthcare workers of 45 transplant centers specializing in kidney (K), liver (L), heart (H), and lung (P) transplants. Seventy-one responses were received from 15 Italian regions. The indicated first-choice therapy was Tac + Antim, except in the hepatic field where Tac monotherapy was favored. According to 44.1% of respondents, the first-choice therapy has changed over the last 15 years due to the replacement of CsA with Tac and increased use of mTOR inhibitors. Regarding the determinants of the index therapy, the choice of schemes to be applied depends mainly on international guidelines, previous experience, and internal protocols within the facility (80.3%; 54.9%; 50.7%, respectively). Compared to standard therapy, the criteria guiding the prescription of different therapies mainly involve the presence of comorbidities (K: 81.3%; L: 88.2%; H: 73.3%; P: 85.7%) and the evaluation of specific clinical parameters of the recipient. Additionally, the majority of respondents are in favor of using generic versions where available. The survey reveals dimensions not detectable by current healthcare administrative flows; such integrations provide a broader picture of the factors influencing the choice of post-transplant immunosuppressive therapeutic schemes.

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.

Temporal and spatial variability of immunosuppressive therapies in transplant patients: An observational study in Italy.

Background: In immunosuppression after transplantation, several multi-drug approaches are used, involving calcineurin inhibitors (CNI: tacrolimus-TAC or cyclosporine-CsA), antimetabolites (antiMs), mammalian target of rapamycin inhibitors (mTORis), and corticosteroids. However, data on immunosuppressive therapy by organ and its space-time variability are lacking. Methods: An Italian multicentre observational cohort study was conducted using health information systems. Patients with incident transplant during 2009-2019 and resident in four regions (Veneto, Lombardy, Lazio, and Sardinia) were enrolled. The post-transplant immunosuppressive regimen was evaluated by organ, region, and year. Results: The most dispensed regimen was triple-drug therapy for the kidneys [tacrolimus (TAC) + antiM + corticosteroids = 41.5%] and heart [cyclosporin + antiM + corticosteroids = 36.6%] and double-drug therapy for liver recipients (TAC + corticosteroids = 35.4%). Several differences between regions and years emerged with regard to agents and the number of drugs used. Conclusion: A high heterogeneity in immunosuppressive therapy post-transplant was found. Further studies are needed in order to investigate the reasons for this variability and to evaluate the risk-benefit profile of treatment schemes adopted in clinical practice.

Marcos GRADE de la evidencia a la decisión (EtD): un enfoque sistemático y transparente para tomar decisiones sanitarias bien informadas. 1: Introducción / GRADE Evidence to Decision (EtD) frameworks: a systematic and transparent approach to making well informed healthcare choices. 1: Introduction

Los médicos y quienes elaboran guías y políticas a veces pasan por alto criterios importantes, les dan un peso indebido o no usan la mejor evidencia disponible para informar sus juicios. Los sistemas explícitos y transparentes para la toma de decisiones pueden ayudar a garantizar que se consideren todos los criterios importantes, y que las decisiones estén basadas en la mejor evidencia disponible. El grupo de trabajo GRADE ha desarrollado marcos «de la evidencia a la decisión» (EtD) para los diferentes tipos de recomendaciones o decisiones. El objetivo de los marcos EtD es ayudar a los paneles a usar la evidencia de una manera estructurada y transparente para informar las decisiones respecto de las recomendaciones clínicas, decisiones de cobertura sanitaria y recomendaciones o decisiones sobre el sistema sanitario o sobre salud pública. Los marcos EtD tienen una estructura común: formulación de una pregunta, evaluación de la evidencia y conclusiones. No obstante, existen diferencias entre los marcos para cada tipo de decisión. Los marcos EtD informan a los usuarios sobre los juicios que se han hecho y la evidencia que los apoya dotando de transparencia la base para las decisiones de los que tienen que tomarlas. Los marcos EtD también facilitan la diseminación de las recomendaciones y permiten a los decisores de otros ámbitos adoptar recomendaciones o decisiones, o adaptarlas a su contexto. El siguiente artículo es una traducción del artículo original publicado en British Medical Journal. Los marcos EtD se utilizan actualmente en el marco del Programa de Guías de Práctica Clínica en el Sistema Nacional de Salud, coordinado por GuíaSalud (AU)

Clinicians, guideline developers, and policymakers sometimes neglect important criteria, give undue weight to criteria, and do not use the best available evidence to inform their judgments. Explicit and transparent systems for decision making can help to ensure that all important criteria are considered and that decisions are informed by the best available research evidence. The GRADE Working Group has developed Evidence to Decision (EtD) frameworks for the different type of recommendations or decisions. The purpose of EtD frameworks is to help people use evidence in a structured and transparent way to inform decisions in the context of clinical recommendations, coverage decisions, and health system or public health recommendations and decisions. EtD frameworks have a common structure that includes formulation of the question, an assessment of the evidence, and drawing conclusions, though there are some differences between frameworks for each type of decision. EtD frameworks inform users about the judgments that were made and the evidence supporting those judgments by making the basis for decisions transparent to target audiences. EtD frameworks also facilitate dissemination of recommendations and enable decision makers in other jurisdictions to adopt recommendations or decisions, or adapt them to their context. This article is a translation of the original article published in British Medical Journal. The EtD frameworks are currently used in the Clinical Practice Guideline Programme of the Spanish National Health System, co-ordinated by GuíaSalud (AU)

Marcos GRADE de la evidencia a la decisión (EtD): un enfoque sistemático y transparente para tomar decisiones sanitarias bien informadas. 2: Guías de práctica clínica / GRADE Evidence to Decision (EtD) frameworks: a systematic and transparent approach to making well informed healthcare choices. 2: Clinical practice guidelines

Los médicos no disponen del tiempo ni de los recursos para considerar la evidencia subyacente en las innumerables decisiones que tienen que tomar diariamente. En consecuencia, dependen de las recomendaciones de las guías de práctica clínica. Los paneles de las guías deben considerar todos los criterios relevantes que influyen en una decisión o recomendación de manera estructurada, explícita y transparente, y proporcionar a los médicos recomendaciones factibles. En este artículo describiremos los marcos de la evidencia a la decisión (EtD) para las recomendaciones de práctica clínica. La estructura general de un marco EtD para recomendaciones clínicas es similar a la de los marcos EtD para otras recomendaciones y decisiones, e incluye la formulación de la pregunta, la evaluación de los distintos criterios y las conclusiones. Las recomendaciones clínicas requieren que los criterios se consideren de forma diferente, dependiendo de si se adopta una perspectiva individual o poblacional. Por ejemplo, desde la perspectiva individual, los gastos personales son un aspecto importante a considerar, mientras que desde la perspectiva poblacional son más importantes el uso de recursos (no solo los gastos personales) y el coste-efectividad. Son también importantes desde la perspectiva poblacional la equidad, la aceptabilidad y la factibilidad, mientras que la importancia de estos criterios suele ser limitada en el caso de la perspectiva individual. Los subgrupos específicos para los cuales pueden necesitarse recomendaciones deben estar claramente identificados y considerados con relación a cada criterio, porque los juicios pueden variar entre subgrupos. El siguiente artículo es una traducción del artículo original publicado en British Medical Journal. Los marcos EtD se utilizan actualmente en el Programa de Guías de Práctica Clínica en el Sistema Nacional de Salud, coordinado por GuíaSalud (AU)

Clinicians do not have the time or resources to consider the underlying evidence for the myriad decisions they must make each day and, as a consequence, rely on recommendations from clinical practice guidelines. Guideline panels should consider all the relevant factors (criteria) that influence a decision or recommendation in a structured, explicit, and transparent way and provide clinicians with clear and actionable recommendations. In this article, we will describe the Evidence to Decision (EtD) frameworks for clinical practice recommendations. The general structure of the EtD framework for clinical recommendations is similar to EtD frameworks for other types of recommendations and decisions, and includes formulation of the question, an assessment of the different criteria, and conclusions. Clinical recommendations require considering criteria differently, depending on whether an individual patient or a population perspective is taken. For example, from an individual patient's perspective, out-of-pocket costs are an important consideration, whereas, from a population perspective, resource use (not only out-of-pocket costs) and cost effectiveness are important. From a population perspective, equity, acceptability, and feasibility are also important considerations, whereas the importance of these criteria is often limited from an individual patient perspective. Specific subgroups for which different recommendations may be required should be clearly identified and considered in relation to each criterion because judgments might vary across subgroups. This article is a translation of the original article published in the British Medical Journal. The EtD frameworks are currently used in the Clinical Practice Guideline Programme of the Spanish National Health System, co-ordinated by GuíaSalud (AU)