Benchmark Outcomes in Deceased Donor Kidney Transplantation: A Multicenter Analysis of 80 996 Transplants From 126 Centers.

Background: We defined clinically relevant benchmark values in deceased donor kidney transplantation (KT), to assess the best achievable results in low-risk patient cohorts from experienced centers. Methods: We identified the "ideal" cases from the United Network for Organ Sharing Standard Transplant Analysis and Research files from centers performing ≥50 KT per year between 2010 and 2018. Cases have been selected based on the kidney donor profile index values (<35%), a cold ischemia time (CIT) ≤18 h, a HLA mismatch ≤4, and excluding blood group (ABO) incompatible, dual and combined transplants. The outcomes of the benchmark cohort have been compared with a group of patients excluded from the benchmark cohort because but not meeting 1 or more of the abovementioned criteria. Results: The 171 424 KT patients in the United Network for Organ Sharing Standard Transplant Analysis and Research files were screened and 8694 benchmark cases of a total of 80 996 KT (10.7%) from 126 centers meeting the selection criteria were identified. The benchmarks for 1-, 3-, and 5-y patient survival are ≥97%, ≥92.5%, and ≥86.7%, and ≥95.4%, ≥87.8%, and ≥79.6% for graft survival. Benchmark cutoff for hospital length of stay is ≤5 d, ≤23.6% for delayed graft function, and ≤7.5% and ≤9.1% for 6-mo and 1-y incidence of acute rejection. Overall 1-, 3-, and 5-y actuarial graft survivals were 96.6%, 91.1%, and 84.2% versus 93.5%, 85.4%, and 75.5% in the benchmark and comparison groups, respectively (P < 0.001). Overall 1-, 3-, and 5-y actuarial patient survivals were 98.1%, 94.8%, and 90.0% versus 96.6%, 91.1%, and 83.0% in the benchmark and comparison groups, respectively (P < 0.001). Conclusions: For the first time, we quantified the best achievable postoperative results in an ideal scenario in deceased donor KT, aimed at improving the clinical practice guided by the comparison of center performances with the ideal outcomes defined.

Multimorbidity and out-of-pocket expenditure on medicine in Europe: Longitudinal analysis of 13 European countries between 2013 and 2015.

Background: Many European Health Systems are implementing or increasing levels of cost-sharing for medicine in response to the growing constrains on public spending on health despite their negative impact on population health due to delay in seeking care. Objective: This study aims to examine the relationships between multimorbidity (two or more coexisting chronic diseases, CDs), complex multimorbidity (three or more CDs impacting at least three different body systems), and out-of-pocket expenditure (OOPE) for medicine across European nations. Methods: This study utilized data on participants aged 50 years and above from two recent waves of the Survey of Health, Aging, and Retirement in Europe conducted in 2013 (n = 55,806) and 2015 (n = 51,237). Pooled cross-sectional and longitudinal study designs were used, as well as a two-part model, to analyse the association between multimorbidity and OOPE for medicine. Results: The prevalence of multimorbidity was 50.4% in 2013 and 48.2% in 2015. Nearly half of those with multimorbidity had complex multimorbidity. Each additional CD was associated with a 34% greater likelihood of incurring any OOPE for medicine (Odds ratio = 1.34, 95% CI = 1.31-1.36). The average incremental OOPE for medicine was 26.4 euros for each additional CD (95% CI = 25.1-27·7), and 32.1 euros for each additional body system affected (95% CI 30.6-33.7). In stratified analyses for country-specific quartiles of household income the average incremental OOPE for medicine was not significantly different across groups. Conclusion: Between 2013 and 2015 in 13 European Health Systems increased prevalence of CDs was associated with greater likelihood of having OOPE on medication and an increase in the average amount spent when one occurred. Monitoring this indicator is important considering the negative association with treatment adherence and subsequent effects on health.

[Liquid biopsy as indication of tumour progression in lung cancer: a potential intervention in tertiary prevention]. / La biopsia liquida quale segnale di progressione tumorale nel carcinoma polmonare: potenziale di intervento in prevenzione terziaria.

In the era of personalised therapies, liquid biopsy is considered an important diagnostic tool in the clinical management of cancer patients. Tissue specimen represents the gold standard for molecular evaluation of specific gene targets alterations that lead cancer patients to benefit of a "tailed therapy" based on molecular features of the tumour. This innovative source of nucleic acids was introduced in clinical setting only for non-small-cell lung cancer (NSCLC) patients to test epidermal grow factor receptor (EGFR) mutations when tissue is not available for a number of reasons (difficult access to the lesion, the presence of other disabling pathologies, especially in elderly patients, rejection by the patient, etcetera) or to monitor acquired resistance mutation after a first line of treatment. The present study aimed at assessing the diagnostic potential of liquid biopsy in balanced tertiary screening modelling. The cases relating to 5 years of activity regarding to molecular diagnostics performed on liquid biopsy specimens in the Predictive diagnostic laboratory of the University hospital "Federico II" of Naples (Campania Region, Southern Italy) were reviewed. Laboratory data were collected through the software SPSS. Non-parametric analysis was performed in order to test the differences between "wild type" patients or not. A multivariate logistic model was performed in order to assess the effect of mutation, age, and gender on the tumour progression. The results of the revision concern 515 total cases (almost of all plasma or peripheral blood), which allowed to evaluate the liquid biopsies for women and men. The average age of the patients is 66.3 years, and the 25° percentile is 59 years. The cases are: 221 basal and 294 by progression. The cases with mutation, as expected, have an odds ratio of 4,15, compared to the basal, to have a tumour progression (95%IC 2,7-6,3), regardless of gender and age. The detected mutations were 131 from different types of pulmonary carcinomas. Working on case data, specifying the characteristics of the patients with mutations will drive a further estimate in tertiary prevention screening designs.

[Impact assessment of the implementation of an integrated care model for thyroid disease at the University Hospital "Federico II" of Naples (Campania Region, Southern Italy): an interrupted time series analysis]. / Valutazione dell'impatto dell'implementazione di un percorso multidisciplinare di presa in carico della patologia nodulare tiroidea presso l'Azienda ospedaliera universitaria "Federico II" di Napoli: studio quasi sperimentale a serie temporale interrotta semplice.

OBJECTIVES: to evaluate the implementation of an integrated care model for thyroid disease on thyroid surgery at the University Hospital "Federico II" of Naples (Campania Region, Southern Italy). DESIGN: quasi-experimental design employing an interrupted time series analysis. SETTING AND PARTICIPANTS: all subjects who were admitted to the University Hospital "Federico II" for thyroid surgery between January 2008 and December 2018. The integrated care model for thyroid disease was implemented starting from January 2016. MAIN OUTCOME MEASURES: rate of partial thyroidectomies over all thyroidectomies; rate of diagnosed thyroid cancers over all diagnosed thyroid tumours; length of stay (LOS). Differences pre- and post-interventions were assessed employing Poisson (for count outcomes) and linear (for continuous outcomes) regression models. Models were adjusted for age, gender, tumour diagnosis (none, benign, malignant), Charlson index, and discharge month. RESULTS: data on 4,233 thyroidectomies were included. There was no difference between pre- and post-intervention trends for the rate of partial thyroidectomies over all thyroidectomies (pre-intervention: IRR 1.00; 95%CI 0.99;1.00 - post-intervention: IRR 1.00; 95%CI 0.98;1.02) and for the rate of diagnosed thyroid cancers over all thyroid tumours (pre-intervention IRR 0.99; 95%CI 0.99;1.00 - post-intervention IRR 1.00; 95%CI 0.99;1.01). On the contrary, the LOS reduced from 4.5 (±4.3) days in 2008 to 3.2 (±3.2) days in 2018. The multivariate analysis confirmed this reduction, estimated to be 1.1 days on average in the pre-intervention eight-year period (pre-intervention coefficient -0.01; 95%CI -0.02;-0.01), followed by an even greater reduction in the post-intervention three-year period which was estimated to be 1.1 day (post-intervention: coefficient -0.03; 95%CI -0.05;-0.01). CONCLUSIONS: the implementation of an integrated care model for thyroid disease contributed to reduce the LOS for thyroidectomies, improving the efficiency in the management of thyroid disease. However, this intervention had no impact in reducing the rate of total thyroidectomies.

Features, reason for testing, and changes with time of 583 paroxysmal nocturnal hemoglobinuria clones from 529 patients: a multicenter Italian study.

In this study, we aimed at disclosing the main features of paroxysmal nocturnal hemoglobinuria (PNH) clones, their association with presentation syndromes, and their changes during follow-up. A large-scale, cooperative collection (583 clones from 529 patients) of flow cytometric and clinical data was entered into a national repository. Reason for testing guidelines were provided to the 41 participating laboratories, which followed the 2010 technical recommendations for PNH testing by Borowitz. Subsequently, the 30 second-level laboratories adopted the 2012 guidelines for high-resolution PNH testing, both upon order by the local clinicians and as an independent laboratory initiative in selected cases. Type3 and Type2 PNH clones (total and partial absence of glycosyl-phosphatidyl-inositol-anchor, respectively) were simultaneously present in 54 patients. In these patients, Type3 component was sevenfold larger than Type2 (p < 0.001). Frequency distribution analysis of solitary Type3 clone size (N = 442) evidenced two discrete patterns: small (20% of peripheral neutrophils) and large (> 70%) clones. The first pattern was significantly associated with bone marrow failure and myelodysplastic syndromes, the second one with hemolysis, hemoglobinuria, and thrombosis. Pediatric patients (N = 34) showed significant preponderance of small clones and bone marrow failure. The majority of PNH clones involved neutrophils, monocytes, and erythrocytes. Nevertheless, we found clones made exclusively by white cells (N = 13) or erythrocytes (N = 3). Rare cases showed clonal white cells restricted only to monocytes (6 cases) or neutrophils (3 cases). Retesting over 1-year follow-up in 151 cases showed a marked clone size increase in 4 cases and a decrease in 13, demonstrating that early breaking-down of PNH clones is not a rare event (8.6% of cases). This collaborative nationwide study demonstrates a clear-cut difference in size between Type2 and Type3 clones, emphasizes the existence of just two classes of PNH presentations based on Type3 clone size, depicts an asymmetric cellular composition of PNH clones, and documents the possible occurrence of changes in clone size during the follow-up.

Association between Lp(a) and small dense LDL in menopausal women without metabolic syndrome.

Background: Lipoprotein (a) (Lp [a]) is associated with premature atherosclerosis in menopausal women without metabolic syndrome (MS). MS is the main confounder in the relationship between Lp(a) and atherosclerosis in menopausal women. We have evaluated the relationship between Lp(a) and small dense-low density lipoprotein (sd-LDL) in 228 menopausal women participating to Progetto Atena. Methods: Lp(a) was measured and LDL particle separation was performed: mean LDL diameter and LDL score (% of sd-LDL) particles calculated. Results: Women without MS and elevated Lp(a) have increased number of sd-LDL (p < .05) and higher LDL score compared with those below the median of the studied population (p < .05). The association between Lp(a) and sd-LDL was evaluated taking into account different adjustment models. Women with elevated levels of Lp(a) show the following OR of having a small LDL diameter (in the lowest quartile): 1.02, p = .003; adjusted for age; 1.02, p = .002; adjusted for age, and triglycerides, or a high LDL score (in the highest quartile): 1.02, p = .006; adjusted for age; 1.02, p = .002; adjusted for age and triglycerides. Conclusions: In this group of menopausal women without MS, the independent association of Lp(a) with sd-LDL might explain at least in part the association of Lp(a) with premature atherosclerosis.

[Network references for rare diseases: state of the art for the paroxysmal nocturnal hemoglobinuria]. / I network di riferimento per le malattie rare: lo stato dell'arte per l'emoglobinuria parossistica notturna.

BACKGROUND: recently, healthcare network models have been proposed to improve general awareness of rare diseases for patients and specific knowledge about diagnosis, treatment, and management for healthcare services. Paroxysmal nocturnal hemoglobinuria (PNH) is a rare haematological disease that still has no framing in an official network. OBJECTIVES: to describe the use of network models in diagnosis, treatment, and management of PNH patients both in Italy and abroad and its impact on patients and healthcare service. DISEGN: literature search was performed using the keywords "Hemoglobinuria", "Network", "PHN", and "Screening" in both MedLine and EMBASE. Search was restricted to the articles published in the last 5 years and written in English, French or Italian language. RESULTS: from the total 251 articles of the initial search, only 21 were finally included in our review. None of the included study explicitly described a network model. In general, we were able to identify two different kind of networks implicitly described in the studies: laboratory networks for diagnostic harmonization or screening of the population at risk of PNH (10/21 studies) and PNH registry as network of clinical information to be use for better understanding of the natural history of the disease and to assess therapeutic effectiveness (11/21 studies). CONCLUSIONS: few network approaches in PNH diagnosis, treatment, and management are described in literature. Despite the scarce application of the networks, our review highlights the positive impact that networks have in both patients and healthcare services.

[Organ donation and transplantation: the "friendly access initiative" in the Federico II Hospital (Naples), between nudging and narrative medicine]. / Donazione e trapianto d'organi: l'esperienza dello "sportello amico" dell'AOU Federico II (Napoli), tra nudging e medicina narrativa.

In Italy, to show the willingness to donate one's organs, there is the principle of the explicit consensus (or disagreement) (Law n. 91 of the 01.04.1999, Art. 23; Decree of the Italian Health Ministry of the 08.04.2000). According to data of the Italian Association for the donation of organs, tissues and cells (AIDO), in 2017 in Campania Region (Southern Italy) an average of 12.5 people x1,000,000 donated their organs vs. a national average of 23.7. This negative discrepancy between national and regional data highlights that it is imperative to promote awareness-raising measures to address to the population of Campania Region in order to improve the following of a practice which is still object of preconceptions and scarce knowledge. This paper describes a pilot project started in 2017 by the "Sportello amico trapianti" (friendly access to transplantation) to promote the donation of organs within the university-hospital "Federico II" (Naples, Campania Region). The first phase of this project was based on the nudge theory, that is the "little push" to direct decisional processes of groups and individuals. This phase took place during the "Atelier della salute" (a health workshop), organized by the Medicine and Surgery school of the university-hospital "Federico II": here, a questionnaire was administered to 60 people. The questionnaire consisted in 12 questions, answered by volunteers, which aim was to test the general knowledge about organ donation and transplantation. Analysing the answers, a panel of 7 experts (2 epidemiologists, 1 social worker, 2 experts in public and institutional communication, 1 biologist expert in donation of haematopoietic progenitor cell, 1 transplant surgeon), responsible for the coordination and monitoring of the activities, identified the critical elements to bring attention to in order to raise awareness in the population. The second phase consisted in a literary workshop which aim was to identify nudge cases. The text used was Never let me go by Kazuo Ishiguro, a novel focused on organ donation in a dystopic context where the protagonists are clones created to facilitate the donation of organs. Six students participated in this workshop: all six considered the dystopic scenario as a potential nudge to humanize the approach to organ donation and transplant. In conclusion, we believe that the nudge methodology may be used in order to improve awareness and adherence to donation of organs.

Association between body shape index and small dense LDL particles in a cohort of mediterranean women: findings from Progetto ATENA.

Small dense LDL particles (sd-LDL) and body shape index (ABSI), were evaluated in 228 women, living in Naples, Italy (Progetto ATENA). Serum cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides, insulin, HOMA, Apo B, hs-CPR and sd-LDL were measured. LDL particle separation was performed by Lipoprint System: seven LDL subfractions were obtained and LDL score (% of sd-LDL particles) calculated. ABSI was calculated according to Krakauer's formula: ABSI (m11/6 kg-2/3). The association between sd-LDL and ABSI was evaluated taking into account different adjustment models. Women with elevated levels of ABSI show the following OR of having high LDL score: 2.39, p = 0.002; unadjusted; 2.47, p = 0.002; adjusted for age; 2.13, p = 0.011; adjusted for age and Apo B; 1.93, p = 0.026; adjusted for age and Apo B and triglycerides. ABSI was associated with elevated LDL score independently of age, Systolic pressure, Apo B and triglycerides. Median of LDL diameter decreased among ABSI quartiles: quartile I: 271.5 nm, quartile II: 270.7 nm, quartile III 270.5 nm, quartile IV 269.4 nm; Kruskall Wallis Test: p = 0.016. These results are in line with the hypothesis that ABSI could be a marker of visceral abdominal associated to adverse metabolic changes including presence of elevated sd-LDL, a risk factor for premature cardiovascular disease.

Vascular preventive measures: the progression from asymptomatic to symptomatic atherosclerosis management. Evidence on usefulness of early diagnosis in women and children.

This review reports our experience in evaluating the progression from asymptomatic to symptomatic atherosclerosis in an evidence-based context. In particular, studies published in the last 5 years were analyzed in more detail and their relevance to cardiovascular prevention in women and children is discussed. The evaluation of carotid artery intima-media thickness by ultrasonography and the measurement of coronary artery calcification using computed tomography scanning can provide evidence for the presence and extent of atherosclerosis in adults. Intima-media thickness was demonstrated to predict prognosis and help in clinical decision making. Computed tomography estimates of advanced coronary atherosclerosis are markers of advanced atherosclerosis and are of value for screening adult men, but their value in women and children is doubtful owing to radiation risk. Intima-media thickness measurement, even when acknowledging its limitations, is a preferred approach, with the promising perspective of the availability of portable devices of lower cost in the near future. Further evaluation of the potential role for the emerging biomarkers and imaging techniques could clarify the clinical relevance of emerging risk profiles such as the metabolic syndrome. Ultrasound methods provide information regarding the extent and progression of early atherosclerotic abnormalities in women and in children and predict cardiovascular prognosis.

[Evaluation of appropriate hospital stay in patients with atherosclerosis without complication (DRG 133)]. / Analisi dell'appropriatezza dei ricoveri per aterosclerosi senza complicanze (DRG 133).

OBJECTIVE: this study evaluates the appropriateness of the clinical activities performed during hospitalization of patients with atherosclerosis without complications (Disease-related Group - DRG 133 in the Italian National Health System), at the Policlinico Universitario Federico II, Naples. DESIGN AND SETTING: coded criteria PRUO - (Protocol for the revision of hospital use) have been used in order to quantify the appropriateness of 94 randomly selected clinical reports for 2001 and 2002. Two independent examiners have evaluated clinical reports, and a supervisor has decided upon the disagreements (majority rule). Appropriateness was rated by tertiles of age and hospital-stay length. RESULTS: global appropriateness was 68%, and increased 93% when it was related to admission days and 64% when was related to the duration of the hospital-stay. Appropriateness of the use of hospital for DRG 133 diagnosis was more frequent for patients older than 70 years and for short duration of hospital stay. Logistic regression has confirmed the trends, indicating a robust statistical significance for the duration of hospital stay but not for age.