Post-traumatic stress disorder and post-traumatic stress symptoms in patients with systemic autoimmune diseases during the COVID-19 pandemic.

OBJECTIVES: The COVID-19 outbreak led to an increase in mental disorders, particularly post-traumatic stress disorder (PTSD), in the general population and especially in high-risk populations such as patients with rheumatologic conditions. Although these latters are considered vulnerable to developing PTSD, few specific data have been particularly reported in the framework of the pandemic. The aim of the present study was to investigate PTSD and post-traumatic stress symptoms (PTSS) in a sample of patients with systemic autoimmune disease (SAD), followed in the framework of a prospective observational study during the pandemic. METHODS: The PERMAS project is a prospective observational study including patients with SAD and involving the Rheumatology and the Psychiatric Clinics of the Azienda Ospedaliero Universitaria Pisana (AOUP, Pisa, Italy) and the Institute of Management of the Scuola Superiore Sant'Anna (Pisa, Italy). The assessments included: a data-sheet for sociodemographic and clinical characteristics; the Trauma and Loss Spectrum-Self Report (TALS-SR) and the Impact of Event Scale-Revised (IES-R), for PTSD and PTSS; the 36-item Short Form Survey (SF-36) to assess quality of life. RESULTS: The total sample consisted of 252 patients with SAD, including 131 with connective tissue disease, 101 with arthritis and 20 with systemic vasculitis. The diagnostic groups differed significantly in age (p<0.001), gender (p<0.001), prevalence of full-blown and partial PTSD (p=0.001), and other psychopathologic variables. Connective tissue disease and SF-36 were significantly associated with the TALS-SR scores in both univariate (p<0.001) and multivariate (p<0.025; p<0.001) analyses. CONCLUSIONS: Patients with SAD, and, in particular, patients with connective tissue diseases reported an increased risk of developing stress-related psychopathological symptoms, indicating the need for special psychological monitoring of this high-risk group.

AI Cardiac MRI Scar Analysis Aids Prediction of Major Arrhythmic Events in the Multicenter DERIVATE Registry.

Background Scar burden with late gadolinium enhancement (LGE) cardiac MRI (CMR) predicts arrhythmic events in patients with postinfarction in single-center studies. However, LGE analysis requires experienced human observers, is time consuming, and introduces variability. Purpose To test whether postinfarct scar with LGE CMR can be quantified fully automatically by machines and to compare the ability of LGE CMR scar analyzed by humans and machines to predict arrhythmic events. Materials and Methods This study is a retrospective analysis of the multicenter, multivendor CarDiac MagnEtic Resonance for Primary Prevention Implantable CardioVerter DebrillAtor ThErapy (DERIVATE) registry. Patients with chronic heart failure, echocardiographic left ventricular ejection fraction (LVEF) of less than 50%, and LGE CMR were recruited (from January 2015 through December 2020). In the current study, only patients with ischemic cardiomyopathy were included. Quantification of total, dense, and nondense scars was carried out by two experienced readers or a Ternaus network, trained and tested with LGE images of 515 and 246 patients, respectively. Univariable and multivariable Cox analyses were used to assess patient and cardiac characteristics associated with a major adverse cardiac event (MACE). Area under the receiver operating characteristic curve (AUC) was used to compare model performances. Results In 761 patients (mean age, 65 years ± 11, 671 men), 83 MACEs occurred. With use of the testing group, univariable Cox-analysis found New York Heart Association class, left ventricle volume and/or function parameters (by echocardiography or CMR), guideline criterion (LVEF of ≤35% and New York Heart Association class II or III), and LGE scar analyzed by humans or the machine-learning algorithm as predictors of MACE. Machine-based dense or total scar conferred incremental value over the guideline criterion for the association with MACE (AUC: 0.68 vs 0.63, P = .02 and AUC: 0.67 vs 0.63, P = .01, respectively). Modeling with competing risks yielded for dense and total scar (AUC: 0.67 vs 0.61, P = .01 and AUC: 0.66 vs 0.61, P = .005, respectively). Conclusion In this analysis of the multicenter CarDiac MagnEtic Resonance for Primary Prevention Implantable CardioVerter DebrillAtor ThErapy (DERIVATE) registry, fully automatic machine learning-based late gadolinium enhancement analysis reliably quantifies myocardial scar mass and improves the current prediction model that uses guideline-based risk criteria for implantable cardioverter defibrillator implantation. ClinicalTrials.gov registration no.: NCT03352648 Published under a CC BY 4.0 license. Supplemental material is available for this article.

Initial 50 consecutive full-robotic pancreatoduodenectomies without conversion by a single surgeon: a learning curve analysis from a tertiary referral high-volume center.

BACKGROUND: Several studies report on a learning curve for robotic pancreatoduodenectomy (R-PD) ranging between 20 and 80 operations, with conversion rates varying between 1.1 and 35%. However, as these publications mostly refer to initial robotic experiences and do not take into account the previous surgical background in pancreatic surgery (PS) and in robotic-assisted surgery (RAS), the center's volume, as well as the platform used, we aimed to perform a surgical outcomes analysis with a particular view to these aspects. METHODS: Intraoperative and perioperative outcomes of the first 50 consecutive R-PD performed with the da Vinci Xi by the same surgeon, within a tertiary referral high-volume center, between January 2018 and March 2022, were analyzed. The surgeon was previously experienced in both PS and RAS. Shewhart control chart and cumulative sum (CUSUM) analysis were used to evaluate the learning curve of R-PD. RESULTS: All the operations were performed with a full-robotic technique, without any conversion to open surgery. Twenty of 50 patients (40%) had a BMI ≥ 25 kg/m2, while 24/50 (48%) had undergone previous abdominal surgery. Mean console time was 276.30 ± 31.16 min. The median post-operative length of hospital stay was 10 days, while 20/50 (40%) patients were discharged within post-operative day 8. Six patients (12%) had major complications (Clavien-Dindo grade 3 or above). There was no 30-day mortality. Shewhart control chart and CUSUM analysis did not show a significant learning curve during the study period. CONCLUSIONS: An extensive prior experience in both PS and RAS, within a tertiary referral high-volume center with availability of the da Vinci Xi platform, can significantly flatten the learning curve and, therefore, enable safe performance of challenging operations, i.e., pancreatoduodenectomies with a minimally invasive approach, with very low risk of conversion to open surgery, even in the first 50 operations.

Robot-assisted pancreatoduodenectomy with the da Vinci Xi: can the costs of advanced technology be offset by clinical advantages? A case-matched cost analysis versus open approach.

BACKGROUND: Robot-assisted pancreatoduodenectomy (RPD) has shown some advantages over open pancreatoduodenectomy (OPD) but few studies have reported a cost analysis between the two techniques. We conducted a structured cost-analysis comparing pancreatoduodenectomy performed with the use of the da Vinci Xi, and the traditional open approach, and considering healthcare direct costs associated with the intervention and the short-term post-operative course. MATERIALS AND METHODS: Twenty RPD and 194 OPD performed between January 2011 and December 2020 by the same operator at our high-volume multidisciplinary center for robot-assisted surgery and for pancreatic surgery, were retrospectively analyzed. Two comparable groups of 20 patients (Xi-RPD-group) and 40 patients (OPD-group) were obtained matching 1:2 the RPD-group with the OPD-group. Perioperative data and overall costs, including overall variable costs (OVCs) and fixed costs, were compared. RESULTS: No difference was reported in mean operative time: 428 min for Xi-RPD-group versus 404 min for OPD, p = 0.212. The median overall length of hospital stay was significantly lower in the Xi-RPD-group: 10 days versus 16 days, p = 0.001. In the Xi-RPD-group, consumable costs were significantly higher (€6149.2 versus €1267.4, p < 0.001), while hospital stay costs were significantly lower: €5231.6 versus €8180 (p = 0.001). No significant differences were found in terms of OVCs: €13,483.4 in Xi-RPD-group versus €11,879.8 in OPD-group (p = 0.076). CONCLUSIONS: Robot-assisted surgery is more expensive because of higher acquisition and maintenance costs. However, although RPD is associated to higher material costs, the advantages of the robotic system associated to lower hospital stay costs and the absence of difference in terms of personnel costs thanks to the similar operative time with respect to OPD, make the OVCs of the two techniques no longer different. Hence, the higher costs of advanced technology can be partially compensated by clinical advantages, particularly within a high-volume multidisciplinary center for both robot-assisted and pancreatic surgery. These preliminary data need confirmation by further studies.

Minimally invasive distal pancreatectomy: a case-matched cost-analysis between robot-assisted surgery and direct manual laparoscopy.

BACKGROUND: Few studies have reported a structured cost analysis of robotic distal pancreatectomy (RDP), and none have compared the relative costs between the robotic-assisted surgery (RAS) and the direct manual laparoscopy (DML) in this setting. The aim of the present study is to address this issue by comparing surgical outcomes and costs of RDP and laparoscopic distal pancreatectomies (LDP). METHODS: Eighty-eight RDP and 47 LDP performed between January 2008 and January 2020 were retrospectively analyzed. Three comparable groups of 35 patients each (Si-RDP-group, Xi-RDP group, LDP-group) were obtained matching 1:1 the RDP-groups with the LDP-group. Overall costs, including overall variable costs (OVC) and fixed costs were compared using generalized linear regression model adjusting for covariates. RESULTS: The conversion rate was significantly lower in the Si-RDP-group and Xi-RDP-group: 2.9% and 0%, respectively, versus 14.3% in the LDP-group (p = 0.045). Although not statistically significant, the mean operative time was lower in Xi-RDP-group: 226 min versus 262 min for Si-RDP-group and 247 min for LDP-group. The overall post-operative complications rate and the length of hospital stay (LOS) were not significantly different between the three groups. In LDP-group, the LOS of converted cases was significantly longer: 15.6 versus 9.8 days (p = 0.039). Overall costs of LDP-group were significantly lower than RDP-groups, (p < 0.001). At multivariate analysis OVC resulted no longer statistically significantly different between LDP-group and Xi-RDP-group (p = 0.099), and between LDP-group and the RDP-groups when the spleen preservation was indicated (p = 0.115 and p = 0.261 for Si-RDP-group and Xi-RDP-group, respectively). CONCLUSIONS: RAS is more expensive than DML for DP because of higher acquisition and maintenance costs. The flattening of these differences considering only the variable costs, in a high-volume multidisciplinary center for RAS, suggests a possible optimization of the costs in this setting. RAS might be particularly indicated for minimally invasive DP when the spleen preservation is scheduled.

Prognostic value of stress echocardiography assessed by the ABCDE protocol.

AIM: The aim of this study was to assess the prognostic value of ABCDE-SE in a prospective, large scale, multicentre, international, effectiveness study. Stress echocardiography (SE) was recently upgraded to the ABCDE protocol: step A, regional wall motion abnormalities; step B, B lines; step C, left ventricular contractile reserve; step D, Doppler-based coronary flow velocity reserve in left anterior descending coronary artery; and step E, electrocardiogram-based heart rate reserve. METHODS AND RESULTS: From July 2016 to November 2020, we enrolled 3574 all-comers (age 65 ± 11 years, 2070 males, 58%; ejection fraction 60 ± 10%) with known or suspected chronic coronary syndromes referred from 13 certified laboratories. All patients underwent clinically indicated ABCDE-SE. The employed stress modality was exercise (n = 952, with semi-supine bike, n = 887, or treadmill, n = 65 with adenosine for step D) or pharmacological stress (n = 2622, with vasodilator, n = 2151; or dobutamine, n = 471). SE response ranged from score 0 (all steps normal) to score 5 (all steps abnormal). All-cause death was the only endpoint. Rate of abnormal results was 16% for A, 30% for B, 36% for C, 28% for D, and 37% for E steps. During a median follow-up of 21 months (interquartile range: 13-36), 73 deaths occurred. Global X2 was 49.5 considering clinical variables, 50.7 after step A only (P = NS (not significant)) and 80.6 after B-E steps (P < 0.001 vs. step A). Annual mortality rate ranged from 0.4% person-year for score 0 up to 2.7% person-year for score 5. CONCLUSION: ABCDE-SE allows an effective prediction of survival in patients with chronic coronary syndromes.

Feeding disorders in preschoolers: a short-term outcome study in an Italian Family Care Program.

PURPOSE: To provide a description about a cohort of preschoolers with feeding disorders (FD) recruited from the therapeutic nursery "Cerco Asilo" of a tertiary care University Hospital, and to evaluate the short-term clinical outcome after 6 months of multidisciplinary treatment. METHODS: The present inception cohort study was based on an observational longitudinal research design comparing families who underwent the multidisciplinary treatment and those who did not. 42 children (47.6% female; 52.4% males-mean age 36.7 months, SD 17.2, range 2.3-65 months) underwent FD assessment according to the DC-0-3R diagnostic criteria (T0). At the end of the assessment, 62% of families with FD children agreed to be included in the family-based treatment. Both treated and untreated children with FD underwent a follow-up clinical evaluation after 6 months (T1) from baseline. Comparison of clinical features at T0 between groups of subjects resolving or not the FD was performed. To evaluate baseline factors associated with FD resolution, principal components analysis (PCA) was used to identify new synthetic variables that were then used in a logistics analysis. Moreover, clinical differences between T1 and T0 were compared with a t test. RESULTS: Two third of the cases (66.7%) resolved the FD, while one third (33.3%) did not. Children who had the FD resolved displayed at T0 significant differences in clinical features with respect to those who did not. Specifically, the FD subtype Feeding Disorder of Caregiver-Infant Reciprocity was strongly associated with resolution, while the subtype Infantile Anorexia was not. In addition, the component depicting "Anxious-Depressed", "Mood" and "Isolation" problems was independently associated with a significantly higher probability of resolution, similar to children having FD other than anorexia. CONCLUSIONS: FD in preschoolers are associated with problems in emotional development and in the relationship with parents. These difficulties tend to accentuate if the disorder persists. The study suggests the need to investigate the maintaining factors of FD in preschool age. LEVEL OF EVIDENCE: Level IV: Evidence obtained from multiple time series with and without the intervention.

Duration of response after DEB-TACE compared to lipiodol-TACE in HCC-naïve patients: a propensity score matching analysis.

OBJECTIVES: To retrospectively compare long-term outcomes of first-line drug-eluting particle (DEB)- transarterial chemoembolization (TACE) and lipiodol-TACE, in patients with unresectable hepatocellular (HCC). METHODS: We retrospectively reviewed our database to identify adult patients with treatment-naïve unresectable HCC, who underwent TACE from 2006 to 2013. Patients were excluded in the absence of complete medical records relative to first TACE, 1-month follow-up, and/or sufficient follow-up data. Periprocedural complications, duration of hospitalization, 1-month tumor response by mRECIST, time to tumor progression (TTP) and target tumor progression (TTTP), and overall survival (OS) were evaluated. RESULTS: Out of an initial series of 656 patients, 329 patients were excluded for unavailability of sufficient baseline and/or follow-up data. The remaining 327 patients underwent either lipiodol-TACE (n = 160) or DEB-TACE (n = 167). Patients treated with lipiodol-TACE had a significantly higher tumor burden. By propensity score, patients were matched according to baseline differences (BCLC stage, uninodular or multinodular HCC, and unilobar or bilobar HCC), resulting in 101 patients in each treatment group. Lipiodol-TACE was associated with a significantly higher incidence of adverse events (p = 0.03), and longer hospitalization (mean, 2.5 days vs 1.9 days; p = 0.03), while tumor response, TTP, and OS were comparable. In patients achieving 1-month complete response (CR) of target tumor, TTTP was significantly (p = 0.009) longer after DEB-TACE compared to lipiodol-TACE (median, 835 vs 353 days), resulting in a lower number of re-treatments during the entire follow-up (0.75 vs 1.6, p = 0.01). CONCLUSION: Compared to lipiodol-TACE, DEB-TACE offers higher tolerability, reduced hospitalization, and more durable target tumor response after CR. KEY POINTS: • Compared to lipiodol-TACE, DEB-TACE is better tolerated and has reduced side effects, which translates into shorter hospitalization. • When complete radiological response according to the mRECIST is obtained 1 month after the procedure, DEB-TACE offers a more durable local tumor control compared to lipiodol-TACE. • In these patients, the longer duration of response after DEB-TACE translates into a lower number of re-interventions.

Adherence to treatment in Behçet's syndrome: a multi-faceted issue.

OBJECTIVES: The aim of this study is to explore the adherence to treatment in patients with Behçet's syndrome (BS), to identify the diverse adherence profiles and their correlations. METHODS: A cross-sectional study among adult BS patients was conducted administering an ad-hoc questionnaire to BS patients with the aim of investigating several dimensions related to BS management, including attitudes towards treatment. A Latent Class Analysis (LCA) was performed to identify adherence profiles and associated characteristics were identified using logistic regression analysis. RESULTS: A total of 207 patients answered the survey and 180 of them declared to take medication for BS, thus representing the study population. More than a third of the respondents have declared that they have skipped treatments before and autonomously modified (reduced or increased) the dosage of the treatment without medical consultation. LCA analysis allowed the identification of two distinct profiles, one more stick with recommended medication and the other less adherent to treatment. The less-adherent BS patient profile seems to be related with being in the third decade of life, being diagnosed with BS for more than 5 years and perceiving greater psychological impact of the disease. CONCLUSIONS: Addressing adherence in BS is not only related to measuring treatment adherence and identifying the barriers and the limitations; in fact, it should also encompass a wider approach that includes the awareness, the socio-psychological impact of the disease as well as patient education.

Utilisation patterns and clinical impact of the introduction of infliximab-biosimilar in Tuscany, Italy: real world evidence following the recommendation of switching for non-medical reasons.

OBJECTIVES: This study was aimed at assessing the impact of a non-medical recommendation on drug-utilisation patterns and clinical outcomes in a central Region of Italy (Tuscany). METHODS: We performed a pre-post study on data collected in Tuscan healthcare administrative databases. We included patients with diagnosis of rheumatoid arthritis, or psoriatic arthritis, or ankylosing spondylitis, or ulcerative colitis, or Crohn's disease, or psoriasis. The first analysis compared patients treated with infliximab on January 1st, 2013 (originator only available) to those on January 1st, 2016 (both originator and biosimilar available). The second analysis compared infliximab-originator users with infliximab-biosimilar ones. Adjusted odds ratios (OR) of persistence on treatment, Emergency Department (ED) admissions, hospitalisations and specialist visits were calculated. RESULTS: The first analysis included 606 patients and the second 434. In both analyses, we did not observe any significant difference in persistence. In the first analysis, the 2016 infliximab-originator cohort showed a significant association with the risk of having at least one ED admission (OR 1.54, 95% CI 1.02 to 2.31). A significant difference of accessing a specialist visit (more frequently rheumatologic) was observed in the 2016 cohort (OR 1.52, 95% CI 1.05 to 2.20). In the second analysis, the risk of having at least one hospitalisation decreased significantly in switchers to infliximab-biosimilar (OR 0.49, 95% CI 0.26 to 0.96). CONCLUSIONS: Our study showed no relevant changes in the clinical outcomes following the introduction of infliximab-biosimilar. The few observed differences observed can be explained mainly by a selective switching to infliximab-biosimilar in patients with lower burden of disease.

CarDiac magnEtic Resonance for prophylactic Implantable-cardioVerter defibrillAtor ThErapy in Non-Ischaemic dilated CardioMyopathy: an international Registry.

AIMS: The aim of this registry was to evaluate the additional prognostic value of a composite cardiac magnetic resonance (CMR)-based risk score over standard-of-care (SOC) evaluation in a large cohort of consecutive unselected non-ischaemic cardiomyopathy (NICM) patients. METHODS AND RESULTS: In the DERIVATE registry (www.clinicaltrials.gov/registration: RCT#NCT03352648), 1000 (derivation cohort) and 508 (validation cohort) NICM patients with chronic heart failure (HF) and left ventricular ejection fraction <50% were included. All-cause mortality and major adverse arrhythmic cardiac events (MAACE) were the primary and secondary endpoints, respectively. During a median follow-up of 959 days, all-cause mortality and MAACE occurred in 72 (7%) and 93 (9%) patients, respectively. Age and >3 segments with midwall fibrosis on late gadolinium enhancement (LGE) were the only independent predictors of all-cause mortality (HR: 1.036, 95% CI: 1.0117-1.056, P < 0.001 and HR: 2.077, 95% CI: 1.211-3.562, P = 0.008, respectively). For MAACE, the independent predictors were male gender, left ventricular end-diastolic volume index by CMR (CMR-LVEDVi), and >3 segments with midwall fibrosis on LGE (HR: 2.131, 95% CI: 1.231-3.690, P = 0.007; HR: 3.161, 95% CI: 1.750-5.709, P < 0.001; and HR: 1.693, 95% CI: 1.084-2.644, P = 0.021, respectively). A composite clinical and CMR-based risk score provided a net reclassification improvement of 63.7% (P < 0.001) for MAACE occurrence when added to the model based on SOC evaluation. These findings were confirmed in the validation cohort. CONCLUSION: In a large multicentre, multivendor cohort registry reflecting daily clinical practice in NICM work-up, a composite clinical and CMR-based risk score provides incremental prognostic value beyond SOC evaluation, which may have impact on the indication of implantable cardioverter-defibrillator implantation.

Translation, cultural adaptation and validation of the Italian version of the Brief Index of Lupus Damage: the BILDit.

OBJECTIVES: The Brief Index of Lupus Damage (BILD) is an instrument of self-evaluation of organ damage for systemic lupus erythematosus (SLE) patients. The objectives of this study were the translation, cultural adaptation and validation of the Italian version of the BILD (BILDit). METHODS: The process of translation and cultural adaptation followed published guidelines. The BILDit was pretested in a pilot study with 30 SLE patients in order to evaluate acceptability, reliability, comprehension and feasibility, and then validated in consecutive SLE patients attending our clinic. RESULTS: A total of 167 SLE patients were enrolled. In the pilot study, the BILDit demonstrated good acceptability, feasibility and comprehensibility and a very high degree of reliability (Cronbach's α = 1). In the validation cohort, the BILDit showed a significant positive correlation with the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI; ρ = 0.69; p < 0.001). Analysing the item-by-item correlation between the BILDit and the SDI, a good correlation (p < 0.001) was found for 73.1% of the items. In the multivariate analysis, the BILDit showed a significant positive correlation with age and disease duration (p < 0.01). CONCLUSIONS: The BILDit seems to be an acceptable and reliable instrument for patient self-evaluation of disease damage, with a good correlation with the SDI. It can be considered as a screening tool for the evaluation of organ damage starting from the patient's perceptive.

Standard echocardiography versus very-low mechanical index contrast-imaging: left ventricle volumes and ejection fraction multi-reader variability and reference values in a subgroup with no risk factors or cardiac disease.

We retrospectively assessed the rest-phase images of 300 contrast stress- echocardiograms, during which very-low mechanical index (VLMI) imaging with ultrasound enhancing agents (UEAs) was routinely acquired in addition to greyscale echocardiography; intra- and inter-reader variability for left ventricle (LV) volumes and ejection fraction (LVEF) at rest was established in the overall cohort and normal values were calculated in the subset of subjects with no cardiac risk factors or cardiac disease and a normal stress-echocardiogram. Current recommendations for chamber quantification using echocardiography advise the use of UEAs in case of insufficient quality of endocardial visualization, but normal values for LV volumes and LVEF using UEAs have never been published using currently recommended VLMI method. Single-centre retrospective study, enrolling subjects referred to contrast stress- echocardiography for suspect coronary artery disease, including the acquisition of both standard 2D greyscale and bolus UEAs with VLMI, regardless of the image quality. This enables offline measurement of the LV volumes and LVEF for both greyscale and UEAs-VLMI images at rest in all subjects. Images were allocated to 3 readers in random order. Normal range for LV volumes and LVEF was also derived in a subset of apparently healthy subjects. In the 298 exams finally assessed, measurement variability among the three readers was lower with UEAs-VLMI, in particular for end-systolic volumes (intra-class correlation coefficient for concordance improved from 0.855 to 0.916, for LVEF from 0.68 to 0.783, p < 0.01), intra- observer variability reduced (Lin's correlation coefficient for LVEF from 0.747 to 0.857, p < 0.01). Normal mean indexed LV end-diastolic volume with UEAs-VLMI, compared to greyscale imaging, was + 14 ml/m2, while LVEF was + 5 to + 6% points. This is the largest study specifically addressing UEAs-VLMI imaging and comparing data with standard greyscale imaging; it demonstrates a reduction in measurement variability of LV volumes and LVEF. Normal reference values for VLMI ultrasound are reported for the first time in comparison with greyscale values.

Scoping review and bibliometric analysis of Big Data applications for Medication adherence: an explorative methodological study to enhance consistency in literature.

BACKGROUND: Medication adherence has been studied in different settings, with different approaches, and applying different methodologies. Nevertheless, our knowledge and efficacy are quite limited in terms of measuring and evaluating all the variables and components that affect the management of medication adherence regimes as a complex phenomenon. The study aim is mapping the state-of-the-art of medication adherence measurement and assessment methods applied in chronic conditions. Specifically, we are interested in what methods and assessment procedures are currently used to tackle medication adherence. We explore whether Big Data techniques are adopted to improve decision-making procedures regarding patients' adherence, and the possible role of digital technologies in supporting interventions for improving patient adherence and avoiding waste or harm. METHODS: A scoping literature review and bibliometric analysis were used. Arksey and O'Malley's framework was adopted to scope the review process, and a bibliometric analysis was applied to observe the evolution of the scientific literature and identify specific characteristics of the related knowledge domain. RESULTS: A total of 533 articles were retrieved from the Scopus academic database and selected for the bibliometric analysis. Sixty-one studies were identified and included in the final analysis. The Morisky medication adherence scale (36%) was the most frequently adopted baseline measurement tool, and cardiovascular/hypertension disease, the most investigated illness (38%). Heterogeneous findings emerged from the types of study design and the statistical methodologies used to assess and compare the results. CONCLUSIONS: Our findings reveal a lack of Big Data applications currently deployed to address or measure medication adherence in chronic conditions. Our study proposes a general framework to select the methods, measurements and the corpus of variables in which the treatment regime can be analyzed.

Association of PCSK9 plasma levels with metabolic patterns and coronary atherosclerosis in patients with stable angina.

OBJECTIVE: Aim of this study was to evaluate the relationship of plasma PCSK9 with metabolic and inflammatory profile and coronary atherosclerotic burden in patients with suspected CAD enrolled in the EVINCI study. METHODS: PCSK9 was measured in 539 patients (60.3 ± 8.6 years, 256 males) with symptoms of CAD characterized by risk factors, bio-humoral profiles, and treatment. N = 412 patients underwent coronary computed tomography angiography (CTA) to assess the presence and characteristics of coronary atherosclerosis. A CTA score, combining extent, severity, composition, and location of plaques was computed. RESULTS: Patients were divided according to PCSK9 quartiles: I (< 136 ng/mL), II-III (136-266 ng/mL), and IV quartile (> 266 ng/mL). Compared with patients in quartile IV, patients in quartile I had a higher prevalence of the metabolic syndrome and higher values of body mass index. LDL- and HDL-cholesterol were significantly lower in patients in the quartile I than in those in quartile IV. Coronary CTA documented normal vessels in 30% and obstructive CAD in 35% of cases without differences among PCSK9 quartiles. Compared with patients with the highest levels, patients with the lowest PCSK9 levels had a higher CTA score mainly due to higher number of mixed non-obstructive coronary plaques. At multivariable analysis including clinical, medications, and lipid variables, PCSK9 was an independent predictor of the CTA score (coefficient - 0.129, SE 0.03, P < 0.0001), together with age, male gender, statins, interleukin-6, and leptin. CONCLUSION: In patients with stable CAD, low PCSK9 plasma levels are associated with a particular metabolic phenotype (low HDL cholesterol, the metabolic syndrome, obesity, insulin resistance and diabetes) and diffuse non-obstructive coronary atherosclerosis. Trial registration ClinicalTrials.gov NCT00979199. Registered September 17, 2009.

Structured cost analysis of robotic TME resection for rectal cancer: a comparison between the da Vinci Si and Xi in a single surgeon's experience.

BACKGROUND: Robotic-assisted surgery by the da Vinci Si appears to benefit rectal cancer surgery in selected patients, but still has some limitations, one of which is its high costs. Preliminary studies have indicated that the use of the new da Vinci Xi provides some added advantages, but their impact on cost is unknown. The aim of the present study is to compare surgical outcomes and costs of rectal cancer resection by the two platforms, in a single surgeon's experience. METHODS: From April 2010 to April 2017, 90 robotic rectal resections were performed, with either the da Vinci Si (Si-RobTME) or the da Vinci Xi (Xi-RobTME). Based on CUSUM analysis, two comparable groups of 40 consecutive Si-RobTME and 40 consecutive Xi-RobTME were obtained from the prospectively collected database and used for the present retrospective comparative study. Data costs were analysed based on the level of experience on the proficiency-gain curve (p-g curve) by the surgeon with each platform. RESULTS: In both groups, two homogeneous phases of the p-g curve were identified: Si1 and Xi1: cases 1-19, Si2 and Xi2: cases 20-40. A significantly higher number of full RAS operations were achieved in the Xi-RobTME group (p < 0.001). A statistically significant reduction in operating time (OT) during Si2 and Xi2 phase was observed (p < 0.001), accompanied by reduced overall variable costs (OVC), personnel costs (PC) and consumable costs (CC) (p < 0.001). All costs were lower in the Xi2 phase compared to Si2 phase: OT 265 versus 290 min (p = 0.052); OVC 7983 versus 10231.9 (p = 0.009); PC 1151.6 versus 1260.2 (p = 0.052), CC 3464.4 versus 3869.7 (p < 0.001). CONCLUSIONS: Our experience confirms a significant reduction of costs with increasing surgeon's experience with both platforms. However, the economic gain was higher with the Xi with shorter OT, reduced PC and CC, in addition to a significantly larger number of cases performed by the fully robotic approach.

Gastroesophageal reflux symptoms among Italian university students: epidemiology and dietary correlates using automatically recorded transactions.

BACKGROUND: Gastroesophageal reflux disease (GERD) is one of the most common gastrointestinal disorders worldwide, with relevant impact on the quality of life and health care costs.The aim of our study is to assess the prevalence of GERD based on self-reported symptoms among university students in central Italy. The secondary aim is to evaluate lifestyle correlates, particularly eating habits, in GERD students using automatically recorded transactions through cashiers at university canteen. METHODS: A web-survey was created and launched through an app, ad-hoc developed for an interactive exchange of information with students, including anthropometric data and lifestyle habits. Moreover, the web-survey allowed users a self-diagnosis of GERD through a simple questionnaire. As regard eating habits, detailed collection of meals consumed, including number and type of dishes, were automatically recorded through cashiers at the university canteen equipped with an automatic registration system. RESULTS: We collected 3012 questionnaires. A total of 792 students (26.2% of the respondents) reported typical GERD symptoms occurring at least weekly. Female sex was more prevalent than male sex. In the set of students with GERD, the percentage of smokers was higher, and our results showed that when BMI tends to higher values the percentage of students with GERD tends to increase. When evaluating correlates with diet, we found, among all users, a lower frequency of legumes choice in GERD students and, among frequent users, a lower frequency of choice of pasta and rice in GERD students. DISCUSSION: The results of our study are in line with the values reported in the literature. Nowadays, GERD is a common problem in our communities, and can potentially lead to serious medical complications; the economic burden involved in the diagnostic and therapeutic management of the disease has a relevant impact on healthcare costs. CONCLUSIONS: To our knowledge, this is the first study evaluating the prevalence of typical GERD-related symptoms in a young population of University students in Italy. Considering the young age of enrolled subjects, our prevalence rate, relatively high compared to the usual estimates, could represent a further negative factor for the future economic sustainability of the healthcare system.

Budget impact analysis of the use of extended half-life recombinant factor VIII (efmoroctocog alfa) for the treatment of congenital haemophilia a: the Italian National Health System perspective.

BACKGROUND: Congenital haemophilia A (HA) is a rare, inherited, life-long bleeding disorder characterised by prolonged or spontaneous bleeding due to the lack of clotting factor VIII (FVIII) in the body. Treatment for HA involves FVIII replacement therapy and poses great economic burden to National Health Systems and to society. Availability of novel products as extended half-life clotting factor products might change treatment approches and their economic evaluation is essential for an informed treatment choice. Accordingly the objective of the present work is to analyse the economic impact of using efmoroctocog alfa (recombinant factor VIII-Fc fusion protein, rFVIIIFc) for the treatment of children and adults with severe congenital haemophilia A (HA). METHODS: A budget impact analysis was performed to estimate the economic impact of the introduction of rFVIIIFc in the market-mix of products for the treatment of HA. The analysis condidered a 3-year time horizon and the Italian National Health System (INHS) perspective. The model estimated drug costs associated with the treatment of HA in the current scenario - representing the marketplace forecast for the time period of interest assuming that rFVIIFc is not introduced - and a new scenario, assuming that rFVIIIFc is available in the market. The size of the target population was calculated using epidemiological national data. Univariate one-way sensitivity analyses and scenario analyses were performed. RESULTS: Overall 3-year costs of treating the HA population in the current scenario were 555,277,691 Euro for the INHS. With the introduction of rFVIIIFc, the costs were reduced to 541,897,466 Euro suggesting potential savings to the INHS of 13,380,255 Euro. Results were consistent at variation of most of the model's parameters; only in case of lower dosage of conventional products and higher dosage of rFVIIIFc, costs for the INHS increased, in both cases, of about 20 million Euro. CONCLUSIONS: The use of rFVIIIFc for the treatment of HA has been recently approved by the Italian Medicines Agency (AIFA) and this is the first study estimating the financial impact of this new therapeutic alternative in the Italian context. The analysis suggests that rFVIIIFc use does not result in higher expenditure for the INHS.

Effect of Coronary Atherosclerosis and Myocardial Ischemia on Plasma Levels of High-Sensitivity Troponin T and NT-proBNP in Patients With Stable Angina.

OBJECTIVE: Circulating levels of high-sensitivity cardiac troponin T (hs-cTnT) and N terminal pro brain natriuretic peptide (NT-proBNP) are predictors of prognosis in patients with coronary artery disease (CAD). We aimed at evaluating the effect of coronary atherosclerosis and myocardial ischemia on cardiac release of hs-cTnT and NT-proBNP in patients with suspected CAD. APPROACH AND RESULTS: Hs-cTnT and NT-proBNP were measured in 378 patients (60.1±0.5 years, 229 males) with stable angina and unknown CAD enrolled in the Evaluation of Integrated Cardiac Imaging (EVINCI) study. All patients underwent stress imaging to detect myocardial ischemia and coronary computed tomographic angiography to assess the presence and characteristics of CAD. An individual computed tomographic angiography score was calculated combining extent, severity, composition, and location of plaques. In the whole population, the median (25-75 percentiles) value of plasma hs-cTnT was 6.17 (4.2-9.1) ng/L and of NT-proBNP was 61.66 (31.2-132.6) ng/L. In a multivariate model, computed tomographic angiography score was an independent predictor of the plasma hs-cTnT (coefficient 0.06, SE 0.02; P=0.0089), whereas ischemia was a predictor of NT-proBNP (coefficient 0.38, SE 0.12; P=0.0015). Hs-cTnT concentrations were significantly increased in patients with CAD with or without myocardial ischemia (P<0.005), whereas only patients with CAD and ischemia showed significantly higher levels of NT-proBNP (P<0.001). CONCLUSIONS: In patients with stable angina, the presence and extent of coronary atherosclerosis is related with circulating levels of hs-cTnT, also in the absence of ischemia, suggesting an ischemia-independent mechanism of hs-cTnT release. Obstructive CAD causing myocardial ischemia is associated with increased levels of NT-proBNP.