Towards the implementation of law n. 219/2017 on informed consent and advance directives for patients with psychiatric disorders and dementia. Physicians' knowledge, attitudes and practices in four Northern Italian health care facilities

Background: On December 2017 the Italian Parliament approved law n. 219/2017 "Provisions for informed consent and advance directives" regarding challenging legal and bioethical issues related to healthcare decisions and end-of life choices. The law promotes the person's autonomy as a right and provides for the centrality of the individual in every scenario of health care by mean of three tools: informed consent, shared care planning and advance directives. Few years after the approval of the law, we conducted a survey among physicians working in four health care facilities specific for the care of people suffering from psychiatric disorders, cognitive disorders and dementia located in the North of Italy aiming to investigate their perceived knowledge and training need, attitudes regarding law n. 219/2017 provisions, and practices of implementation of the law. Methods: A semi-structured questionnaire was developed on an online platform. The invitation to participate in the survey was sent by email to the potential participants. Information was collected by means of the online platform (Google Forms) which allows to export data in a spreadsheet (Windows Excel) to perform basic statistical analysis (frequency distributions, bar chart representation). Results: Twenty-five out of sixty physicians participated in the survey. None of the respondents value their knowledge of the law as very good, 10 good, 13 neither poor nor good, 1 poor and 1 very poor. All the respondents want to learn more about the law (21 yes and 4 absolutely yes). The majority of respondents agrees with the content of the law as a whole (3 absolutely agree, 13 agree), and on each provision. The question on the clarity of the concept of capacity in the law received mixed answers and this impacted on the physicians' opinion regarding the legitimacy in principle for our groups of patients to realize shared care planning and write advance directives. Thirteen physicians neither introduced the theme of shared care planning nor arranged for shared care planning and the main reason for this was that no patient was in a clinical situation to require it. When shared care planning is realized, a variability in terms of type and number of meetings, mode of tracking and communication is registered. Conclusions: Our survey results indicate a need for more clarity regarding the interpretation and implementation of the law in the patient groups under study. There are in particular two related areas that deserve further discussion: (1) the question of whether these patient groups are in principle legitimized by the law to realize shared care planning or write advance directives; (2) the notion of capacity required by the law and how this notion can be declined in real-life situations

A note on prognostic accuracy evaluation of regression models applied to longitudinal autocorrelated binary data

Background: Focus of this work was on evaluating the prognostic accuracy of two approaches for modelling binary longitudinal outcomes, a Generalized Estimating Equation (GEE) and a likelihood based method, Marginalized Transition Model (MTM), in which a transition model is combined with a marginal generalized linear model describing the average response as a function of measured predictors. Methods: A retrospective study on cardiovascular patients and a prospective study on sciatic pain were used to evaluate discrimination by computing the Area Under the Receiver-Operating-Characteristics curve, (AUC), the Integrated Discrimination Improvement (IDI) and the Net Reclassification Improvement (NRI) at different time occasions. Calibration was also evaluated. A simulation study was run in order to compare model’s performance in a context of a perfect knowledge of the data generating mechanism. Results: Similar regression coefficients estimates and comparable calibration were obtained; an higher discrimination level for MTM was observed. No significant differences in calibration and MSE (Mean Square Error) emerged in the simulation study, that instead confirmed the MTM higher discrimination level. Conclusions: The choice of the regression approach should depend on the scientific question being addressed, i.e. if the overall population-average and calibration or the subject-specific patterns and discrimination are the objectives of interest, and some recently proposed discrimination indices are useful in evaluating predictive accuracy also in a context of longitudinal studie

A note on prognostic accuracy evaluation of regression models applied to longitudinal autocorrelated binary data

Background: Focus of this work was on evaluating the prognostic accuracy of two approaches for modelling binary longitudinal outcomes, a Generalized Estimating Equation (GEE) and a likelihood based method, Marginalized Transition Model (MTM), in which a transition model is combined with a marginal generalized linear model describing the average response as a function of measured predictors. Methods: A retrospective study on cardiovascular patients and a prospective study on sciatic pain were used to evaluate discrimination by computing the Area Under the Receiver-Operating-Characteristics curve, (AUC ), the Integrated Discrimination Improvement (IDI) and the Net Reclassification Improvement (NRI) at different time occasions. Calibration was also evaluated. A simulation study was run in order to compare model’s performance in a context of a perfect knowledge of the data generating mechanism. Results: Similar regression coefficients estimates and comparable calibration were obtained; an higher discrimination level for MTM was observed. No significant differences in calibration and MSE (Mean Square Error) emerged in the simulation study; MTM higher discrimination level was confirmed. ConclusionS: The choice of the regression approach should depend on the scientific question being addressed: whether the overall population-average and calibration are the objectives of interest, or the subject-specific patterns and discrimination. Moreover, some recently proposed discrimination indices are useful in evaluating predictive accuracy also in a context of longitudinal studies

Interhemispheric Asymmetries of Motor Cortex Excitability in the Postacute Stroke Stage

Background and Purpose— Changes in the intracortical inhibition (ICI) and facilitation (ICF) of motor cortex paired-pulse transcranial magnetic stimulation were reported in the affected (AH) and unaffected (UH) hemispheres of stroke patients and reflect some of the mechanisms related to motor cortex plasticity and different degrees of functional recovery. The interhemispheric differences of the ICI/ICF slopes have been found to have a nearly identical time course in the 2 hemispheres of healthy subjects, and whether such symmetry is modified after monohemispheric stroke has not yet been examined. Our goal was to investigate the interhemispheric asymmetries of the time course of ICI/ICF between the AH and UH of stroke patients in the postacute phase of recovery. Methods— ICI/ICF recovery curves to subthreshold-conditioning suprathreshold-test magnetic stimuli were recorded from the paretic and nonparetic hand muscles of 10 well-recovered stroke patients and compared with those of a population of 10 control subjects. Results— In the healthy subjects, ICI/ICF showed a symmetrical time evolution between the 2 hemispheres. In stroke patients, the ICI/ICF slopes were significantly different between the UH and AH; the intracortical inhibition was reduced in the AH and normal in the UH. Conclusions— The defective AH ICI associated with the effective UH ICI could represent a marker of poststroke cortical plasticity implicated as a mechanism relevant to functional recovery. Analysis of the interhemispheric asymmetries of the ICI/ICF recovery curves might provide a valuable neurophysiological parameter in the prognosis and follow-up of patients with monohemispheric stroke

In-cell western assay as a high-throughput approach for Chlamydia trachomatis quantification and susceptibility testing to antimicrobials

Chlamydia trachomatis, the leading cause of bacterial sexually transmitted diseases in developed countries, with around 127 million new cases per year, is mainly responsible for urethritis and cervicitis in women, and urethritis and epididymitis in men. Most C. trachomatis infections remain asymptomatic (>50%) and, hence, untreated, leading to severe reproductive complications in both women and men, like infertility. Therefore, the detection of C. trachomatis as well as the antimicrobial susceptibility testing becomes a priority, and, along the years, several methods have been recommended, like cell culture and direct immunofluorescence (DFA) on cell cultures. Herein, we described the application of In-Cell Western assay (ICW) via Odyssey CLx as a fast, more accessible, and high-throughput platform for the quantification of C. trachomatis and the screening of anti-chlamydial drugs. As a first step, we set up a standard curve by infecting cell monolayers with 2-fold serial dilutions of C. trachomatis Elementary Body (EB) suspension. Then, different unknown C. trachomatis EB suspensions were quantified and the chlamydial susceptibility testing to erythromycin was performed, using the DFA as comparison. Our results showed a very high concordance between these two assays, as evidenced by the enumeration of chlamydial IFUs as well as the determination of erythromycin Minimum Inhibitory Concentration (MIC). In conclusion,the ICW assay may be a promising candidate as an accurate and accessible methodology for C. trachomatis antimicrobial susceptibility testing

Better communication for better management of persons with hemophilia. Results from a patients’-clinicians’ project to address the new therapeutic landscape

Applying the Delphi method, this study aims at characterizing the perceptions and needs of physicians, individuals with hemophilia, and their caregivers in relation to the management of routine visits during regular follow-ups. A single structured questionnaire, prepared by an advisory board, was administered to 139 participants, comprising hemophilia treaters, patients and caregivers, during the period from May to June 2023. Agreement (defined following the Delphi method as developed by RAND Corporation) was reached on several topics. The Principal Component Analysis methods identified the four most relevant areas where consensus was reached among the interviewees, underscoring the necessity for in-depth discussions during routine visits: (1) medical aspects related to symptoms, life-limitations, pain, etc.; (2) non-medical related aspects (ambitions, lifestyle, network, etc.); (3) logistical-organizational aspects (home-hospital distance, alternative modalities of communication); and (4) visit duration and telemedicine integration. The results of both the Delphi and Principal Component Analysis underline that the care of individuals with hemophilia extends beyond merely prescribing drugs or treatment regimens. Instead, it necessitates consideration of numerous variables from both therapeutic and non-therapeutic domains, all of which are deemed important for the holistic management of the individuals. As a result, these aspects are routinely discussed and addressed during visits

Ferric carboxymaltose versus ferric gluconate in hemodialysis patients. Reduction of erythropoietin dose in 4 years of follow-up

Background: Ferric carboxymaltose (FCM) is a parenteral, dextran-free iron formulation designed to overcome the limitations of existing iron preparations. The main aim of this study was to retrospectively examine results obtained from a long period of FCM therapy in hemodialysis patients who have been previously treated with ferric gluconate (FX). Markers of iron metabolism, erythropoietin (EPO) doses, and effects on anemic status have been analysed. Methods: The study was performed with a follow up period of 4 years, when patients were treated before with FX and then switched to FCM. A total of 25 patients were included in the study. Results: FCM increased transferrin saturation (TSAT) levels by 11.9% (P < 0.001) with respect to FX. Events of TSAT less than 20% were reduced during FCM. The monthly dose of EPO was reduced in the FCM period (-6,404.1 international unit [IU]; 95% confidence interval, -10,643.5 IU; -2,164.6 IU; P = 0.003), as well as the erythropoietin resistance index (P = 0.004). During the period with FCM, ferritin levels were higher than during FX (P < 0.001), while transferrin was reduced (P = 0.001). Conclusion: During FCM treatment, minor doses of EPO were administered if compared to those delivered during FX therapy. Stable and on target levels of hemoglobin were maintained with better control of anemia through high levels of ferritin and TSA

Diabetes and metabolic disorders. Their impact on cardiovascular events in liver transplant patients

Cardiovascular diseases are currently one of the most important causes of morbidity and mortality in liver transplant patients over the long term. Therefore, evaluating prognostic factors for cardiovascular events (CVEs) in this population is essential for taking preventive measures. The aim of this study was to identify the impact of diabetes and other metabolic disorders on CVEs in liver transplant patients. Three hundred fifty-six liver transplant recipients who survived at least 6 months after surgery were enrolled. Patients were followed for a median time of 118 months (12–250 months). All cardiovascular events were carefully recorded and detailed in the patients’ charts. Demographic data, diabetes, hypertension, dyslipidemia, weight changes, and a diagnosis of metabolic syndrome both before and after transplantation were noted to assess their possible relationship with CVE. The presence of a diagnosis of metabolic-associated fatty liver disease (MAFLD) was also evaluated. Immunosuppressive therapy was included in the analysis. Diabetes mellitus (DM), especially when present before transplantation, was strongly associated with CVEs (hazard risk HR 3.10; 95% confidence interval CI: 1.60–6.03). Metabolic syndrome was found to be associated with CVEs in univariate analysis (HR 3.24; 95% CI: 1.36–7.8), while pretransplantation and de novo MAFLD were not. Immunosuppressive therapy had no influence on predisposing transplanted patients to CVEs during follow-up. Further prospective studies may be useful in investigating the risk factors for CVEs after liver transplantation and improving the long-term survival of transplant patients

optimizing patient referral and center capacity in the management of chronic hepatitis c lessons from the italian experience

Abstract Aims In 2017 the Italian Drug Agency (Agenzia Italiana del Farmaco, AIFA) revised the criteria for access to therapy for patients with chronic hepatitis C as part of a three-year plan to eradicate HCV. We conducted a Delphi study to determine strategies to identify and treat patients with HCV and to develop through a shared pathway, a model to manage patient referral and optimize prescription center capacity with the overall aim of increasing access to therapy. Methods The process took place in two phases – Phase I (January 2017), before the criteria for treatment of HCV were revised and Phase II (May 2017) when AIFA developed a framework for the eradication of HCV infection in Italy. Two questionnaires were devised with Q1 administered in Phase I and Q2 in Phase II. Results Q1 was sent to 823 hepatitis specialists working in 235 Italian HCV centers authorized to prescribe direct-acting antiviral drugs (DAAs). Overall, 167 centers (71%) participated with a good geographical representativeness (North 69%, Centre 74%; South and islands 70%). 548 prescribers (68.8%) provided responses to Q1 and 443 (80%) specialists who responded to Q1 completed Q2. Over 70% considered that to meet the new therapy targets local/regional networks need to be consolidated and reinforced with GPs providing the 'missing link' in current regional networks. Adherence to therapy was considered important by 75% of clinicians with reduction in follow-up intervals/length considered important by 65% – to free up staff/resources to manage increasing numbers of new patients. About 80% of respondents stated that medical personnel were principally involved in follow-up with follow-up having a significant impact on center capacity. Conclusion Enhancing patient referral, the need for an increased role of GPs, increasing center capacity in particular medical personnel in outpatient centers and greater liaison between Hub centers and healthcare professionals currently managing high-risk groups as yet untreated, were factors that need to be streamlined in order to meet treatment targets for eradication of HCV

TMS-EEG biomarkers of amnestic mild cognitive impairment due to Alzheimer\u27s disease: A proof-of-concept six years prospective study

Background: Early and affordable identification of subjects with amnestic mild cognitive impairment (aMCI) who will convert to Alzheimer’s disease (AD) is a major scientific challenge. Objective: To investigate the neurophysiological hallmarks of sensorimotor cortex function in aMCI under the hypothesis that some may represent the plastic rearrangements induced by neurodegeneration, hence predictors of future conversion to AD. We sought to determine (1) whether the sensorimotor network shows peculiar alterations in patients with aMCI and (2) if sensorimotor network alterations predict long-term disease progression at the individual level. Methods: We studied several transcranial magnetic stimulation (TMS)-electroencephalogram (EEG) parameters of the sensorimotor cortex in a group of patients with aMCI and followed them for 6 years. We then identified aMCI who clinically converted to AD [prodromal to AD-MCI (pAD-MCI)] and those who remained cognitively stable [non-prodromal to AD-MCI (npAD-MCI)]. Results: Patients with aMCI showed reduced motor cortex (M1) excitability and disrupted EEG synchronization [decreased intertrial coherence (ITC)] in alpha, beta and gamma frequency bands compared to the control subjects. The degree of alteration in M1 excitability and alpha ITC was comparable between pAD-MCI and npAD-MCI. Importantly, beta and gamma ITC impairment in the stimulated M1 was greater in pAD-MCI than npAD-MCI. Furthermore, an additional parameter related to the waveform shape of scalp signals, reflecting time-specific alterations in global TMS-induced activity [stability of the dipolar activity (sDA)], discriminated npAD-MCI from MCI who will convert to AD. Discussion: The above mentioned specific cortical changes, reflecting deficit of synchronization within the cortico-basal ganglia-thalamo-cortical loop in aMCI, may reflect the pathological processes underlying AD. These changes could be tested in larger cohorts as neurophysiological biomarkers of AD