In silico analysis of TTR gene (coding and non-coding regions, and interactive network) and its implications in transthyretin-related amyloidosis.

Introduction: Transthyretin (TTR)-related amyloidosis is a life-threatening disease. Currently, several questions about the pathogenic mechanisms of TTR-related amyloidosis remain unanswered. Methods: We have investigated various TTR-related issues using different in silico approaches. Results: Using an amino acid similarity-based analysis, we have indicated the most relevant TTR secondary structures in determining mutation impact. Our amyloidogenic propensity analysis of TTR missense substitutions has highlighted a similar pattern for wild-type and mutated TTR amino b acid sequences. However, some mutations present differences with respect to the general distribution. We have identified non-coding variants in cis-regulatory elements of the TTR gene, and our analysis on V122I-related haplotypes has indicated differences in non-coding regulatory variants, suggesting differences among V122I carriers. The analysis of methylation status indicated CpG sites that may affect TTR expression. Finally, our interactive network analysis revealed functional partners of TTR that may play a modifier role in the pathogenesis of TTR-related amyloidosis. Discussion and conclusion: Our data provided new insights into the pathogenesis of TTR-related amyloidosis that, if they were to be confirmed through experimental investigations, could significantly improve our understanding of the disease

Human pharmacogenomic variation of antihypertensive drugs: from population genetics to personalized medicine.

AIM: To investigate the human pharmacogenetic variation related to antihypertensive drugs, providing a survey of functional interpopulation differences in hypertension pharmacogenes. MATERIALS & METHODS: The study was divided into two stages. In the first stage, we analyzed 1249 variants located in 57 hypertension pharmacogenes. This first-stage analysis confirmed that geographic origin strongly affects hypertension pharmacogenomic variation and that 31 pharmacogenes are geographically differentiated. In the second stage, we focused our attention on the ethnic-differentiated pharmacogenes, investigating 55,521 genetic variants. In silico analyses were performed to predict the effect of genetic variation. RESULTS: Our analyses indicated functional interpopulation differences, suggesting insight into the mechanisms of antihypertensive drug response. Moreover, our data suggested that rare variants mainly determine the functionality of genes related to antihypertensive drugs. CONCLUSION: Our study provided important knowledge about the genetics of the antihypertensive drug response, suggesting that next-generation sequencing technologies may develop reliable pharmacogenetic tests for antihypertensive drugs

Left ventricular midwall mechanics at 24 weeks' gestation in high-risk normotensive pregnant women: Relationship to placenta-related complications of pregnancy

Most studies during pregnancy have assessed maternal left ventricular (LV) function by load-dependent indices, assessing only chamber function. The aim of this study was to assess afterload-adjusted LV myocardial and chamber systolic function at 24 weeks' gestation and 6 months postpartum in high-risk normotensive pregnant women

Modelling Hospital Medical Wards to Address Patient Complexity: A Case-Based Simulation-Optimization Approach

In this paper we focus on patient flows inside Internal Medicine Departments, with the aim of supporting new organizational models taking into account the patient relevant characteristics such as complexity and frailty. The main contribution of this paper is to develop a Discrete Event Simulation model to describe in detail the pathways of complex patients through medical hospital wards. The model has been applied to reproduce a case study of an Italian middle size hospital. The objective is quantifying the impact on resource use and outcome of introducing a new organizational model for medical departments. The re-organization is mainly focused on changing the available beds assignment among the wards to better address the complexity of care of patients with comorbidities. Following a patient-centered approach, patients are segmented considering the clinical characteristics (i.e. the pathology, proxy of Diagnoses Related Groups classification) and sub-grouped considering other characteristics, such as comorbidities and ward of admission. Then, an optimization component embedded into the model chooses the best pooling strategy to reorganize medical wards, determining the corresponding number of beds able to improve process indicators, such as length of stay. The simulation model is presented, and preliminary results are analyzed and discussed

I diritti negati agli anziani: quali implicazioni per la salute?

Perchè gli internisti devono occuparsi dei diritti negati agli anziani? M. Campanini, P. Gnerre, A. Fontanella Diritti negati, abusi, maltrattamenti e neglect nell’anziano: macrofenomeno mondiale sommerso, sostanzialmente misconosciuto o trascurato P. Calogero, A. Salsi Il diritto al coordinamento delle cure e alla continuità assistenziale nella gestione delle malattie croniche: strumenti disponibili oggi e quali potenzialmente fruibili in futuro? F. Orlandini La mancata pianificazione dei fabbisogni di medici e di specialisti in Italia nel Servizio Sanitario pubblico. Quali conseguenze in rapporto all’invecchiamento della popolazione? D. Montemurro, M. D’Arienzo, C. Rivetti, E. Marcante, F. Ragazzo, P. Di Silverio, A. Rossi, C. Palermo I rischi di un eccesso di cure negli anziani: fare di più non significa fare meglio anche nell’anziano M. Bobbio Pensionamento: ritirarsi dal lavoro, non dalla vita né da un futuro di buona salute R. Nardi, D. Borioni, D. Tirotta, F. Berti, G. Pinna¸ S. Ehrlich, G. Pentella, P. Cosma, R. Rapetti, A. Fontanella Gestione della depressione, inevitabile compagna del paziente anziano E. Pecoraro, S. La Carrubba La sessualità nell’anziano V. Duretto, G. Pinna Gli ostacoli metodologici nella comunicazione con il paziente anziano M. Felici, A. Tufi, A. Pulerà, S. Lenti L’importanza della capacità di educare all’autogestione delle malattie croniche (self-management) per prevenire l’aggravamento e i ricoveri ripetuti non programmati M. La Regina, A. Greco Le cure di fine vita negli anziani: il diritto di morire bene L. Lusiani, C. Santini Il programma delle otto R: utopia o possibile realtà per migliorare l’assistenza agli anziani? F. D’Amore

Green line hospital-territory study: A single-blind randomized clinical trial for evaluation of technological challenges of continuous wireless monitoring in internal medicine, preliminary results

Background: Wireless vital parameter continuous monitoring (WVPCM) after discharge is compared to regular monitoring to provide data on the clinical-economic impact of complex patients (CPs) discharged from Internal Medicine Units of Ospedale dei Castelli, Lazio. Primary outcome: Major complications (MC) reduction. Secondary outcomes: Patients who reached discharge criteria within the 7th day from admission; difference in MC incidence at the conclusion of the standard telemonitoring/clinical monitoring phase, 5 and 30 days after discharge; and conditions predisposing to MC occurrence. Methods: Open label randomized controlled trial with wearable wireless system that creates alerts on portable devices. Continuous glycemic monitoring is performed for patients with diabetes mellitus. Results: There were 110 patients enrolled (mean age: 76.2 years). Comorbidity: Cumulative Illness Rating Scale CIRS-CI (comorbidities index): 3.93, CIRS SI (severity index): 1.93. About 19% scored a BRASS (Blaylock Risk Assessment Screening Score) ≥20 indicating need for discharge planning requiring step-down care. Globally, 48% of patients in the control group had major complications (27 out of 56 patients), in contrast to 22% in the intervention group (12 out of 54 patients). Conclusions: Since WVPCM detects early complications during the post-discharge CPs monitoring, it increases safety and reduces inappropriate access to the Emergency Room, preventing avoidable re-hospitalizations

Predicting candidemia in internal medicine departments: are we chasing the Holy Grail?

Candidemia is a challenging clinical condition with high rates of morbidity and mortality.1 Key requirements for its prompt management include early identification and timely initiation of appropriate systemic antifungal therapy, consistently reported as a major determinant of survival. However, the diagnosis of candidemia can be challenging and is often delayed as there are no specific clinical signs, blood cultures have low sensitivity, and detection of fungal blood cultures takes a long time. In addition, there is evidence that a significant percentage of such infections occurs in patients admitted to internal medicine departments. This is not particularly surprising given the advanced age of many inpatients at internal medicine departments and multiple complex comorbidities. Moreover, related therapies and healthcare system contacts often involve the use of central venous catheters and other indwelling devices, potentially entailing high risk of candidemia.2 Therefore, optimization of the diagnostic and therapeutic approach is an important and still unfulfilled need for the management of candidemia in internal medicine department

Blood pressure control and treatment adherence in hypertensive patients with metabolic syndrome: protocol of a randomized controlled study based on home blood pressure telemonitoring vs. conventional management and assessment of psychological determinants of adherence (TELEBPMET Study).

BACKGROUND: Inadequate blood pressure control and poor adherence to treatment remain among the major limitations in the management of hypertensive patients, particularly of those at high risk of cardiovascular events. Preliminary evidence suggests that home blood pressure telemonitoring (HBPT) might help increasing the chance of achieving blood pressure targets and improve patient's therapeutic adherence. However, all these potential advantages of HBPT have not yet been fully investigated. METHODS/DESIGN: The purpose of this open label, parallel group, randomized, controlled study is to assess whether, in patients with high cardiovascular risk (treated or untreated essential arterial hypertension--both in the office and in ambulatory conditions over 24 h--and metabolic syndrome), long-term (48 weeks) blood pressure control is more effective when based on HBPT and on the feedback to patients by their doctor between visits, or when based exclusively on blood pressure determination during quarterly office visits (conventional management (CM)). A total of 252 patients will be enrolled and randomized to usual care (n = 84) or HBPT (n = 168). The primary study endpoint will be the rate of subjects achieving normal daytime ambulatory blood pressure targets (< 135/85 mmHg) 24 weeks and 48 weeks after randomization. In addition, the study will assess the psychological determinants of adherence and persistence to drug therapy, through specific psychological tests administered during the course of the study. Other secondary study endpoints will be related to the impact of HBPT on additional clinical and economic outcomes (number of additional medical visits, direct costs of patient management, number of antihypertensive drugs prescribed, level of cardiovascular risk, degree of target organ damage and rate of cardiovascular events, regression of the metabolic syndrome). DISCUSSION: The TELEBPMET Study will show whether HBPT is effective in improving blood pressure control and related medical and economic outcomes in hypertensive patients with metabolic syndrome. It will also provide a comprehensive understanding of the psychological determinants of medication adherence and blood pressure control of these patients

Stratification of the risk of developing severe or lethal Covid-19 using a new score from a large Italian population: A population-based cohort study

Objectives To develop a population-based risk stratification model (COVID-19 Vulnerability Score) for predicting severe/fatal clinical manifestations of SARS-CoV-2 infection, using the multiple source information provided by the healthcare utilisation databases of the Italian National Health Service. Design Retrospective observational cohort study. Setting Population-based study using the healthcare utilisation database from five Italian regions. Participants Beneficiaries of the National Health Service, aged 18-79 years, who had the residentship in the five participating regions. Residents in a nursing home were not included. The model was built from the 7 655 502 residents of Lombardy region. Main outcome measure The score included gender, age and 29 conditions/diseases selected from a list of 61 conditions which independently predicted the primary outcome, that is, severe (intensive care unit admission) or fatal manifestation of COVID-19 experienced during the first epidemic wave (until June 2020). The score performance was validated by applying the model to several validation sets, that is, Lombardy population (second epidemic wave), and the other four Italian regions (entire 2020) for a total of about 15.4 million individuals and 7031 outcomes. Predictive performance was assessed by discrimination (areas under the receiver operating characteristic curve) and calibration (plot of observed vs predicted outcomes). Results We observed a clear positive trend towards increasing outcome incidence as the score increased. The areas under the receiver operating characteristic curve of the COVID-19 Vulnerability Score ranged from 0.85 to 0.88, which compared favourably with the areas of generic scores such as the Charlson Comorbidity Score (0.60). A remarkable performance of the score on the calibration of observed and predicted outcome probability was also observed. Conclusions A score based on data used for public health management accurately predicted the occurrence of severe/fatal manifestations of COVID-19. Use of this score may help health decision-makers to more accurately identify high-risk citizens who need early preventive or treatment interventions